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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 | Safety and Efficacy of Antigen-Specific Regulatory T-Cell Therapy for Patients With Refractory Crohn’s Disease显示文摘 | Pierre Desreumaux Arnaud Foussat Matthieu Allez Laurent Beaugerie Xavier Hébuterne Yoram Bouhnik Maria Nachury Valérie Brun Hervé Bastian Nathalie Belmonte Michel Ticchioni Agnès Duchange Patricia Morel–Mandrino Virginie Neveu Nathalie Clerget–Chossat Mig | 2012 | Gastroenterology2012，，5： | 4 |
| 3 | Viral evasion of DNA-stimulated innate immune responses显示文摘导出病毒的 nucleic 酸的细胞的察觉到为对病毒感染的早防卫是必要的。在最近的年里,包括周期的 GMP 安培 synthase (cGAS ) 和 gamma-interferon-inducible 蛋白质(IFI16 ) ,察觉到蛋白质的 DNA 的发现导致了房间怎么对带 DNA 染色体的到来的病原体唤起强壮的天生的有免疫力的回答的理解。发信号由 DNA 传感器刺激了取决于适配器蛋白质圈套(干扰素基因的激发器) ,到启用抗病毒的蛋白质的表示,包括类型我干扰素。便于有效感染,病毒发展了大量避免策略,指向的主人 DNA 传感器,适配器蛋白质和抄写因素。在这评论, STING 小径的导致病毒的激活上的当前的文学被介绍,我们讨论在这条抗病毒的小径指向不同的步的最近识别的病毒的避免机制。 | Maria H Christensen Sфren R Paludan | 2017 | Cellular & Molecular Immunology2017，14，1： | 4 |
| 4 | Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes: The LEAD (Liraglutide Effect and Action in Diabetes)-2 study显示文摘 | Nauck Michael Frid Anders Hermansen Kjeld Shah Nalini S Tankova Tsvetalina Mitha Ismail H Zdravkovic Milan Düring Maria Matthews David R | 2009 | Diabetes Care2009，，： | 2 |
| 5 | Effective use of FibroTest to generate decision trees in hepatitis C显示文摘AIM:To assess the usefulness of FibroTest to forecast scores by constructing decision trees in patients with chronic hepatitis C.METHODS:We used the C4.5 classification algorithm to construct decision trees with data from 261 patients with chronic hepatitis C without a liver biopsy.The FibroTest attributes of age,gender,bilirubin,apolipoprotein,haptoglobin,α2 macroglobulin,and γ-glutamyl transpeptidase were used as predictors,and the FibroTest score as the target.For testing,a 10-fold cross validation was used.RESULTS:The overall classification error was 14.9%(accuracy 85.1%).FibroTest's cases with true scores of F0 and F4 were classified with very high accuracy(18/20 for F0,9/9 for F0-1 and 92/96 for F4) and the largest confusion centered on F3.The algorithm produced a set of compound rules out of the ten classification trees and was used to classify the 261 patients.The rules for the classification of patients in F0 and F4 were effective in more than 75% of the cases in which they were tested.CONCLUSION:The recognition of clinical subgroups should help to enhance our ability to assess differences in fibrosis scores in clinical studies and improve our understanding of fibrosis progression. | Dana Lau-Corona Luís Alberto Pineda Héctor Hugo Avilés Gabriela Gutiérrez-Reyes Blanca Eugenia Farfan-Labonne Rafael Núez-Nateras Alan Bonder Rosalinda Martínez-García Clara Corona-Lau Marco Antonio Olivera-Martínez Maria Concepción Gutiérrez-Ruiz Guillermo Robles-Díaz David Kershenobich | 2009 | World Journal of Gastroenterology2009，15，21： | 2 |
| 6 | Langerhans cells utilize CDla and langerin to efficiently present nonpeptide antigens to T cells显示文摘 | Robert E H Peter A S Maria T | 2004 | J Clin Invest2004，113，5： | 1 |
| 7 | Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial显示文摘 | John R Teerlink Gad Cotter Beth A Davison G Michael Felker Gerasimos Filippatos Barry H Greenberg Piotr Ponikowski Elaine Unemori Adriaan A Voors Kirkwood F Adams Maria I Dorobantu Liliana R Grinfeld Guillaume Jondeau Alon Marmor Josep Masip Peter S Pang | 2013 | The Lancet . 2013 (9860)2013，，9860： | 1 |
| 8 | Face Transplation:Clinical Application of the Concept显示文摘 | Maria S Mikael H | 2008 | POLSKI PRZEGL?D CHIRURGICZNY2008，80，10： | 1 |
| 9 | Simple Accurate Expressions for Planar Spiral Inductances显示文摘 | Sunderarajan S M Maria M H Stephen P B | 1999 | IEEE Journal of Soild-state Circuits1999，34，10： | 1 |
| 10 | Microwave reduction of a nickeliferous laterite ore 显示文摘 | MICHAIL S MARIA T RON H | 2012 | Minerals Engineering2012，34，： | 1 |
| 11 | Malignancies after renal transplantation during 33 years at a single center显示文摘 | Gyula Végs? Maria Tóth Márta Hídvégi éva Toronyi Robert Mlanger Elek Dinya András Tóth Ferenc Perner Jen? Járay | 2007 | Pathology & Oncology Research2007，，1： | 1 |
| 12 | Long- term changes in summer phytoplankton communities of the open northern Baltic Sea 显示文摘 | Sanna S Maria L Maija H | 2006 | Estuarine Coastal and Shelt Science2006，71，34： | 1 |
| 13 | A radiation controlled molecular switch for use in gene therapy of cancer显示文摘 | Scott S D Maria lesB Hendry J H | 2000 | Gene Ther2000，7，： | 1 |
| 14 | Safety and Tolerability of Montelukast in Placebo-Controlled Pediatric Studies and Their Open-Label Extensions显示文摘 | Bisgaard H David S Maria L B | 2009 | Pediatr Pulmonology2009，44，： | 1 |
| 15 | Anti-ulcergenic activity of xanthanolide sesquiterpenes from Xanthium cavaniUesii in rats显示文摘 | Favier L S Maria A O M Wendel G H | 2005 | J Ethnopharmacol2005，100，3： | 1 |
| 16 | Autoimmune pancreatitis:an underdiagnosed autoimmune disease with clinical, imaging and serological features 显示文摘 | Maria S Gonzalo H Marcos L | 2010 | Autoimrnunity Reviews2010，9，4： | 1 |
| 17 | Hydroresin dispersions: New emulsifier free binders for aqueous coatings显示文摘 | Bernhard S Maria G R Sylke H | 1995 | Prog Org Coatings1995，26，2： | 1 |
| 18 | Asynahronous development of stigmatic re- ceptivity in the pear(Pyrus communis, Rosaceae) flower显示文摘 | Javier S Pilar R Maria H | 2003 | American Journal of Botany2003，90，1： | 1 |
| 19 | Reinforcing poly(e-caprolactone) nanoflbers with cellulose nanocrystals显示文摘 | Justin O Z Maria S P Youssef H | 2009 | Applied Materials and Interfaces2009，1，9： | 1 |
| 20 | Long-term changes in summer phytoplankton communities of the open northern Baltic Sea显示文摘 | Sanna S Maria L Maua H | 2006 | Estuarin Coastal and Shelf Science2006，71，3： | 1 |
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