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AdAR2 deficiency ameliorates non-alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1

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Journal of Cachexia, Sarcopenia and Muscle 2024年第3期15卷 949-962页

作者： Kung, Mei-Lang Yang, Tai-Hua Lin, Chia-Chi Ho, Jia-Yun Hung, Tzu-Chi Chang, Chih-Hsiang Huang, Kuan-Wen Chen, Chien-Chin Chen, Yun-Wen Department of Medical Education and Research Kaohsiung Veterans General Hospital Kaohsiung Taiwan Department of Biomedical Engineering College of Engineering National Cheng Kung University Tainan Taiwan Department of Orthopedic Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Department of Pharmacology College of Medicine National Cheng Kung University Tainan Taiwan Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan Taiwan

Background: Non-alcoholic fatty liver disease (NAFLd) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLd. Adenosine-to-inosine editing, catalysed by adenosine deaminase acting on RNA (AdAR), is an important post-transcriptional modification of genome-encoded RNA transcripts. Three AdAR gene family members, including AdAR1, AdAR2 and AdAR3, have been identified. However, the functional role of AdAR2 in obesity-associated NAFLd and sarcopenia remains unclear. Methods: AdAR2^+/+/GluR-B^R/R mice (wild type [WT]) and AdAR2^−/−/GluR-B^R/R mice (AdAR2 knockout [KO]) were subjected to feeding with standard chow or high-fat diet (HFd) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross-sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. Results: AdAR2 KO mice fed with HFd exhibited lower body weight (−7.7%, P < 0.05), lower liver tissue weight (−20%, P < 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (−24%, P < 0.001) and liver injury (P < 0.01). AdAR2 KO mice displayed protection against HFd-induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P < 0.01), muscle strength (P < 0.05), muscle endurance (P < 0.001) and fibre size (CSA;P < 0.0001) were improved in AdAR2 KO mice fed with HFd compared with WT mice fed with HFd. Muscle atrophy-associated transcripts, such as forkhead box protein O1, muscle atrophy F-box/atrogin-1 and muscle RING finger 1/tripartite motif-containing 63, were decreased in AdAR2 KO mice fed with HFd compare

关键词： AdAR2 diabetes inflammation muscle atrophy NAFLd SAA1

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A METHOd FOR ASSESSING RESIdUAL NAPL BASEd ON ORGANIC-CHEMICAL CONCENTRATIONS IN SOIL SAMPLES

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GROUNd WATER MONITORING ANd REMEdIATION 1991年第2期11卷 128-136页

作者： FEENSTRA, S MACKAY, dM CHERRY, JA Stan Feenstra is a hydrogeochemist and president of Applied Groundwater Research Ltd. in Mississauga Ontario He received a B.Sc. in earth sciences and an M.Sc. in hydrogeology from the University of Waterloo in 1978 and 1980 respectively and was designated a Certified Ground Water Professional by AGWSE in 1989. Since 1980 he has been a ground water consultant with Golder Associates in Mississauga Ontario and Zenon Environmental in Burlington Ontario and founded Applied Groundwater Research Ltd. in 1987. Feenstra specializes in the hydrogeochemical evaluation of ground water contamination at waste disposal facilities and chemical spill sites. He is currently a Ph.D. candidate in hydrogeology and research associate in the Waterloo Centre for Ground Water Research at the University of Waterloo (Waterloo Ontario N2L 3G1) and is involved in research related to the behavior of dense organic solvents in ground water. Douglas M. Mackay is an adjunct professor at the Waterloo Centre for Groundwater Research at the University of Waterloo Waterloo Ontario (N2L3G1). Dr. Mackay received a B.S. in engineering and M.S. and Ph.D. in civil engineering from Stanford University in 1970 1973 and 1981 respectively. From 1986 to 1990 he was a faculty member of the Environmental Science and Engineering Program of the UCLA School of Public Health. His research focuses on field studies of transport and fate of organic chemicals in ground water various scale studies of decontamination of soil and ground water and ground water monitoring technologies. John A. Cherry is a professor at the Waterloo Centre for Groundwater Research at the University of Waterloo Waterloo Ontario (N2L 3G1). He received his B.S. in geological engineering from the University of Saskatchewan in 1962. He received his M.S. from the University of California at Berkeley in 1964 and his Ph.D. from the Department of Geology at the University of Illinois in 1966. His research interests include the field study and modeling of contaminants in ground wat

Ground water contamination by non-aqueous phase liquid (NAPL) chemicals is a serious concern at many industrial facilities and waste disposal sites. NAPL in the form of immobile residual contamination, or pools of mobile or potentially mobile NAPL, can represent continuing sources of ground water contamination. In order to develop rational and cost-effective plans for remediation of soil and ground water contamination at such sites, it is essential to determine if non-aqueous phase liquid (NAPL) chemicals are present in the subsurface and delineate the zones of NAPL contamination. The presence of NAPL pools may be evident as a floating or sinking phase in monitoring wells. The residual NAPL contamination may be identified in soil samples if residual contents are high and contaminated zones in the soil cores are thick. However, visual identification may not be effective if residual contents ar elow or if the NAPL residual is distributed heterogeneously in the samples. The chemical analysis of soil samples provides a measure of the total chemical concentration in the soil but cannot determine directly whether NAPL is present in the samples. Qualitatively, soil analyses that exhibit chemical concentrations in the percent range or > 10,000 mg/kg would generally be considered to indicate the presence of NAPL. However, the results of soil analyses are seldom used in a quantitative manner to assess the possible presence of residual NAPL contamination when chemical concentrations are lower and the presence of NAPL is not obvious. The assessment of the presence of NAPL in soil samples is possible using the results of chemical and physical analyses of the soil, and the fundamental principles of chemical partitioning in unsaturated or saturated soil. The method requires information on the soil of the type typically considered in ground water contamination studies and provides a simple tool for the investigators of chemical spill and waste disposal sites to assess whether soil

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Ser38-His93-Asn91 triad confers resistance of JFH1 HCV NS5A-Y93H variant to NS5A inhibitors

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FEBS Journal 2024年第6期291卷 1264-1274页

作者： Lee, Wei-Ping Tsai, Keng-Chang Liao, Shi-Xian Huang, Yi-Hsiang Hou, Ming-Chih Lan, Keng-Hsin Department of Medical Research Taipei Veterans General Hospital Taiwan Institute of Biochemistry and Molecular Biology School of Life Sciences National Yang Ming Chiao Tung University Taipei Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei Taiwan The Ph.D. Program for Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taiwan Division of Gastroenterology and Hepatology Department of Medicine Taipei Veterans General Hospital Taiwan School of Medicine College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Pharmacology College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan

HCV NS5A is a dimeric phosphoprotein involved in HCV replication. NS5A inhibitors are among direct-acting antivirals (dAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, but the precise mechanism remains unclear. In this report, we proposed a Ser38-His93-Asn91 triad to dissect the mechanism. Using pymol 1.3 software, the homology structure of JFH1 NS5A was determined based on the dimer structure of genotype 1b extracted from the database Protein dataBank (***/pdbsum) with codes 1ZH1 and 3FQM/3FQQ. FLAG-NS5A-WT failed to form dimer in the absence of nonstructural proteins from subgenomic replicon (NS3-5A);however, FLAG-NS5A-Y93H was able to form dimer without the aid of NS3-5A. The Ser38-His93-Asn91 triad in the dimer of the Y93H variant predicts a structural crash of the cleft receiving the NS5A inhibitor daclatasvir. The dimerization assay revealed that the existence of JFH1-NS5A-1ZH1 and -3FQM homology dimers depended on each other for existence and that both NS5A-WT 1ZH1 and 3FQM dimers cooperated to facilitate RNA replication. However, NS5A-Y93H 1ZH1 alone could form dimer and conduct RNA replication in the absence of the 3FQM structure. In conclusion, this study provides novel insight into the functional significance of the Ser38-His93-Asn91 triad in resistance of the Y93H variant to NS5A inhibitors. © 2023 Federation of European Biochemical Societies.

关键词： dimerization drug resistance Hepatitis C virus inhibitor NS5A Y93H mutant

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The Journal of Rural Health 1987年第2期3卷 47-60页

作者： Hertzler, Ann A. Caldwell, John S. Mark‐Teo, Miew Leng ANN A. HERTZLER Ph.D. R.D. is an Associate Professor of Human Nutrition and Foods and an Extension Specialist in Food and Nutrition College of Human Resources Virginia Polytechnic Institute and State University. Dr. Hertzler completed her undergraduate degree at Pennsylvania State University her M.S. degree at Drexel University and received her Ph.D. from Cornell University. She has previously served on the faculties of Drexel University Nor them Illinois University and the University of Missouri-Columbia. She spent a sabbatic year on the faculty at the University of Hawaii. She also has experience as a therapeutic dietitian in the United States and in London England. Dr. Hertzler has published extensively in nutrition related journals JOHN A. CALDWELL Ph.D. is Title XI1 Chairman for International Vegetable Production in the Department of Horticulture at Virginia Polytechnic Institute and State University. Dr. Caldwell has degrees from the University of Kansas Tokyo University and Louisiana State University. He has worked a total of approximately 10 years in The Philippines Taiwan Japan and The Gambia West Africa. He has written extensively on farming systems research and extension MIEW LENG MARK-TEO M.S. received her B.S. and M.S. degrees from Virginia Polytechnic Institute and State University. She has done additional studies in dietetics in Saskatoon. Currently she is an instructor in the Early Childhood Development Program in the Gabriel Dumont Institute in Saskatoon-Teo

A case study approach was used to study 10 limited resource farm families to identify factors relative to the farm family situation that are associated with adequate or inadequate food habits. dietary measures were developed and adequacy of diets was analyzed in relation to gender, women's off‐ or on‐farm employment, predominant farm activities, and cohesiveness. Traditional families, with two adults present and the women employed on the farm, had the most adequate diets and higher cohesiveness ratings. Families in transition, with women employed off the farm or headed by widowed women farmers, had the poorest diets nutritionally and tended to have lower cohesiveness ratings. The presence of a food source raised or grown for income purposes did not guarantee the use of the food for family consumption. Copyright © 1987, Wiley Blackwell. All rights reserved

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MEdICAL ANTHROPOLOGY HEALTH POLICY ANd THE STATE: A CASE STUdY OF SUdAN

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Review of Policy research 1981年第1期1卷 47-65页

作者： Gruenbaum, Ellen ELLEN GRUENBAUM spent five years in Sudan lecturing at the University of Khartoum and researching rural health services. Since 1979 she has been a research associate in the Department of Community Medicine at the University of Connecticut Health Center where she served as editor of the Comparative Health Systems Newsletter and coordinated the Cross-National Study of Health Systems Program. She received her B.A. from Stanford University M.A. in anthropology from the University of Connecticut and is currently completing her Ph.D. in anthropology at the University of Connecticut. The title of her dissertation is “Health Services” Health and Development in Sudan: The Impact of the Gezira Irrigated Scheme.

Medical anthropologists have frequently limited themselves to studying cultural factors in illness, curing or resistance to the acceptance of modern Western medical services. This prevailing “socioculturalist” approach has serious analytical shortcomings resulting from underestimating the importance of the social formations in which cultural factors occur. Consequently, the policy recommendations produced in medical anthropology are often crippled by theoretical limitations. It is argued that the historically specific constellation of social relations governing production and the appropriation and distribution of the economic surplus‐commonly embodied in the functions of the state‐have profound effects on the pattern of health and illness as well as on the availability of health services. In underdeveloped countries an analysis of the role of the state in health is especially important, since the organs of state power play a stronger role in health care than in countries with well developed markets for medical services. In the case of Sudan, the interests of the state in colonial and postindependence periods required a development strategy involving large‐scale irrigated agriculture utilizing seasonal migrant labor. The labor and health policies aimed at economic productivity and political stability are analyzed here in relation to the adverse health effects and serious maldistribution of health services which resulted. Copyright © 1981, Wiley Blackwell. All rights reserved

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diosgenin Reduces Acute Kidney Injury and Ameliorates the Progression to Chronic Kidney disease by Modifying the NOX4/p65 Signaling Pathways( vol 72,pg 17444,2024)

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JOURNAL OF AGRICULTURAL ANd FOOd CHEMISTRY 2024年第43期72卷 24130-24130页

作者： Chiang, Chih-Hung Lan, Tien-Yun Hsieh, Jung-Hung Lin, Su-Chu Chen, Jaw-Wen Chang, Ting-Ting Division of Urology Department of Surgery and Department of Research and Development Taoyuan General Hospital Ministry of Health and Welfare Taoyuan 330 Taiwan Department of Urology National Taiwan University Hospital Taipei 100 Taiwan Department and Institute of Pharmacology School of Medicine National Yang Ming Chiao Tung University Taipei 112 Taiwan Department of Surgery Taipei Veterans General Hospital Yuan-Shan Branch Yilan 264 Taiwan Department of Medical Research and Education Taipei Veterans General Hospital Yuan-Shan Branch Yilan 264 Taiwan Cardiovascular Research Center Taipei Medical University Hospital and Taipei Medical University Taipei 110 Taiwan Division of Cardiology Department of Medicine and Department of Research Taipei Medical University Hospital Taipei 110 Taiwan Division of Cardiology Department of Medicine Taipei Veterans General Hospital Taipei 112 Taiwan Cardiovascular Research Center National Yang Ming Chiao Tung University Taipei 112 Taiwan Biomedical Industry Ph.D. Program National Yang Ming Chiao Tung University Taipei 112 Taiwan

Acute kidney injury (AKI), if not well controlled, may progress to chronic kidney disease (CKd). diosgenin is a natural phytosteroid sapogenin from plants. This study aimed to investigate the mechanistic effects of diosgenin on AKI and AKI related development of CKd. The mouse model of ischemia/reperfusion (I/R)-induced AKI was used, and its progressive changes were followed. Human renal proximal tubular epithelial cells were used, and hypoxia stimulation was applied to mimic the in vivo I/R. diosgenin, given after renal injury, preserved kidney function, as evidenced by a reduction in serum levels of BUN, creatinine, and UACR in both acute and chronic phases of AKI. diosgenin alleviated I/R-induced tubular injury and prevented macrophage infiltration and renal fibrosis in AKI mice. Furthermore, diosgenin also mitigated the development of CKd from AKI with reduced renal expression of inflammatory, fibrotic, and epithelial–mesenchymal transition markers. In human renal tubular epithelial cells, diosgenin downregulated the hypoxia-induced oxidative stress and cellular damages that were dependent on the NOX4/p65 signaling pathways. Taken together, diosgenin treatment reduced I/R-induced AKI and ameliorated the progression to CKd from AKI probably by modifying the NOX4/p65 signaling pathways.

关键词： acute kidney injury chronic kidney disease diosgenin fibrosis inflammation

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Community Service and Political Identity development in Adolescence

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Journal of Social Issues 2010年第3期54卷 495-512页

作者： Miranda Yates James Youniss Covenant House MIRANDA YATES received a Ph.D. in Human Development from the Catholic University of America. She is currently a program supervisor at Covenant House in California. Her research interests are in the areas of moral and political development and identity formation. The Catholic University of America JAMES YOUNISS is Professor of Psychology and Director of the Life Cycle Institute at the Catholic University of America. With Miranda Yates and Jeffrey McLellan he has studied the effects of community service in youth.

This article addresses the interconnection of political socialization and identity development. We begin with Erikson's work, which identified the development of political commitment in adolescence as a key aspect of identity formation. We then seek to shed light on the social processes through which youth become engaged in political activities and issues. We discuss the influences of family and peers as well as participation in community service and other civic activities. The development of social responsibility and agency, and an understanding of the complexity of social issues are considered as important facets of political commitment. data from a case study of Black urban adolescents who participated in a year-long service learning program are used to illustrate our perspective. We conclude that social-historical context, instantiated in social relationships and actions, plays a pivotal role in the process and shape of political socialization and identity formation.

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RIPPLES ANd TRICKLES: IMPACT ASSESSMENT ANd POLICY ANALYSIS IN ASIA

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Review of Policy research 1988年第1期8卷 116-125页

作者： Koppel, Bruce Research Associate at the East-West Center. He received his Ph.D. in rural sociology from Cornell University. He has pub- lished and consulted widely on issues of rural development planning and impact assessment in Asia. He is currently leading a research program on the transformation of rural Asia.

Advocacy of impact assessment has exceeded documentation of the un‐ even influence of impact assessment information on policy analysis. Start‐ ing with a simple distinction between pluralist and hierarchical policy systems, an analysis is presented of relations between impact assessment and policy processes in Asia, with special emphasis on the philippines. Conclusions are drawn about the political significance of impact assessment information in different policy contexts. Copyright © 1988, Wiley Blackwell. All rights reserved

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16-Hydroxybriaranes from the octocoral Briareum stechei

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phytochemistry Letters 2023年第1期57卷 92-95页

作者： Liu, Chia-Jung Wang, Chien-Chiao Chang, Chun-Feng Zhang, Mingzi M. Tsou, Lun Kelvin Wen, Zhi-Hong Hwang, Tsong-Long Chen, You-Ying Sung, Ping-Jyun Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung 804201 Taiwan National Museum of Marine Biology and Aquarium Pingtung 944401 Taiwan Graduate Institute of Natural Products College of Medicine Chang Gung University Taoyuan 333323 Taiwan Graduate Institute of Biomedical Sciences College of Medicine Chang Gung University Taoyuan 333323 Taiwan Division of Urology Department of Surgery Kaohsiung Armed Forces General Hospital Kaohsiung 802301 Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Zhunan 350401 Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Miaoli Zhunan 350401 Taiwan Department of Anesthesiology Chang Gung Memorial Hospital Taoyuan 333008 Taiwan Research Center for Chinese Herbal Medicine Graduate Institute of Healthy Industry Technology College of Human Ecology Chang Gung University of Science and Technology Taoyuan 333324 Taiwan Department of Chemical Engineering Ming Chi University of Technology New Taipei 243303 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung 404394 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung 807378 Taiwan Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City 242062 Taiwan

Two new 16-hydroxybriaranes, 11-dehydroxybriavioid B (1) and 12-epi-briastecholide L (2), have been isolated from an algal-containing octocoral identified as Briareum stechei. The structures of metabolites 1 and 2 were corroborated by extensive 2d-NMR studies and comparison with literature data. Briarane 2 was found to reduce the release of inducible nitric oxide synthase (iNOS) to 87.92 %, at a concentration of 10 μM. © 2023 phytochemical Society of Europe

关键词： Briarane Briareum stechei Briastecholide Briavioid iNOS

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Curcumin suppresses doxorubicin-induced epithelial-mesenchymal transition via the inhibition of TGF-β and PI3K/AKT signaling pathways in triple-negative breast cancer cells

Curcumin suppresses doxorubicin-induced epithelial-mesenchym...

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作者： Chen, Wei-Chih Lai, Ying-An Lin, Ying-Chao Ma, Jui-Wen Huang, Li-Fen Yang, Ning-Sun Ho, Chi-Tang Kuo, Sheng-Chu Way, Tzong-der Ph.D. Program for Cancer Biology and Drug Discovery College of Medicine China Medical University Taichung 40402 Taiwan Department of Biological Science and Technology College of Life Sciences China Medical University Taichung 40402 Taiwan Division of Neurosurgery Buddhist Tzu Chi General Hospital Taichung Branch Taichung 427 Taiwan Institute of Biochemistry College of Life Science National Chung Hsing University Taichung 402 Taiwan Graduate School of Biotechnology and Bioengineering Yuan Ze University Taoyuan 320 Taiwan Agricultural Biotechnology Research Center Academia Sinica Taipei 115 Taiwan Department of Food Science Rutgers State University of New Jersey New Brunswick NJ 08901 United States Graduate Institute of Pharmaceutical Chemistry College of Pharmacy China Medical University Taichung 40402 Taiwan Department of Health and Nutrition Biotechnology College of Health Science Asia University Taichung 413 Taiwan

Triple-negative breast cancer (TNBC) is defined by a lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER 2). Therefore, targeted therapy agents may not be used, and therapy is largely limited to chemotherapy. doxorubicin treatment consequently acquires undesired malignance characteristics [i.e., epithelial-mesenchymal transition (EMT) and multi-drug resistance]. Our results illustrated that doxorubicin triggered EMT and resulted in the acquisition of a mesenchymal phenotype in TNBC cells. Moreover, we found that transforming growth factor-β (TGF-β) and PI3K/AKT signaling pathways were acquired for doxorubicin-induced EMT. Interestingly, we found that curcumin suppressed doxorubicin-induced EMT. Curcumin reversed doxorubicin-induced morphological changes, inhibited doxorubicin-induced downregulation of E-cadherin expressions, and inhibited doxorubicin-induced upregulation of vimentin expression. We also found that curcumin inhibited doxorubicin-induced EMT by inhibiting the TGF-β and PI3K/AKT signaling pathways. Moreover, curcumin enhanced the antiproliferative effects of doxorubicin in TNBC cells. In summary, our results suggest that doxorubicin in combination with curcumin may be a potential therapy for TNBC. © 2013 American Chemical Society.

关键词： Chemotherapy

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