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| 1 | Metabolic and hepatic effects of liraglutide,obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH) in obese mouse models of biopsy-confirmedNASH.METHODS Male wild-type C57 BL/6 J mice(DIO-NASH) and Lep^(ob/ob)(ob/ob-NASH) mice were fed a diet high in trans-fat(40%), fructose(20%) and cholesterol(2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score(NAS) and fibrosis staging system. The mice were kept on the diet and received vehicle, liraglutide(0.2 mg/kg, SC, BID), obeticholic acid(OCA, 30 mg/kg PO, QD), or elafibranor(30 mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1 a1.RESULTS Liraglutide and elafibranor, but not OCA, reduced body weight in both models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA reduced total liver fat, collagen 1 a1, and galectin-3 content, driven by significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported by global gene expression(RNA sequencing) and liver lipid biochemistry.CONCLUSION DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical drug development for NASH. | Kirstine S Tolbol Maria NB Kristiansen Henrik H Hansen Sanne S Veidal Kristoffer TG Rigbolt Matthew P Gillum Jacob Jelsing Niels Vrang Michael Feigh | 2018 | World Journal of Gastroenterology2018，24，2： | 5 |
| 2 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 3 | Socio - economic patterns of sport demandand ggeing 显示文摘 | CHRISTOPH B KIRSTIN H PAMELA W etal | 2010 | Academic literature review2010，7，2： | 1 |
| 4 | Small interfering RNA (siRNA) delivery into routine bone marrow -derived macropha- ges by electroporation 显示文摘 | Melanie W Kirstin C Michael H | 2010 | J Immunological Methods2010，353，12： | 1 |
| 5 | Mesenchymal stem cells: paradoxes of passaging显示文摘 | Elisabeth H Javazon Kirstin J Beggs Alan W Flake | 2004 | Experimental Hematology2004，，5： | 1 |
| 6 | Mesenchymal stem cells : Paradoxes of passaging 显示文摘 | Elisabeth H Javazon Kirstin J Beggs Alan W | 2004 | Experimental Hematol2004，32，： | 1 |
| 7 | Triggering cryptic natu- ral product biosynthesis in microorganisms 显示文摘 | KIRSTIN S CHRISTIAN H | 2009 | Org Biomol Chem2009，7，9： | 1 |
| 8 | Gold complexes with potentially Tri-and Tetradentate phosphinothiolate Ligands显示文摘 | KIRSTIN O LOUISE H | 2000 | Inorg Chem2000，39，： | 1 |
| 9 | Bismuth(III) n-Hexanoate and Tin(H) 2-Ethylhexanoate Initiated Copolymerizations of e-Caprolactone and L-laetide 显示文摘 | Hans R K Kirstin B Heiko H T | 2005 | Macromolecules2005，38，12： | 1 |
| 10 | Diag-nosis and mortality in 47,XYY persons:a registry study显示文摘 | Kirstine Stochholm Svend Juul and Claus H Gravholt | 2010 | Orphanet Journal of Rare Diseases2010，5，： | 1 |
| 11 | 丹麦国家海事博物馆显示文摘丹麦海事博物馆位于独特的历史和空间环境中:在丹麦最重要和最著名的建筑之一克伦堡城堡和文化庭院——一个新的、雄心勃勃的文化中心之间。BIG建议将博物馆放在地下,就在船坞的墙壁外侧,以便将船坞保留为开放的户外展示空间,保存其强有力的结构作为海事博物馆中心。将博物馆这样设置,使它在成为与克伦堡城堡和邻近的文化庭院相联系的文化环境的一部分的同时,彰显自身. | John Pries Jensen Henrik Kania Ariel Joy Norback Wallner Rasmus Pedersen Annette Jensen Dennis Rasmussen Jan Magasanik Jeppe Ecklon Karsten Hammer Hansen Rasmus Rodam Rune Hansen Alina Tamosiunaite Alysen Hiller Ana Merino Armen Menendian Andy Yu Andreas Johansen Baptiste Blot Christian Alvarez Christin Svensson Claudia Hertrich Claudio Moretti Cory Mattheis Eskild Nordbud Felicia Guldberg Finn N■rkj■r Gül Ertekin Jan Borgstr■m James Schrader Johan Cool Jonas M■nster Kirstine Ragnhild Malte Kloe Michael Andersen Michal Kristof Marc Jay Maria Mavriku Masatoshi Oka Oana Simionescu Pablo Labra Peter Rieff Qianyi Lim Sara Sosio Sebastian Latz Tina Lund H■jgaard Tina Troster Todd Bennet Xi Chen Xing Xiong Xu Li Zoltan Kalaszi Iwan Baan Rasmus Hjortshoj Luca Santiago Mora Dragoer Luftfoto Jens Lindhe Lorenzon Boddi Thiks Wolzak 陈子钰(译) | 2019 | 城市环境设计2019，0，2： | 0 |
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