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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 | 西双版纳傣族及上海汉族群体HLA-DR2相关的DR/DQ单倍型分析显示文摘对44名西双版纳傣族和9名上海地区汉族DK2阳性个体进行了与其相关的DR/DQ单倍型组合的分析。傣族群体中DRBI-DR2亚型分布以*1602与*1502为最常见,其等位基因频率分别为43.6%与,40.0%和汉族群体中以*1501为主明显不同。傣族群体中共检出10种与DR2相关联的DR/DQ单倍型;最常见的是DRB1*1602、DRB5*0101、DQA1*0102、DQB1*0502(34.5%)与汉族及其他群体明显不同,本研究表明傣族不仅具有高频率的DR2,而且与DR2相关联的DRB1、DRB5、DQA1、DQB1单倍型组合有其独特性。 | 范丽安 杨珏琴 姚芳娟 董建中 许玲娣 陈仁彪 M Sirkong R Vongrathna P Longta S Lekmak D Chandanayingyong A Smith J Hansen | 1995 | 中华医学遗传学杂志1995，12，3： | 2 |
| 3 | Virtual-flux-based direct power control of three-phase PWM rectifier显示文摘 | Aalinowski M Kazmierkowski M P Hansen S | 2001 | IEEE Transaction on Industry Applications2001，37，： | 1 |
| 4 | Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development显示文摘 | Hansen L A Alexander N Hogan M E Sundberg J P Dlugosz A Threadgill D W Magnuson T Yuspa S H | | 0，，06： | 1 |
| 5 | Improved and standardized methodology for oil spill fingerprinting显示文摘 | Daling P S Faksness L G Hansen A B | 2002 | Environmental Forensics2002，3，3： | 1 |
| 6 | Rapid lateral expansion of optical luminosity in lightning-induced ionospheric flashes refered to as '' elves' 显示文摘 | lnan U S Barrington-Leigh C P Hansen S | 1997 | Geophysical Research Letters1997，24，： | 1 |
| 7 | Review of the direct sulfation reaction of limestone 显示文摘 | HU G DAM-JOHANSEN K WEDEL S HANSEN J P | 2006 | Prog Energy Combust Sci2006，32，4： | 1 |
| 8 | Patterns of nonclassical MHC antigen presentation显示文摘 | HANSEN T H HUANG S ARNOLD P L | 2007 | Nature Immunology2007，8，6： | 1 |
| 9 | All Optical Wavelength Conversion Schemes for Increased Input Power Dynamic Range显示文摘 | DANIELSEN S L HANSEN P B STUBKJAER K E | 1998 | IEEE Photonics Technology Letters1998，10，01： | 1 |
| 10 | The atmospheric input of trace species to the world ocean显示文摘 | Duce R A Liss P S Merrill J T Atlas L L Buat-Menard P Hicks B B Miller J M Prospero J M Arimoto R Church T M Ellis W Galloway F N Hansen L Jickells T D Knap A H Reinhardt K H Schneider B Soudine A Tokos J J Tsunogai S Wollast R Zhou M | 1991 | Global Biogeochemical Cycles1991，5，： | 1 |
| 11 | How outbreaks can contribute to prevention of nosocornial infection:analysis of 1022 outbreaks显示文摘 | Gastmeier P Stamm-Balderjahn S Hansen S | | 0，，04： | 1 |
| 12 | Vasoconstrictor and vasodilator effects of adenosine in the mouse kidney due to preferential activation of A1 or A2 adenosine receptors显示文摘 | Hansen P B Hashimoto S Oppermann M | 2005 | J Pharmacol Exp Ther2005，315，3： | 1 |
| 13 | Is the temperature-humidity index the best indicator of heat stress in lactating dairy cows in a sub- tropical environment 显示文摘 | Dikmen S Hansen P J | 2009 | Journal of Dairy Science2009，92，1： | 1 |
| 14 | Controlling SOz emission 显示文摘 | Miller S W Hansen J P | 2004 | Cement International2004，，2： | 1 |
| 15 | Nuclear Halos显示文摘 | HANSEN P G JENSEN A S JONSON B | 1995 | Annu Rev Nucl Part Sci1995，45，： | 1 |
| 16 | Highly birefringent index-guiding photonic crystal fibers显示文摘 | Hansen T P Broeng J B libori S E | 2001 | IEEE Photon Technol Lett2001，13，6： | 1 |
| 17 | A heuristic solution to the warehouse location-routing problem显示文摘 | Hansen P H Hegedahl B Hjortkj? r S Obel B | 1994 | European Journal of Operational Research1994，，76： | 1 |
| 18 | Virtual-flux-based direct power control of three -phase PWM rectifiers显示文摘 | Malinowski M Kazmierkowski M P Hansen S | 2001 | IEEE Trans on Industry Applications2001，37，4： | 1 |
| 19 | Centralized power control of wind farm with doubly fed induction generators显示文摘 | Hansen D S(o)rensen P Iov F | | 0，，07： | 1 |
| 20 | Regression in autism: prevalence and associated factors in the CHARGE Study显示文摘 | Hansen RL Ozonoff S Krakowiak P Angkustsiri k Jones C Deprey LJ | 2008 | Ambul Pediatr2008，8，1： | 1 |
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