start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=23 article-no= start-page=5374 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Effect of Honeycomb beta-Tricalcium Phosphate on Zygomatic Bone Regeneration in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, artificial bones with high biocompatibility have been developed for hard tissue reconstruction. However, current bone replacement methods are inadequate for large defects, causing infection, exposure, and damage. We have developed a new honeycomb beta-tricalcium phosphate (TCP) material, which achieved good bone regeneration after implantation in a rat complete zygomatic bone defect. In this study, we further investigated the ability of honeycomb beta- TCP for remodeling after bone regeneration as a long-term result. Bone morphogenic protein (BMP)-2-free honeycomb beta-TCP (TCP group) and honeycomb beta-TCP with BMP-2 (BMP group) were implanted in the zygomatic bone of rats. Micro-computed tomography was performed to track the zygomatic bone morphology, and specimens were histologically examined for osteogenesis and remodeling. In the TCP group, no bone formation was observed at 1 month, but it was observed at 6 months. Bone formation was observed in the BMP group at 1 month, and beta-TCP absorption reproducing the zygomatic bone morphology was observed at 6 months. This honeycomb beta-TCP with BMP-2 may provide appropriate remodeling that reproduces good bone formation in the early stage and good morphology in the long term, offering an alternative bone reconstruction material to vascularized bone grafts. en-copyright= kn-copyright= en-aut-name=NakagiriRyoko en-aut-sei=Nakagiri en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeSatoko en-aut-sei=Watanabe en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeToshiyuki en-aut-sei=Watanabe en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Life Science, Faculty of Science, University Science kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bioceramic kn-keyword=bioceramic en-keyword=bone tissue regeneration kn-keyword=bone tissue regeneration en-keyword=honeycomb beta-TCP kn-keyword=honeycomb beta-TCP en-keyword=bone remodeling kn-keyword=bone remodeling en-keyword=reproduction of morphology kn-keyword=reproduction of morphology END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=24 article-no= start-page=9504 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular Features and Clinical Management of Hereditary Gynecological Cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests. en-copyright= kn-copyright= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Center for Medical Genetics, Keio Cancer Center, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=hereditary gynecological cancer kn-keyword=hereditary gynecological cancer en-keyword=multi-gene testing kn-keyword=multi-gene testing en-keyword=tumor profiling kn-keyword=tumor profiling en-keyword=hereditary breast and ovarian cancer (HBOC) kn-keyword=hereditary breast and ovarian cancer (HBOC) en-keyword=Lynch kn-keyword=Lynch en-keyword=Li–Fraumeni kn-keyword=Li–Fraumeni en-keyword=Cowden kn-keyword=Cowden en-keyword=Peutz–Jeghers kn-keyword=Peutz–Jeghers en-keyword=syndrome kn-keyword=syndrome END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=24 article-no= start-page=9352 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Inhibitory Role of Rab11b in Osteoclastogenesis through Triggering Lysosome-Induced Degradation of c-Fms and RANK Surface Receptors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rab11b, abundantly enriched in endocytic recycling compartments, is required for the establishment of the machinery of vesicle trafficking. Yet, no report has so far characterized the biological function of Rab11b in osteoclastogenesis. Using in vitro model of osteoclasts differentiated from murine macrophages like RAW-D cells or bone marrow-derived macrophages, we elucidated that Rab11b served as an inhibitory regulator of osteoclast differentiation sequentially via (i) abolishing surface abundance of RANK and c-Fms receptors; and (ii) attenuating nuclear factor of activated T-cells c1 (NFATc-1) upstream signaling cascades, following RANKL stimulation. Rab11b was localized in early and late endosomes, Golgi complex, and endoplasmic reticulum; moreover, its overexpression enlarged early and late endosomes. Upon inhibition of lysosomal function by a specific blocker, chloroquine (CLQ), we comprehensively clarified a novel function of lysosomes on mediating proteolytic degradation of c-Fms and RANK surface receptors, drastically ameliorated by Rab11b overexpression in RAW-D cell-derived osteoclasts. These findings highlight the key role of Rab11b as an inhibitor of osteoclastogenesis by directing the transport of c-Fms and RANK surface receptors to lysosomes for degradation via the axis of early endosomes-late endosomes-lysosomes, thereby contributing towards the systemic equilibrium of the bone resorption phase. en-copyright= kn-copyright= en-aut-name=TranManh Tien en-aut-sei=Tran en-aut-mei=Manh Tien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FengYunxia en-aut-sei=Feng en-aut-mei=Yunxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuMasatoshi en-aut-sei=Morimatsu en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WeiPenggong en-aut-sei=Wei en-aut-mei=Penggong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KadowakiTomoko en-aut-sei=Kadowaki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakaiEiko en-aut-sei=Sakai en-aut-mei=Eiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsukubaTakayuki en-aut-sei=Tsukuba en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Frontier Oral Science, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=9 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=10 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=13 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Rab11b kn-keyword=Rab11b en-keyword=c-Fms kn-keyword=c-Fms en-keyword=RANK kn-keyword=RANK en-keyword=NFATc-1 kn-keyword=NFATc-1 en-keyword=osteoclasts kn-keyword=osteoclasts en-keyword=vesicular transport kn-keyword=vesicular transport END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=12 article-no= start-page=2947 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Flexural Strength of Resin Core Build-Up Materials: Correlation to Root Dentin Shear Bond Strength and Pull-Out Force en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aims of this study were to investigate the effects of root dentin shear bond strength and pull-out force of resin core build-up materials on flexural strength immediately after setting, after one-day water storage, and after 20,000 thermocycles. Eight core build-up and three luting materials were investigated, using 10 specimens (n = 10) per subgroup. At three time periods-immediately after setting, after one-day water storage, and after 20,000 thermocycles, shear bond strengths to root dentin and pull-out forces were measured. Flexural strengths were measured using a 3-point bending test. For all core build-up and luting materials, the mean data of flexural strength, shear bond strength and pull-out force were the lowest immediately after setting. After one-day storage, almost all the materials yielded their highest results. A weak, but statistically significant, correlation was found between flexural strength and shear bond strength (r = 0.508, p = 0.0026, n = 33). As the pull-out force increased, the flexural strength of core build-up materials also increased (r = 0.398, p = 0.0218, n = 33). Multiple linear regression analyses were conducted using these three independent factors of flexural strength, pull-out force and root dentin shear bond strength, which showed this relationship: Flexural strength = 3.264 x Shear bond strength + 1.533 x Pull out force + 10.870, p = 0.002). For all the 11 core build-up and luting materials investigated immediately after setting, after one-day storage and after 20,000 thermocycles, their shear bond strengths to root dentin and pull-out forces were correlated to the flexural strength in core build-up materials. It was concluded that the flexural strength results of the core build-up material be used in research and quality control for the predictor of the shear bond strength to the root dentin and the retentive force of the post. en-copyright= kn-copyright= en-aut-name=IrieMasao en-aut-sei=Irie en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishigawaGoro en-aut-sei=Nishigawa en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Occlusion and Removable Prosthodontics, Okayama University kn-affil= affil-num=3 en-affil=Department of Occlusion and Removable Prosthodontics, Okayama University kn-affil= affil-num=4 en-affil=National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute kn-affil= affil-num=5 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=flexural strength kn-keyword=flexural strength en-keyword=resin core build-up materials kn-keyword=resin core build-up materials en-keyword=durability kn-keyword=durability en-keyword=pull-out force kn-keyword=pull-out force en-keyword=bond strength kn-keyword=bond strength END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=4 article-no= start-page=269 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary Manifestations of Plasma Cell Type Idiopathic Multicentric Castleman Disease: A Clinicopathological Study in Comparison with IgG4-Related Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage. en-copyright= kn-copyright= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IgawaTakuro en-aut-sei=Igawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GionYuka en-aut-sei=Gion en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaSakura en-aut-sei=Tomita en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueDai en-aut-sei=Inoue en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IzumozakiAkira en-aut-sei=Izumozaki en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UbaraYoshifumi en-aut-sei=Ubara en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Tokai University School of Medicine kn-affil= affil-num=5 en-affil=Department of Radiology, Kanazawa University Graduate School of Medical Sciences kn-affil= affil-num=6 en-affil=Department of Radiology, Kanazawa University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Nephrology Center, Toranomon Hospital Kajigaya kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=plasma cell type idiopathic multicentric Castleman disease kn-keyword=plasma cell type idiopathic multicentric Castleman disease en-keyword=IL-6 kn-keyword=IL-6 en-keyword=IgG4-related disease kn-keyword=IgG4-related disease en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=hyper IL-6 syndrome kn-keyword=hyper IL-6 syndrome END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=995 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of the Clinico-Microbiological Characteristics of Culture-Positive and Culture-Negative Septic Pulmonary Embolism: A 10-Year Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Septic pulmonary embolism (SPE) is a rare yet serious infectious disorder with nonspecific clinical findings due to microorganism-containing emboli disseminating from extrapulmonary infectious foci. It is unknown whether a positive blood culture correlates with a worse clinical outcome. We compared the clinical and microbiologic characteristics of patients with SPE divided into the culture-positive group and the culture-negative one. This study was a retrospective observational study of the patients diagnosed with SPE and treated in an academic hospital from April 2010 to May 2020. We identified six culture-positive and four culture-negative patients with SPE during the study period. The culture-positive group had significantly longer periods of hospitalization (median: 75 days, range: 45-125 days) than the culture-negative group (median: 14.5 days, range: 3-43 days) (p < 0.05), as well as significantly elevated serum C-reactive protein and procalcitonin. Patients with culture-negative SPE more commonly had odontogenic infections as the primary infectious foci. Our study highlights the importance of giving extra attention to SPE patients who have a positive blood culture, as they may have worse clinical outcomes. Physicians need to collaborate with dentists when faced with patients with culture-negative SPE, since they may have primary odontogenic infections. en-copyright= kn-copyright= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= en-keyword=septic pulmonary embolism kn-keyword=septic pulmonary embolism en-keyword=blood culture kn-keyword=blood culture en-keyword=procalcitonin kn-keyword=procalcitonin END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=2650 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Mobility Group Box-1 and Blood-Brain Barrier Disruption en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood–brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer’s amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption. en-copyright= kn-copyright= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=high mobility group box-1 kn-keyword=high mobility group box-1 en-keyword=blood-brain barrier kn-keyword=blood-brain barrier en-keyword=inflammation kn-keyword=inflammation en-keyword=stroke kn-keyword=stroke en-keyword=trauma kn-keyword=trauma en-keyword=vascular endothelial cell kn-keyword=vascular endothelial cell en-keyword=pericyte kn-keyword=pericyte en-keyword=monoclonal antibody kn-keyword=monoclonal antibody END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=2623 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuron-Astrocyte Interactions in Parkinson's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=astrocyte kn-keyword=astrocyte en-keyword=Parkinson’s disease kn-keyword=Parkinson’s disease en-keyword=dopaminergic neuron kn-keyword=dopaminergic neuron en-keyword=neuroinflammation kn-keyword=neuroinflammation en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=alpha-synuclein kn-keyword=alpha-synuclein en-keyword=mitochondria kn-keyword=mitochondria END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=12 article-no= start-page=1070 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Lipid Bilayer Formed on a Hydrogel Bead for Single Ion Channel Recordings en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ion channel proteins play important roles in various cell functions, making them attractive drug targets. Artificial lipid bilayer recording is a technique used to measure the ion transport activities of channel proteins with high sensitivity and accuracy. However, the measurement efficiency is low. In order to improve the efficiency, we developed a method that allows us to form bilayers on a hydrogel bead and record channel currents promptly. We tested our system by measuring the activities of various types of channels, including gramicidin, alamethicin, alpha-hemolysin, a voltage-dependent anion channel 1 (VDAC1), a voltage- and calcium-activated large conductance potassium channel (BK channel), and a potassium channel from Streptomyces lividans (KcsA channel). We confirmed the ability for enhanced measurement efficiency and measurement system miniaturizion. en-copyright= kn-copyright= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoDaiki en-aut-sei=Yamamoto en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayakawaTohru en-aut-sei=Hayakawa en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiseShintaro en-aut-sei=Mise en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoAkinobu en-aut-sei=Matsumoto en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Bio Photonics Laboratory, The Graduate School for the Creation of New Photonics Industries kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=6 en-affil=Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=7 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=ion channel kn-keyword=ion channel en-keyword=lipid bilayer kn-keyword=lipid bilayer en-keyword=single-channel recording kn-keyword=single-channel recording END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=22 article-no= start-page=5155 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Geometrical Structure of Honeycomb TCP to Control Dental Pulp-Derived Cell Differentiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, dental pulp has been attracting attention as a promising source of multipotent mesenchymal stem cells (MSCs) for various clinical applications of regeneration fields. To date, we have succeeded in establishing rat dental pulp-derived cells showing the characteristics of odontoblasts under in vitro conditions. We named them Tooth matrix-forming, GFP rat-derived Cells (TGC). However, though TGC form massive dentin-like hard tissues under in vivo conditions, this does not lead to the induction of polar odontoblasts. Focusing on the importance of the geometrical structure of an artificial biomaterial to induce cell differentiation and hard tissue formation, we previously have succeeded in developing a new biomaterial, honeycomb tricalcium phosphate (TCP) scaffold with through-holes of various diameters. In this study, to induce polar odontoblasts, TGC were induced to form odontoblasts using honeycomb TCP that had various hole diameters (75, 300, and 500 mu m) as a scaffold. The results showed that honeycomb TCP with 300-mu m hole diameters (300TCP) differentiated TGC into polar odontoblasts that were DSP positive. Therefore, our study indicates that 300TCP is an appropriate artificial biomaterial for dentin regeneration. en-copyright= kn-copyright= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=QiushengShan en-aut-sei=Qiusheng en-aut-mei=Shan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FushimiShigeko en-aut-sei=Fushimi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=dental pulp kn-keyword=dental pulp en-keyword=honeycomb TCP kn-keyword=honeycomb TCP en-keyword=matrix formation kn-keyword=matrix formation en-keyword=dentin formation kn-keyword=dentin formation en-keyword=geometrical structure kn-keyword=geometrical structure en-keyword=scaffold kn-keyword=scaffold END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=22 article-no= start-page=8623 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between Household Exposure to Secondhand Smoke and Dental Caries among Japanese Young Adults: A Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The long-term effects of secondhand smoke (SHS) on dental caries among Japanese young adults remain unclear. The purpose of this cross-sectional study was to evaluate whether household exposure to SHS is associated with dental caries in permanent dentition among Japanese young adults. The study sample included 1905 first-year university students (age range: 18-19 years) who answered a questionnaire and participated in oral examinations. The degree of household exposure to SHS was categorized into four levels according to the SHS duration: no experience (-), past, current SHS < 10 years, and current SHS >= 10 years. Dental caries are expressed as the total number of decayed, missing, and filled teeth (DMFT) score. The relationships between SHS and dental caries were determined by logistic regression analysis. DMFT scores (median (25th percentile, 75th percentile)) were significantly higher in the current SHS >= 10 years (median: 1.0 (0.0, 3.0)) than in the SHS-(median: 0.0 (0.0, 2.0)); p = 0.001). DMFT >= 1 was significantly associated with SHS >= 10 years (adjusted odds ratio: 1.50, 95% confidence interval: 1.20-1.87, p < 0.001). Long-term exposure to SHS (>= 10 years) was associated with dental caries in permanent dentition among Japanese young adults. en-copyright= kn-copyright= en-aut-name=SahoHikari en-aut-sei=Saho en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Taniguchi-TabataAyano en-aut-sei=Taniguchi-Tabata en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoiAya en-aut-sei=Yokoi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaKouta en-aut-sei=Kataoka en-aut-mei=Kouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IslamMd Monirul en-aut-sei=Islam en-aut-mei=Md Monirul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawadaNanami en-aut-sei=Sawada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakashimaYukiho en-aut-sei=Nakashima en-aut-mei=Yukiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DeguchiJunya en-aut-sei=Deguchi en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YonedaToshiki en-aut-sei=Yoneda en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Health Service Center, Okayama University kn-affil= affil-num=16 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=secondhand smoke kn-keyword=secondhand smoke en-keyword=dental caries kn-keyword=dental caries en-keyword=permanent dentition kn-keyword=permanent dentition en-keyword=young adult kn-keyword=young adult END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=3158 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Organic Matter Clogging Results in Undeveloped Hardpan and Soil Mineral Leakage in the Rice Terraces in the Philippine Cordilleras en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice terraces in Cordillera, Philippines, a world cultural heritage site, are threatened by the risk of collapse. It is crucial to manage these rice terraces for their conservation, while simultaneously practicing traditional farming. We examined the soil environment and investigated its effects on rice terrace conservation, by focusing on the hardpan condition; infiltration process, which is related to the collapse of rice terraces; and soil nutrition conditions in these sites. Field survey and soil analysis revealed that in areas where the hardpan was not sufficiently developed and water infiltration was effectively suppressed, organic matter content was significantly high, suggesting organic matter clogging. In these rice terraces, the amounts of P, K, Ca, and Mn were significantly low, showing the mineral leaching under reductive soil conditions. Therefore, hardpan formation, rather than organic matter clogging, is essential for the suppression of infiltration and prevention of potential terrace collapse. Because hardpan formation or organic matter clogging cannot be identified from the surface of flooded rice paddies, it is difficult to identify the influencing factor. Thus, we suggest that the hard soil layer should be checked before the planting season and drainage is allowed after the cropping season in the rainy season. en-copyright= kn-copyright= en-aut-name=KurozumiTomoyo en-aut-sei=Kurozumi en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriYasushi en-aut-sei=Mori en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SomuraHiroaki en-aut-sei=Somura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=O-HowMilagros en-aut-sei=O-How en-aut-mei=Milagros kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Universal Harvester Inc. kn-affil= en-keyword=rice terrace kn-keyword=rice terrace en-keyword=hardpan kn-keyword=hardpan en-keyword=infiltration kn-keyword=infiltration en-keyword=organic matter kn-keyword=organic matter en-keyword=clogging kn-keyword=clogging en-keyword=Philippine Cordillera kn-keyword=Philippine Cordillera END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=22 article-no= start-page=5099 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Micro-Architectural Investigation of Teleost Fish Rib Inducing Pliant Mechanical Property en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite the fact that various reports have been discussing bone tissue regeneration, precise bone tissue manipulation, such as controlling the physical properties of the regenerated bone tissue, still remains a big challenge. Here, we focused on the teleost fish ribs showing flexible and tough mechanical properties to obtain a deeper insight into the structural and functional features of bone tissue from different species, which would be valuable for the superior design of bone-mimicking materials. Herein, we examined their compositions, microstructure, histology, and mechanical properties. The first rib of Carassius langsdorfii showed a higher Young's modulus with a small region of chondrocyte clusters compared with other smaller ribs. In addition, highly oriented collagen fibers and osteocytes were observed in the first rib, indicating that the longest first rib would be more mature. Moreover, the layer-by-layer structure of the oriented bone collagen was observed in each rib. These microarchitectural and compositional findings of fish rib bone would give one the useful idea to reproduce such a highly flexible rib bone-like material. en-copyright= kn-copyright= en-aut-name=JiaoYu Yang en-aut-sei=Jiao en-aut-mei=Yu Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=XieShi Chao en-aut-sei=Xie en-aut-mei=Shi Chao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoTakayoshi en-aut-sei=Nakano en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University kn-affil= affil-num=7 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bone-like material kn-keyword=bone-like material en-keyword=mechanical property kn-keyword=mechanical property en-keyword=orientation kn-keyword=orientation en-keyword=layered structure kn-keyword=layered structure END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=11 article-no= start-page=1534 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep Learning for Osteoporosis Classification Using Hip Radiographs and Patient Clinical Covariates en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study considers the use of deep learning to diagnose osteoporosis from hip radiographs, and whether adding clinical data improves diagnostic performance over the image mode alone. For objective labeling, we collected a dataset containing 1131 images from patients who underwent both skeletal bone mineral density measurement and hip radiography at a single general hospital between 2014 and 2019. Osteoporosis was assessed from the hip radiographs using five convolutional neural network (CNN) models. We also investigated ensemble models with clinical covariates added to each CNN. The accuracy, precision, recall, specificity, negative predictive value (npv), F1 score, and area under the curve (AUC) score were calculated for each network. In the evaluation of the five CNN models using only hip radiographs, GoogleNet and EfficientNet b3 exhibited the best accuracy, precision, and specificity. Among the five ensemble models, EfficientNet b3 exhibited the best accuracy, recall, npv, F1 score, and AUC score when patient variables were included. The CNN models diagnosed osteoporosis from hip radiographs with high accuracy, and their performance improved further with the addition of clinical covariates from patient records. en-copyright= kn-copyright= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitamuraAkira en-aut-sei=Kitamura en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoRyosuke en-aut-sei=Goto en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NodaTomoyuki en-aut-sei=Noda en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawasakiKeisuke en-aut-sei=Kawasaki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Search Space Inc. kn-affil= affil-num=4 en-affil=Search Space Inc. kn-affil= affil-num=5 en-affil=Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=osteoporosis kn-keyword=osteoporosis en-keyword=deep learning kn-keyword=deep learning en-keyword=hip radiograph kn-keyword=hip radiograph en-keyword=ensemble model kn-keyword=ensemble model END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=11 article-no= start-page=2384 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-kappa B ligand (RANKL). Rab11A GTPase, belonging to Rab11 subfamily representing the largest branch of Ras superfamily of small GTPases, has been identified as one of the crucial regulators of cell surface receptor recycling. Nevertheless, the regulatory role of Rab11A in osteoclast differentiation has been completely unknown. In this study, we found that Rab11A was strongly upregulated at a late stage of osteoclast differentiation derived from bone marrow-derived macrophages (BMMs) or RAW-D murine osteoclast precursor cells. Rab11A silencing promoted osteoclast formation and significantly increased the surface levels of c-fms and receptor activator of nuclear factor-kappa B (RANK) while its overexpression attenuated osteoclast formation and the surface levels of c-fms and RANK. Using immunocytochemical staining for tracking Rab11A vesicular localization, we observed that Rab11A was localized in early and late endosomes, but not lysosomes. Intriguingly, Rab11A overexpression caused the enhancement of fluorescent intensity and size-based enlargement of early endosomes. Besides, Rab11A overexpression promoted lysosomal activity via elevating the endogenous levels of a specific lysosomal protein, LAMP1, and two key lysosomal enzymes, cathepsins B and D in osteoclasts. More importantly, inhibition of the lysosomal activity by chloroquine, we found that the endogenous levels of c-fms and RANK proteins were enhanced in osteoclasts. From these observations, we suggest a novel function of Rab11A as a negative regulator of osteoclastogenesis mainly through (i) abolishing the surface abundance of c-fms and RANK receptors, and (ii) upregulating lysosomal activity, subsequently augmenting the degradation of c-fms and RANK receptors, probably via the axis of early endosomes-late endosomes-lysosomes in osteoclasts. en-copyright= kn-copyright= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TranManh Tien en-aut-sei=Tran en-aut-mei=Manh Tien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItagakiMami en-aut-sei=Itagaki en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KadowakiTomoko en-aut-sei=Kadowaki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakaiEiko en-aut-sei=Sakai en-aut-mei=Eiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukubaTakayuki en-aut-sei=Tsukuba en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery and Biopathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Frontier Life Science, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=9 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=10 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Rab11A kn-keyword=Rab11A en-keyword=c-fms kn-keyword=c-fms en-keyword=RANK kn-keyword=RANK en-keyword=NFATc-1 kn-keyword=NFATc-1 en-keyword=osteoclast kn-keyword=osteoclast en-keyword=vesicular transport kn-keyword=vesicular transport END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=21 article-no= start-page=4761 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Honeycomb β-TCP Geometrical Structure on Bone Tissue Regeneration in Skull Defect en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effect of the geometric structure of artificial biomaterials on skull regeneration remains unclear. In a previous study, we succeeded in developing honeycomb beta-tricalcium phosphate (beta-TCP), which has through-and-through holes and is able to provide the optimum bone microenvironment for bone tissue regeneration. We demonstrated that beta-TCP with 300-mu m hole diameters induced vigorous bone formation. In the present study, we investigated how differences in hole directions of honeycomb beta-TCP (horizontal or vertical holes) influence bone tissue regeneration in skull defects. Honeycomb beta-TCP with vertical and horizontal holes was loaded with BMP-2 using Matrigel and Collagen gel as carriers, and transplanted into skull bone defect model rats. The results showed that in each four groups (Collagen alone group, Matrigel alone group, Collagen + BMP group and Matrigel + BMP-2), vigorous bone formation was observed on the vertical beta-TCP compared with horizontal beta-TCP. The osteogenic area was larger in the Matrigel groups (with and without BMP-2) than in the Collagen group (with and without BMP-2) in both vertical beta-TCP and horizontal beta-TCP. However, when BMP-2 was added, the bone formation area was not significantly different between the Collagen group and the Matrigel group in the vertical beta-TCP. Histological finding showed that, in vertical honeycomb beta-TCP, new bone formation extended to the upper part of the holes and was observed from the dura side to the periosteum side as added to the inner walls of the holes. Therefore, we can control efficient bone formation by creating a bone microenvironment provided by vertical honeycomb beta-TCP. Vertical honeycomb beta-TCP has the potential to be an excellent biomaterial for bone tissue regeneration in skull defects and is expected to have clinical applications. en-copyright= kn-copyright= en-aut-name=WatanabeToshiyuki en-aut-sei=Watanabe en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeSatoko en-aut-sei=Watanabe en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakagiriRyoko en-aut-sei=Nakagiri en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Life Science, Faculty of Science, Okayama University Science kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword= honeycomb β-TCP kn-keyword= honeycomb β-TCP en-keyword=bone tissue regeneration kn-keyword=bone tissue regeneration en-keyword=bone microenvironment kn-keyword=bone microenvironment en-keyword=Vertical and Horizontal holes kn-keyword=Vertical and Horizontal holes en-keyword=geometrical structure kn-keyword=geometrical structure END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=21 article-no= start-page=6016 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnosis of Occlusal Tooth Wear Using 3D Imaging of Optical Coherence Tomography Ex Vivo en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study was to assess the utility of 3D imaging of optical coherence tomography (OCT) for the diagnosis of occlusal tooth wear ex vivo. Sixty-three extracted human molars with or without visible tooth wear were collected to take digital intraoral radiography and 3D OCT images. The degree of tooth wear was evaluated by 12 examiners and scored using 4-rank scale: 1-slight enamel wear; 2-distinct enamel wear; 3-tooth wear with slight dentin exposure; 4-tooth wear with distinct involvement of dentin. The degree of tooth wear was validated by the histological view of confocal laser scanning microscopy (CLSM). The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic analysis were calculated. Diagnostic accuracy was compared with the agreement with CLSM observation using weighted kappa. The results were statistically analyzed at a significance level of alpha = 0.05. Three-dimensional OCT showed significantly higher sensitivity (p < 0.05) for all the diagnostic thresholds of enamel wear and dentin exposure than digital radiography (0.82, 0.85, and 0.79 vs. 0.56, 0.52, and 0.57, respectively). Three-dimensional OCT showed higher AUC and kappa coefficients than digital radiography (p < 0.05), where mean AUC and Kappa values were 0.95 and 0.76 for OCT and 0.92 and 0.47 for radiography, respectively. No significant difference of specificity was observed (p > 0.05). Three-dimensional OCT could visualize and estimate the degree of tooth wear and detect the dentin exposure at the tooth wear surface accurately and reproducibly. Consequently, a new guideline for tooth wear assessment can be proposed using OCT. en-copyright= kn-copyright= en-aut-name=KashiwaMisa en-aut-sei=Kashiwa en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimadaYasushi en-aut-sei=Shimada en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SadrAlireza en-aut-sei=Sadr en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiyamaMasahiro en-aut-sei=Yoshiyama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SumiYasunori en-aut-sei=Sumi en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TagamiJunji en-aut-sei=Tagami en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cariology and Operative Dentistry Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=2 en-affil=Department of Operative Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cariology and Operative Dentistry Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=4 en-affil=Department of Operative Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Center of Advanced Medicine for Dental and Oral Diseases, Department for Advanced Dental Research, National Center for Geriatrics and Gerontology kn-affil= affil-num=6 en-affil=Department of Cariology and Operative Dentistry Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= en-keyword=occlusal tooth wear kn-keyword=occlusal tooth wear en-keyword=erosive tooth wear kn-keyword=erosive tooth wear en-keyword=SS-OCT kn-keyword=SS-OCT en-keyword=3D imaging kn-keyword=3D imaging en-keyword=enamel thickness kn-keyword=enamel thickness en-keyword=dentin exposure kn-keyword=dentin exposure en-keyword=demineralization kn-keyword=demineralization END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=21 article-no= start-page=7967 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201027 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) have been regarded as the major cytokines promoting bone formation, however, several studies have reported unexpected results with failure of bone formation or bone resorption of these growth factors. In this study, BMP-2 and FGF-2 adsorbed into atellocollagen sponges were transplanted into bone defects in the bone marrow-scarce calvaria (extramedullary environment) and bone marrow-abundant femur (medullary environment) for analysis of their in vivo effects not only on osteoblasts, osteoclasts but also on bone marrow cells. The results showed that BMP-2 induced high bone formation in the bone marrow-scarce calvaria, but induced bone resorption in the bone marrow-abundant femurs. On the other hand, FGF-2 showed opposite effects compared to those of BMP-2. Analysis of cellular dynamics revealed numerous osteoblasts and osteoclasts present in the newly-formed bone induced by BMP-2 in calvaria, but none were seen in either control or FGF-2-transplanted groups. On the other hand, in the femur, numerous osteoclasts were observed in the vicinity of the BMP-2 pellet, while a great number of osteoblasts were seen near the FGF-2 pellets or in the control group. Of note, FCM analysis showed that both BMP-2 and FGF-2 administrated in the femur did not significantly affect the hematopoietic cell population, indicating a relatively safe application of the two growth factors. Together, these results indicate that BMP-2 could be suitable for application in extramedullary bone regeneration, whereas FGF-2 could be suitable for application in medullary bone regeneration. en-copyright= kn-copyright= en-aut-name=NoshoShuji en-aut-sei=Nosho en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TosaIkue en-aut-sei=Tosa en-aut-mei=Ikue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshibashiKei en-aut-sei=Ishibashi en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikaiAkihiro en-aut-sei=Mikai en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaYukie en-aut-sei=Tanaka en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Kimura-OnoAya en-aut-sei=Kimura-Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KomoriTaishi en-aut-sei=Komori en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=BMP-2 kn-keyword=BMP-2 en-keyword=FGF-2 kn-keyword=FGF-2 en-keyword=bone formation kn-keyword=bone formation en-keyword=bone marrow kn-keyword=bone marrow END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=19 article-no= start-page=7028 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=BMP-2/beta-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (beta-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/beta-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/beta-TCP transplanted group. For treatment studies, BMP-2/beta-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/beta-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/beta-TCP could become a suitable therapy for the management of MRONJ. en-copyright= kn-copyright= en-aut-name=MikaiAkihiro en-aut-sei=Mikai en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TosaIkue en-aut-sei=Tosa en-aut-mei=Ikue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Ha Thi ThuNguyen en-aut-sei=Ha Thi Thu en-aut-mei=Nguyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NoshoShuji en-aut-sei=Nosho en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kimura-OnoAya en-aut-sei=Kimura-Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NawachiKumiko en-aut-sei=Nawachi en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=BMP-2 kn-keyword=BMP-2 en-keyword=MRONJ kn-keyword=MRONJ en-keyword=bone regeneration kn-keyword=bone regeneration END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=19 article-no= start-page=7135 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Survey of Barley PIP Aquaporin Ionic Conductance Reveals Ca2+-Sensitive HvPIP2;8 Na+ and K+ Conductance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some plasma membrane intrinsic protein (PIP) aquaporins can facilitate ion transport. Here we report that one of the 12 barley PIPs (PIP1 and PIP2) tested, HvPIP2;8, facilitated cation transport when expressed in Xenopus laevis oocytes. HvPIP2;8-associated ion currents were detected with Na+ and K+, but not Cs+, Rb+, or Li+, and was inhibited by Ba2+, Ca2+, and Cd2+ and to a lesser extent Mg2+, which also interacted with Ca2+. Currents were reduced in the presence of K+, Cs+, Rb+, or Li+ relative to Na+ alone. Five HvPIP1 isoforms co-expressed with HvPIP2;8 inhibited the ion conductance relative to HvPIP2;8 alone but HvPIP1;3 and HvPIP1;4 with HvPIP2;8 maintained the ion conductance at a lower level. HvPIP2;8 water permeability was similar to that of a C-terminal phosphorylation mimic mutant HvPIP2;8 S285D, but HvPIP2;8 S285D showed a negative linear correlation between water permeability and ion conductance that was modified by a kinase inhibitor treatment. HvPIP2;8 transcript abundance increased in barley shoot tissues following salt treatments in a salt-tolerant cultivar Haruna-Nijo, but not in salt-sensitive I743. There is potential for HvPIP2;8 to be involved in barley salt-stress responses, and HvPIP2;8 could facilitate both water and Na+/K+ transport activity, depending on the phosphorylation status. en-copyright= kn-copyright= en-aut-name=Sen Thi HuongTran en-aut-sei=Sen Thi Huong en-aut-mei=Tran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HorieTomoaki en-aut-sei=Horie en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImranShahin en-aut-sei=Imran en-aut-mei=Shahin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiuJiaen en-aut-sei=Qiu en-aut-mei=Jiaen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=McGaugheySamantha en-aut-sei=McGaughey en-aut-mei=Samantha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ByrtCaitlin S. en-aut-sei=Byrt en-aut-mei=Caitlin S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TyermanStephen D. en-aut-sei=Tyerman en-aut-mei=Stephen D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Australian Research Council Centre of Excellence in Plant Energy Biology, Waite Research Institute and School of Agriculture, Food and Wine, The University of Adelaide kn-affil= affil-num=5 en-affil=Research School of Biology, Australian National University kn-affil= affil-num=6 en-affil=Australian Research Council Centre of Excellence in Plant Energy Biology, Waite Research Institute and School of Agriculture, Food and Wine, The University of Adelaide kn-affil= affil-num=7 en-affil=Australian Research Council Centre of Excellence in Plant Energy Biology, Waite Research Institute and School of Agriculture, Food and Wine, The University of Adelaide kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=aquaporins kn-keyword=aquaporins en-keyword=barley kn-keyword=barley en-keyword=ion transport kn-keyword=ion transport en-keyword=oocytes kn-keyword=oocytes en-keyword=plasma membrane intrinsic proteins (PIPs) kn-keyword=plasma membrane intrinsic proteins (PIPs) END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=20 article-no= start-page=7110 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201013 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hybrid Set Covering and Dynamic Modular Covering Location Problem: Application to an Emergency Humanitarian Logistics Problem en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper presents an extension of the covering location problem as a hybrid covering model that utilizes the set covering and maximal covering location problems. The developed model is a multi-period model that considers strategic and tactical planning decisions. Hybrid covering location problem (HCLP) determines the location of the capacitated facilities by using dynamic set covering location problem as strategic decisions and assigns the constructive units of facilities and allocates the demand points by using dynamic modular capacitated maximal covering location problem as tactical decisions. One of the applications of the proposed model is locating first aid centers in humanitarian logistic services that have been addressed by studying a threat case study in Japan. In addition to validating the developed model, it has been compared to other possible combined problems, and several randomly generated examples have been solved. The results of the case study and model validation tests approve that the main hybrid developed model (HCLP) is capable of providing better coverage percentage compared to conventional covering models and other hybrid variants. en-copyright= kn-copyright= en-aut-name=AlizadehRoghayyeh en-aut-sei=Alizadeh en-aut-mei=Roghayyeh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiTatsushi en-aut-sei=Nishi en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Mathematical Science for Social Systems, Department of Systems Innovation, Graduate School of Engineering Science, Osaka University kn-affil= affil-num=2 en-affil=Graduate School of Natural Sciences, Department of Industrial Innovation Engineering, Okayama University kn-affil= en-keyword=covering location kn-keyword=covering location en-keyword=multi-period kn-keyword=multi-period en-keyword=strategic and tactical planning kn-keyword=strategic and tactical planning en-keyword=modular kn-keyword=modular en-keyword=maximal covering kn-keyword=maximal covering en-keyword=set covering kn-keyword=set covering END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=21 article-no= start-page=8103 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor alpha (PDGFR alpha)(+) MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated beta galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration. en-copyright= kn-copyright= en-aut-name=AungKyaw Thu en-aut-sei=Aung en-aut-mei=Kyaw Thu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaKentaro en-aut-sei=Akiyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KunitomoMasayoshi en-aut-sei=Kunitomo en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MunAung Ye en-aut-sei=Mun en-aut-mei=Aung Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TosaIkue en-aut-sei=Tosa en-aut-mei=Ikue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NguyenHa Thi Thu en-aut-sei=Nguyen en-aut-mei=Ha Thi Thu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangJiewen en-aut-sei=Zhang en-aut-mei=Jiewen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KohnoTeisaku en-aut-sei=Kohno en-aut-mei=Teisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=mesenchymal stem cell kn-keyword=mesenchymal stem cell en-keyword=aging kn-keyword=aging en-keyword=tissue destruction kn-keyword=tissue destruction en-keyword=periodontitis kn-keyword=periodontitis en-keyword=immunomodulation kn-keyword=immunomodulation en-keyword=bone resorption kn-keyword=bone resorption END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=20 article-no= start-page=7714 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201018 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Solid tumors consist of the tumor parenchyma and stroma. The standard concept of oncology is that the tumor parenchyma regulates the tumor stroma and promotes tumor progression, and that the tumor parenchyma represents the tumor itself and defines the biological characteristics of the tumor tissue. Thus, the tumor stroma plays a pivotal role in assisting tumor parenchymal growth and invasiveness and is regarded as a supporter of the tumor parenchyma. The tumor parenchyma and stroma interact with each other. However, the influence of the stroma on the parenchyma is not clear. Therefore, in this study, we investigated the effect of the stroma on the parenchyma in oral squamous cell carcinoma (OSCC). We isolated tumor stroma from two types of OSCCs with different invasiveness (endophytic type OSCC (ED-st) and exophytic type OSCC (EX-st)) and examined the effect of the stroma on the parenchyma in terms of proliferation, invasion, and morphology by co-culturing and co-transplanting the OSCC cell line (HSC-2) with the two types of stroma. Both types of stroma were partially positive for alpha-smooth muscle actin. The tumor stroma increased the proliferation and invasion of tumor cells and altered the morphology of tumor cells in vitro and in vivo. ED-st exerted a greater effect on the tumor parenchyma in proliferation and invasion than EX-st. Morphological analysis showed that ED-st changed the morphology of HSC-2 cells to the invasive type of OSCC, and EX-st altered the morphology of HSC-2 cells to verrucous OSCC. This study suggests that the tumor stroma influences the biological characteristics of the parenchyma and that the origin of the stroma is strongly associated with the biological characteristics of the tumor. en-copyright= kn-copyright= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriHaruka en-aut-sei=Omori en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiushengShan en-aut-sei=Qiusheng en-aut-mei=Shan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=tumor stroma kn-keyword=tumor stroma en-keyword=tumor parenchyma kn-keyword=tumor parenchyma en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=biological characteristics kn-keyword=biological characteristics END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=20 article-no= start-page=7556 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201013 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-beta gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21. en-copyright= kn-copyright= en-aut-name=KuwaharaMiho en-aut-sei=Kuwahara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadoyaKoichi en-aut-sei=Kadoya en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoSei en-aut-sei=Kondo en-aut-mei=Sei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FuShanqi en-aut-sei=Fu en-aut-mei=Shanqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeYoshiko en-aut-sei=Miyake en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgoAyako en-aut-sei=Ogo en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SasakiTakako en-aut-sei=Sasaki en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MinagiShogo en-aut-sei=Minagi en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HattoriTakako en-aut-sei=Hattori en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Biochemistry, Faculty of Medicine, Oita University kn-affil= affil-num=11 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cellular communication network factor 3 kn-keyword=cellular communication network factor 3 en-keyword=CCN3 kn-keyword=CCN3 en-keyword=NOV kn-keyword=NOV en-keyword=primary chondrocytes kn-keyword=primary chondrocytes en-keyword=aging kn-keyword=aging en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=senescence kn-keyword=senescence en-keyword=p21 kn-keyword=p21 en-keyword=p53 kn-keyword=p53 en-keyword=SASP kn-keyword=SASP END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=10 article-no= start-page=2149 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44(High) cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44(High) cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future. en-copyright= kn-copyright= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasuiSeiji en-aut-sei=Yasui en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaAi en-aut-sei=Ueda en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeKaori en-aut-sei=Watanabe en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HanafusaTadashi en-aut-sei=Hanafusa en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchikawaYasuaki en-aut-sei=Ichikawa en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshihashiSachiko en-aut-sei=Yoshihashi en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsuchidaKazuki en-aut-sei=Tsuchida en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KamiyaAtsunori en-aut-sei=Kamiya en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FuruyaShuichi en-aut-sei=Furuya en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=3 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=4 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=5 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=6 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=7 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Engineering, Nagoya University kn-affil= affil-num=9 en-affil=Graduate School of Engineering, Nagoya University kn-affil= affil-num=10 en-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= en-keyword=boron neutron capture therapy (BNCT) kn-keyword=boron neutron capture therapy (BNCT) en-keyword=BSH-polyR kn-keyword=BSH-polyR en-keyword=CD44 kn-keyword=CD44 en-keyword=translational machinery kn-keyword=translational machinery en-keyword=bioinformatics kn-keyword=bioinformatics END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=9 article-no= start-page=1303 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200826 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of Chitin-Dependent Growth and Natural Competence in Vibrio parahaemolyticus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vibrios can degrade chitin surfaces to soluble N-acetyl glucosamine oligosaccharides (GlcNAc(n)) that can be utilized as a carbon source and also induce a state of natural genetic competence. In this study, we characterized chitin-dependent growth and natural competence in Vibrio parahaemolyticus and its regulation. We found that growth on chitin was regulated through chitin sensors ChiS (sensor histidine kinase) and TfoS (transmembrane transcriptional regulator) by predominantly controlling the expression of chitinase VPA0055 (ChiA2) in a TfoX-dependent manner. The reduced growth of Delta chiA2, Delta chiS and Delta tfoS mutants highlighted the critical role played by ChiA2 in chitin breakdown. This growth defect of Delta chiA2 mutant could be recovered when chitin oligosaccharides GlcNAc(2) or GlcNAc(6) were supplied instead of chitin. The Delta tfoS mutant was also able to grow on GlcNAc(2) but the Delta chiS mutant could not, which indicates that GlcNAc(2) catabolic operon is dependent on ChiS and independent of TfoS. However, the Delta tfoS mutant was unable to utilize GlcNAc(6) because the periplasmic enzymes required for the breakdown of GlcNAc(6) were found to be downregulated at the mRNA level. We also showed that natural competence can be induced only by GlcNAc(6), not GlcNAc(2), because the expression of competence genes was significantly higher in the presence of GlcNAc(6) compared to GlcNAc(2). Moreover, this might be an indication that GlcNAc(2) and GlcNAc(6) were detected by different receptors. Therefore, we speculate that GlcNAc(2)-dependent activation of ChiS and GlcNAc(6)-dependent activation of TfoS might be crucial for the induction of natural competence in V. parahaemolyticus through the upregulation of the master competence regulator TfoX. en-copyright= kn-copyright= en-aut-name=DebnathAnusuya en-aut-sei=Debnath en-aut-mei=Anusuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MizunoTamaki en-aut-sei=Mizuno en-aut-mei=Tamaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiShin-Ichi en-aut-sei=Miyoshi en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=chitin kn-keyword=chitin en-keyword=chitinase kn-keyword=chitinase en-keyword=GlcNAc(6) kn-keyword=GlcNAc(6) en-keyword=natural competence kn-keyword=natural competence en-keyword=ChiA2 kn-keyword=ChiA2 en-keyword=ChiS kn-keyword=ChiS en-keyword=TfoS kn-keyword=TfoS END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=9 article-no= start-page=2655 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=FUCCI Real-Time Cell-Cycle Imaging as a Guide for Designing Improved Cancer Therapy: A Review of Innovative Strategies to Target Quiescent Chemo-Resistant Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Progress in chemotherapy of solid cancer has been tragically slow due, in large part, to the chemoresistance of quiescent cancer cells in tumors. The fluorescence ubiquitination cell-cycle indicator (FUCCI) was developed in 2008 by Miyawaki et al., which color-codes the phases of the cell cycle in real-time. FUCCI utilizes genes linked to different color fluorescent reporters that are only expressed in specific phases of the cell cycle and can, thereby, image the phases of the cell cycle in real-time. Intravital real-time FUCCI imaging within tumors has demonstrated that an established tumor comprises a majority of quiescent cancer cells and a minor population of cycling cancer cells located at the tumor surface or in proximity to tumor blood vessels. In contrast to most cycling cancer cells, quiescent cancer cells are resistant to cytotoxic chemotherapy, most of which target cells in S/G2/M phases. The quiescent cancer cells can re-enter the cell cycle after surviving treatment, which suggests the reason why most cytotoxic chemotherapy is often ineffective for solid cancers. Thus, quiescent cancer cells are a major impediment to effective cancer therapy. FUCCI imaging can be used to effectively target quiescent cancer cells within tumors. For example, we review how FUCCI imaging can help to identify cell-cycle-specific therapeutics that comprise decoy of quiescent cancer cells from G1 phase to cycling phases, trapping the cancer cells in S/G2 phase where cancer cells are mostly sensitive to cytotoxic chemotherapy and eradicating the cancer cells with cytotoxic chemotherapy most active against S/G2 phase cells. FUCCI can readily image cell-cycle dynamics at the single cell level in real-time in vitro and in vivo. Therefore, visualizing cell cycle dynamics within tumors with FUCCI can provide a guide for many strategies to improve cell-cycle targeting therapy for solid cancers. en-copyright= kn-copyright= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoffmanRobert M. en-aut-sei=Hoffman en-aut-mei=Robert M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=AntiCancer, Inc. kn-affil= en-keyword=cell cycle kn-keyword=cell cycle en-keyword=fluorescent proteins kn-keyword=fluorescent proteins en-keyword=FUCCI kn-keyword=FUCCI en-keyword=imaging kn-keyword=imaging en-keyword=targeted cancer therapy kn-keyword=targeted cancer therapy en-keyword=quiescent cancer cells kn-keyword=quiescent cancer cells en-keyword=decoy kn-keyword=decoy en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=9 article-no= start-page=1334 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bacterial and Fungal Microbiota Associated with the Ensiling of Wet Soybean Curd Residue under Prompt and Delayed Sealing Conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Wet soybean curd residue (SCR) obtained from two tofu factories (F1 and F2) was anaerobically stored with or without added beet pulp (BP). Sealing was performed on the day of tofu production (prompt sealing (PS)) or 2 days after SCR was piled and unprocessed (delayed sealing (DS)). Predominant lactic acid fermentation was observed regardless of the sealing time and BP addition.Acinetobacterspp. were the most abundant (>67%) bacteria in pre-ensiled SCR, regardless of the factory and sealing time. In PS silage, the abundances of typical lactic acid-producing bacteria, such asLactobacillus,Pediococcus, andStreptococcusspp. reached >50%. In DS silage,Acinetobacterspp. were the most abundant in F1 products, whereasBacillusspp. were the most abundant in long-stored F2 products. The fungal microbiota were highly diverse. AlthoughCandida,Aspergillus,Cladosporium,Hannaella, andWallemiaspp. were found to be the most abundant fungal microbiota, no specific genera were associated with factory, sealing time, or fermentation products. These results indicated that owing to preceding processing, including heating, distinctive microbiota may have participated in the ensiling of wet by-products. Lactic acid fermentation was observed even in DS silage, and an association ofBacillusspp. was suggested. en-copyright= kn-copyright= en-aut-name=WaliAjmal en-aut-sei=Wali en-aut-mei=Ajmal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinoNaoki en-aut-sei=Nishino en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=amplicon sequencing kn-keyword=amplicon sequencing en-keyword=bacteria kn-keyword=bacteria en-keyword=fungi kn-keyword=fungi en-keyword=silage kn-keyword=silage en-keyword=soybean curd residue kn-keyword=soybean curd residue END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=18 article-no= start-page=6748 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Introducing the Amphibious Mudskipper Goby as a Unique Model to Evaluate Neuro/Endocrine Regulation of Behaviors Mediated by Buccal Sensation and Corticosteroids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some fish have acquired the ability to breathe air, but these fish can no longer flush their gills effectively when out of water. Hence, they have developed characteristic means for defense against external stressors, including thirst (osmolarity/ions) and toxicity. Amphibious fish, extant air-breathing fish emerged from water, may serve as models to examine physiological responses to these stressors. Some of these fish, including mudskipper gobies such asPeriophthalmodon schlosseri,Boleophthalmus boddartiand ourPeriophthalmus modestus, display distinct adaptational behaviors to these factors compared with fully aquatic fish. In this review, we introduce the mudskipper goby as a unique model to study the behaviors and the neuro/endocrine mechanisms of behavioral responses to the stressors. Our studies have shown that a local sensation of thirst in the buccal cavity-this being induced by dipsogenic hormones-motivates these fish to move to water through a forebrain response. The corticosteroid system, which is responsive to various stressors, also stimulates migration, possibly via the receptors in the brain. We suggest that such fish are an important model to deepen insights into the stress-related neuro/endocrine-behavioral effects. en-copyright= kn-copyright= en-aut-name=KatayamaYukitoshi en-aut-sei=Katayama en-aut-mei=Yukitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoKazuhiro en-aut-sei=Saito en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= en-keyword=stressors kn-keyword=stressors en-keyword=thirst kn-keyword=thirst en-keyword=angiotensin II kn-keyword=angiotensin II en-keyword=corticosteroids kn-keyword=corticosteroids en-keyword=amphibious fish kn-keyword=amphibious fish END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=17 article-no= start-page=3842 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200824 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis and Physicochemical Properties of 2,7-Disubstituted Phenanthro[2,1-b:7,8-b']dithiophenes en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the design, synthesis, and physicochemical properties of an array of phenanthro[2,1-b:7,8-b']dithiophene (PDT-2) derivatives by introducing five types of alkyl (CnH2n+1; n = 8, 10, 12, 13, and 14) or two types of decylthienyl groups at 2,7-positions of the PDT-2 core. Systematic investigation revealed that the alkyl length and the type of side chains have a great effect on the physicochemical properties. For alkylated PDT-2, the solubility was gradually decreased as the chain length was increased. For instance, C-8-PDT-2 exhibited the highest solubility (5.0 g/L) in chloroform. Additionally, substitution with 5-decylthienyl groups showed poor solubility in both chloroform and toluene, whereas PDT-2 with 4-decylthienyl groups resulted in higher solubility. Furthermore, UV-vis absorption of PDT-2 derivatives substituted by decylthienyl groups showed a redshift, indicating the extension of their pi-conjugation length. This work reveals that modification of the conjugated core by alkyl or decylthienyl side chains may be an efficient strategy by which to change the physicochemical properties, which might lead to the development of high-performance organic semiconductors. en-copyright= kn-copyright= en-aut-name=JiZhenfei en-aut-sei=Ji en-aut-mei=Zhenfei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChengZeliang en-aut-sei=Cheng en-aut-mei=Zeliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriHiroki en-aut-sei=Mori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiharaYasushi en-aut-sei=Nishihara en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=phenacene-type compounds kn-keyword=phenacene-type compounds en-keyword=thiophene ring kn-keyword=thiophene ring en-keyword=cross-coupling kn-keyword=cross-coupling en-keyword=alkyl side chains kn-keyword=alkyl side chains en-keyword=UV-vis absorption kn-keyword=UV-vis absorption en-keyword=p-type organic semiconductors kn-keyword=p-type organic semiconductors en-keyword=organic field-effect transistor (OFET) kn-keyword=organic field-effect transistor (OFET) END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=1810 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ligation of MHC Class II Induces PKC-Dependent Clathrin-Mediated Endocytosis of MHC Class II en-subtitle= kn-subtitle= en-abstract= kn-abstract=In addition to antigen presentation to CD4(+)T cells, aggregation of cell surface major histocompatibility complex class II (MHC-II) molecules induces signal transduction in antigen presenting cells that regulate cellular functions. We previously reported that crosslinking of MHC-II induced the endocytosis of MHC-II, which was associated with decreased surface expression levels in murine dendritic cells (DCs) and resulted in impaired activation of CD4(+)T cells. However, the downstream signal that induces MHC-II endocytosis remains to be elucidated. In this study, we found that the crosslinking of MHC-II induced intracellular Ca(2+)mobilization, which was necessary for crosslinking-induced MHC-II endocytosis. We also found that these events were suppressed by inhibitors of Syk and phospholipase C (PLC). Treatments with a phorbol ester promoted MHC-II endocytosis, whereas inhibitors of protein kinase C (PKC) suppressed crosslinking-induced endocytosis of MHC-II. These results suggest that PKC could be involved in this process. Furthermore, crosslinking-induced MHC-II endocytosis was suppressed by inhibitors of clathrin-dependent endocytosis. Our results indicate that the crosslinking of MHC-II could stimulate Ca(2+)mobilization and induce the clathrin-dependent endocytosis of MHC-II in murine DCs. en-copyright= kn-copyright= en-aut-name=MasakiKento en-aut-sei=Masaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirakiYuhji en-aut-sei=Hiraki en-aut-mei=Yuhji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnishiHiroka en-aut-sei=Onishi en-aut-mei=Hiroka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohYuka en-aut-sei=Satoh en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RochePaul A. en-aut-sei=Roche en-aut-mei=Paul A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunobiology, Faculty of Pharmacy and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Experimental Immunology Branch, National Cancer Institute, National Institutes of Health kn-affil= affil-num=6 en-affil=Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=MHC-II kn-keyword=MHC-II en-keyword=dendritic cells kn-keyword=dendritic cells en-keyword=endocytosis kn-keyword=endocytosis en-keyword=crosslink kn-keyword=crosslink en-keyword=PKC kn-keyword=PKC END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=8 article-no= start-page=1202 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudo Random Binary Sequence Based on Cyclic Difference Set en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the increasing reliance on technology, it has become crucial to secure every aspect of online information where pseudo random binary sequences (PRBS) can play an important role in today's world of Internet. PRBS work in the fundamental mathematics behind the security of different protocols and cryptographic applications. This paper proposes a new PRBS namely MK (Mamun, Kumu) sequence for security applications. Proposed sequence is generated by primitive polynomial, cyclic difference set in elements of the field and binarized by quadratic residue (QR) and quadratic nonresidue (QNR). Introduction of cyclic difference set makes a special contribution to randomness of proposed sequence while QR/QNR-based binarization ensures uniformity of zeros and ones in sequence. Besides, proposed sequence has maximum cycle length and high linear complexity which are required properties for sequences to be used in security applications. Several experiments are conducted to verify randomness and results are presented in support of robustness of the proposed MK sequence. The randomness of proposed sequence is evaluated by popular statistical test suite, i.e., NIST STS 800-22 package. The test results confirmed that the proposed sequence is not affected by approximations of any kind and successfully passed all statistical tests defined in NIST STS 800-22 suite. Finally, the efficiency of proposed MK sequence is verified by comparing with some popular sequences in terms of uniformity in bit pattern distribution and linear complexity for sequences of different length. The experimental results validate that the proposed sequence has superior cryptographic properties than existing ones. en-copyright= kn-copyright= en-aut-name=Al MamunMd. Selim en-aut-sei=Al Mamun en-aut-mei=Md. Selim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkhterFatema en-aut-sei=Akhter en-aut-mei=Fatema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Computer Science and Engineering, Jatiya Kabi Kazi Nazrul Islam University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=finite field kn-keyword=finite field en-keyword=primitive polynomial kn-keyword=primitive polynomial en-keyword=quadratic residue kn-keyword=quadratic residue en-keyword=pseudo random binary sequence kn-keyword=pseudo random binary sequence en-keyword=NIST statistical test suite kn-keyword=NIST statistical test suite END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=6 article-no= start-page=792 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= Cell division control 37 (CDC37) increases the stability of heat shock protein 90 (HSP90) client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SREZBP-CTfin51-AW1-Number 18 cDNA (SCAN) transcription factor family-MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1/ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced the tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in the CDC37 gene, negatively regulated the CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1. en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PrinceThomas L en-aut-sei=Prince en-aut-mei=Thomas L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Manh Tien Tran en-aut-sei=Manh Tien Tran en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LangBenjamin J en-aut-sei=Lang en-aut-mei=Benjamin J kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CalderwoodStuart K en-aut-sei=Calderwood en-aut-mei=Stuart K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil= Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil= Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=CDC37 kn-keyword=CDC37 en-keyword=MZF1 kn-keyword=MZF1 en-keyword=SCAN zinc finger kn-keyword=SCAN zinc finger en-keyword=SCAND1 kn-keyword=SCAND1 en-keyword=prostate cancer kn-keyword=prostate cancer END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=15 article-no= start-page=5455 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Eicosapentaenoic Acid on Arterial Calcification en-subtitle= kn-subtitle= en-abstract= kn-abstract=Arterial calcification is a hallmark of advanced atherosclerosis and predicts cardiovascular events. However, there is no clinically accepted therapy that prevents progression of arterial calcification. HMG-CoA reductase inhibitors, statins, lower low-density lipoprotein-cholesterol and reduce cardiovascular events, but coronary artery calcification is actually promoted by statins. The addition of eicosapentaenoic acid (EPA) to statins further reduced cardiovascular events in clinical trials, JELIS and REDUCE-IT. Additionally, we found that EPA significantly suppressed arterial calcification in vitro and in vivo via suppression of inflammatory responses, oxidative stress and Wnt signaling. However, so far there is a lack of evidence showing the effect of EPA on arterial calcification in a clinical situation. We reviewed the molecular mechanisms of the inhibitory effect of EPA on arterial calcification and the results of some clinical trials. en-copyright= kn-copyright= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=eicosapentaenoic acid kn-keyword=eicosapentaenoic acid en-keyword=atherosclerosis kn-keyword=atherosclerosis en-keyword=Klotho kn-keyword=Klotho END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=15 article-no= start-page=5327 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200727 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cellular Fragments as Biomaterial for Rapid In Vitro Bone-Like Tissue Synthesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Current stem cell-based techniques for bone-like tissue synthesis require at least two to three weeks. Therefore, novel techniques to promote rapid 3D bone-like tissue synthesis in vitro are still required. In this study, we explored the concept of using cell nanofragments as a substrate material to promote rapid bone formation in vitro. The methods for cell nanofragment fabrication were ultrasonication (30 s and 3 min), non-ionic detergent (triton 0.1% and 1%), or freeze-dried powder. The results showed that ultrasonication for 3 min allowed the fabrication of homogeneous nanofragments of less than 150 nm in length, which mineralized surprisingly in just one day, faster than the fragments obtained from all other methods. Further optimization of culture conditions indicated that a concentration of 10 mM or 100 mM of beta-glycerophosphate enhanced, whereas fetal bovine serum (FBS) inhibited in a concentration-dependent manner, the mineralization of the cell nanofragments. Finally, a 3D collagen-cell nanofragment-mineral complex mimicking a bone-like structure was generated in just two days by combining the cell nanofragments in collagen gel. In conclusion, sonication for three min could be applied as a novel method to fabricate cell nanofragments of less than 150 nm in length, which can be used as a material for in vitro bone tissue engineering. en-copyright= kn-copyright= en-aut-name=AkhterMst Nahid en-aut-sei=Akhter en-aut-mei=Mst Nahid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadoyaKoichi en-aut-sei=Kadoya en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name=卓也 kn-aut-sei= kn-aut-mei=卓也 aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bone tissue engineering kn-keyword=bone tissue engineering en-keyword=cell nanofragments kn-keyword=cell nanofragments en-keyword=dead cells kn-keyword=dead cells en-keyword=mineralization kn-keyword=mineralization en-keyword=osteogenesis kn-keyword=osteogenesis END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=47 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs en-subtitle= kn-subtitle= en-abstract= kn-abstract=Extracellular vesicles (EVs), such as exosomes or oncosomes, often carry oncogenic molecules derived from tumor cells. In addition, accumulating evidence indicates that tumor cells can eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing drug resistance phenotype is often coupled with cellular dedifferentiation and transformation in cells undergoing epithelial-mesenchymal transition (EMT), and the adoption of a cancer stem cell phenotype. The release of EVs is also involved in immunosuppression. Herein, we address different aspects by which EVs modulate the tumor microenvironment to become resistant to anticancer and antibody-based drugs, as well as the concept of the resistance-associated secretory phenotype (RASP). en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TahaEman Ahmed en-aut-sei=Taha en-aut-mei=Eman Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name=喜章 kn-aut-sei= kn-aut-mei=喜章 aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Hospital kn-affil= en-keyword=extracellular vesicle (EV) kn-keyword=extracellular vesicle (EV) en-keyword=exosome kn-keyword=exosome en-keyword=oncosome kn-keyword=oncosome en-keyword=drug resistance kn-keyword=drug resistance en-keyword=epithelial-mesenchymal transition (EMT) kn-keyword=epithelial-mesenchymal transition (EMT) en-keyword=heat shock protein (HSP) kn-keyword=heat shock protein (HSP) en-keyword=cell stress response kn-keyword=cell stress response en-keyword=resistance-associated secretory phenotype (RASP) kn-keyword=resistance-associated secretory phenotype (RASP) en-keyword=hypoxia kn-keyword=hypoxia en-keyword=acidosis kn-keyword=acidosis en-keyword=tumor immunology kn-keyword=tumor immunology END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=7 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200709 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep Learning Could Diagnose Diabetic Nephropathy with Renal Pathological Immunofluorescent Images en-subtitle= kn-subtitle= en-abstract= kn-abstract=Artificial Intelligence (AI) imaging diagnosis is developing, making enormous steps forward in medical fields. Regarding diabetic nephropathy (DN), medical doctors diagnose them with clinical course, clinical laboratory data and renal pathology, mainly evaluate with light microscopy images rather than immunofluorescent images because there are no characteristic findings in immunofluorescent images for DN diagnosis. Here, we examined the possibility of whether AI could diagnose DN from immunofluorescent images. We collected renal immunofluorescent images from 885 renal biopsy patients in our hospital, and we created a dataset that contains six types of immunofluorescent images of IgG, IgA, IgM, C3, C1q and Fibrinogen for each patient. Using the dataset, 39 programs worked without errors (Area under the curve (AUC): 0.93). Five programs diagnosed DN completely with immunofluorescent images (AUC: 1.00). By analyzing with Local interpretable model-agnostic explanations (Lime), the AI focused on the peripheral lesion of DN glomeruli. On the other hand, the nephrologist diagnostic ratio (AUC: 0.75833) was slightly inferior to AI diagnosis. These findings suggest that DN could be diagnosed only by immunofluorescent images by deep learning. AI could diagnose DN and identify classified unknown parts with the immunofluorescent images that nephrologists usually do not use for DN diagnosis. en-copyright= kn-copyright= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiKensaku en-aut-sei=Takahashi en-aut-mei=Kensaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SangYizhen en-aut-sei=Sang en-aut-mei=Yizhen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=immunofluorescent image kn-keyword=immunofluorescent image en-keyword=renal pathology kn-keyword=renal pathology en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=deep learning kn-keyword=deep learning en-keyword=diabetic nephropathy kn-keyword=diabetic nephropathy END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=12 article-no= start-page=4527 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 +/- 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 20 or 40 mg/kg/day, or saline via oral gavage. AngII infusion developed vascular senescence, which was confirmed by senescence associated-beta-galactosidase (SA-beta-gal) staining. CGA administration attenuated vascular senescence in a dose-dependent manner, in association with the increase of Sirtuin 1 (Sirt1) and endothelial nitric oxide synthase (eNOS), and with the decrease of p-Akt, PAI-1, p53, and p21. In an in vitro study, with or without pre-treatment of CGA, Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with H(2)O(2)for an hour, then cultured in the absence or presence of 0.5-5.0 mu M CGA for the indicated time. Endothelial cell senescence was induced by H2O2, which was attenuated by CGA treatment. Pre-treatment of CGA increased Nrf2 in HUVECs. After H(2)O(2)treatment, translocation of Nrf2 into the nucleus and the subsequent increase of Heme Oxygenase-1 (HO-1) were observed earlier in CGA-treated cells. Furthermore, the HO-1 inhibitor canceled the beneficial effect of CGA on vascular senescence in mice. In conclusion, CGA exerts a beneficial effect on vascular senescence, which is at least partly dependent on the Nuclear factor erythroid 2-factor 2 (Nrf2)/HO-1 pathway. en-copyright= kn-copyright= en-aut-name=HadaYoshiko en-aut-sei=Hada en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtakaNozomu en-aut-sei=Otaka en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoShugo en-aut-sei=Okamoto en-aut-mei=Shugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiwakiMariko en-aut-sei=Nishiwaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakemotoRika en-aut-sei=Takemoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= en-keyword=chlorogenic acid kn-keyword=chlorogenic acid en-keyword=vascular senescence kn-keyword=vascular senescence en-keyword=nuclear factor erythroid 2-related factor 2 kn-keyword=nuclear factor erythroid 2-related factor 2 en-keyword=heme oxygenase-1 kn-keyword=heme oxygenase-1 END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=7 article-no= start-page=984 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep Neural Networks for Dental Implant System Classification en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we used panoramic X-ray images to classify and clarify the accuracy of different dental implant brands via deep convolutional neural networks (CNNs) with transfer-learning strategies. For objective labeling, 8859 implant images of 11 implant systems were used from digital panoramic radiographs obtained from patients who underwent dental implant treatment at Kagawa Prefectural Central Hospital, Japan, between 2005 and 2019. Five deep CNN models (specifically, a basic CNN with three convolutional layers, VGG16 and VGG19 transfer-learning models, and finely tuned VGG16 and VGG19) were evaluated for implant classification. Among the five models, the finely tuned VGG16 model exhibited the highest implant classification performance. The finely tuned VGG19 was second best, followed by the normal transfer-learning VGG16. We confirmed that the finely tuned VGG16 and VGG19 CNNs could accurately classify dental implant systems from 11 types of panoramic X-ray images. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiiKazumasa en-aut-sei=Yoshii en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraTakeshi en-aut-sei=Hara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaKatsusuke en-aut-sei=Yamashita en-aut-mei=Katsusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=3 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=4 en-affil=Polytechnic Center Kagawa kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil= kn-affil= en-keyword=dental implant kn-keyword=dental implant en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=classification kn-keyword=classification en-keyword=deep learning kn-keyword=deep learning en-keyword=convolutional neural networks kn-keyword=convolutional neural networks END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=14 article-no= start-page=4883 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200716 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Finite Element Study of the Effect of Internal Cracks on Surface Profile Change due to Low Loading of Turbine Blade en-subtitle= kn-subtitle= en-abstract= kn-abstract=Turbine blades for thermal power plants are exposed to severe environments, making it necessary to ensure safety against damage, such as crack formation. A previous method detected internal cracks by applying a small load to a target member. Changes in the surface properties of the material were detected before and after the load using a digital holographic microscope and a digital height correlation method. In this study, this technique was applied in combination with finite element analysis using a 2D and 3D model simulating the turbine blades. Analysis clarified that the change in the surface properties under a small load varied according to the presence or absence of a crack, and elucidated the strain distribution that caused the difference in the change. In addition, analyses of the 2D model considering the material anisotropy and thermal barrier coating were conducted. The difference in the change in the surface properties and strain distribution according to the presence or absence of cracks was elucidated. The difference in the change in the top surface height distribution of the materials with and without a crack was directly proportional to the crack length. As the value was large with respect to the vertical resolution of 0.2 nm of the digital holographic microscope, the change could be detected by the microscope. en-copyright= kn-copyright= en-aut-name=SakamotoJunji en-aut-sei=Sakamoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TadaNaoya en-aut-sei=Tada en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemoriTakeshi en-aut-sei=Uemori en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuniyasuHayato en-aut-sei=Kuniyasu en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Shimadzu Corporation kn-affil= en-keyword=nondestructive inspection kn-keyword=nondestructive inspection en-keyword=crack detection kn-keyword=crack detection en-keyword=low loading kn-keyword=low loading en-keyword=surface profile kn-keyword=surface profile en-keyword=turbine blade kn-keyword=turbine blade en-keyword=finite element analysis kn-keyword=finite element analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=6 article-no= start-page=1576 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients' disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis. en-copyright= kn-copyright= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OyamaAtsushi en-aut-sei=Oyama en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AdachiTakuya en-aut-sei=Adachi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WadaNozomu en-aut-sei=Wada en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnishiHideki en-aut-sei=Onishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=chronic hepatitis kn-keyword=chronic hepatitis en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=12 article-no= start-page=4422 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague-Dawley rats under urethane-chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested. en-copyright= kn-copyright= en-aut-name=KobashiMotoi en-aut-sei=Kobashi en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimataniYuichi en-aut-sei=Shimatani en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujitaMasako en-aut-sei=Fujita en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuoRyuji en-aut-sei=Matsuo en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Engineering, Faculty of Science and Engineering, Tokyo City University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=GLP-1 kn-keyword=GLP-1 en-keyword=orexin kn-keyword=orexin en-keyword=SB334867 kn-keyword=SB334867 en-keyword=swallowing kn-keyword=swallowing en-keyword=NTS kn-keyword=NTS en-keyword=rats kn-keyword=rats END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=6 article-no= start-page=779 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Easy-to-Use InDel Markers for Genetic Mapping between Col-0 and Ler-0 Accessions of Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Map-based gene cloning has played a key role in many genetic studies using the model plant,Arabidopsis thaliana. In the post-next generation sequencing era, identification of point mutations and their corresponding genes is increasingly becoming a powerful and important approach to define plant gene function. To perform initial mapping experiments efficiently on Arabidopsis mutants, enrichment of easy-to-use and reliable polymorphic DNA markers would be desirable. We present here a list of InDel polymorphic markers between Col-0 and Ler-0 accessions that can be detected in standard agarose gel electrophoresis. en-copyright= kn-copyright= en-aut-name=TanakaTakahiro en-aut-sei=Tanaka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiiYuichi en-aut-sei=Nishii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuoHirotoshi en-aut-sei=Matsuo en-aut-mei=Hirotoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiTaku en-aut-sei=Takahashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=InDel markers kn-keyword=InDel markers en-keyword=SSLP kn-keyword=SSLP en-keyword=chromosome mapping kn-keyword=chromosome mapping en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=mutants kn-keyword=mutants END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=822 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lanthanide-Dependent Methanol and Formaldehyde Oxidation inMethylobacterium aquaticumStrain 22A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lanthanides (Ln) are an essential cofactor for XoxF-type methanol dehydrogenases (MDHs) in Gram-negative methylotrophs. The Ln(3+)dependency of XoxF has expanded knowledge and raised new questions in methylotrophy, including the differences in characteristics of XoxF-type MDHs, their regulation, and the methylotrophic metabolism including formaldehyde oxidation. In this study, we genetically identified one set of Ln(3+)- and Ca2+-dependent MDHs (XoxF1 and MxaFI), that are involved in methylotrophy, and an ExaF-type Ln(3+)-dependent ethanol dehydrogenase, among six MDH-like genes inMethylobacterium aquaticumstrain 22A. We also identified the causative mutations in MxbD, a sensor kinase necessary formxaFexpression andxoxF1repression, for suppressive phenotypes inxoxF1mutants defective in methanol growth even in the absence of Ln(3+). Furthermore, we examined the phenotypes of a series of formaldehyde oxidation-pathway mutants (fae1,fae2,mchin the tetrahydromethanopterin (H4MPT) pathway andhgdin the glutathione-dependent formaldehyde dehydrogenase (GSH) pathway). We found that MxaF produces formaldehyde to a toxic level in the absence of the formaldehyde oxidation pathways and that either XoxF1 or ExaF can oxidize formaldehyde to alleviate formaldehyde toxicity in vivo. Furthermore, the GSH pathway has a supportive role for the net formaldehyde oxidation in addition to the H4MPT pathway that has primary importance. Studies on methylotrophy inMethylobacteriumspecies have a long history, and this study provides further insights into genetic and physiological diversity and the differences in methylotrophy within the plant-colonizing methylotrophs. en-copyright= kn-copyright= en-aut-name=YanpiratPatcha en-aut-sei=Yanpirat en-aut-mei=Patcha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakatsujiYukari en-aut-sei=Nakatsuji en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiragaShota en-aut-sei=Hiraga en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaniYoshiko en-aut-sei=Fujitani en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IzumiTerumi en-aut-sei=Izumi en-aut-mei=Terumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasudaSachiko en-aut-sei=Masuda en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsuiRyoji en-aut-sei=Mitsui en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakagawaTomoyuki en-aut-sei=Nakagawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaniAkio en-aut-sei=Tani en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Department of Biochemistry, Faculty of Science, Okayama University of Science kn-affil= affil-num=8 en-affil=The United Graduate School of Agricultural Science, Gifu University kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=lanthanide kn-keyword=lanthanide en-keyword=methylotroph kn-keyword=methylotroph en-keyword=XoxF kn-keyword=XoxF en-keyword=methanol dehydrogenase kn-keyword=methanol dehydrogenase en-keyword=Methylobacteriumspecies kn-keyword=Methylobacteriumspecies END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=743 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Friction-Induced Martensitic Transformation and Wear Properties of Stainless Steel under Dry and Wet Conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=The wear characteristics of SUS304 and SUS316 stainless steels were evaluated at the rotation speeds of 100 m/s, 200 m/s, and 300 m/s under dry and wet conditions. The transition of friction-induced martensite occurred in wear-affected regions of two materials, regardless of the wear test conditions. The specific wear rates (W-s) of both stainless steels increase with increasing rotation speeds, regardless of the circumstances. Moreover,W(s)of SUS304 and SUS316, obtained under dry conditions, is significantly higher than that of SUS304 and SUS316 obtained under wet conditions, respectively. This is because that the water film on the wet ring can act as a liquid lubricant between the ring and the block during the tests. After the wear tests, the hardness changes of both SUS304 and SUS316 are much higher under dry conditions, compared to those under wet conditions. en-copyright= kn-copyright= en-aut-name=LeeYoon-Seok en-aut-sei=Lee en-aut-mei=Yoon-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoYuta en-aut-sei=Kondo en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkayasuMitsuhiro en-aut-sei=Okayasu en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=stainless steels kn-keyword=stainless steels en-keyword=friction-induced transformation kn-keyword=friction-induced transformation en-keyword=lubricant kn-keyword=lubricant en-keyword=wear kn-keyword=wear en-keyword=martensite kn-keyword=martensite END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=6 article-no= start-page=80 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Observation of Atmospheric Neutrinos en-subtitle= kn-subtitle= en-abstract= kn-abstract=In 1998, the Super-Kamiokande discovered neutrino oscillation using atmospheric neutrino anomalies. It was the first direct evidence of neutrino mass and the first phenomenon to be discovered beyond the standard model of particle physics. Recently, more precise measurements of neutrino oscillation parameters using atmospheric neutrinos have been achieved by several detectors, such as Super-Kamiokande, IceCube, and ANTARES. In addition, precise predictions and measurements of atmospheric neutrino flux have been performed. This paper presents the history, current status, and future prospects of the atmospheric neutrino observation. en-copyright= kn-copyright= en-aut-name=KoshioYusuke en-aut-sei=Koshio en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Experimental Particle Physics Group, Department of Physics, Okayama University kn-affil= en-keyword=neutrino oscillation kn-keyword=neutrino oscillation en-keyword=atmospheric neutrino kn-keyword=atmospheric neutrino END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=12 article-no= start-page=4545 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Acute kidney injury (AKI) has been increasingly recognized as a risk factor for transition to chronic kidney disease. Recent evidence suggests that endothelial damage in peritubular capillaries can accelerate the progression of renal injury. Vasohibin-2 (VASH2) is a novel proangiogenic factor that promotes tumor angiogenesis. However, the pathophysiological roles of VASH2 in kidney diseases remain unknown. In the present study, we examined the effects of VASH2 deficiency on the progression of ischemia-reperfusion (I/R) injury-induced AKI. I/R injury was induced by bilaterally clamping renal pedicles for 25 min in male wild-type (WT) andVash2homozygous knockout mice. Twenty-four hours later, I/R injury-induced renal dysfunction and tubular damage were more severe in VASH2-deficient mice than in WT mice, with more prominent neutrophil infiltration and peritubular capillary loss. After induction of I/R injury, VASH2 expression was markedly increased in injured renal tubules. These results suggest that VASH2 expression in renal tubular epithelial cells might be essential for alleviating I/R injury-induced AKI, probably through protecting peritubular capillaries and preventing inflammatory infiltration. en-copyright= kn-copyright= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanimuraSatoshi en-aut-sei=Tanimura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakashimaYuri en-aut-sei=Nakashima en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriokaTomoyo en-aut-sei=Morioka en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasudaKana en-aut-sei=Masuda en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoYasufumi en-aut-sei=Sato en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=New Industry Creation Hatchery Center, Tohoku University kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=acute kidney injury kn-keyword=acute kidney injury en-keyword=ischemia-reperfusion kn-keyword=ischemia-reperfusion en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=vasohibin-2 kn-keyword=vasohibin-2 en-keyword=peritubular capillaries kn-keyword=peritubular capillaries END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=6 article-no= start-page=1360 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200526 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Paclitaxel and Sorafenib: The Effective Combination of Suppressing the Self-Renewal of Cancer Stem Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Combination therapy, which is a treatment modality combining two or more therapeutic agents, is considered a cornerstone of cancer therapy. The combination of anticancer drugs, of which functions are different from the other, enhances the efficiency compared to the monotherapy because it targets cancer cells in a synergistic or an additive manner. In this study, the combination of paclitaxel and sorafenib in low concentration was evaluated to target cancer stem cells, miPS-BT549cmP and miPS-Huh7cmP cells, developed from mouse induced pluripotent stem cells. The synergistic effect of paclitaxel and sorafenib on cancer stem cells was assessed by the inhibition of proliferation, self-renewal, colony formation, and differentiation. While the IC(50)values of paclitaxel and sorafenib were approximately ranging between 250 and 300 nM and between 6.5 and 8 mu M, respectively, IC(50)of paclitaxel reduced to 20 and 25 nM, which was not toxic in a single dose, in the presence of 1 mu M sorafenib, which was not toxic to the cells. Then, the synergistic effect was further assessed for the potential of self-renewal of cancer stem cells by sphere formation ability. As a result, 1 mu M of sorafenib significantly enhanced the effect of paclitaxel to suppress the number of spheres. Simultaneously, paclitaxel ranging in 1 to 4 nM significantly suppressed not only the colony formation but also the tube formation of the cancer stem cells in the presence of 1 mu M sorafenib. These results suggest the combination therapy of paclitaxel and sorafenib in low doses should be an attractive approach to target cancer stem cells with fewer side effects. en-copyright= kn-copyright= en-aut-name=NawaraHend M. en-aut-sei=Nawara en-aut-mei=Hend M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AtallahMarwa N. en-aut-sei=Atallah en-aut-mei=Marwa N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MansourHager en-aut-sei=Mansour en-aut-mei=Hager kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Abu QuoraHagar A. en-aut-sei=Abu Quora en-aut-mei=Hagar A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AlamMd Jahangir en-aut-sei=Alam en-aut-mei=Md Jahangir kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OsmanAmira en-aut-sei=Osman en-aut-mei=Amira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HamadaHiroki en-aut-sei=Hamada en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name=妹尾彬正 kn-aut-sei=妹尾 kn-aut-mei=彬正 aut-affil-num=12 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name=妹尾昌治 kn-aut-sei=妹尾 kn-aut-mei=昌治 aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Vertebrates Embryology and Comparative Anatomy, Zoology Department, Faculty of Science, Menoufia University kn-affil= affil-num=6 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=12 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=combination therapy kn-keyword=combination therapy en-keyword=paclitaxel kn-keyword=paclitaxel en-keyword=sorafenib kn-keyword=sorafenib END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=3713 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Caries Increment and Salivary Microbiome during University Life: A Prospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of this 3-year prospective cohort study was to explore the relationship between an increase in dental caries and oral microbiome among Japanese university students. We analyzed 487 students who volunteered to receive oral examinations and answer baseline (2013) and follow-up (2016) questionnaires. Of these students, salivary samples were randomly collected from 55 students at follow-up and analyzed using next-generation sequencing. Students were divided into two groups: increased group (Delta decayed, missing, and filled teeth (Delta DMFT) score increased during the 3-year period) and non-increased group (Delta DMFT did not increase). Thirteen phyla, 21 classes, 32 orders, 48 families, 72 genera, and 156 species were identified. Microbial diversity in the increased group (n = 14) was similar to that in the non-increased group (n = 41). Relative abundances of the family Prevotellaceae (p = 0.007) and genera Alloprevotella (p = 0.007) and Dialister (p = 0.039) were enriched in the increased group compared with the non-increased group. Some bacterial taxonomic clades were differentially present between the two groups. These results may contribute to the development of new dental caries prevention strategies, including the development of detection kits and enlightenment activities for these bacteria. en-copyright= kn-copyright= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IslamMd Monirul en-aut-sei=Islam en-aut-mei=Md Monirul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Taniguchi-TabataAyano en-aut-sei=Taniguchi-Tabata en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiTerumasa en-aut-sei=Kobayashi en-aut-mei=Terumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujimoriKohei en-aut-sei=Fujimori en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SawadaNanami en-aut-sei=Sawada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Health Service Center, Okayama University kn-affil= affil-num=12 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=salivary microbiome kn-keyword=salivary microbiome en-keyword=sequence analysis kn-keyword=sequence analysis en-keyword=young adult kn-keyword=young adult en-keyword=dental caries kn-keyword=dental caries en-keyword=saliva kn-keyword=saliva en-keyword=oral health kn-keyword=oral health END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=11 article-no= start-page=4099 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury. en-copyright= kn-copyright= en-aut-name=SangYizhen en-aut-sei=Sang en-aut-mei=Yizhen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Inoue-ToriiAkiko en-aut-sei=Inoue-Torii en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate kn-affil= en-keyword=semaphorin3A kn-keyword=semaphorin3A en-keyword=podocyte kn-keyword=podocyte en-keyword=proteinuria kn-keyword=proteinuria en-keyword=apoptosis kn-keyword=apoptosis en-keyword=c-Jun N-terminal kinase kn-keyword=c-Jun N-terminal kinase END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=11 article-no= start-page=4054 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i-HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD. en-copyright= kn-copyright= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SangYizhen en-aut-sei=Sang en-aut-mei=Yizhen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=sodium glucose co-transporter 2 inhibitor kn-keyword=sodium glucose co-transporter 2 inhibitor en-keyword=mammalian target of rapamycin (mTOR) kn-keyword=mammalian target of rapamycin (mTOR) en-keyword=autophagy kn-keyword=autophagy en-keyword=obesity kn-keyword=obesity en-keyword=multi lamellar body kn-keyword=multi lamellar body END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=11 article-no= start-page=4137 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for "oxidative phosphorylation" was significantly upregulated while fourteen other gene sets including "apoptosis", "hypoxia" and "reactive oxygen species" showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis. en-copyright= kn-copyright= en-aut-name=KidaniNaoya en-aut-sei=Kidani en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HishikawaTomohito en-aut-sei=Hishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishihiroShingo en-aut-sei=Nishihiro en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuraiSatoshi en-aut-sei=Murai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=apoptosis kn-keyword=apoptosis en-keyword=cerebral blood flow kn-keyword=cerebral blood flow en-keyword=crossed cerebellar diaschisis kn-keyword=crossed cerebellar diaschisis en-keyword=ischemic stroke kn-keyword=ischemic stroke en-keyword=oxidative stress kn-keyword=oxidative stress END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=5 article-no= start-page=625 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of Continuous Casting Speeds on Cast Microstructure and Mechanical Properties of an ADC14 Alloy en-subtitle= kn-subtitle= en-abstract= kn-abstract=To improve the mechanical properties of the casting alloys, various attempts have been made to use alternative casting technologies. The Ohno continuous casting (OCC) process is a unidirectional solidification method, which leads to high-quality cast samples. In this study, the Al-Si-Cu-Mg alloy was cast at casting speeds of 1 mm/s, 2 mm/s, and 3 mm/s, by the OCC process. The aim of this study is to investigate the effects of the casting process parameters, such as casting speeds and cooling conditions, on the crystallization characteristics and mechanical properties of OCC-Al-Si-Cu-Mg alloy. Particularly, secondary dendrite arms spacing of alpha-Al dendrites in OCC samples significantly decreases with increasing casting speed. Moreover, the mean tensile strength of the samples, produced at the highest casting speed of 4.0 mm/s, is significantly higher than that for the samples produced at a casting speed of 1.0 mm/s. en-copyright= kn-copyright= en-aut-name=LeeYoon-Seok en-aut-sei=Lee en-aut-mei=Yoon-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakinoYuya en-aut-sei=Makino en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NittaJun en-aut-sei=Nitta en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeeEunkyung en-aut-sei=Lee en-aut-mei=Eunkyung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Ocean Advanced Materials Convergence Engineering, Korea Maritime and Ocean University kn-affil= en-keyword=aluminum alloy kn-keyword=aluminum alloy en-keyword=casting speed kn-keyword=casting speed en-keyword=solidification kn-keyword=solidification en-keyword=Ohno continuous casting kn-keyword=Ohno continuous casting en-keyword=gravity casting kn-keyword=gravity casting en-keyword=dendritic spacing kn-keyword=dendritic spacing END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=5 article-no= start-page=1301 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnostic Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Gastric Mesenchymal Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=There have been no comparative studies investigating the results of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with gastric mesenchymal tumors, including leiomyomas, leiomyosarcomas, schwannomas, and gastrointestinal stromal tumors (GISTs). We retrospectively reviewed the data of 142 patients with pathologically diagnosed gastric mesenchymal tumors treated at 11 institutions. We analyzed the correlation between the maximum standardized uptake value (SUVmax) evaluated using fluorodeoxyglucose-positron emission tomography (FDG-PET) and the tumor size. The correlation between the SUVmax and mitotic index was also investigated in GISTs. The SUVmax (mean +/- standard deviation) was 0.5 +/- 0.6 in very low-risk GISTs (n = 42), 2.1 +/- 0.7 in low-risk GISTs (n = 26), 4.9 +/- 0.8 in intermediate-risk GISTs (n = 22), 12.3 +/- 0.8 in high-risk GISTs (n = 20), 1.0 +/- 1.0 in leiomyomas (n = 15), 6.9 +/- 1.2 in schwannomas (n = 10), and 3.5 in a leiomyosarcoma (n = 1). The SUVmax of GISTs with an undetermined risk classification was 4.2 +/- 1.3 (n = 8). Linear associations were observed between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax of GISTs with a high mitotic index was significantly higher than that of GISTs with a low mitotic index (9.6 +/- 7.6 vs. 2.4 +/- 4.2). In conclusion, we observed positive correlations between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax also positively correlated with the mitotic index and risk grade in GISTs. Schwannomas showed a higher FDG uptake than GISTs and leiomyomas. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyaharaKoji en-aut-sei=Miyahara en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaguchiChihiro en-aut-sei=Sakaguchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakenakaRyuta en-aut-sei=Takenaka en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiSayo en-aut-sei=Kobayashi en-aut-mei=Sayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MouriHirokazu en-aut-sei=Mouri en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaShigetomi en-aut-sei=Tanaka en-aut-mei=Shigetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaShouichi en-aut-sei=Tanaka en-aut-mei=Shouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraMamoru en-aut-sei=Nishimura en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamauchiKenji en-aut-sei=Yamauchi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Hiroshima City Hospital kn-affil= affil-num=3 en-affil=Department of Endoscopy, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Iwakuni Clinical Center kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Mitoyo General Hospital kn-affil= affil-num=12 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=18F-fluorodeoxyglucose-positron emission tomography kn-keyword=18F-fluorodeoxyglucose-positron emission tomography en-keyword=mesenchymal tumor kn-keyword=mesenchymal tumor en-keyword=gastric neoplasms kn-keyword=gastric neoplasms en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=schwannoma kn-keyword=schwannoma END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles en-subtitle= kn-subtitle= en-abstract= kn-abstract=The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (200-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 led to a significant reduction in tumoroid size and the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. Moreover, CD63, another member of the tetraspanin family, was significantly reduced only in the EVs fractions of the MMP3-KO cells compared to their counterpart. These weakened phenotypes of MMP3-KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3, resulting in increasing the proliferation and tumorigenesis, indicating crucial roles of MMP3 in tumor progression. en-copyright= kn-copyright= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ElseoudiAbdellatif en-aut-sei=Elseoudi en-aut-mei=Abdellatif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LuYanyin en-aut-sei=Lu en-aut-mei=Yanyin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medical Bioengineering, Okayama University Graduate School of Natural Science and Technology kn-affil= affil-num=11 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=matrix metalloproteinase 3 (MMP3) kn-keyword=matrix metalloproteinase 3 (MMP3) en-keyword=extracellular vesicles (EVs) kn-keyword=extracellular vesicles (EVs) en-keyword=tumoroid kn-keyword=tumoroid en-keyword=tumor organoid kn-keyword=tumor organoid en-keyword=tumorigenesis kn-keyword=tumorigenesis en-keyword=three-dimensional (3D) culture system kn-keyword=three-dimensional (3D) culture system END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=8 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of Interaction between CCN2 and Rab14 in Aggrecan Production by Chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=To identify proteins that cooperate with cellular communication network factor 2 (CCN2), we carried out GAL4-based yeast two-hybrid screening using a cDNA library derived from the chondrocytic cell line HCS-2/8. Rab14 GTPase (Rab14) polypeptide was selected as a CCN2-interactive protein. The interaction between CCN2 and Rab14 in HCS-2/8 cells was confirmed using the in situ proximity ligation assay. We also found that CCN2 interacted with Rab14 through its IGFBP-like domain among the four domains in CCN2 protein. To detect the colocalization between CCN2 and Rab14 in the cells in detail, CCN2, wild-type Rab14 (Rab14WT), a constitutive active form (Rab14CA), and a dominant negative form (Rab14DN) of Rab14 were overexpressed in monkey kidney-tissue derived COS7 cells. Ectopically overexpressed Rab14 showed a diffuse cytosolic distribution in COS7 cells; however, when Rab14WT was overexpressed with CCN2, the Rab14WT distribution changed to dots that were evenly distributed within the cytosol, and both Rab14 and CCN2 showed clear colocalization. When Rab14CA was overexpressed with CCN2, Rab14CA and CCN2 also showed good localization as dots, but their distribution was more widespread within cytosol. The coexpression of Rab14DN and CCN2 also showed a dotted codistribution but was more concentrated in the perinuclear area. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that the reduction in RAB14 or CCN2 mRNA by their respective siRNA significantly enhanced the expression of ER stress markers, BIP and CHOP mRNA in HCS-2/8 chondrocytic cells, suggesting that ER and Golgi stress were induced by the inhibition of membrane vesicle transfer via the suppression of CCN2 or Rab14. Moreover, to study the effect of the interaction between CCN2 and its interactive protein Rab14 on proteoglycan synthesis, we overexpressed Rab14WT or Rab14CA or Rab14DN in HCS-2/8 cells and found that the overexpression of Rab14DN decreased the extracellular proteoglycan accumulation more than the overexpression of Rab14WT/CA did in the chondrocytic cells. These results suggest that intracellular CCN2 is associated with Rab14 on proteoglycan-containing vesicles during their transport from the Golgi apparatus to endosomes in chondrocytes and that this association may play a role in proteoglycan secretion by chondrocytes. en-copyright= kn-copyright= en-aut-name=HoshijimaMitsuhiro en-aut-sei=Hoshijima en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HattoriTakako en-aut-sei=Hattori en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishidaTakashi en-aut-sei=Nishida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cellular communication network factor 2 kn-keyword=cellular communication network factor 2 en-keyword=CCN2 kn-keyword=CCN2 en-keyword=CTGF kn-keyword=CTGF en-keyword=Rab14 kn-keyword=Rab14 en-keyword=yeast two-hybrid kn-keyword=yeast two-hybrid en-keyword=chondrocyte kn-keyword=chondrocyte en-keyword=ER stress kn-keyword=ER stress en-keyword=aggrecan kn-keyword=aggrecan END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas. en-copyright= kn-copyright= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=hTERT kn-keyword=hTERT en-keyword=autophagy kn-keyword=autophagy en-keyword=GFP kn-keyword=GFP en-keyword=p53 kn-keyword=p53 END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=4 article-no= start-page=879 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment: A Hypothetical View from the Potential of iPSCs en-subtitle= kn-subtitle= en-abstract= kn-abstract=The tumor microenvironment (TME) has an essential role in tumor initiation and development. Tumor cells are considered to actively create their microenvironment during tumorigenesis and tumor development. The TME contains multiple types of stromal cells, cancer-associated fibroblasts (CAFs), Tumor endothelial cells (TECs), tumor-associated adipocytes (TAAs), tumor-associated macrophages (TAMs) and others. These cells work together and with the extracellular matrix (ECM) and many other factors to coordinately contribute to tumor growth and maintenance. Although the types and functions of TME cells are well understood, the origin of these cells is still obscure. Many scientists have tried to demonstrate the origin of these cells. Some researchers postulated that TME cells originated from surrounding normal tissues, and others demonstrated that the origin is cancer cells. Recent evidence demonstrates that cancer stem cells (CSCs) have differentiation abilities to generate the original lineage cells for promoting tumor growth and metastasis. The differentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity. Using induced pluripotent stem cells (iPSCs), our group postulates that CSCs could be one of the key sources of CAFs, TECs, TAAs, and TAMs as well as the descendants, which support the self-renewal potential of the cells and exhibit heterogeneity. In this review, we summarize TME components, their interactions within the TME and their insight into cancer therapy. Especially, we focus on the TME cells and their possible origin and also discuss the multi-lineage differentiation potentials of CSCs exploiting iPSCs to create a society of cells in cancer tissues including TME. en-copyright= kn-copyright= en-aut-name=OsmanAmira en-aut-sei=Osman en-aut-mei=Amira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FuXiaoying en-aut-sei=Fu en-aut-mei=Xiaoying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=CAFs kn-keyword=CAFs en-keyword=TECs kn-keyword=TECs en-keyword=TAAs kn-keyword=TAAs en-keyword=TAMs kn-keyword=TAMs en-keyword=CSCs kn-keyword=CSCs END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=6 article-no= start-page=1659 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200317 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnosis of Occlusal Caries with Dynamic Slicing of 3D Optical Coherence Tomography Images en-subtitle= kn-subtitle= en-abstract= kn-abstract=Detecting the extent of occlusal caries is a clinically important but challenging task required for treatment decision making. The aim of this study was to assess the diagnostic power of 3D swept-source optical coherence tomography (OCT) for evaluation of occlusal caries in comparison with X-ray radiography. Extracted human molars not exhibiting American Dental Association (ADA) criteria advanced caries were mounted in a silicone block and digital dental radiographs were captured from the buccal side. Subsequently, occlusal surfaces were scanned with a prototype Yoshida Dental OCT. Thirteen examiners evaluated the presence and extent of caries on radiographs and dynamically sliced 3D OCT video images, using a 4 level scale-0: intact; 1: enamel demineralization without cavitation; 2: enamel caries with cavitation; 3: dentin caries with or without cavitation. Sensitivity, specificity and area under operating characteristic curves (Az) were statistically analyzed (alpha = 0.05). Reliability analysis showed an excellent agreement among the 13 examiners for both methods. The OCT presented a significantly higher sensitivity and Az value for the detection of caries compared to radiographs (p < 0.05). Radiography showed especially low sensitivity for dentin caries (0-2 versus 3). Dynamic slicing of 3D OCT volumes is a powerful adjunct tool to visual inspection to diagnose the dentin occlusal caries in vitro. en-copyright= kn-copyright= en-aut-name=LuongMinh N. en-aut-sei=Luong en-aut-mei=Minh N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimadaYasushi en-aut-sei=Shimada en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakiKazuyuki en-aut-sei=Araki en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiyamaMasahiro en-aut-sei=Yoshiyama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TagamiJunji en-aut-sei=Tagami en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SadrAlireza en-aut-sei=Sadr en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Restorative Dentistry, University of Washington kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Radiology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=6 en-affil=Department of Restorative Dentistry, University of Washington kn-affil= en-keyword=dentin kn-keyword=dentin en-keyword=enamel kn-keyword=enamel en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=radiograph kn-keyword=radiograph en-keyword=receiver operating characteristic (ROC) analysis kn-keyword=receiver operating characteristic (ROC) analysis en-keyword=hidden caries kn-keyword=hidden caries en-keyword=dentino-enamel junction DEJ kn-keyword=dentino-enamel junction DEJ END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=7 article-no= start-page=2447 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of Dinaphtho[2,3-d:2',3'-d']anthra[1,2-b:5,6-b']dithiophene (DNADT) Derivatives: Effect of Alkyl Chains on Transistor Properties en-subtitle= kn-subtitle= en-abstract= kn-abstract=To investigate organic field-effect transistor (OFET) properties, a new thienoacene-type molecule, 4,14-dihexyldinaphtho[2,3-d:2',3'-d']anthra[1,2-b:5,6-b']dithiophene (C6-DNADT), consisting of pi-conjugated nine aromatic rings and two hexyl chains along the longitudinal molecular axis has been successfully synthesized by sequential reactions, including Negishi coupling, epoxidation, and cycloaromatization. The fabricated OFET using thin films of C6-DNADT exhibited p-channel FET properties with field-effect mobilities (mu) of up to 2.6 x 10(-2) cm(2) V-1 s(-1), which is ca. three times lower than that of the parent DNADT molecule (8.5 x 10(-2) cm(2) V-1 s(-1)). Although this result implies that the installation of relatively short alkyl chains into the DNADT core is not suitable for transistor application, the origins for the FET performance obtained in this work is fully discussed, based on theoretical calculations and solid-state structure of C6-DNADT by grazing incidence wide-angle X-ray scattering (GIWAXS) and atomic force microscopy (AFM) analyses. The results obtained in this study disclose the effect of alkyl chains introduced onto the molecule on transistor characteristics. en-copyright= kn-copyright= en-aut-name=IshidaTakumi en-aut-sei=Ishida en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawanakaYuta en-aut-sei=Sawanaka en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyamaRyota en-aut-sei=Toyama en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JiZhenfei en-aut-sei=Ji en-aut-mei=Zhenfei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriHiroki en-aut-sei=Mori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiharaYasushi en-aut-sei=Nishihara en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=organic field-effect transistor (OFET) kn-keyword=organic field-effect transistor (OFET) en-keyword=thienoacene kn-keyword=thienoacene en-keyword=p-type semiconductor kn-keyword=p-type semiconductor en-keyword=Negishi coupling reaction kn-keyword=Negishi coupling reaction en-keyword=cycloaromatization kn-keyword=cycloaromatization en-keyword=fastener effect kn-keyword=fastener effect END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=High mobility group box-1 (HMGB1), a nonhistone chromatin DNA-binding protein, is released from neurons into the extracellular space under ischemic, hemorrhagic, and traumatic insults. However, the details of the time-dependent translocation of HMGB1 and the subcellular localization of HMGB1 through the release process in neurons remain unclear. In the present study, we examined the subcellular localization of HMGB1 during translocation of HMGB1 in the cytosolic compartment using a middle cerebral artery occlusion and reperfusion model in rats. Double immunofluorescence microscopy revealed that HMGB1 immunoreactivities were colocalized with MTCO1(mitochondrially encoded cytochrome c oxidase I), a marker of mitochondria, and catalase, a marker of peroxisomes, but not with Rab5/Rab7 (RAS-related GTP-binding protein), LC3A/B (microtubule-associated protein 1 light chain 3), KDEL (KDEL amino acid sequence), and LAMP1 (Lysosomal Associated Membrane Protein 1), which are endosome, phagosome, endoplasmic reticulum, and lysosome markers, respectively. Immunoelectron microscopy confirmed that immune-gold particles for HMGB1 were present inside the mitochondria and peroxisomes. Moreover, HMGB1 was found to be colocalized with Drp1 (Dynamin-related protein 1), which is involved in mitochondrial fission. These results revealed the specific subcellular localization of HMGB1 during its release process under ischemic conditions. en-copyright= kn-copyright= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuyasuYusuke en-aut-sei=Fukuyasu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TeshigawaraKiyoshi en-aut-sei=Teshigawara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuLi en-aut-sei=Fu en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Human Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=middle cerebral artery occlusion kn-keyword=middle cerebral artery occlusion en-keyword=high-mobility group box 1 kn-keyword=high-mobility group box 1 en-keyword=subcellular localization and subcellular organelle kn-keyword=subcellular localization and subcellular organelle END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=3 article-no= start-page=913 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC's serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD. en-copyright= kn-copyright= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuganumaMutsumi en-aut-sei=Suganuma en-aut-mei=Mutsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeichiTakuya en-aut-sei=Takeichi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KonoMichihiro en-aut-sei=Kono en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IsokaneYuki en-aut-sei=Isokane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobashiMina en-aut-sei=Kobashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KajitaAi en-aut-sei=Kajita en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyakeTomoko en-aut-sei=Miyake en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraiYoji en-aut-sei=Hirai en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkiyamaMasashi en-aut-sei=Akiyama en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Dermatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Dermatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Dermatology and Plastic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=11 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=12 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=13 en-affil=Department of Dermatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= en-keyword=atopic dermatitis kn-keyword=atopic dermatitis en-keyword=serine proteases kn-keyword=serine proteases en-keyword=kallikrein-related peptidases kn-keyword=kallikrein-related peptidases en-keyword=epidermal barrier dysfunction kn-keyword=epidermal barrier dysfunction en-keyword=lympho-epithelial Kazal-type-related inhibitor (LEKTI) kn-keyword=lympho-epithelial Kazal-type-related inhibitor (LEKTI) en-keyword=SPINK5 kn-keyword=SPINK5 en-keyword=filaggrin kn-keyword=filaggrin END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=9 article-no= start-page=3254 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chronic Systemic Exposure to Low-Dose Rotenone Induced Central and Peripheral Neuropathology and Motor Deficits in Mice: Reproducible Animal Model of Parkinson's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epidemiological studies demonstrated that pesticide exposure, such as rotenone and paraquat, increases the risk of Parkinson's disease (PD). Chronic systemic exposure to rotenone, a mitochondrial complex I inhibitor, could reproduce many features of PD. However, the adoption of the models is limiting because of variability in animal sensitivity and the inability of other investigators to consistently reproduce the PD neuropathology. In addition, most of rotenone models were produced in rats. Here, we tried to establish a high-reproducible rotenone model using C57BL/6J mice. The rotenone mouse model was produced by chronic systemic exposure to a low dose of rotenone (2.5 mg/kg/day) for 4 weeks by subcutaneous implantation of rotenone-filled osmotic mini pump. The rotenone-treated mice exhibited motor deficits assessed by open field, rotarod and cylinder test and gastrointestinal dysfunction. Rotenone treatment decreased the number of dopaminergic neuronal cells in the substantia nigra pars compacta (SNpc) and lesioned nerve terminal in the striatum. In addition, we observed significant reduction of cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) and the intestinal myenteric plexus. Moreover, alpha-synuclein was accumulated in neuronal soma in the SNpc, DMV and intestinal myenteric plexus in rotenone-treated mice. These data suggest that the low-dose rotenone mouse model could reproduce behavioral and central and peripheral neurodegenerative features of PD and be a useful model for investigation of PD pathogenesis. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImafukuFuminori en-aut-sei=Imafuku en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunJin en-aut-sei=Sun en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurukawaChieko en-aut-sei=Furukawa en-aut-mei=Chieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=rotenone kn-keyword=rotenone en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=dopaminergic neuron kn-keyword=dopaminergic neuron en-keyword=dorsal motor nucleus of the vagus kn-keyword=dorsal motor nucleus of the vagus en-keyword=myenteric plexus kn-keyword=myenteric plexus en-keyword=neurodegeneration kn-keyword=neurodegeneration en-keyword=α-synuclein kn-keyword=α-synuclein en-keyword=motor deficit kn-keyword=motor deficit END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=3 article-no= start-page=756 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mesenchymal stem cells (MSCs) have immunomodulatory and regenerative effects in many organs, including the kidney. Emerging evidence has shown that the trophic effects from MSCs are mainly mediated by the paracrine mechanism rather than the direct differentiation of MSCs into injured tissues. These secretomes from MSCs include cytokines, growth factors, chemokines and extracellular vesicles (EVs) containing microRNAs, mRNAs, and proteins. Many research studies have revealed that secretomes from MSCs have potential to ameliorate renal injury in renal disease models, including acute kidney injury and chronic kidney disease through a variety of mechanisms. These trophic mechanisms include immunomodulatory and regenerative effects. In addition, accumulating evidence has uncovered the specific factors and therapeutic mechanisms in MSC-derived EVs. In this article, we summarize the recent advances of immunomodulatory and regenerative effects of EVs from MSCs, especially focusing on the microRNAs. en-copyright= kn-copyright= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=mesenchymal stem cell kn-keyword=mesenchymal stem cell en-keyword=extracellular vesicles kn-keyword=extracellular vesicles en-keyword=microRNA kn-keyword=microRNA en-keyword=immunomodulation kn-keyword=immunomodulation en-keyword=renal regeneration kn-keyword=renal regeneration en-keyword=acute kidney injury kn-keyword=acute kidney injury en-keyword=chronic kidney disease kn-keyword=chronic kidney disease END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=9 article-no= start-page=3140 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction of CEMIP in Chondrocytes by Inflammatory Cytokines: Underlying Mechanisms and Potential Involvement in Osteoarthritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=In patients with osteoarthritis (OA), there is a decrease in both the concentration and molecular size of hyaluronan (HA) in the synovial fluid and cartilage. Cell migration-inducing hyaluronidase 1 (CEMIP), also known as hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID), was recently reported as an HA depolymerization-related molecule expressed in the cartilage of patients with OA. However, the underlying mechanism of CEMIP regulation is not well understood. We found that CEMIP expression was transiently increased by interleukine-1 beta (IL-1 beta) stimulation in chondrocytic cells. We also observed that ERK activation and NF-kappa B nuclear translocation were involved in the induction of CEMIP by IL-1 beta. In addition, both administration of HA and mechanical strain attenuated the CEMIP induction in IL-1 beta-stimulated chondrocytes. In conclusion, we clarified the regulatory mechanism of CEMIP in chondrocytes by inflammatory cytokines and suggested the potential involvement in osteoarthritis development. en-copyright= kn-copyright= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HatipogluOmer F. en-aut-sei=Hatipoglu en-aut-mei=Omer F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanoKeiichi en-aut-sei=Asano en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InagakiJunko en-aut-sei=Inagaki en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaediac Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=cell migration-inducing hyaluronidase 1 (CEMIP) kn-keyword=cell migration-inducing hyaluronidase 1 (CEMIP) en-keyword=chondrocyte kn-keyword=chondrocyte en-keyword=hyaluronan kn-keyword=hyaluronan en-keyword=mechanical strain kn-keyword=mechanical strain en-keyword=nuclear factor kappa B (NF-kappa B) kn-keyword=nuclear factor kappa B (NF-kappa B) en-keyword=osteoarthritis kn-keyword=osteoarthritis END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between Sleep Quality and Duration and Periodontal Disease among University Students: A Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of this cross-sectional study was to investigate the association between sleep quality and duration, and periodontal disease among a group of young Japanese university students. First-year students (n = 1934) at Okayama University who voluntarily underwent oral health examinations were included in the analysis. Sleep quality and duration were assessed by the Japanese version of the Pittsburgh Sleep Quality Index. Dentists examined Oral Hygiene Index-Simplified (OHI-S), probing pocket depth (PPD), and percentage of sites with bleeding on probing (BOP). Periodontal disease was defined as presence of PPD >= 4 mm and BOP >= 30%. Overall, 283 (14.6%) students had periodontal disease. Poor sleep quality was observed among 372 (19.2%) students. Mean (+/- standard deviation) sleep duration was 7.1 +/- 1.1 (hours/night). In the logistic regression analysis, periodontal disease was significantly associated with OHI-S (odds ratio [OR]: 2.30, 95% confident interval [CI]: 1.83-2.90; p < 0.001), but not sleep quality (OR: 1.09, 95% CI: 0.79-1.53; p = 0.577) or sleep duration (OR: 0.98, CI: 0.87-1.10; p = 0.717). In conclusion, sleep quality and duration were not associated with periodontal disease among this group of young Japanese university students. en-copyright= kn-copyright= en-aut-name=IslamMd Monirul en-aut-sei=Islam en-aut-mei=Md Monirul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Taniguchi-TabataAyano en-aut-sei=Taniguchi-Tabata en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SahoHikari en-aut-sei=Saho en-aut-mei=Hikari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawadaNanami en-aut-sei=Sawada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakashimaYukiho en-aut-sei=Nakashima en-aut-mei=Yukiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=11 en-affil=Health Service Center, Okayama University kn-affil= affil-num=12 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=sleep quality kn-keyword=sleep quality en-keyword=sleep duration kn-keyword=sleep duration en-keyword=periodontal disease kn-keyword=periodontal disease en-keyword=university students kn-keyword=university students END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=4 article-no= start-page=881 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF): CRISPR against Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Matrix metalloproteinase 3 (MMP3) plays multiple roles in extracellular proteolysis as well as intracellular transcription, prompting a new definition of moonlighting metalloproteinase (MMP), according to a definition of protein moonlighting (or gene sharing), a phenomenon by which a protein can perform more than one function. Indeed, connective tissue growth factor (CTGF, aka cellular communication network factor 2 (CCN2)) is transcriptionally induced as well as cleaved by MMP3. Moreover, several members of the MMP family have been found within tumor-derived extracellular vesicles (EVs). We here investigated the roles of MMP3-rich EVs in tumor progression, molecular transmission, and gene regulation. EVs derived from a rapidly metastatic cancer cell line (LuM1) were enriched in MMP3 and a C-terminal half fragment of CCN2/CTGF. MMP3-rich, LuM1-derived EVs were disseminated to multiple organs through body fluid and were pro-tumorigenic in an allograft mouse model, which prompted us to define LuM1-EVs as oncosomes in the present study. Oncosome-derived MMP3 was transferred into recipient cell nuclei and thereby trans-activated the CCN2/CTGF promoter, and induced CCN2/CTGF production in vitro. TRENDIC and other cis-elements in the CCN2/CTGF promoter were essential for the oncosomal responsivity. The CRISPR/Cas9-mediated knockout of MMP3 showed significant anti-tumor effects such as the inhibition of migration and invasion of tumor cells, and a reduction in CCN2/CTGF promoter activity and fragmentations in vitro. A high expression level of MMP3 or CCN2/CTGF mRNA was prognostic and unfavorable in particular types of cancers including head and neck, lung, pancreatic, cervical, stomach, and urothelial cancers. These data newly demonstrate that oncogenic EVs-derived MMP is a transmissive trans-activator for the cellular communication network gene and promotes tumorigenesis at distant sites. en-copyright= kn-copyright= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TranManh T. en-aut-sei=Tran en-aut-mei=Manh T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaKaya en-aut-sei=Yoshida en-aut-mei=Kaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItagakiMami en-aut-sei=Itagaki en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KozakiKen-Ichi en-aut-sei=Kozaki en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Healthcare Education, Institute of Biomedical Sciences, Tokushima University Graduate School kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Morphology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=13 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=matrix metalloproteinase kn-keyword=matrix metalloproteinase en-keyword=moonlighting metalloproteinase (MMP) kn-keyword=moonlighting metalloproteinase (MMP) en-keyword=protein moonlighting kn-keyword=protein moonlighting en-keyword=transcription factor kn-keyword=transcription factor en-keyword=extracellular vesicles kn-keyword=extracellular vesicles en-keyword=oncosome kn-keyword=oncosome en-keyword=genome editing kn-keyword=genome editing en-keyword=CRISPR kn-keyword=CRISPR en-keyword=cellular communication network factor kn-keyword=cellular communication network factor en-keyword=CCN2/CTGF kn-keyword=CCN2/CTGF END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=5 article-no= start-page=1144 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Systematic Investigations of Annealing and Functionalization of Carbon Nanotube Yarns en-subtitle= kn-subtitle= en-abstract= kn-abstract=Carbon nanotube yarns (CNY) are a novel carbonaceous material and have received a great deal of interest since the beginning of the 21st century. CNY are of particular interest due to their useful heat conducting, electrical conducting, and mechanical properties. The electrical conductivity of carbon nanotube yarns can also be influenced by functionalization and annealing. A systematical study of this post synthetic treatment will assist in understanding what factors influences the conductivity of these materials. In this investigation, it is shown that the electrical conductivity can be increased by a factor of 2 and 5.5 through functionalization with acids and high temperature annealing respectively. The scale of the enhancement is dependent on the reducing of intertube space in case of functionalization. For annealing, not only is the highly graphitic structure of the carbon nanotubes (CNT) important, but it is also shown to influence the residual amorphous carbon in the structure. The promising results of this study can help to utilize CNY as a replacement for common materials in the field of electrical wiring. en-copyright= kn-copyright= en-aut-name=ScholzMaik en-aut-sei=Scholz en-aut-mei=Maik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiYasuhiko en-aut-sei=Hayashi en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EckertVictoria en-aut-sei=Eckert en-aut-mei=Victoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KhavrusVyacheslav en-aut-sei=Khavrus en-aut-mei=Vyacheslav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeonhardtAlbrecht en-aut-sei=Leonhardt en-aut-mei=Albrecht kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BüchnerBernd en-aut-sei=Büchner en-aut-mei=Bernd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MertigMichael en-aut-sei=Mertig en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HampelSilke en-aut-sei=Hampel en-aut-mei=Silke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Leibniz Institute for Solid State and Material Research Dresden, Helmholtzstr. 20 kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Leibniz Institute for Solid State and Material Research Dresden, Helmholtzstr. 20 kn-affil= affil-num=4 en-affil=Leibniz Institute for Solid State and Material Research Dresden, Helmholtzstr. 20 kn-affil= affil-num=5 en-affil=Leibniz Institute for Solid State and Material Research Dresden, Helmholtzstr. 20 kn-affil= affil-num=6 en-affil=Leibniz Institute for Solid State and Material Research Dresden, Helmholtzstr. 20 kn-affil= affil-num=7 en-affil=Institute for Physical Chemistry, Technische Universität Dresden kn-affil= affil-num=8 en-affil=Leibniz Institute for Solid State and Material Research Dresden, Helmholtzstr. 20 kn-affil= en-keyword=carbon nanotube yarns kn-keyword=carbon nanotube yarns en-keyword=carbon nanotube kn-keyword=carbon nanotube en-keyword=functionalization kn-keyword=functionalization en-keyword=electrical conductivity kn-keyword=electrical conductivity en-keyword=annealing kn-keyword=annealing en-keyword=acid treatment kn-keyword=acid treatment END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=1764 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200309 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship of Salivary Microbiome with the Worsening of the Periodontal Health Status in Young Adults: A 3-Year Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of this prospective cohort study was to investigate the influence of the salivary microbiome on the worsening of the periodontal health status among Japanese young adults. We assessed the data of systemically healthy and non-smoking young (18-22 years) university students (n = 457) from Okayama University at baseline (2013) and follow-up (2016). The worsening group was defined based on an increase in the percentage of bleeding on probing (%BOP) or an increase in probing pocket depth (PPD) from <4 mm to >= 4 mm. Unstimulated saliva samples were randomly collected from 69 students for microbiome analysis at follow-up. The salivary microbiome was assessed through 16S rRNA metagenomic sequencing. The type of community in the salivary microbiome clustered by statistical analysis and diversity was not significantly associated with the worsening of the periodontal health status in cases of increasing %BOP and PPD (p > 0.05). The prevalence of some species was significantly higher in the worsening group than in the non-worsening group (p < 0.05) in both cases. The worsening of the periodontal health status was associated with some species, but not the type of community and diversity in the salivary microbiome among Japanese young adults. en-copyright= kn-copyright= en-aut-name=IslamMd Monirul en-aut-sei=Islam en-aut-mei=Md Monirul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiTerumasa en-aut-sei=Kobayashi en-aut-mei=Terumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimoriKohei en-aut-sei=Fujimori en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaYoko en-aut-sei=Uchida en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Taniguchi-TabataAyano en-aut-sei=Taniguchi-Tabata en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Health Service Center, Okayama University kn-affil= affil-num=11 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=salivary microbiome kn-keyword=salivary microbiome en-keyword=periodontal health status kn-keyword=periodontal health status en-keyword=oral hygiene kn-keyword=oral hygiene en-keyword=cohort study kn-keyword=cohort study en-keyword=young adults kn-keyword=young adults END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=755 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200319 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cell Stress Induced Stressome Release Including Damaged Membrane Vesicles and Extracellular HSP90 by Prostate Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tumor cells exhibit therapeutic stress resistance-associated secretory phenotype involving extracellular vesicles (EVs) such as oncosomes and heat shock proteins (HSPs). Such a secretory phenotype occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as a soluble form known as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in the release of EV proteins including CD9 and epithelial-to-mesenchymal transition (EMT), a key event in tumor progression. EVs derived from CRPC cells promoted EMT in normal prostate epithelial cells. Some HSP family members and their potential receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein types found by mass spectrometry. The small EVs (30-200 nm in size) were released even in a non-heated condition from the prostate cancer cells, whereas the EMT-coupled release of EVs (200-500 nm) and damaged membrane vesicles with associated HSP90 alpha was increased after heat shock stress (HSS). GAPDH and lactate dehydrogenase, a marker of membrane leakage/damage, were also found in conditioned media upon HSS. During this stress response, the intracellular chaperone CDC37 was transcriptionally induced by heat shock factor 1 (HSF1), which activated the CDC37 core promoter, containing an interspecies conserved heat shock element. In contrast, knockdown of CDC37 decreased EMT-coupled release of CD9-containing vesicles. Triple siRNA targeting CDC37, HSP90 alpha, and HSP90 beta was required for efficient reduction of this chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, we define "stressome" as cellular stress-induced all secretion products, including EVs (200-500 nm), membrane-damaged vesicles and remnants, and extracellular HSP90 and GAPDH. Our data also indicated that CDC37 is crucial for the release of vesicular proteins and tumor progression in prostate cancer. en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoMasaki en-aut-sei=Matsumoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Manh TienTran en-aut-sei=Manh Tien en-aut-mei=Tran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LangBenjamin J. en-aut-sei=Lang en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=cell stress response kn-keyword=cell stress response en-keyword=stressome kn-keyword=stressome en-keyword=extracellular vesicle kn-keyword=extracellular vesicle en-keyword=heat shock protein 90 (HSP90) kn-keyword=heat shock protein 90 (HSP90) en-keyword=cell division control 37 (CDC37) kn-keyword=cell division control 37 (CDC37) en-keyword=prostate cancer kn-keyword=prostate cancer en-keyword=exosome kn-keyword=exosome en-keyword=ectosome kn-keyword=ectosome END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=6 article-no= start-page=1974 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200313 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oxidative stress plays a crucial role in Alzheimer's disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid beta (A beta) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the A beta cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD. en-copyright= kn-copyright= en-aut-name=TadokoroKoh en-aut-sei=Tadokoro en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InufusaHaruhiko en-aut-sei=Inufusa en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LoonAlan Foo Nyuk en-aut-sei=Loon en-aut-mei=Alan Foo Nyuk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Anti-Oxidant Research, Life Science Research Center, Gifu University kn-affil= affil-num=4 en-affil=Hovid Berhad kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimer's disease kn-keyword=Alzheimer's disease en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=supplement kn-keyword=supplement END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=5 article-no= start-page=1843 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Significance of Cytoplasmic IgE-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (Fc epsilon RI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. Fc epsilon RI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis. en-copyright= kn-copyright= en-aut-name=GionYuka en-aut-sei=Gion en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkanoMitsuhiro en-aut-sei=Okano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoyamaTakahisa en-aut-sei=Koyama en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OuraTokie en-aut-sei=Oura en-aut-mei=Tokie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OritaYorihisa en-aut-sei=Orita en-aut-mei=Yorihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TachibanaTomoyasu en-aut-sei=Tachibana en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MarunakaHidenori en-aut-sei=Marunaka en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishizakiKazunori en-aut-sei=Nishizaki en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology, Head and Neck Surgery, Kumamoto University Graduate School kn-affil= affil-num=7 en-affil=Department of Otolaryngology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=8 en-affil=Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=mast cell kn-keyword=mast cell en-keyword=eosinophilic chronic rhinosinusitis kn-keyword=eosinophilic chronic rhinosinusitis en-keyword=c-kit kn-keyword=c-kit en-keyword=IgE kn-keyword=IgE END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page=335 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adult T-cell leukemia/lymphoma (ATL), an aggressive type of T-cell malignancy, is caused by the human T-cell leukemia virus type I (HTLV-1) infections. The outcomes, following therapeutic interventions for ATL, have not been satisfactory. Photodynamic therapy (PDT) exerts selective cytotoxic activity against malignant cells, as it is considered a minimally invasive therapeutic procedure. In PDT, photosensitizing agent administration is followed by irradiation at an absorbance wavelength of the sensitizer in the presence of oxygen, with ultimate direct tumor cell death, microvasculature injury, and induced local inflammatory reaction. This review provides an overview of the present status and state-of-the-art ATL treatments. It also focuses on the photodynamic detection (PDD) of hematopoietic malignancies and the recent progress of 5-Aminolevulinic acid (ALA)-PDT/PDD, which can efficiently induce ATL leukemic cell-specific death with minor influence on normal lymphocytes. Further consideration of the ALA-PDT/PDD system along with the circulatory system regarding the clinical application in ATL and others will be discussed. ALA-PDT/PDD can be promising as a novel treatment modality that overcomes unmet medical needs with the optimization of PDT parameters to increase the effectiveness of the tumor-killing activity and enhance the innate and adaptive anti-tumor immune responses by the optimized immunogenic cell death. en-copyright= kn-copyright= en-aut-name=OkaTakashi en-aut-sei=Oka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UtsunomiyaAtae en-aut-sei=Utsunomiya en-aut-mei=Atae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology & Respiratory Med., Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology & Respiratory Med., Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology, Imamura General Hospital kn-affil= en-keyword=ATL kn-keyword=ATL en-keyword=HTLV-1 kn-keyword=HTLV-1 en-keyword=PDT kn-keyword=PDT en-keyword=PDD kn-keyword=PDD en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=allogeneic hematopoietic cell transplantation kn-keyword=allogeneic hematopoietic cell transplantation en-keyword=immunotherapy kn-keyword=immunotherapy en-keyword=GVHD kn-keyword=GVHD en-keyword=ALA-PDT/PDD kn-keyword=ALA-PDT/PDD END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=5 article-no= start-page=1564 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Retrotransposons Manipulating Mammalian Skeletal Development in Chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Retrotransposons are genetic elements that copy and paste themselves in the host genome through transcription, reverse-transcription, and integration processes. Along with their proliferation in the genome, retrotransposons inevitably modify host genes around the integration sites, and occasionally create novel genes. Even now, a number of retrotransposons are still actively editing our genomes. As such, their profound role in the evolution of mammalian genomes is obvious; thus, their contribution to mammalian skeletal evolution and development is also unquestionable. In mammals, most of the skeletal parts are formed and grown through a process entitled endochondral ossification, in which chondrocytes play central roles. In this review, current knowledge on the evolutional, physiological, and pathological roles of retrotransposons in mammalian chondrocyte differentiation and cartilage development is summarized. The possible biological impact of these mobile genetic elements in the future is also discussed. en-copyright= kn-copyright= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaTakanori en-aut-sei=Ishikawa en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawataKazumi en-aut-sei=Kawata en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HattoriTakako en-aut-sei=Hattori en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaTakashi en-aut-sei=Nishida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=retrotransposon kn-keyword=retrotransposon en-keyword=endogenous retrovirus kn-keyword=endogenous retrovirus en-keyword=chondrocyte kn-keyword=chondrocyte en-keyword=cartilage kn-keyword=cartilage en-keyword=skeletal development kn-keyword=skeletal development END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=82 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer stem cells (CSCs) represent the subpopulation of cancer cells with the ability to differentiate into other cell phenotypes and initiated tumorigenesis. Previously, we reported generating CSCs from mouse induced pluripotent stem cells (miPSCs). Here, we investigated the ability of the CSCs to differentiate into hematopoietic cells. First, the primary cells were isolated from malignant tumors that were formed by the CSCs. Non-adherent cells (NACs) that arose from adherent cells were collected and their viability, as well as the morphology and expression of hematopoietic cell markers, were analyzed. Moreover, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. Finally, CSCs were induced to differentiate to macrophages while using IL3 and SCF. The round nucleated NACs were found to be viable, positive for hematopoietic lineage markers and CD34, and expressed hematopoietic markers, just like homing to the bone marrow. When NACs were injected into mice, Wright-Giemsa staining showed that the number of white blood cells got higher than those in the control mice after four weeks. CSCs also showed the ability to differentiate toward macrophages. CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology, and homing ability to the bone marrow, which could give new insight into the tumor microenvironment according to the plasticity of CSCs. en-copyright= kn-copyright= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NairNeha en-aut-sei=Nair en-aut-mei=Neha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumonKazuki en-aut-sei=Kumon en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OsmanAmira en-aut-sei=Osman en-aut-mei=Amira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DuJuan en-aut-sei=Du en-aut-mei=Juan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MansourHager en-aut-sei=Mansour en-aut-mei=Hager kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Abu QuoraHagar A. en-aut-sei=Abu Quora en-aut-mei=Hagar A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NawaraHend M. en-aut-sei=Nawara en-aut-mei=Hend M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkadaNobuhiro en-aut-sei=Okada en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil= kn-affil=Graduate School of Natural Science and Technology, Okayama University affil-num=8 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=12 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=14 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Induced pluripotent stem cells kn-keyword=Induced pluripotent stem cells en-keyword=Cancer stem cells differentiation kn-keyword=Cancer stem cells differentiation en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=hematopoietic cells kn-keyword=hematopoietic cells END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page=523 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antiparkinson Drug Benztropine Suppresses Tumor Growth, Circulating Tumor Cells, and Metastasis by Acting on SLC6A3/DAT and Reducing STAT3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tumor growth, progression, and therapy resistance are crucial factors in the prognosis of cancer. The properties of three-dimensional (3D) tumor-like organoids (tumoroids) more closely resemble in vivo tumors compared to two-dimensionally cultured cells and are therefore effectively used for assays and drug screening. We here established a repurposed drug for novel anticancer research and therapeutics using a 3D tumoroid-based screening system. We screened six pharmacologically active compounds by using an original tumoroid-based multiplex phenotypic screening system with a matrix metalloproteinase 9 (MMP9) promoter-driven fluorescence reporter for the evaluation of both tumoroid formation and progression. The antiparkinson drug benztropine was the most effective compound uncovered by the screen. Benztropine significantly inhibited in vitro tumoroid formation, cancer cell survival, and MMP9 promoter activity. Benztropine also reduced the activity of oncogenic signaling transducers and trans-activators for MMP9, including STAT3, NF-kappa B, and beta-catenin, and the properties of cancer stem cells/cancer-initiating cells. Benztropine and GBR-12935 directly targeted the dopamine transporter DAT/SLC6A3, whose genetic alterations such as amplification were correlated with poor prognosis for cancer patients. Benztropine also inhibited the tumor growth, circulating tumor cell (CTC) number, and rate of metastasis in a tumor allograft model in mice. In conclusion, we propose the repurposing of benztropine for anticancer research and therapeutics that can suppress tumor progression, CTC, and metastasis of aggressive cancers by reducing key pro-tumorigenic factors. en-copyright= kn-copyright= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TranManh Tien en-aut-sei=Tran en-aut-mei=Manh Tien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshigeMasayuki en-aut-sei=Ishige en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TrinKilian en-aut-sei=Trin en-aut-mei=Kilian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TahaEman Ahmed en-aut-sei=Taha en-aut-mei=Eman Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LuYanyin en-aut-sei=Lu en-aut-mei=Yanyin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KozakiKen-Ichi en-aut-sei=Kozaki en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=On-Chip Biotechnologies, Co., Ltd. kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Dental Pharmacology, Matsumoto Dental University kn-affil= affil-num=11 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=13 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=drug repositioning/repurposing kn-keyword=drug repositioning/repurposing en-keyword=three-dimensional (3D) culture kn-keyword=three-dimensional (3D) culture en-keyword=tumoroids kn-keyword=tumoroids en-keyword=dopamine transporter (DAT) kn-keyword=dopamine transporter (DAT) en-keyword=benztropine kn-keyword=benztropine en-keyword=signal transducer and activator of transcription (STAT) kn-keyword=signal transducer and activator of transcription (STAT) en-keyword=circulating tumor cell (CTC) kn-keyword=circulating tumor cell (CTC) END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=84 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=X-ray and Neutron Study on the Structure of Hydrous SiO2 Glass up to 10 GPa en-subtitle= kn-subtitle= en-abstract= kn-abstract=The structure of hydrous amorphous SiO2 is fundamental in order to investigate the effects of water on the physicochemical properties of oxide glasses and magma. The hydrous SiO2 glass with 13 wt.% D2O was synthesized under high-pressure and high-temperature conditions and its structure was investigated by small angle X-ray scattering, X-ray diffraction, and neutron diffraction experiments at pressures of up to 10 GPa and room temperature. This hydrous glass is separated into two phases: a major phase rich in SiO2 and a minor phase rich in D2O molecules distributed as small domains with dimensions of less than 100 angstrom. Medium-range order of the hydrous glass shrinks compared to the anhydrous SiO2 glass by disruption of SiO4 linkage due to the formation of Si-OD deuterioxyl, while the response of its structure to pressure is almost the same as that of the anhydrous SiO2 glass. Most of D2O molecules are in the small domains and hardly penetrate into the void space in the ring consisting of SiO4 tetrahedra. en-copyright= kn-copyright= en-aut-name=UrakawaSatoru en-aut-sei=Urakawa en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueToru en-aut-sei=Inoue en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HattoriTakanori en-aut-sei=Hattori en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Sano-FurukawaAsami en-aut-sei=Sano-Furukawa en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoharaShinji en-aut-sei=Kohara en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakabayashiDaisuke en-aut-sei=Wakabayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoTomoko en-aut-sei=Sato en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FunamoriNobumasa en-aut-sei=Funamori en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FunakoshiKen-ichi en-aut-sei=Funakoshi en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Earth and Planetary Systems Science, Hiroshima University kn-affil= affil-num=3 en-affil=J-PARC Center, Japan Atomic Energy Agency kn-affil= affil-num=4 en-affil=J-PARC Center, Japan Atomic Energy Agency kn-affil= affil-num=5 en-affil=Research Center for Advanced Measurement and Characterization, National Institute for Materials Science (NIMS) kn-affil= affil-num=6 en-affil=Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), kn-affil= affil-num=7 en-affil=Department of Earth and Planetary Systems Science, Hiroshima University kn-affil= affil-num=8 en-affil=Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=9 en-affil=Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society kn-affil= en-keyword=hydrous silica glass kn-keyword=hydrous silica glass en-keyword=medium-range order kn-keyword=medium-range order en-keyword=first sharp diffraction peak kn-keyword=first sharp diffraction peak en-keyword=phase separation kn-keyword=phase separation en-keyword=small angle X-ray scattering kn-keyword=small angle X-ray scattering en-keyword=X-ray diffraction kn-keyword=X-ray diffraction en-keyword=neutron diffraction kn-keyword=neutron diffraction en-keyword=high pressure kn-keyword=high pressure END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=2 article-no= start-page=238 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural Optimization of Alkylbenzenes as Graphene Dispersants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Among the several methods of producing graphene, the liquid-phase exfoliation of graphite is attractive because of a simple and easy procedure, being expected for mass production. The dispersibility of graphene can be improved by adding a dispersant molecule that interacts with graphene, but the appropriate molecular design has not been proposed. In this study, we focused on aromatic compounds with alkyl chains as dispersing agents. We synthesized a series of alkyl aromatic compounds and evaluated their performance as a dispersant for graphene. The results suggest that the alkyl chain length and solubility in the solvent play a vital role in graphene dispersion. en-copyright= kn-copyright= en-aut-name=TakedaShimpei en-aut-sei=Takeda en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= en-keyword=graphene kn-keyword=graphene en-keyword=graphite kn-keyword=graphite en-keyword=dispersant kn-keyword=dispersant en-keyword=alkylbenzene kn-keyword=alkylbenzene en-keyword=liquid-phase exfoliation kn-keyword=liquid-phase exfoliation END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=175 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation of Superconducting Pairing Symmetry and Non-Magnetic Impurity Effects in Vortex States en-subtitle= kn-subtitle= en-abstract= kn-abstract=Non-magnetic impurity scattering effects on the vortex core states are theoretically studied to clarify the contributions from the sign-change of the pairing function in anisotropic superconductors. The vortex states are calculated by the Eilenberger theory in superconductors with px-wave pairing symmetry, as well as the corresponding anisotropic s-wave symmetry. From the spatial structure of the pair potential and the local electronic states around a vortex, we examine the differences between anisotropic superconductors with and without sign-change of the pairing function, and estimate how twofold symmetric vortex core images change with increasing the impurity scattering rate both in the Born and the unitary limits. We found that twofold symmetric vortex core image of zero-energy local density of states changes the orientation of the twofold symmetry with increasing the scattering rate when the sign change occurs in the pairing function. Without the sign change, the vortex core shape reduces to circular one with approaching dirty cases. These results of the impurity effects are valuable for identifying the pairing symmetry by observation of the vortex core image by the STM observation. en-copyright= kn-copyright= en-aut-name=SeraYasuaki en-aut-sei=Sera en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaTakahiro en-aut-sei=Ueda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AdachiHiroto en-aut-sei=Adachi en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiokaMasanori en-aut-sei=Ichioka en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Physics, Okayama University kn-affil= affil-num=2 en-affil=Department of Physics, Okayama University kn-affil= affil-num=3 en-affil=Department of Physics, Okayama University kn-affil= affil-num=4 en-affil=Department of Physics, Okayama University kn-affil= en-keyword=unconventional superconductivity kn-keyword=unconventional superconductivity en-keyword=pairing symmetry kn-keyword=pairing symmetry en-keyword=vortex states kn-keyword=vortex states en-keyword=non-magnetic impurity scattering kn-keyword=non-magnetic impurity scattering END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=16 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Expression and Ion Transport Activity of Rice OsHKT1;1 Variants en-subtitle= kn-subtitle= en-abstract= kn-abstract=OsHKT1;1 in rice, belongs to the high-affinity K+ Transporter family, has been found to be involved in salt tolerance. OsHKT1;1 in japonica rice (Nipponbare) produces mRNA variants, but their functions remain elusive. In salt tolerant rice, Pokkali, eight OsHKT1;1 variants (V1-V8) were identified in addition to the full-length OsHKT1;1 (FL) cDNA. Absolute quantification by qPCR revealed that accumulation of OsHKT1;1-FL mRNA is minor in contrast to that of OsHKT1;1-V1, -V2, -V4, and -V7 mRNAs, all of which are predominant in shoots, while only V1 and V7 mRNAs are predominant in roots. Two electrode voltage clamp (TEVC) experiments using Xenopus laevis oocytes revealed that oocytes-expressing OsHKT1;1-FL from Pokkali exhibited inward-rectified currents in the presence of 96 mM Na+ as reported previously. Further TEVC analyses indicated that six of eight OsHKT1;1 variants elicited currents in a Na+ or a K+ bath solution. OsHKT1;1-V6 exhibited a similar inward rectification to the FL protein. Contrastingly, however, the rests mediated bidirectional currents in both Na+ and K+ bath solutions. These data suggest possibilities that novel mechanisms regulating the transport activity of OsHKT1;1 might exist, and that OsHKT1;1 variants might also carry out distinct physiological roles either independently or in combination with OsHKT1;1-FL. en-copyright= kn-copyright= en-aut-name=ImranShahin en-aut-sei=Imran en-aut-mei=Shahin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HorieTomoaki en-aut-sei=Horie en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Biology, Faculty of the Textile Science and Technology, Shinshu University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=HKT kn-keyword=HKT en-keyword=rice kn-keyword=rice en-keyword=salt tolerance kn-keyword=salt tolerance en-keyword=Na+ transport kn-keyword=Na+ transport en-keyword=K+ transport kn-keyword=K+ transport en-keyword=mRNA variants kn-keyword=mRNA variants END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=13 article-no= start-page=2495 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alpinia zerumbet (Pers.): Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND/AIM:Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers.
METHODS:The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model.
RESULTS:A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively.
CONCLUSION:Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet. en-copyright= kn-copyright= en-aut-name=ZahraMaram Hussein en-aut-sei=Zahra en-aut-mei=Maram Hussein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SalemTarek A. R. en-aut-sei=Salem en-aut-mei=Tarek A. R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=El-AaragBishoy en-aut-sei=El-Aarag en-aut-mei=Bishoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YosriNermeen en-aut-sei=Yosri en-aut-mei=Nermeen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EL-GhlbanSamah en-aut-sei=EL-Ghlban en-aut-mei=Samah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZakiKholoud en-aut-sei=Zaki en-aut-mei=Kholoud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MareiAmel H. en-aut-sei=Marei en-aut-mei=Amel H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Abd El-WahedAida en-aut-sei=Abd El-Wahed en-aut-mei=Aida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SaeedAamer en-aut-sei=Saeed en-aut-mei=Aamer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KhatibAlfi en-aut-sei=Khatib en-aut-mei=Alfi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AlAjmiMohamed F. en-aut-sei=AlAjmi en-aut-mei=Mohamed F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShathiliAbdulrahman M. en-aut-sei=Shathili en-aut-mei=Abdulrahman M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=XiaoJianbo en-aut-sei=Xiao en-aut-mei=Jianbo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KhalifaShaden A. M. en-aut-sei=Khalifa en-aut-mei=Shaden A. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=El-SeediHesham R. en-aut-sei=El-Seedi en-aut-mei=Hesham R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biochemistry, College of Medicine, Qassim University kn-affil= affil-num=3 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=5 en-affil=Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University kn-affil= affil-num=6 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=7 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=8 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=9 en-affil=Department of Chemistry, Quaid-i-Azam University kn-affil= affil-num=10 en-affil=Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia kn-affil= affil-num=11 en-affil=Pharmacognosy Group, College of Pharmacy, King Saud University kn-affil= affil-num=12 en-affil=Al-Rayan Research and Innovation Center, Al-Rayan Colleges kn-affil= affil-num=13 en-affil=Institute of Chinese Medical Sciences, University of Macau kn-affil= affil-num=14 en-affil=Clinical Research Centre, Karolinska University Hospital kn-affil= affil-num=15 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= en-keyword=Alpinia zerumbet kn-keyword=Alpinia zerumbet en-keyword=5,6-dehydrokawain kn-keyword=5,6-dehydrokawain en-keyword=Ehrlich ascites carcinoma kn-keyword=Ehrlich ascites carcinoma en-keyword=anti-tumor kn-keyword=anti-tumor en-keyword=anti-oxidant kn-keyword=anti-oxidant END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=24 article-no= start-page=5130 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Geographical Differences and the National Meeting Effect in Patients with Out-of-Hospital Cardiac Arrests: A JCS-ReSS Study Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=The "national meeting effect" refers to worse patient outcomes when medical professionals attend academic meetings and hospitals have reduced staffing. The aim of this study was to examine differences in outcomes of patients with out-of-hospital cardiac arrest (OHCA) admitted during, before, and after meeting days according to meeting location and considering regional variation of outcomes, which has not been investigated in previous studies. Using data from a nationwide, prospective, population-based, observational study in Japan, we analyzed adult OHCA patients who underwent resuscitation attempts between 2011 and 2015. Favorable one-month neurological outcomes were compared among patients admitted during the relevant annual meeting dates of three national scientific societies, those admitted on identical days the week before, and those one week after the meeting dates. We developed a multivariate logistic regression model after adjusting for confounding factors, including meeting location and regional variation (better vs. worse outcome areas), using the "during meeting days" group as the reference. A total of 40,849 patients were included in the study, with 14,490, 13,518, and 12,841 patients hospitalized during, before, and after meeting days, respectively. The rates of favorable neurological outcomes during, before, and after meeting days was 1.7, 1.6, and 1.8%, respectively. After adjusting for covariates, favorable neurological outcomes did not differ among the three groups (adjusted OR (95% CI) of the before and after meeting dates groups was 1.03 (0.83-1.28) and 1.01 (0.81-1.26), respectively. The "national meeting effect" did not exist in OHCA patients in Japan, even after comparing data during, before, and after meeting dates and considering meeting location and regional variation. en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaitouHiromichi en-aut-sei=Naitou en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaharaYoshio en-aut-sei=Tahara en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonemotoNaohiro en-aut-sei=Yonemoto en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NonogiHiroshi en-aut-sei=Nonogi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaoKen en-aut-sei=Nagao en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkedaTakanori en-aut-sei=Ikeda en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoNaoki en-aut-sei=Sato en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsutsuiHiroyuki en-aut-sei=Tsutsui en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center kn-affil= affil-num=5 en-affil=National Center of Neurology and Psychiatry kn-affil= affil-num=6 en-affil=Intensive Care Center, Shizuoka General Hospital kn-affil= affil-num=7 en-affil=Cardiovascular Center, Nihon University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Toho University Faculty of Medicine kn-affil= affil-num=9 en-affil=Cardiovascular Medicine, Kawaguchi Cardiovascular and Respiratory Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Kyushu University Faculty of Medical Sciences kn-affil= en-keyword=out-of-hospital cardiac arrest kn-keyword=out-of-hospital cardiac arrest en-keyword=outcome kn-keyword=outcome en-keyword=national meeting kn-keyword=national meeting en-keyword=cardiopulmonary resuscitation kn-keyword=cardiopulmonary resuscitation END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=24 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that 4T1 murine breast cancer cells produce GM-CSF that up-regulates macrophage expression of several cancer promoting genes, including Mcp-1/Ccl2, Ccl17 and Rankl, suggesting a critical role of cancer cell-derived GM-CSF in cancer progression. Here, we attempted to define whether 4T1 cell-derived GM-CSF contributes to the expression of these genes by 4T1tumors, and their subsequent progression. Intraperitoneal injection of anti-GM-CSF neutralizing antibody did not decrease the expression of Mcp-1, Ccl17 or Rankl mRNA by 4T1 tumors. To further examine the role of cancer cell-derived GM-CSF, we generated GM-CSF-deficient 4T1 cells by using the Crisper-Cas9 system. As previously demonstrated, 4T1 cells are a mixture of cells and cloning of cells by itself significantly reduced tumor growth and lung metastasis. By contrast, GM-CSF-deficiency did not affect tumor growth, lung metastasis or the expression of these chemokine and cytokine genes in tumor tissues. By in-situ hybridization, the expression of Mcp-1 mRNA was detected in both F4/80-expressing and non-expressing cells in tumors of GM-CSF-deficient cells. These results indicate that cancer cell-derived GM-CSF is dispensable for the tuning of the 4T1 tumor microenvironment and the production of MCP-1, CCL17 or RANKL in the 4T1 tumor microenvironment is likely regulated by redundant mechanisms. en-copyright= kn-copyright= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKaoru en-aut-sei=Nakamura en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShiinaTsuyoshi en-aut-sei=Shiina en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImamuraMayu en-aut-sei=Imamura en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiTiantian en-aut-sei=Li en-aut-mei=Tiantian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MukaidaNaofumi en-aut-sei=Mukaida en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=macrophages kn-keyword=macrophages en-keyword=chemokines kn-keyword=chemokines en-keyword=cytokines kn-keyword=cytokines en-keyword=inflammation kn-keyword=inflammation en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=breast cancer kn-keyword=breast cancer END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=10 article-no= start-page=223 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191013 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differential Response of Sugar Beet to Long-Term Mild to Severe Salinity in a Soil-Pot Culture en-subtitle= kn-subtitle= en-abstract= kn-abstract=Attempts to cultivate sugar beet (Beta vulgaris spp. vulgaris) in the sub-tropical saline soils are ongoing because of its excellent tolerance to salinity. However, the intrinsic adaptive physiology has not been discovered yet in the sub-tropical climatic conditions. In this study, we investigated morpho-physiological attributes, biochemical responses, and yield of sugar beet under a gradient of salinity in the soil-pot culture system to evaluate its adaptive mechanisms. Results exhibited that low and high salinity displayed a differential impact on growth, photosynthesis, and yield. Low to moderate salt stress (75 and 100 mM NaCl) showed no inhibition on growth and photosynthetic attributes. Accordingly, low salinity displayed simulative effect on chlorophyll and antioxidant enzymes activity which contributed to maintaining a balanced H2O2 accumulation and lipid peroxidation. Furthermore, relative water and proline content showed no alteration in low salinity. These factors contributed to improving the yield (tuber weight). On the contrary, 250 mM salinity showed a mostly inhibitory role on growth, photosynthesis, and yield. Collectively, our findings provide insights into the mild-moderate salt adaptation strategy in the soil culture test attributed to increased water content, elevation of photosynthetic pigment, better photosynthesis, and better management of oxidative stress. Therefore, cultivation of sugar beet in moderately saline-affected soils will ensure efficient utilization of lands. en-copyright= kn-copyright= en-aut-name=Tahjib-UI-ArifMd. en-aut-sei=Tahjib-UI-Arif en-aut-mei=Md. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SohagAbdullah Al Mamun en-aut-sei=Sohag en-aut-mei=Abdullah Al Mamun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AfrinSonya en-aut-sei=Afrin en-aut-mei=Sonya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BasharKazi Khayrul en-aut-sei=Bashar en-aut-mei=Kazi Khayrul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AfrinTania en-aut-sei=Afrin en-aut-mei=Tania kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MahamudA. G. M. Sofi Uddin en-aut-sei=Mahamud en-aut-mei=A. G. M. Sofi Uddin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PolashMohammed Arif Sadik en-aut-sei=Polash en-aut-mei=Mohammed Arif Sadik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HossainMd. Tahmeed en-aut-sei=Hossain en-aut-mei=Md. Tahmeed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SohelMd. Abu Taher en-aut-sei=Sohel en-aut-mei=Md. Abu Taher kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BresticMarian en-aut-sei=Brestic en-aut-mei=Marian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Biology, Faculty of Agriculture, Bangladesh Agricultural University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Bangladesh Jute Research Institute kn-affil= affil-num=5 en-affil=Graduate Training Institute, Bangladesh Agricultural University kn-affil= affil-num=6 en-affil=Food Biochemistry Laboratory, Department of Biochemistry and Molecular Biology, Faculty of Agriculture, Bangladesh Agricultural University kn-affil= affil-num=7 en-affil=Department of Crop Botany, Faculty of Agriculture, Bangladesh Agricultural University kn-affil= affil-num=8 en-affil=Department of Biochemistry and Molecular Biology, Faculty of Agriculture, Bangladesh Agricultural University kn-affil= affil-num=9 en-affil=Agronomy and Farming System Division, Bangladesh Sugar Crop Research Institute kn-affil= affil-num=10 en-affil=Department of Plant Physiology, Faculty of Agrobiology and Food Resources, Slovak University of Agriculture kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=antioxidant enzymes kn-keyword=antioxidant enzymes en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=reactive oxygen species kn-keyword=reactive oxygen species en-keyword=salinity kn-keyword=salinity en-keyword=sugar beet kn-keyword=sugar beet en-keyword=yield kn-keyword=yield END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=22 article-no= start-page=3681 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advantage of Alveolar Ridge Augmentation with Bioactive/Bioresorbable Screws Made of Composites of Unsintered Hydroxyapatite and Poly-L-lactide en-subtitle= kn-subtitle= en-abstract= kn-abstract=We studied human bone healing characteristics and the histological osteogenic environment by using devices made of a composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-L-lactide (PLLA). In eight cases of fixation, we used u-HA/PLLA screws for maxillary alveolar ridge augmentation, for which mandibular cortical bone block was used in preimplantation surgery. Five appropriate samples with screws were evaluated histologically and immunohistochemically for runt-related transcription factor 2 (RUNX2), transcription factor Sp7 (Osterix), and leptin receptor (LepR). In all cases, histological evaluation revealed that bone components had completely surrounded the u-HA/PLLA screws, and the bone was connected directly to the biomaterial. Inflammatory cells did not invade the space between the bone and the u-HA/PLLA screw. Immunohistochemical evaluation revealed that many cells were positive for RUNX2 or Osterix, which are markers for osteoblast and osteoprogenitor cells, in the tissues surrounding u-HA/PLLA. In addition, many bone marrow-derived mesenchymal stem cells were notably positive for both LepR and RUNX2. The u-HA/PLLA material showed excellent bioactive osteoconductivity and a highly biocompatibility with bone directly attached. In addition, our findings suggest that many bone marrow-derived mesenchymal stem cells and mature osteoblast are present in the osteogenic environment created with u-HA/PLLA screws and that this environment is suitable for osteogenesis. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KannoTakahiro en-aut-sei=Kanno en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= en-keyword=poly-L-lactide kn-keyword=poly-L-lactide en-keyword=uncalcined and unsintered hydroxyapatite kn-keyword=uncalcined and unsintered hydroxyapatite en-keyword=biocompatibility kn-keyword=biocompatibility en-keyword=osteoconductivity kn-keyword=osteoconductivity en-keyword=mesenchymal stem cell kn-keyword=mesenchymal stem cell END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=9 article-no= start-page=1557 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biomechanical Loading Comparison between Titanium and Unsintered Hydroxyapatite/Poly-L-Lactide Plate System for Fixation of Mandibular Subcondylar Fractures en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteosynthesis absorbable materials made of uncalcined and unsintered hydroxyapatite (u-HA) particles, poly-l-lactide (PLLA), and u-HA/PLLA are bioresorbable, and these plate systems have feasible bioactive osteoconductive capacities. However, their strength and stability for fixation in mandibular subcondylar fractures remain unclear. This in vitro study aimed to assess the biomechanical strength of u-HA/PLLA bioresorbable plate systems after internal fixation of mandibular subcondylar fractures. Tensile and shear strength were measured for each u-HA/PLLA and titanium plate system. To evaluate biomechanical behavior, 20 hemimandible replicas were divided into 10 groups, each comprising a titanium plate and a bioresorbable plate. A linear load was applied anteroposteriorly and lateromedially to each group to simulate the muscular forces in mandibular condylar fractures. All samples were analyzed for each displacement load and the displacement obtained by the maximum load. Tensile and shear strength of the u-HA/PLLA plate were each approximately 45% of those of the titanium plates. Mechanical resistance was worst in the u-HA/PLLA plate initially loaded anteroposteriorly. Titanium plates showed the best mechanical resistance during lateromedial loading. Notably, both plates showed similar resistance when a lateromedially load was applied. In the biomechanical evaluation of mandibular condylar fracture treatment, the u-HA/PLLA plates had sufficiently high resistance in the two-plate fixation method. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KannoTakahiro en-aut-sei=Kanno en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= en-keyword=mandibular condylar fracture kn-keyword=mandibular condylar fracture en-keyword=unsintered hydroxyapatite kn-keyword=unsintered hydroxyapatite en-keyword=poly-l-lactide composite plate kn-keyword=poly-l-lactide composite plate en-keyword=bioactive resorbable plate kn-keyword=bioactive resorbable plate en-keyword=biomechanical loading evaluation kn-keyword=biomechanical loading evaluation en-keyword=fracture fixation kn-keyword=fracture fixation END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=1007 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Relationship between Uterine, Fecal, Bedding, and Airborne Dust Microbiota from Dairy Cows and Their Environment: A Pilot Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary After calving, dairy cows face the risk of negative energy balance, inflammation, and immunosuppression, which may result in bacterial infection and disruption of the normal microbiota, thus encouraging the development of metritis and endometritis. This study characterized uterine, fecal, bedding, and airborne dust microbiota from postpartum dairy cows and their environment during summer and winter. The results clarify the importance of microbiota in cowshed environments, i.e., bedding and airborne dust, in understanding the postpartum uterine microbiota of dairy cows.

Abstract The aim of this study was to characterize uterine, fecal, bedding, and airborne dust microbiota from postpartum dairy cows and their environment. The cows were managed by the free-stall housing system, and samples for microbiota and serum metabolite assessment were collected during summer and winter when the cows were at one and two months postpartum. Uterine microbiota varied between seasons; the five most prevalent taxa were Enterobacteriaceae, Moraxellaceae, Ruminococcaceae, Staphylococcaceae, and Lactobacillaceae during summer, and Ruminococcaceae, Lachnospiraceae, Bacteroidaceae, Moraxellaceae, and Clostridiaceae during winter. Although Actinomycetaceae and Mycoplasmataceae were detected at high abundance in several uterine samples, the relationship between the uterine microbiota and serum metabolite concentrations was unclear. The fecal microbiota was stable regardless of the season, whereas bedding and airborne dust microbiota varied between summer and winter. With regards to uterine, bedding, and airborne dust microbiota, Enterobacteriaceae, Moraxellaceae, Staphylococcaceae, and Lactobacillaceae were more abundant during summer, and Ruminococcaceae, Lachnospiraceae, Bacteroidaceae, and Clostridiaceae were more abundant during winter. Canonical analysis of principal coordinates confirmed the relationship between uterine and cowshed microbiota. These results indicated that the uterine microbiota may vary when the microbiota in cowshed environments changes. en-copyright= kn-copyright= en-aut-name=NguyenThuong T. en-aut-sei=Nguyen en-aut-mei=Thuong T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyakeAyumi en-aut-sei=Miyake en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TranTu T. M. en-aut-sei=Tran en-aut-mei=Tu T. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsurutaTakeshi en-aut-sei=Tsuruta en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishinoNaoki en-aut-sei=Nishino en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Okayama Prefecture Livestock Research Institute kn-affil= affil-num=3 en-affil=Faculty of Agriculture and Food Technology, Tien Giang University kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=cowshed kn-keyword=cowshed en-keyword=environment kn-keyword=environment en-keyword=microbiota kn-keyword=microbiota en-keyword=uterus kn-keyword=uterus END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=23 article-no= start-page=5992 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comprehensive Identification of PTI Suppressors in Type III Effector Repertoire Reveals that Ralstonia solanacearum Activates Jasmonate Signaling at Two Different Steps en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ralstonia solanacearum is the causative agent of bacterial wilt in many plants. To identify R. solanacearum effectors that suppress pattern-triggered immunity (PTI) in plants, we transiently expressed R. solanacearum RS1000 effectors in Nicotiana benthamiana leaves and evaluated their ability to suppress the production of reactive oxygen species (ROS) triggered by flg22. Out of the 61 effectors tested, 11 strongly and five moderately suppressed the flg22-triggered ROS burst. Among them, RipE1 shared homology with the Pseudomonas syringae cysteine protease effector HopX1. By yeast two-hybrid screening, we identified jasmonate-ZIM-domain (JAZ) proteins, which are transcriptional repressors of the jasmonic acid (JA) signaling pathway in plants, as RipE1 interactors. RipE1 promoted the degradation of JAZ repressors and induced the expressions of JA-responsive genes in a cysteine-protease-activity-dependent manner. Simultaneously, RipE1, similarly to the previously identified JA-producing effector RipAL, decreased the expression level of the salicylic acid synthesis gene that is required for the defense responses against R. solanacearum. The undecuple mutant that lacks 11 effectors with a strong PTI suppression activity showed reduced growth of R. solanacearum in Nicotiana plants. These results indicate that R. solanacearum subverts plant PTI responses using multiple effectors and manipulates JA signaling at two different steps to promote infection. en-copyright= kn-copyright= en-aut-name=NakanoMasahito en-aut-sei=Nakano en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiharaTakafumi en-aut-sei=Mukaihara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Biological Sciences, Okayama (RIBS) kn-affil= en-keyword=Ralstonia solanacearum kn-keyword=Ralstonia solanacearum en-keyword=type III effector kn-keyword=type III effector en-keyword=jasmonic acid kn-keyword=jasmonic acid en-keyword=salicylic acid kn-keyword=salicylic acid en-keyword=Nicotiana plants kn-keyword=Nicotiana plants END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=23 article-no= start-page=5885 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I-2) (PGI(2)), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI(2)), phosphodiesterase type-5 (PDE5) inhibitors, and endothelin receptor antagonists (ERAs), have been shown to be effective, however, PAH remains a severe clinical condition and the long-term survival of patients with PAH is still suboptimal. The full therapeutic abilities of available drugs are reduced by medication, patient non-compliance, and side effects. Nanoparticles are expected to address these problems by providing a novel drug delivery approach for the treatment of PAH. Drug-loaded nanoparticles for local delivery can optimize the efficacy and minimize the adverse effects of drugs. Prostacyclin (PGI(2)) analogue, PDE5 inhibitors, ERA, pitavastatin, imatinib, rapamycin, fasudil, and oligonucleotides-loaded nanoparticles have been reported to be effective in animal PAH models and in vitro studies. However, the efficacy and safety of nanoparticle mediated-drug delivery systems for PAH treatment in humans are unknown and further clinical studies are required to clarify these points. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsubaraHiromi en-aut-sei=Matsubara en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Cardiology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=10 en-affil= Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=prostaglandin I-2 kn-keyword=prostaglandin I-2 en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=endothelin kn-keyword=endothelin END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=23 article-no= start-page=6078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multipotent Neurotrophic Effects of Hepatocyte Growth Factor in Spinal Cord Injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spinal cord injury (SCI) results in neural tissue loss and so far untreatable functional impairment. In addition, at the initial injury site, inflammation induces secondary damage, and glial scar formation occurs to limit inflammation-mediated tissue damage. Consequently, it obstructs neural regeneration. Many studies have been conducted in the field of SCI; however, no satisfactory treatment has been established to date. Hepatocyte growth factor (HGF) is one of the neurotrophic growth factors and has been listed as a candidate medicine for SCI treatment. The highlighted effects of HGF on neural regeneration are associated with its anti-inflammatory and anti-fibrotic activities. Moreover, HGF exerts positive effects on transplanted stem cell differentiation into neurons. This paper reviews the mechanisms underlying the therapeutic effects of HGF in SCI recovery, and introduces recent advances in the clinical applications of HGF therapy. en-copyright= kn-copyright= en-aut-name=YamaneKentaro en-aut-sei=Yamane en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MisawaHaruo en-aut-sei=Misawa en-aut-mei=Haruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakigawaTomoyuki en-aut-sei=Takigawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoYoshihiro en-aut-sei=Ito en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Intelligent Orthopaedic System Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Nano Medical Engineering Laboratory, RIKEN kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=hepatocyte growth factor kn-keyword=hepatocyte growth factor en-keyword=spinal cord injury kn-keyword=spinal cord injury en-keyword=neural regeneration kn-keyword=neural regeneration END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=21 article-no= start-page=E5402 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Animal Models for Parkinson's Disease Research: Trends in the 2000s en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is a chronic and progressive movement disorder and the second most common neurodegenerative disease. Although many studies have been conducted, there is an unmet clinical need to develop new treatments because, currently, only symptomatic therapies are available. To achieve this goal, clarification of the pathology is required. Attempts have been made to emulate human PD and various animal models have been developed over the decades. Neurotoxin models have been commonly used for PD research. Recently, advances in transgenic technology have enabled the development of genetic models that help to identify new approaches in PD research. However, PD animal model trends have not been investigated. Revealing the trends for PD research will be valuable for increasing our understanding of the positive and negative aspects of each model. In this article, we clarified the trends for animal models that were used to research PD in the 2000s, and we discussed each model based on these trends. en-copyright= kn-copyright= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KamedaMasahiro en-aut-sei=Kameda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil= Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=animal model kn-keyword=animal model en-keyword=alpha-synuclein kn-keyword=alpha-synuclein en-keyword=DJ-1 kn-keyword=DJ-1 en-keyword=neurotoxin kn-keyword=neurotoxin en-keyword=Parkin kn-keyword=Parkin en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=pesticide kn-keyword=pesticide en-keyword=PINK1 kn-keyword=PINK1 en-keyword=1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine kn-keyword=1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine en-keyword=6-hydroxydopamine kn-keyword=6-hydroxydopamine END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=7 article-no= start-page=783 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190712 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Lubrication and Forging Load on Surface Roughness, Residual Stress, and Deformation of Cold Forging Tools en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cold forging is a metal forming that which uses localized compressive force at room temperature. During the cold forging process, the tool is subjected to extremely high loads and abrasive wear. Lubrication plays an important role in cold forging to improve product quality and tool life by preventing direct metallic contact. Surface roughness and residual stress also greatly affects the service life of a tool. In this study, variations in surface roughness, residual stress, and specimen deformation with the number of cold forging cycles were investigated under different forging conditions. Specimens that were made of heat-treated SKH51 (59-61 HRC), a high-speed tool steel with a polished working surface, were used. The specimens were subjected to an upsetting process. Compressive residual stress, surface roughness, and specimen deformation showed a positive relationship with the number of forging cycles up to a certain limit and became almost constant in most of the forging conditions. A larger change in residual stress and surface roughness was observed at the center of the specimens in all the forging conditions. The effect of the magnitude of the forging load on the above discussed parameters is large when compared to the effect of the lubrication conditions. en-copyright= kn-copyright= en-aut-name=KarunathilakaNuwan en-aut-sei=Karunathilaka en-aut-mei=Nuwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TadaNaoya en-aut-sei=Tada en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemoriTakeshi en-aut-sei=Uemori en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanamitsuRyota en-aut-sei=Hanamitsu en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiiMasahiro en-aut-sei=Fujii en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmiyaYuya en-aut-sei=Omiya en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawanoMasahiro en-aut-sei=Kawano en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Zeno Tech Co., Ltd kn-affil= en-keyword=cold forging kn-keyword=cold forging en-keyword=high-speed tool steel kn-keyword=high-speed tool steel en-keyword=lubrication kn-keyword=lubrication en-keyword=residual stress kn-keyword=residual stress en-keyword=surface roughness kn-keyword=surface roughness en-keyword=tool deformation kn-keyword=tool deformation END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=12 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Switching between Three Types of Mesalazine Formulation and Sulfasalazine in Patients with Active Ulcerative Colitis Who Have Already Received High-Dose Treatment with These Agents en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and aim: Oral mesalazine and sulfasalazine (SASP) are key drugs for treating ulcerative colitis (UC). The efficacy of switching from one of the several mesalazine formulations to another is largely unknown. This study assessed the efficacy of switching among three types of mesalazine formulation and SASP for UC therapy. Methods: UC patients receiving high-dose mesalazine/SASP who switched to other formulations due to disease activity were considered eligible. Efficacy was evaluated 2, 6, and 12 months after switching. Results: A total of 106 switches in 88 UC patients were analyzed. The efficacy at 2 months after switching was observed in 23/39 (59%) cases from any mesalazine formulation to SASP, in 18/55 (33%) cases from one mesalazine to another, and in 2/12 (17%) cases from SASP to any mesalazine formulation. Nine of 43 effective cases showed inefficacy or became intolerant post-switching. Delayed efficacy more than two months after switching was observed in four cases. Steroid-free remission was achieved in 42/106 (39%) cases—within 100 days in 35 of these cases (83%). Conclusions: Switching from mesalazine to SASP was effective in more than half of cases. The efficacy of switching between mesalazine formulations was lower but may be worth attempting in clinical practice from a safety perspective. en-copyright= kn-copyright= en-aut-name=YasutomiEriko en-aut-sei=Yasutomi en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoShumpei en-aut-sei=Yamamoto en-aut-mei=Shumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkaShohei en-aut-sei=Oka en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiraiMami en-aut-sei=Hirai en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaradaKeita en-aut-sei=Harada en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ulcerative colitis kn-keyword=ulcerative colitis en-keyword=salicylates kn-keyword=salicylates en-keyword=mesalazine kn-keyword=mesalazine en-keyword=sulfasalazine kn-keyword=sulfasalazine END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=18 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 2–12 were characterized using elemental, spectral (1H-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV–Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7. en-copyright= kn-copyright= en-aut-name=El-SaiedFathy en-aut-sei=El-Saied en-aut-mei=Fathy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=El-AaragBishoy en-aut-sei=El-Aarag en-aut-mei=Bishoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SalemTarek en-aut-sei=Salem en-aut-mei=Tarek kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaidGhada en-aut-sei=Said en-aut-mei=Ghada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KhalifaShaden A. M. en-aut-sei=Khalifa en-aut-mei=Shaden A. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=El-SeediHesham R. en-aut-sei=El-Seedi en-aut-mei=Hesham R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=2 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Molecular Biology, Genetic Engineering & Biotechnology Institute, University of Sadat City kn-affil= affil-num=4 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=5 en-affil=Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University kn-affil= affil-num=6 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= en-keyword=metal complexes kn-keyword=metal complexes en-keyword=isatin-N(4)antipyrinethiosemicarbazone kn-keyword=isatin-N(4)antipyrinethiosemicarbazone en-keyword=Ehrlich ascites carcinoma kn-keyword=Ehrlich ascites carcinoma en-keyword=tumor volume kn-keyword=tumor volume en-keyword=VEGF kn-keyword=VEGF en-keyword=caspase-7 kn-keyword=caspase-7 END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=20 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective Effects of Flavone from Tamarix aphylla against CCl4-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl4 caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl4 model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human. en-copyright= kn-copyright= en-aut-name=El-AaragBishoy en-aut-sei=El-Aarag en-aut-mei=Bishoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KhairyAsmaa en-aut-sei=Khairy en-aut-mei=Asmaa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KhalifaShaden A. M. en-aut-sei=Khalifa en-aut-mei=Shaden A. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=El-SeediHesham R. en-aut-sei=El-Seedi en-aut-mei=Hesham R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Chemistry Department, Faculty of Science, Menoufia University kn-affil= affil-num=3 en-affil=Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University kn-affil= affil-num=4 en-affil=Chemistry Department, Faculty of Science, Menoufia University kn-affil= en-keyword=liver injury kn-keyword=liver injury en-keyword=CCl4 kn-keyword=CCl4 en-keyword=Tamarix aphylla kn-keyword=Tamarix aphylla en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=apoptosis kn-keyword=apoptosis en-keyword=angiogenesis kn-keyword=angiogenesis END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=8 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Melittin (MEL) is a 26-amino acid peptide with numerous biological activities. Paraquat (PQ) is one of the most widely used herbicides, although it is extremely toxic to humans. To date, PQ poisoning has no effective treatment, and therefore the current study aimed to assess for the first time the possible effects of MEL on PQ-induced lung injuries in mice. Mice received a single intraperitoneal (IP) injection of PQ (30 mg/kg), followed by IP treatment with MEL (0.1 and 0.5 mg/kg) twice per week for four consecutive weeks. Histological alterations, oxidative stress, and apoptosis in the lungs were studied. Hematoxylin and eosin (H&E) staining indicated that MEL markedly reduced lung injuries induced by PQ. Furthermore, treatment with MEL increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, and decreased malonaldehyde (MDA) and nitric oxide (NO) levels in lung tissue homogenates. Moreover, immunohistochemical staining showed that B-cell lymphoma-2 (Bcl-2) and survivin expressions were upregulated after MEL treatment, while Ki-67 expression was downregulated. The high dose of MEL was more effective than the low dose in all experiments. In summary, MEL efficiently reduced PQ-induced lung injuries in mice. Specific pharmacological examinations are required to determine the effectiveness of MEL in cases of human PQ poisoning. en-copyright= kn-copyright= en-aut-name=El-AaragBishoy en-aut-sei=El-Aarag en-aut-mei=Bishoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MagdyMohamed en-aut-sei=Magdy en-aut-mei=Mohamed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AlAjmiMohamed F. en-aut-sei=AlAjmi en-aut-mei=Mohamed F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KhalifaShaden A. M. en-aut-sei=Khalifa en-aut-mei=Shaden A. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=El-SeediHesham R. en-aut-sei=El-Seedi en-aut-mei=Hesham R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= affil-num=3 en-affil=Department of Pharmacognosy, College of Pharmacy, King Saud University kn-affil= affil-num=4 en-affil=Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University kn-affil= affil-num=5 en-affil=Department of Chemistry, Faculty of Science, Menoufia University kn-affil= en-keyword=paraquat kn-keyword=paraquat en-keyword=lung injury kn-keyword=lung injury en-keyword=melittin kn-keyword=melittin en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=apoptosis kn-keyword=apoptosis END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=11 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cryptolepine, neocryptolepine and isocryptolepine are naturally occurring indoloquinoline alkaloids with various spectrum of biological properties. Structural modification is an extremely effective means to improve their bioactivities. This review enumerates several neocryptolepine and isocryptolepine analogues with potent antiproliferative activity against MV4-11 (leukemia), A549 (lung cancer), HCT116 (colon cancer) cell lines in vitro. Its activity towards normal mouse fibroblasts BALB/3T3 was also evaluated. Furthermore, structure activity relationships (SAR) are briefly discussed. The anticancer screening of neocryptolepine derivatives was performed in order to determine their cytotoxic and growth inhibitory activities across the JFCR39 cancer cell line panel. en-copyright= kn-copyright= en-aut-name=WangNing en-aut-sei=Wang en-aut-mei=Ning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ŚwitalskaMarta en-aut-sei=Świtalska en-aut-mei=Marta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangLi en-aut-sei=Wang en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShabanElkhabiry en-aut-sei=Shaban en-aut-mei=Elkhabiry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HossainMd Imran en-aut-sei=Hossain en-aut-mei=Md Imran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=El SayedIbrahim El Tantawy en-aut-sei=El Sayed en-aut-mei=Ibrahim El Tantawy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WietrzykJoanna en-aut-sei=Wietrzyk en-aut-mei=Joanna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InokuchiTsutomu en-aut-sei=Inokuchi en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences kn-affil= affil-num=3 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences kn-affil= affil-num=8 en-affil=Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=cryptolepine kn-keyword=cryptolepine en-keyword=neocryptolepine kn-keyword=neocryptolepine en-keyword=isocryptolepine kn-keyword=isocryptolepine en-keyword=antiproliferative activity kn-keyword=antiproliferative activity en-keyword=structure activity relationships kn-keyword=structure activity relationships END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=21 article-no= start-page=E4252 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quasi-Randomized Trial of Effects of Perioperative Oral Hygiene Instruction on Inpatients with Heart Diseases Using a Behavioral Six-Step Method en-subtitle= kn-subtitle= en-abstract= kn-abstract= The assessor-blinded, parallel-design, quasi-randomized study (alternating allocation) aimed to determine the effects of the six-step method on postoperative numbers of oral bacteria, periodontal status, and atrial fibrillation (AF) among inpatients with heart diseases and periodontitis. Seventy inpatients who received preoperative periodontal treatment were quasi-randomly assigned to intervention and control groups at University Hospital. The intervention group received intensive oral hygiene instruction using a six-step method for 15 minutes per week and the control group received routine oral hygiene instruction. Significantly fewer oral bacteria were identified on the tongue at discharge compared with baseline in the intervention than the control group (ANCOVA) (large effect size, p = 0.02). Changes in scores for self-efficacy, plaque scores, probed pocket depth, and bleeding on probing between baseline and discharge were significantly greater in the intervention, than in the control group (p < 0.05). The period of postoperative AF (days) was significantly shorter in the intervention, than in the control group (p = 0.019). In conclusion, oral hygiene instruction using the six-step method decreased the numbers of oral bacteria on the tongue and improved self-efficacy, oral health behaviors, oral hygiene status, periodontal status, and period of postoperative AF among inpatients with periodontitis and heart diseases. en-copyright= kn-copyright= en-aut-name=OmoriChie en-aut-sei=Omori en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhbayashiYumiko en-aut-sei=Ohbayashi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeMinoru en-aut-sei=Miyake en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= Department of Preventive Dentistry, Okayama University graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= Department of Preventive Dentistry, Okayama University graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Hospital kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa University Hospital kn-affil= affil-num=5 en-affil= Department of Preventive Dentistry, Okayama University graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oral hygiene instruction kn-keyword=oral hygiene instruction en-keyword=perioperative period kn-keyword=perioperative period en-keyword=self-efficacy kn-keyword=self-efficacy en-keyword=six-step method kn-keyword=six-step method END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=19 article-no= start-page= 3540 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of Occupational Stress and Coping Style on Periodontitis Among Japanese Workers: A Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract= The aim of this cross-sectional study was to evaluate the association between the influence of occupational stress and coping style on periodontitis among Japanese workers. The study sample included 738 workers (age range: 19-65 years) at a manufacturing company in Kagawa Prefecture, Japan. To analyze occupational stress and coping style, all participants answered a self-report questionnaire composed of items on their work environment and oral health behavior. Oral examinations were performed by calibrated dentists. Among all workers, 492 (66.7%) workers were diagnosed with periodontitis, and 50 (6.8%) were diagnosed with a high stress-low coping condition. Significant differences (p < 0.05) were observed between the periodontitis and non-periodontitis groups in terms of age, gender, body mass index, smoking status, daily alcohol drinking, monthly overtime work, worker type, and stress-coping style. Logistic regression analysis showed that a high stress-low coping condition was associated with an increased risk of periodontitis (odds ratio: 2.79, 95% confidence interval: 1.05-7.43, p = 0.039). These findings suggest that a high stress-low coping condition is associated with periodontitis among the 19-65 years of age group of Japanese workers. en-copyright= kn-copyright= en-aut-name=Md Monirul Islam en-aut-sei=Md Monirul Islam en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YonedaToshiki en-aut-sei=Yoneda en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoiAya en-aut-sei=Yokoi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Japanese workers kn-keyword=Japanese workers en-keyword=coping kn-keyword=coping en-keyword=occupational stress kn-keyword=occupational stress en-keyword=periodontitis kn-keyword=periodontitis END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=5 article-no= start-page=1042 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel en-subtitle= kn-subtitle= en-abstract= kn-abstract=Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15⁻20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies. en-copyright= kn-copyright= en-aut-name=Apriliana Cahya Khayrani en-aut-sei=Apriliana Cahya Khayrani en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MahmudHafizah en-aut-sei=Mahmud en-aut-mei=Hafizah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Aung Ko Ko Oo en-aut-sei=Aung Ko Ko Oo en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzeMiharu en-aut-sei=Oze en-aut-mei=Miharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DuJuan en-aut-sei=Du en-aut-mei=Juan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AlamMd Jahangir en-aut-sei=Alam en-aut-mei=Md Jahangir kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Hagar A. Abu Quora en-aut-sei=Hagar A. Abu Quora en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShigehiroTsukasa en-aut-sei=Shigehiro en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Anna Sanchez Calle en-aut-sei=Anna Sanchez Calle en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkadaNobuhiro en-aut-sei=Okada en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujitaKoki en-aut-sei=Fujita en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HamadaHiroki en-aut-sei=Hamada en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SenoYuhki en-aut-sei=Seno en-aut-mei=Yuhki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MandaiTadakatsu en-aut-sei=Mandai en-aut-mei=Tadakatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil= Division of Molecular and Cellular Medicine, National Cancer Center Research Institute kn-affil= affil-num=12 en-affil= Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=14 en-affil=Ensuiko Sugar Refining Co., Ltd. kn-affil= affil-num=15 en-affil=Faculty of Science, Okayama University of Science kn-affil= affil-num=16 en-affil= Graduate School of Pharmaceutical Science, Tokushima University kn-affil= affil-num=17 en-affil= Faculty of Life Science, Kurashiki University of Science and the Arts kn-affil= affil-num=18 en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=CD44 kn-keyword=CD44 en-keyword=glycosylated paclitaxel kn-keyword=glycosylated paclitaxel en-keyword=liposome kn-keyword=liposome en-keyword=modified paclitaxel kn-keyword=modified paclitaxel en-keyword=ovarian cancer kn-keyword=ovarian cancer en-keyword=specific targeting kn-keyword=specific targeting END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=3 article-no= start-page=345 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conversion of Stem Cells to Cancer Stem Cells: Undercurrent of Cancer Initiation en-subtitle= kn-subtitle= en-abstract= kn-abstract= Cancer stem cells (CSCs) also known as cancer-initiating cells (CIC), are responsible for the sustained and uncontrolled growth of malignant tumors and are proposed to play significant roles in metastasis and recurrence. Several hypotheses have proposed that the events in either stem and/or differentiated cells, such as genomic instability, inflammatory microenvironment, cell fusion, and lateral gene transfer, should be considered as the possible origin of CSCs. However, until now, the exact origin of CSC has been obscure. The development of induced pluripotent stem cells (iPSCs) in 2007, by Yamanaka's group, has been met with much fervency and hailed as a breakthrough discovery by the scientific and research communities, especially in regeneration therapy. The studies on the development of CSC from iPSCs should also open a new page of cancer research, which will help in designing new therapies applicable to CSCs. Currently most reviews have focused on CSCs and CSC niches. However, the insight into the niche before the CSC niche should also be of keen interest. This review introduces the novel concept of cancer initiation introducing the conversion of iPSCs to CSCs and proposes a relationship between the inflammatory microenvironment and cancer initiation as the key concept of the cancer-inducing niche responsible for the development of CSC. en-copyright= kn-copyright= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=cancer-inducing niche kn-keyword=cancer-inducing niche en-keyword=chronic inflammation kn-keyword=chronic inflammation en-keyword=induced pluripotent stem cells kn-keyword=induced pluripotent stem cells en-keyword=stem cell kn-keyword=stem cell END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=690 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Awareness of Clenching and Underweight are Risk Factors for Onset of Crowding in Young Adults: A Prospective 3-Year Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract= Bruxism is a parafunctional activity that can seriously affect quality of life. Although bruxism induces many problems in the oral and maxillofacial area, whether it contributes to the onset of malocclusion remains unclear. The purpose of this prospective cohort study was to investigate the association between the onset of malocclusion and awareness of clenching during the daytime in young adults. Among 1,092 Okayama University students who underwent normal occlusion at baseline, we analysed 238 who had undergone a dental examination and had complete data after 3 years (2013⁻2016). We also performed subgroup analysis to focus on the association between awake bruxism and the onset of crowding (n = 216). Odds ratios (ORs) were calculated using multivariate logistic regression analyses. The incidences of malocclusion and crowding were 53.8% and 44.5%, respectively. In multivariate logistic regression, awareness of clenching was a risk factor for crowding (OR: 3.63; 95% confidence interval [CI]: 1.08⁻12.17). Moreover, underweight (body mass index < 18.5 kg/m²) was related to the onset of malocclusion (OR: 2.34; 95%CI: 1.11⁻4.92) and crowding (OR: 2.52, 95%CI: 1.25⁻5.76). These results suggest that awareness of clenching during the daytime and underweight are risk factors for the onset of crowding in young adults. en-copyright= kn-copyright= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Taniguchi-TabataAyano en-aut-sei=Taniguchi-Tabata en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Yamane-TakeuchiMayu en-aut-sei=Yamane-Takeuchi en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimoriKohei en-aut-sei=Fujimori en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiTerumasa en-aut-sei=Kobayashi en-aut-mei=Terumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuharaDaiki en-aut-sei=Fukuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IrieKoichiro en-aut-sei=Irie en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AzumaTetsuji en-aut-sei=Azuma en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Microbiology and Immunology, Columbia University Medical Center kn-affil= affil-num=10 en-affil=Department of Community Oral Health, Asahi University School of Dentistry kn-affil= affil-num=11 en-affil= Health Service Center, Okayama University kn-affil= affil-num=12 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bruxism kn-keyword=bruxism en-keyword=cohort study kn-keyword=cohort study en-keyword=malocclusion kn-keyword=malocclusion en-keyword=underweight kn-keyword=underweight en-keyword=young adults kn-keyword=young adults END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=7 article-no= start-page=1412 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of Numerical Aperture on Molten Area Formation in Fusion Micro-Welding of Glass by Picosecond Pulsed Laser en-subtitle= kn-subtitle= en-abstract= kn-abstract= Focusing condition such as numerical aperture (N.A.) has a great influence on the creation of molten area and the stable welding process in fusion micro-welding of glass. In this study, a picosecond pulsed laser of 1064 nm in wavelength and 12.5 ps in pulse duration was tightly focused inside a borosilicate glass using objective lenses of numerical apertures 0.45, 0.65, and 0.85 with spherical aberration correction. Influence of numerical aperture on molten area formation was experimentally investigated through analysis of focusing situation in glass, and movement of absorption point, and then molten area characteristics were discussed. It is concluded that N.A. of 0.65 with superior focusing characteristics can form a large and continuous molten area without cracks, which enables achievement of stable joining of glass material by picosecond pulsed laser. en-copyright= kn-copyright= en-aut-name=OuyangZhiyong en-aut-sei=Ouyang en-aut-mei=Zhiyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoYasuhiro en-aut-sei=Okamoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OginoYuta en-aut-sei=Ogino en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakagawaTomokazu en-aut-sei=Sakagawa en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkadaAkira en-aut-sei=Okada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=ultrashort pulsed laser kn-keyword=ultrashort pulsed laser en-keyword=glass material kn-keyword=glass material en-keyword=absorption point kn-keyword=absorption point en-keyword=molten area kn-keyword=molten area en-keyword=numerical aperture kn-keyword=numerical aperture END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=177 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness en-subtitle= kn-subtitle= en-abstract= kn-abstract= Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy. en-copyright= kn-copyright= en-aut-name=KatsuraYuki en-aut-sei=Katsura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaTakayuki en-aut-sei=Ninomiya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoHiroaki en-aut-sei=Sato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KomotoSatoshi en-aut-sei=Komoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NarusakaToru en-aut-sei=Narusaka en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TomonoYasuko en-aut-sei=Tomono en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=XingBoyi en-aut-sei=Xing en-aut-mei=Boyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Kasai Tomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil= Shigei Medical Research Institute kn-affil= affil-num=11 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=School of Bioscience and Biotechnology, Tokyo University of Technology kn-affil= affil-num=17 en-affil= Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=18 en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=combination therapy kn-keyword=combination therapy en-keyword=iron kn-keyword=iron en-keyword=stemness kn-keyword=stemness END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=8 article-no= start-page=1973 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190423 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Notch Signaling Affects Oral Neoplasm Cell Differentiation and Acquisition of Tumor-Specific Characteristics en-subtitle= kn-subtitle= en-abstract= kn-abstract= Histopathological findings of oral neoplasm cell differentiation and metaplasia suggest that tumor cells induce their own dedifferentiation and re-differentiation and may lead to the formation of tumor-specific histological features. Notch signaling is involved in the maintenance of tissue stem cell nature and regulation of differentiation and is responsible for the cytological regulation of cell fate, morphogenesis, and/or development. In our previous study, immunohistochemistry was used to examine Notch expression using cases of odontogenic tumors and pleomorphic adenoma as oral neoplasms. According to our results, Notch signaling was specifically associated with tumor cell differentiation and metaplastic cells of developmental tissues. Notch signaling was involved in the differentiation of the ductal epithelial cells of salivary gland tumors and ameloblast-like cells of odontogenic tumors. However, Notch signaling was also involved in squamous metaplasia, irrespective of the type of developmental tissue. In odontogenic tumors, Notch signaling was involved in epithelial-mesenchymal interactions and may be related to tumor development and tumorigenesis. This signaling may also be associated with the malignant transformation of ameloblastomas. Overall, Notch signaling appears to play a major role in the formation of the characteristic cellular composition and histological features of oral neoplasms, and this involvement has been reviewed here. en-copyright= kn-copyright= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaHatsuhiko en-aut-sei=Maeda en-aut-mei=Hatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawakamiToshiyuki en-aut-sei=Kawakami en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name=長塚仁 kn-aut-sei=長塚 kn-aut-mei=仁 aut-affil-num=7 ORCID= affil-num=1 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil= Department of Oral Pathology, School of Dentistry, Aichi Gakuin University, kn-affil= affil-num=6 en-affil= Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine kn-affil= affil-num=7 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cell differentiation kn-keyword=cell differentiation en-keyword=epithelial-mesenchymal interaction kn-keyword=epithelial-mesenchymal interaction en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=malignant transformation kn-keyword=malignant transformation en-keyword=notch signaling kn-keyword=notch signaling en-keyword=odontogenic tumor kn-keyword=odontogenic tumor en-keyword=pleomorphic adenoma kn-keyword=pleomorphic adenoma END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=6 article-no= start-page=792 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= Cell division control 37 (CDC37) increases the stability of heat shock protein 90 (HSP90) client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SREZBP-CTfin51-AW1-Number 18 cDNA (SCAN) transcription factor family—MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1/ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced the tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in the CDC37 gene, negatively regulated the CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1. en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PrinceThomas L. en-aut-sei=Prince en-aut-mei=Thomas L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Manh Tien Tran en-aut-sei=Manh Tien Tran en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LangBenjamin J. en-aut-sei=Lang en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword= SCAN zinc finger kn-keyword= SCAN zinc finger en-keyword=SCAND1 kn-keyword=SCAND1 en-keyword=CDC37 kn-keyword=CDC37 en-keyword=MZF1 kn-keyword=MZF1 en-keyword=prostate cancer kn-keyword=prostate cancer END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=371 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20171204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat (Eidolon helvum). en-subtitle= kn-subtitle= en-abstract= kn-abstract= Bats are important reservoirs for emerging zoonotic viruses. For extensive surveys of potential pathogens in straw-colored fruit bats (Eidolon helvum) in Zambia, a total of 107 spleen samples of E. helvum in 2006 were inoculated onto Vero E6 cells. The cell culture inoculated with one of the samples (ZFB06-106) exhibited remarkable cytopathic changes. Based on the ultrastructural property in negative staining and cross-reactivity in immunofluorescence assays, the virus was suspected to be an adenovirus, and tentatively named E. helvum adenovirus 06-106 (EhAdV 06-106). Analysis of the full-length genome of 30,134 bp, determined by next-generation sequencing, showed the presence of 28 open reading frames. Phylogenetic analyses confirmed that EhAdV 06-106 represented a novel bat adenovirus species in the genus Mastadenovirus. The virus shared similar characteristics of low G + C contents with recently isolated members of species Bat mastadenoviruses E, F and G, from which EhAdV 06-106 diverged by more than 15% based on the distance matrix analysis of DNA polymerase amino acid sequences. According to the taxonomic criteria, we propose the tentative new species name "Bat mastadenovirus H". Because EhAdV 06-106 exhibited a wide in vitro cell tropism, the virus might have a potential risk as an emerging virus through cross-species transmission. en-copyright= kn-copyright= en-aut-name=OgawaHirohito en-aut-sei=Ogawa en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajiharaMasahiro en-aut-sei=Kajihara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaoNaganori en-aut-sei=Nao en-aut-mei=Naganori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigenoAsako en-aut-sei=Shigeno en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujikuraDaisuke en-aut-sei=Fujikura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Hang’ombeBernard M. en-aut-sei=Hang’ombe en-aut-mei=Bernard M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MweeneAaron S. en-aut-sei=Mweene en-aut-mei=Aaron S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MutemwaAlisheke en-aut-sei=Mutemwa en-aut-mei=Alisheke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SquarreDavid en-aut-sei=Squarre en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMasao en-aut-sei=Yamada en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HigashiHideaki en-aut-sei=Higashi en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SawaHirofumi en-aut-sei=Sawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakadaAyato en-aut-sei=Takada en-aut-mei=Ayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University kn-affil= affil-num=3 en-affil= Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University kn-affil= affil-num=4 en-affil= Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University kn-affil= affil-num=5 en-affil=Division of Infection and Immunity, Research Center for Zoonosis Control, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Paraclinical Studies, School of Veterinary Medicine, University of Zambia kn-affil= affil-num=7 en-affil=Department of Disease Control, School of Veterinary Medicine, University of Zambia kn-affil= affil-num=8 en-affil= Provincial Veterinary Office, Department of Veterinary Services, Ministry of Fisheries and Livestock kn-affil= affil-num=9 en-affil=Department of National Parks and Wildlife, Ministry of Tourism and Arts kn-affil= affil-num=10 en-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Infection and Immunity, Research Center for Zoonosis Control, Hokkaido University kn-affil= affil-num=12 en-affil= Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University kn-affil= affil-num=13 en-affil=Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University kn-affil= en-keyword=Eidolon helvum kn-keyword=Eidolon helvum en-keyword=Zambia kn-keyword=Zambia en-keyword=adenovirus kn-keyword=adenovirus en-keyword=bat kn-keyword=bat END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=10 article-no= start-page=8815 end-page=8832 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20111020 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the Synthesis of DMAP Derivatives by Diastereoselective Ugi Reactions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diastereoselective Ugi reactions of DMAP-based aldehydes with α-amino acids and tert-butyl isocyanide were examined. The reactions of 4-(dimethylamino)-2-pyridine-carboxaldehyde with various α-amino acids afforded 2-substituted DMAP derivatives with low diastereoselectivity. On the contrary, reactions with 4-(dimethylamino)-3-pyridine-carboxaldehyde delivered 3-substituted DMAP derivatives with moderate to high diastereoselectivity. The combination of α-amino acid and DMAP-based aldehyde is thus important to achieve high diastereoselectivity. Kinetic resolution of a secondary alcohol using a chiral DMAP derivative obtained through these reactions was also examined. en-copyright= kn-copyright= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IrieShunsuke en-aut-sei=Irie en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University affil-num=2 en-affil= kn-affil=Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University affil-num=3 en-affil= kn-affil=Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University affil-num=4 en-affil= kn-affil=Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University en-keyword=multicomponent reaction kn-keyword=multicomponent reaction en-keyword=Ugi reaction kn-keyword=Ugi reaction en-keyword=chiral DMAP kn-keyword=chiral DMAP en-keyword=kinetic resolution kn-keyword=kinetic resolution END