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Creatine and l-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish

Scientific Reports 2024年第1期14卷 1-19页

作者： Pan, Shao-Wei Wang, Horng-Dar Hsiao, He-Yun Hsu, Po-Jui Tseng, Yung-Che Liang, Wen-Chen Jong, Yuh-Jyh Yuh, Chiou-Hwa Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Zhunan Taiwan Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan Department of Laboratory Medicine Mackay Memorial Hospital Taipei Taiwan Department of Medical Laboratory Science and Biotechnology Yuanpei University of Medical Technology Hsinchu Taiwan Department of Nursing MacKay Medical College Taipei Taiwan Marine Research Station Institute of Cellular and Organism Biology Academia Sinica I-Lan Taiwan Department of Pediatrics School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Graduate Institute of Clinical Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Pediatrics Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Translational Research Center of Neuromuscular Diseases Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Department of Laboratory Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan Ph.D. Program in Environmental and Occupational Medicine Kaohsiung Medical University Kaohsiung Taiwan

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathw

关键词： Creatine l-Carnitine LMNA Striated muscle laminopathy Zebrafish

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Front Cover: Design, Synthesis, and Characterization of Novel Styryl Dyes as Fluorescent Probes for Tau Aggregate Detectionin Vitroand in Cells (Chem. Asian J. 6/2024)

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Chemistry – An Asian Journal 2024年第6期19卷

作者： Withsakorn Sangsuwan Kriangsak Faikhruea Kotchakorn Supabowornsathit Don Sangsopon Praewphan Ingrungruanglert Hathaichanok Chuntakaruk Napatsaporn Nuntavanotayan Kittiporn Nakprasit Nipan Israsena Thanyada Rungrotmongkol Pitak Chuawong Tirayut Vilaivan Chanat Aonbangkhen Center of Excellence in Natural Products Chemistry (CENP) Department of Chemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand Department of Chemistry and Center of Excellence for Innovation in Chemistry Faculty of Science Special Research Unit for Advanced Magnetic Resonance (AMR) Kasetsart University Bangkok 10900 Thailand These authors are contributed equally. Organic Synthesis Research Unit Department of Chemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand Stem Cell and Cell Therapy Research Unit and Department of Pharmacology Faculty of Medicine Chulalongkorn University Bangkok 10330 Thailand Program in Bioinformatics and Computational Biology Graduate School Chulalongkorn University Bangkok 10330 Thailand Center of Excellence in Structural and Computational Biology Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand

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Proceedings of the 16th Annual UT-KBRIN bioinformatics Summit 2016: bioinformatics

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BMC bioinformatics 2017年第9期18卷 1-9页

作者： Eric C. Rouchka Juw Won Park Julia H. Chariker David A. Tieri Shreedharkumar Rajurkar Vikas Singh Nishchal K. Verma Yan Cui Mark Farman Bradford Condon Jolanta Jaromczyk Neil Moore Jerzy Jaromczyk Daniel Harris Patrick Calie Eun Kyong Shin Robert L. Davis Arash Shaban-Nejad Joshua M. Mitchell Hunter N. B. Moseley Robert M. Flight Qing Jun Wang Richard M. Higashi Teresa W-M Fan Andrew N. Lane Liangqun Lu Bernie J Daigle Jr. Xi Chen Andrey Smelter Jerzy W. Jaromczyk Bailey K. Phan Nathaniel J. Serpico Ethan G. Toney Li Chen Caroline E. Melton Jennifer R. Mandel Bernie J. Daigle Jr. Hao Chen Kazi I. Zaman Ramin Homayouni Patrick J. Trainor Andrew P. DeFilippis Samantha M. Carlisle Shesh N. Rai Department of Computer Engineering and Computer Science University of Louisville Duthie Center for Engineering Louisville KY 40292 USA Kentucky Biomedical Research Infrastructure (KBRIN) Bioinformatics Core 522 East Gray Street Louisville KY 40292 USA Department of Psychological and Brain Sciences University of Louisville Louisville KY 40292 USA Department of Anatomical Sciences and Neurobiology University of Louisville Louisville KY 40292 USA Department of Electrical Engineering IIT Kanpur India Department of Microbiology Immunology and Biochemistry University of Tennessee Health Science Center Memphis TN 38103 USA Center for Integrative and Translational Genomics University of Tennessee Health Science Center Memphis TN 38103 USA Department of Plant Pathology University of Kentucky Lexington KY 40546 USA UK Healthcare Genomics University of Kentucky Lexington KY 40536 USA Department of Entomology & Plant Pathology University of Tennessee Knoxville TN 37996 USA Department of Forestry University of Kentucky Lexington KY 40506 USA Department of Computer Science University of Kentucky Lexington KY 40506 USA Department of Computer Science University of Kentucky Lexington KY 40508 USA Department of Biological Sciences Eastern Kentucky University Richmond KY 40475 USA University of Tennessee Health Science Center – Oak-Ridge National Lab (UTHSC-ORNL) Center for Biomedical Informatics Department of Pediatrics Memphis TN 38103 USA Department of Molecular & Cellular Biochemistry University of Kentucky Lexington KY 40536 USA Markey Cancer Center University of Kentucky Lexington KY 40536 USA Center for Environmental and Systems Biochemistry University of Kentucky Lexington KY 40536 USA Institute for Biomedical Informatics University of Kentucky Lexington KY 40536 USA Department of Molecular and Cellular Biochemistry University of Kentucky Lexington KY 40536 USA Department of Statistics University of Kentucky Louisville KY

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A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy

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Journal of Experimental and Clinical Cancer Research 2023年第1期42卷 29-29页

作者： Chen, Chia-Hung Weng, Tzu-Han Huang, Hsiao-Hsuan Huang, Ling-Ya Huang, Kai-Yao Chen, Pin-Rong Yeh, Kuang-Yu Huang, Chi-Ting Chien, Yu-Tzu Chuang, Po-Ya Lin, Yu-Ling Tsai, Nu-Man Liu, Shih-Jen Su, Yu-Cheng Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan Department of Dermatology MacKay Memorial Hospital Taipei City 10449 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Medicine MacKay Medical College New Taipei City 25245 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Agricultural Biotechnology Research Center Academia Sinica Taipei 11529 Taiwan Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung City 40201 Taiwan Department of Pathology and Clinical Laboratory Chung Shan Medical University Hospital Taichung City 40201 Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli 350401 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City 11260 Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung City 80708 Taiwan College of Dental Medicine Kaohsiung Medical University School of Dentistry Kaohsiung City 80708 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City 70101 Taiwan Center for Intelligent Drug Systems and Smart Bio-Devices National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan

Background: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. Methods: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells’ membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. Results: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to st

关键词： Costimulatory molecules Immunotherapy LPPC personalized cancer therapy Tumor heterogenicity

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Persistence and dynamic structures of diverse cephalosporinase genes in nontyphoidal Salmonella in cross-sectional surveillance in Taiwan

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International Journal of Antimicrobial Agents 2023年第4期62卷 106944-106944页

作者： Lee, Yuarn-Jang Chang, Yu-Chu Lee, I-Hui Ho, Kuo-Hao Fang, Shiuh-Bin Lauderdale, Tsai-Ling Chen, Ting-Wen Chen, Ku-Chung Huang, Chih-Hung Huang, Tzu-Wen Division of Infectious Diseases Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Division of Infectious Diseases Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Biochemistry and Molecular Cell Biology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan Division of Pediatric Gastroenterology and Hepatology Department of Pediatrics Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Department of Medical Research Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Department of Pediatrics School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Master Program in Clinical Pharmacogenomics and Pharmacoproteomics College of Pharmacy Taipei Medical University Taipei Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Zhunan Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Chemical Engineering and Biotechnology Institute of Chemical Engineering National Taipei University of Technology Taipei Taiwan

Objectives: Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteraemia, particularly in paediatric and elderly patients. Antimicrobial resistance of NTS, especially resistance to extended-spectrum cephalosporins, has emerged over the past decades. Methods: Thirteen NTS isolates resistant to ceftriaxone or cefotaxime were collected from a teaching hospital in Taipei, and another three from a tertiary hospital, in New Taipei City, Taiwan, from September 2018 to December 2019. Ten other archived isolates from 2000 to 2017 were also obtained. Complete genomes of the 26 isolates were obtained. Serovars, sequence types, resistomes, genetic relatedness, and sequence comparison of plasmids were analyzed. Results: Serogroups B, C2 and E were significantly associated with ampicillin resistance. Over 90% of these 26 isolates are susceptible to carbapenems and colistin. Genomic epidemiology of these isolates shows that bla_CMY-2-harbouring isolates in different serovars were prevalent over two decades, presumably resulting from highly mobile IncI1 plasmid harbouring bla_CMY-2. One type of the IncI1 plasmids contained a mobile element, IS26, which might be involved in the acquisition of antimicrobial resistance genes. Two emerging serovars, S. Goldcoast ST358 harbouring bla_CTX-M-55 on IncHI2 plasmids and S. Anatum ST64 harbouring bla_DHA-1 on IncA/C₂ plasmids persisted in Taiwan, possibly through the clonal spread. Integration of complete or partial plasmid sequences into host chromosomes or multiplications of the antimicrobial resistance genes also appears to be mediated by IS26, in the two emerging clones. Conclusion: The dynamic movement of cephalosporinase genes mediated by IS26 in NTS is of great concern. © 2023 The Authors

关键词： Amplification Chromosome integration Epidemiology Foodborne pathogen Insertion sequence Whole-genome sequencing

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Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

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The Lancet Respiratory Medicine 2020年第7期8卷 696-708页

作者： Moll, Matthew Sakornsakolpat, Phuwanat Shrine, Nick Hobbs, Brian D DeMeo, Dawn L John, Catherine Guyatt, Anna L McGeachie, Michael J Gharib, Sina A Obeidat, Ma'en Lahousse, Lies Wijnant, Sara R A Brusselle, Guy Meyers, Deborah A Bleecker, Eugene R Li, Xingnan Tal-Singer, Ruth Manichaikul, Ani Rich, Stephen S Won, Sungho Kim, Woo Jin Do, Ah Ra Washko, George R Barr, R Graham Psaty, Bruce M Bartz, Traci M Hansel, Nadia N Barnes, Kathleen Hokanson, John E Crapo, James D Lynch, David Bakke, Per Gulsvik, Amund Hall, Ian P Wain, Louise Soler Artigas, María Jackson, Victoria E Strachan, David P Hui, Jennie James, Alan L Kerr, Shona M Polasek, Ozren Vitart, Veronique Marten, Jonathan Rudan, Igor Kähönen, Mika Surakka, Ida Gieger, Christian Karrasch, Stefan Rawal, Rajesh Schulz, Holger Deary, Ian J Harris, Sarah E Enroth, Stefan Gyllensten, Ulf Imboden, Medea Probst-Hensch, Nicole M Lehtimäki, Terho Raitakari, Olli T Langenberg, Claudia Luan, Jian'an Wareham, Nick Zhao, Jing Hua Hayward, Caroline Murray, Alison Porteous, David J Smith, Blair H Jarvelin, Marjo-Riitta Wielscher, Matthias Joshi, Peter K Kentistou, Katherine A Timmers, Paul RHJ Wilson, James F Cook, James P Lind, Lars Mahajan, Anubha Morris, Andrew P Ewert, Ralf Homuth, Georg Stubbe, Beate Weiss, Stefan Zeggini, Eleftheria Weiss, Scott T Silverman, Edwin K Dudbridge, Frank Tobin, Martin D Cho, Michael H Channing Division of Network Medicine Brigham and Women's Hospital Boston MA United States Division of Pulmonary and Critical Care Medicine Brigham and Women's Hospital Boston MA United States Department of Medicine Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand Genetic Epidemiology Group Department of Health Sciences University of Leicester Leicester United Kingdom Computational Medicine Core Center for Lung Biology Department of Medicine University of Washington Seattle WA United States Division of Pulmonary Critical Care and Sleep Medicine Department of Medicine University of Washington Seattle WA United States Cardiovascular Health Research Unit Department of Medicine University of Washington Seattle WA United States University of British Columbia Center for Heart Lung Innovation St Paul's Hospital Vancouver BC Canada Department of Epidemiology Erasmus Medical Centre Rotterdam Netherlands Department of Respiratory Medicine Erasmus Medical Centre Rotterdam Netherlands Department of Bioanalysis Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium Department of Respiratory Medicine Ghent University Hospital Ghent Belgium Department of Medicine University of Arizona Tucson AZ United States GlaxoSmithKline Research and Development Collegeville PA United States Center for Public Health Genomics University of Virginia Charlottesville VA United States Department of Public Health Sciences University of Virginia Charlottesville VA United States Department of Public Health Sciences Graduate School of Public Health Seoul National University Seoul South Korea Interdisciplinary Program of Bioinformatics College of National Sciences Seoul National University Seoul South Korea Institute of Health and Environment Seoul National University Seoul South Korea Department of Internal Medicine Kangwon National University Chuncheon South Korea Department of Medicine and Department of Epidemiology Columbia Universit

Background: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV₁ and FEV₁/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV₁/FVC <0·7 and FEV₁ <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. Findings: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74–1·88] and non-European (1·42 [1·34–1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56–9·72) in European ancestry and 4·83 (3·45–6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79–0·81] vs 0·76 [0·75–0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The po

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Author Correction: Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease

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Nature communications 2023年第1期14卷 4370页

作者： Matteo D'Antonio Jennifer P Nguyen Timothy D Arthur Hiroko Matsui Agnieszka D'Antonio-Chronowska Kelly A Frazer Department of Pediatrics University of California San Diego La Jolla CA 92093 USA. madantonio@ucsd.edu. Division of Biomedical Informatics University of California San Diego La Jolla CA 92093 USA. madantonio@ucsd.edu. Institute of Genomic Medicine University of California San Diego 9500 Gilman Dr La Jolla CA 92093 USA. madantonio@ucsd.edu. Division of Biomedical Informatics University of California San Diego La Jolla CA 92093 USA. Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA 92093 USA. Biomedical Sciences Graduate Program University of California San Diego La Jolla CA 92093 USA. Institute of Genomic Medicine University of California San Diego 9500 Gilman Dr La Jolla CA 92093 USA. Department of Pediatrics University of California San Diego La Jolla CA 92093 USA. Department of Pediatrics University of California San Diego La Jolla CA 92093 USA. kafrazer@health.ucsd.edu. Institute of Genomic Medicine University of California San Diego 9500 Gilman Dr La Jolla CA 92093 USA. kafrazer@health.ucsd.edu.

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Publisher Correction: Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport

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Scientific reports 2018年第1期8卷 8019页

作者： Shiori Toba Mingyue Jin Masami Yamada Kanako Kumamoto Sakiko Matsumoto Takuo Yasunaga Yuko Fukunaga Atsuo Miyazawa Sakiko Fujita Kyoko Itoh Shinji Fushiki Hiroaki Kojima Hideki Wanibuchi Yoshiyuki Arai Takeharu Nagai Shinji Hirotsune Department of Genetic Disease Research Osaka City University Graduate School of Medicine Asahi-machi 1-4-3 Abeno Osaka 545-8585 Japan. Department of Bioscience and Bioinformatics Faculty of Computer Science and Systems Engineering Kyushu Institute of Technology Kawazu 680-4 Iizuka Fukuoka 820-850 Japan. JST-SENTAN 4-1-8 Honcho Kawaguchi Saitama 332-0012 Japan. JST-CREST 4-1-8 Honcho Kawaguchi Saitama 332-0012 Japan. Graduate School of Life Science University of Hyogo 3-2-1 Kouto Kamigori-cho Ako-gun Hyogo 678-1297 Japan. RSC-University of Hyogo Leading Program Center RIKEN SPring-8 Center 1-1-1 Kouto Sayo-cho Sayo-gun Hyogo 679-5148 Japan. Graduate School of Materials Science Nara Institute of Science and Technology 8916-5 Takayama Ikoma Nara 630-0101 Japan. Department of Pathology and Applied Neurobiology Kyoto Prefectural University of Medicine Graduate School of Medical Sciences Kajii-cho Kawaramachi-Hirokoji Kamigyo-ku Kyoto 602-8566 Japan. Advanced ICT Research Institute National Institute of Information and Communications Technology 588-2 Iwaoka Nishi-ku Kobe 651-2492 Japan. Department of Pathology Osaka City University Graduate School of Medicine Asahi-machi 1-4-3 Abeno Osaka 545-8586 Japan. Department of Biomolecular Science and Engineering Institute of Scientific and Industrial Research Osaka University Mihoga-oka 8-1 Osaka 567-0047 Japan. Department of Genetic Disease Research Osaka City University Graduate School of Medicine Asahi-machi 1-4-3 Abeno Osaka 545-8585 Japan. shinjih@med.osaka-cu.ac.jp.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

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Anethole mitigates H2O2-induced inflammation in HIG-82 synoviocytes by suppressing the aquaporin 1 expression and activating the protein kinase A pathway

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Environmental Toxicology 2024年第2期39卷 965-978页

作者： Huang, Tai-Lung Chang, Yu-Chun Tsai, Bruce Chi-Kang Chen, Tung-Sheng Kao, Shih-Wen Tsai, Yung-Yun Lin, Shinn-Zong Yao, Chun-Hsu Lin, Kuan-Ho Kuo, Wei-Wen Huang, Chih-Yang Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan Department of Orthopedics Chung-Kang Branch Cheng Ching General Hospital Taichung Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan School of Life Science National Taiwan Normal University Taipei Taiwan Department of Orthopaedic Surgery Chung-Shan Medical University Hospital Taichung Taiwan Department of Physical Therapy Asia University Taichung Taiwan Department of Neurosurgery Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Bioinnovation Center Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Biomedical Imaging and Radiological Science China Medical University Taichung Taiwan School of Chinese Medicine China Medical University Taichung Taiwan Biomaterials Translational Research Center China Medical University Hospital Taichung Taiwan Department of Bioinformatics and Medical Engineering Asia University Taichung Taiwan Division of Cardiovascular Medicine Department of Internal Medicine China Medical University Hospital Taichung Taiwan Department of Emergency Medicine China Medical University Hospital Taichung Taiwan College of Medicine China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien Taiwan

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting approximately 1% of the global population, with a higher prevalence in women than in men. Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of RA. Anethole, a prominent compound derived from fennel (Foeniculum vulgare), possesses a spectrum of therapeutic properties, including anti-arthritic, anti-inflammatory, antioxidant, and tumor-suppressive effects. However, its specific impact on RA remains underexplored. This study sought to uncover the potential therapeutic value of anethole in treating RA by employing an H2O2-induced inflammation model with HIG-82 synovial cells. Our results demonstrated that exposure to H2O2 induced the inflammation and apoptosis in these cells. Remarkably, anethole treatment effectively countered these inflammatory and apoptotic processes triggered by H2O2. Moreover, we identified the aquaporin 1 (AQP1) and protein kinase A (PKA) pathway as critical regulators of inflammation and apoptosis. H2O2 stimulation led to an increase in the AQP1 expression and a decrease in p-PKA-C, contributing to cartilage degradation. Conversely, anethole not only downregulated the AQP1 expression but also activated the PKA pathway, effectively suppressing cell inflammation and apoptosis. Furthermore, anethole also inhibited the enzymes responsible for cartilage degradation. In summary, our findings highlight the potential of anethole as a therapeutic agent for mitigating H2O2-induced inflammation and apoptosis in synovial cells, offering promising prospects for future RA treatments. © 2023 Wiley Periodicals LLC.

关键词： Cell death

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Author Correction: Cellular deconvolution of GTEx tissues powers discovery of disease and cell-type associated regulatory variants

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Nature communications 2020年第1期11卷 4426页

作者： Margaret K R Donovan Agnieszka D'Antonio-Chronowska Matteo D'Antonio Kelly A Frazer Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA 92093 USA. Department of Biomedical Informatics University of California San Diego La Jolla CA 92093 USA. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. madantonio@health.ucsd.edu. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. kafrazer@health.ucsd.edu. Institute for Genomic Medicine University of California San Diego La Jolla CA 92093 USA. kafrazer@health.ucsd.edu.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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