start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=11 article-no= start-page=1596 end-page=1601 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of the Expression of Serine Protease in Vibrio vulnificus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vibrio vulnificus is a Gram-negative estuarine bacterium that causes infection in immuno-compromised patients, eels, and shrimp. V. vulnificus NCIMB2137, a metalloprotease-negative strain isolated from a diseased eel, produces a 45-kDa chymotrypsin-like alkaline serine protease known as VvsA. The gene encoding vvsA also includes another gene, vvsB with an unknown function; however, it is assumed to be an essential molecular chaperone for the maturation of VvsA. In the present study, we used an in vitro cell-free translation system to examine the maturation pathway of VvsA. We individually expressed the vvsA and vvsB genes and detected their mRNAs. However, the sample produced from vvsA did not exhibit protease activity. A sodium dodecyl sulfate (SDS) analysis detected the VvsB protein, but not the VvsA protein. A Western blotting analysis using a histidine (His)-tag at the amino terminus of proteins also showed no protein production by vvsA. These results suggested the translation, but not the transcription of vvsA. Factors derived from Escherichia coli were used in the in vitro cell-free translation system employed in the present study. The operon of the serine protease gene containing vvsA and vvsB was expressed in E. coli. Although serine proteases were produced, they were cleaved at different sites and no active mature forms were detected. These results indicate that the operon encoding vvsA and vvsB is a gene constructed to be specifically expressed in V. vulnificus. en-copyright= kn-copyright= en-aut-name=KawaseTomoka en-aut-sei=Kawase en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DebnathAnusuya en-aut-sei=Debnath en-aut-mei=Anusuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=MiyakeYui en-aut-sei=Miyake en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Vibrio vulnificus serine protease kn-keyword=Vibrio vulnificus serine protease en-keyword=intermolecular chaperone kn-keyword=intermolecular chaperone en-keyword=cell-free translation system kn-keyword=cell-free translation system END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=1119 end-page=1122 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epigenetic Regulation of Carbonic Anhydrase 9 Expression by Nitric Oxide in Human Small Airway Epithelial Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=DNA methylation is a crucial epigenetic modification that regulates gene expression and determines cell fate; however, the triggers that alter DNA methylation levels remain unclear. Recently, we showed that S-nitrosylation of DNA methyltransferase (DNMT) induces DNA hypomethylation and alters gene expression. Furthermore, we identified DBIC, a specific inhibitor of S-nitrosylation of DNMT3B, to suppress nitric oxide (NO)-induced gene alterations. However, it remains unclear how NO-induced DNA hypomethylation regulates gene expression and whether this mechanism is maintained in normal cells and triggers disease-related changes. To address these issues, we focused on carbonic anhydrase 9 (CA9), which is upregulated under nitrosative stress in cancer cells. We pharmacologically evaluated its regulatory mechanisms using human small airway epithelial cells (SAECs) and DBIC. We demonstrated that nitrosative stress promotes the recruitment of hypoxia-inducible factor 1 alpha to the CA9 promoter region and epigenetically induces CA9 expression in SAECs. Our results suggest that nitrosative stress is a key epigenetic regulator that may cause diseases by altering normal cell function. en-copyright= kn-copyright= en-aut-name=MoriyaYuto en-aut-sei=Moriya en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IijimaYuta en-aut-sei=Iijima en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara 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 Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=human small airway epithelial cell kn-keyword=human small airway epithelial cell en-keyword=epigenetics kn-keyword=epigenetics en-keyword=DNA methylation kn-keyword=DNA methylation en-keyword=carbonic anhydrase 9 kn-keyword=carbonic anhydrase 9 en-keyword=hypoxia-inducible factor 1 alpha kn-keyword=hypoxia-inducible factor 1 alpha END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=2 article-no= start-page=154 end-page=164 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of a Functionally Efficient and Thermally Stable Outward Sodium-Pumping Rhodopsin (BeNaR) from a Thermophilic Bacterium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhodopsins are transmembrane proteins with retinal chromophores that are involved in photo-energy conversion and photo-signal transduction in diverse organisms. In this study, we newly identified and characterized a rhodopsin from a thermophilic bacterium, Bellilinea sp. Recombinant Escherichia coli cells expressing the rhodopsin showed light-induced alkalization of the medium only in the presence of sodium ions (Na+), and the alkalization signal was enhanced by addition of a protonophore, indicating an outward Na+ pump function across the cellular membrane. Thus, we named the protein Bellilinea Na+-pumping rhodopsin, BeNaR. Of note, its Na+-pumping activity is significantly greater than that of the known Na+-pumping rhodopsin, KR2. We further characterized its photochemical properties as follows: (i) Visible spectroscopy and HPLC revealed that BeNaR has an absorption maximum at 524?nm with predominantly (>96%) the all-trans retinal conformer. (ii) Time-dependent thermal denaturation experiments revealed that BeNaR showed high thermal stability. (iii) The time-resolved flash-photolysis in the nanosecond to millisecond time domains revealed the presence of four kinetically distinctive photointermediates, K, L, M and O. (iv) Mutational analysis revealed that Asp101, which acts as a counterion, and Asp230 around the retinal were essential for the Na+-pumping activity. From the results, we propose a model for the outward Na+-pumping mechanism of BeNaR. The efficient Na+-pumping activity of BeNaR and its high stability make it a useful model both for ion transporters and optogenetics tools. en-copyright= kn-copyright= en-aut-name=KuriharaMarie en-aut-sei=Kurihara en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ThielVera en-aut-sei=Thiel en-aut-mei=Vera kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiHirona en-aut-sei=Takahashi en-aut-mei=Hirona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WardDavid M. en-aut-sei=Ward en-aut-mei=David M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BryantDonald A. en-aut-sei=Bryant en-aut-mei=Donald A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaiMakoto en-aut-sei=Sakai en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biological Sciences, Tokyo Metropolitan University kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Science, Okayama University of Science kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Land Resources and Environmental Sciences, Montana State University kn-affil= affil-num=6 en-affil=Department of Biochemistry and Molecular Biology, The Pennsylvania State University kn-affil= affil-num=7 en-affil=Department of Chemistry, Graduate School of Science, Okayama University of Science kn-affil= affil-num=8 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=9 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=ion transport kn-keyword=ion transport en-keyword=retinal kn-keyword=retinal en-keyword=isomerization kn-keyword=isomerization en-keyword=optogenetics kn-keyword=optogenetics END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=2 article-no= start-page=146 end-page=154 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of Scaled-Up Synthetic Method for Retinoid X Receptor Agonist NEt-3IB Contributing to Sustainable Development Goals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Abstract Small-molecular drugs, which are generally inexpensive compared with biopharmaceuticals and can often be taken orally, may contribute to the Sustainable Development Goals (SDGs) adopted by the United Nations. We previously reported the retinoid X receptor (RXR) agonist 4-(ethyl(3-isobutoxy-4-isopropylphenyl)amino)benzoic acid (NEt-3IB, 1) as a small-molecular drug candidate to replace biopharmaceuticals for the treatment of inflammatory bowel disease. The previous synthetic method to 1 required a large amount of organic solvent and extensive purification. In line with the SDGs, we aimed to develop an environmentally friendly, inexpensive method for the large-scale synthesis of 1. The developed method requires only a hydrophobic ether and EtOH as reaction and extraction solvents. The product was purified by recrystallization twice to afford 99% pure 1 at 100?mmol scale in about 30% yield. The optimized process showed a 35-fold improvement of the E-factor (an index of environmental impact) compared to the original method. This work, which changes the solvent used to environmentally preferable ones based on the existing synthetic method for 1, illustrates how synthetic methods for small-molecular drugs can be adapted and improved to contribute to the SDGs. en-copyright= kn-copyright= en-aut-name=TakamuraYuta en-aut-sei=Takamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorishitaKen-ichi en-aut-sei=Morishita en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuzawaShota en-aut-sei=Kikuzawa en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMasaki en-aut-sei=Watanabe en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=10 article-no= start-page=1357 end-page=1363 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microbial Rhodopsins as Multi-functional Photoreactive Membrane Proteins for Optogenetics en-subtitle= kn-subtitle= en-abstract= kn-abstract=In life science research, methods to control biological activities with stimuli such as light, heat, pressure and chemicals have been widely utilized to understand their molecular mechanisms. The knowledge obtained by those methods has built a basis for the development of medicinal products. Among those various stimuli, light has the advantage of a high spatiotemporal resolution that allows for the precise control of biological activities. Photoactive membrane protein rhodopsins from microorganisms (called microbial rhodopsins) absorb visible light and that light absorption triggers the trans?cis photoisomerization of the chromophore retinal, leading to various functions such as ion pumps, ion channels, transcriptional regulators and enzymes. In addition to their biological significance, microbial rhodopsins are widely utilized as fundamental molecular tools for optogenetics, a method to control biological activities by light. In this review, we briefly introduce the molecular basis of representative rhodopsin molecules and their applications for optogenetics. Based on those examples, we discuss the high potential of rhodopsin-based optogenetics tools for basic and clinical research in pharmaceutical sciences. en-copyright= kn-copyright= en-aut-name=NakaoShin en-aut-sei=Nakao en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Division of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=optogenetics kn-keyword=optogenetics en-keyword=retinal kn-keyword=retinal en-keyword=signal transduction kn-keyword=signal transduction END start-ver=1.4 cd-journal=joma no-vol=141 cd-vols= no-issue=10 article-no= start-page=1155 end-page=1160 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Biophysical and Biochemical Research of Animal Rhodopsins kn-title=光受容タンパク質・ロドプシンの生物物理化学研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Opsins (also called animal rhodopsins) are universal photoreceptive proteins that provide the molecular basis of visual and nonvisual photoreception in animals, including humans. Opsins consist of seven helical a-transmembrane domains and use retinal, a derivative of vitamin A, as a chromophore. In many opsins, light absorption triggers photoisomerization from 11-cis retinal to all-trans retinal, resulting in activation via dynamic structural changes in the protein moiety. Activated opsins stimulate cognate trimeric G proteins to induce signal transduction cascades in cells. Recently, molecular and physiological analyses of diverse opsins have progressively advanced. This review introduces the molecular basis and physiological unctions of opsins. Based on the functions of opsins, I will discuss the potential of opsins as target molecules to treat and prevent visual and nonvisual diseases such as sleep disorder and depression. en-copyright= kn-copyright= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name=小島慧一 kn-aut-sei=小島 kn-aut-mei=慧一 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=opsin kn-keyword=opsin en-keyword=retinal kn-keyword=retinal en-keyword=G protein coupled receptor kn-keyword=G protein coupled receptor en-keyword=vision kn-keyword=vision END start-ver=1.4 cd-journal=joma no-vol=141 cd-vols= no-issue=5 article-no= start-page=647 end-page=653 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202151 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=立体培養法を利用した疾患微小環境モデルの開発と病態解析 kn-title=Modeling and Analysis of Disease Microenvironments with 3D Cell Culture Technology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Remarkable progress in our ability to analyze diseased tissue has revolutionized our understanding of disease. From a simplistic understanding of abnormalities in bulk tissue, there is now increasing recognition that the heterogeneous and dynamically evolving disease microenvironment plays a crucial role in disease pathogenesis and progression as well as in the determination of therapeutic response. The disease microenvironment consists of multiple cell types as well as the various factors that these cells secrete. There is now immense interest in treatment strategies that target or modify the abnormal disease microenvironment, and a deeper understanding of the mechanisms that drive the formation, maintenance, and progression of the disease microenvironment is thus necessary. The advent of 3-dimensional (3D) cell culture technology has made possible the reconstitution of the disease microenvironment to a previously unimaginable extent in vitro. As an intermediate between traditional in vitro models based on 2-dimensional (2D) cell culture and in vivo models, 3D models of disease enable the in vitro reconstitution of complex interactions within the disease microenvironment which were unamenable in 2D while simultaneously allowing the mechanistic analysis of these interactions that would be difficult to perform in vivo. This symposium review aims to highlight the promise of using 3D cell culture technology to model and analyze the disease microenvironment using pancreatic cancer as an example. en-copyright= kn-copyright= en-aut-name=TanakaHiroyoshi en-aut-sei=Tanaka en-aut-mei=Hiroyoshi kn-aut-name=田中啓祥 kn-aut-sei=田中 kn-aut-mei=啓祥 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=3-dimensional cell culture kn-keyword=3-dimensional cell culture en-keyword=disease model kn-keyword=disease model en-keyword=disease microenvironment kn-keyword=disease microenvironment END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=7 article-no= start-page=910 end-page=919 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PC3-secreted microprotein is expressed in glioblastoma stem-like cells and human glioma tissues en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor with a high recurrence rate. Despite multimodal therapy including surgical resection, chemotherapy, and radiotherapy, the median survival time after the initial diagnosis of GBM is approximately 14 months. Since cancer stem cells (CSCs) are considered the leading cause of cancer recurrence, glioblastoma stem cell-targeted therapy is a promising strategy for the treatment of GBM. However, because CSC heterogeneity has been implicated in the difficulties of CSC-target therapy, more in-depth knowledge of CSC biology is still required to develop novel therapies. In this study, we established single cell-derived tumorspheres from human glioblastoma U87MG cells. One of these tumorspheres, P4E8 clone, showed CSC-like phenotypes, such as self-renewal capacity, expression of CSC markers, resistance to anti-cancer agents, and in vivo tumorigenicity. Therefore, we used P4E8 cells as a cell-based model of glioblastoma stem cells (GSCs). Gene expression analysis using microarray indicated that the most highly expressed genes in P4E8 cells compared to the parental U87MG were PC3-secreted microprotein (MSMP). Furthermore, MSMP was expressed in patient-derived GSCs and human glioma tissues at the protein level, implying that MSMP might contribute to glioma development and progression. en-copyright= kn-copyright= en-aut-name=MaruyamaMasato en-aut-sei=Maruyama en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoYousuke en-aut-sei=Nakano en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraTakuya en-aut-sei=Nishimura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataRyoichi en-aut-sei=Iwata en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsudaSatoshi en-aut-sei=Matsuda en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashiMikio en-aut-sei=Hayashi en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakaiYuki en-aut-sei=Nakai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NonakaMasahiro en-aut-sei=Nonaka en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoTetsuo en-aut-sei=Sugimoto en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Anatomy and Brain Science, Kansai Medical University kn-affil= affil-num=2 en-affil=Department of Anatomy and Brain Science, Kansai Medical University kn-affil= affil-num=3 en-affil=Department of Anatomy and Brain Science, Kansai Medical University kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Cell Signaling, Institute of Biomedical Science, Kansai Medical University kn-affil= affil-num=6 en-affil=Department of Physiology, Kansai Medical University kn-affil= affil-num=7 en-affil=Department of Anatomy and Brain Science, Kansai Medical University kn-affil= affil-num=8 en-affil=Department of Neurosurgery, Kansai Medical University kn-affil= affil-num=9 en-affil=Department of Anatomy and Brain Science, Kansai Medical University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=1 article-no= start-page=96 end-page=102 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acute Peripheral Inflammation Increases Plasma Concentration of Hypoglycemic Agent Nateglinide with Decreased Hepatic Drug-Metabolizing Activity in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of inflammation on hypoglycemic agents were evaluated in male rats with acute peripheral inflammation (API). Nateglinide (NTG) was utilized as a model compound, since it is a hepatically-metabolized compound and its metabolism is mainly mediated by CYP 2C11 enzyme. In the experiments, rats were subjected to carrageenan injection into their hind paws for API induction, and the plasma concentration profiles of NTG were then examined. In addition, pooled liver microsomes were prepared from control and API rats, and the hepatic drug-metabolizing activity toward NTG and the hepatic expression of CYP2C11 protein were evaluated. It was shown that the plasma concentration of NTG following its intravenous administration decreases at a slower rate in API rats than that in control rats. It was also indicated in the incubation study with the liver microsomes that the hepatic drug-metabolizing activity toward NTG decreases in API rats. Additionally, it was revealed in Western immunoblotting that the hepatic expression of CYP2C11 protein decreases in API rats. These findings suggest that inflammation occurring in peripheral tissues brings about a decrease in hepatic NTG metabolism by suppressing the hepatic expression of CYP2C11 protein, causing an alteration of the plasma concentration profile of NTG with its impaired elimination. en-copyright= kn-copyright= en-aut-name=KojinaMoeko en-aut-sei=Kojina en-aut-mei=Moeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiKeiichiro en-aut-sei=Suzuki en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiwakiAkane en-aut-sei=Nishiwaki en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AibaTetsuya en-aut-sei=Aiba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute inflammation kn-keyword=acute inflammation en-keyword=CYP2C11 kn-keyword=CYP2C11 en-keyword=hepatic drug metabolism, nateglinide kn-keyword=hepatic drug metabolism, nateglinide END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=8 article-no= start-page=1288 end-page=1291 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Low Viability of Cholera Toxin-Producing Vibrio cholerae O1 in the Artificial Low Ionic Strength Aquatic Solution en-subtitle= kn-subtitle= en-abstract= kn-abstract=It has been well known that Vibrio cholerae inhabit in environmental water. As many patients infected with cholera toxin-producing V. cholerae O1 (toxigenic V. cholerae O1) emerge in Kolkata, India, it has been thought that toxigenic V. cholerae O1 is easily detected in environmental water in Kolkata. However, we could not isolate toxigenic V. cholerae O1 from environmental water in Kolkata, though NAG Vibrio (generic name of V. cholerae non-O1/non-O139) is constantly detected. To clear the reason for the non-isolation of toxigenic V. cholerae O1, we examined the viability of V. cholera O1 and NAG Vibrios in the artificial low ionic strength aquatic solution. We found that the viability of toxigenic V. cholerae O1 in the solution is low, but that of NAG Vibrios is high. Subsequently, we examined the viability of NAG Vibrios possessing cholera toxin gene (ctx) in the same condition and found that the viability of these NAG Vibrios is low. These results indicate that the existence of ctx in V. cholerae affects the viability of V. cholerae in the aquatic solution used in this experiment. We thought that there was closely relation between the low viability of toxigenic V. cholerae O1 in the artificial low ionic strength aquatic solution and the low frequency of isolation of the strain from environmental water. en-copyright= kn-copyright= en-aut-name=PaulSubha Sankar en-aut-sei=Paul en-aut-mei=Subha Sankar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiEizo en-aut-sei=Takahashi en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKeinosuke en-aut-sei=Okamoto en-aut-mei=Keinosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= affil-num=2 en-affil=Department of Health Pharmacy, Yokohama University of Pharmacy kn-affil= affil-num=3 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University kn-affil= affil-num=6 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=7 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=8 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=cholera toxin kn-keyword=cholera toxin en-keyword=aquatic solution kn-keyword=aquatic solution en-keyword=viability kn-keyword=viability END start-ver=1.4 cd-journal=joma no-vol=139 cd-vols= no-issue=6 article-no= start-page=887 end-page=890 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Problems with Laboratory Notebooks in Academia and How to Resolve Them kn-title=アカデミアにおける実験記録の悩み それを解決するには en-subtitle= kn-subtitle= en-abstract= kn-abstract= There is currently a major effort to promote drug discovery in academia as a way to seed new drug development in the pharmaceutical industry. However, there are concerns in industry about the quality of drug candidates generated in academic institutions. These concerns encompass culture and perceptions with respect to intellectual property management, the process of product development, and the reliability of scientific data. Questions about data reliability underscore the particularly serious problem of mistrust in academic research. Therefore, the author became interested in the topic of industry standards for quality assurance (QA) and arranged training workshops at Okayama University on the appropriate methods for recording experimental notes by lecturers involved in QA. The outcomes are presented here. en-copyright= kn-copyright= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name=加来田博貴 kn-aut-sei=加来田 kn-aut-mei=博貴 aut-affil-num=1 ORCID= affil-num=1 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科 en-keyword=research record kn-keyword=research record en-keyword=laboratory notebook kn-keyword=laboratory notebook en-keyword=good practice standard kn-keyword=good practice standard en-keyword=attributable kn-keyword=attributable en-keyword=legible kn-keyword=legible en-keyword=contemporaneous kn-keyword=contemporaneous en-keyword=original kn-keyword=original en-keyword=and accurate (ALCOA) and complete kn-keyword=and accurate (ALCOA) and complete en-keyword=consistent kn-keyword=consistent en-keyword=enduring kn-keyword=enduring en-keyword=and available (CCEA) standards kn-keyword=and available (CCEA) standards en-keyword=data integrity kn-keyword=data integrity END