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| 1 | Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart显示文摘出生后的心通过 hypertrophic 生长适应应力和超载,可能病理学或有益的一个过程(生理的肥大) 。生理的肥大改进心脏的性能在健康并且 diseased 个人,然而,宣传这有利改编的机制仍然保持糟糕定义。我们识别 cytokine cardiotrophin (CT1 ) 1 作为能够包括导致的导出 cardiomyocyte 的 angiogenic 信号的心肌层,和刺激的短暂、可逆的肥大概括心的生理的生长的特色的一个因素增加了由脉管形成。CT1 的能力从 caspase 激活的调停 CK2 的制止发源导致生理的肥大,阻止到无限制的病理学的生长的转变。外长的 CT1 蛋白质交货稀释了病理并且在正确的心失败的一个严格的模型恢复了可收缩的功能,建议为这难处理的心脏病的一种新奇处理选择。 | Mohammad Abdul-Ghani Colin Suen Baohua Jiang Yupu Deng Jonathan J Weldrick Charis Putinski Steve Brunette Pasan Femando Tom T Lee Peter Flynn Frans H H Leenen Patrick G Burgon Duncan J Stewar Lynn A Megeney | 2017 | Cell Research2017，27，10： | 8 |
| 2 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 3 | Chronic overexpression of PNPLA3^sup I148M^ in mouse liver causes hepatic steatosis显示文摘 | Li John Zhong Huang Yongcheng Karaman Ruchan Ivanova Pavlina T Brown H Alex Roddy Thomas Castro-Perez Jose Cohen Jonathan C Hobbs Helen H | 2012 | EN2012，，11： | 3 |
| 4 | Defying gravity显示文摘 | Jonathan H C Stephen F T | 1998 | Civil Engineering1998，68，2： | 1 |
| 5 | Thickness and growth temperature dependence of structure and magnetism in FePt thin films 显示文摘 | Michael F T Wenyaung L Jonathan A H | 2003 | J App Phys2003，93，： | 1 |
| 6 | Phosphorylation of phosp- hazenes and its effects on thermal properties and rire re- tardant behavior显示文摘 | Allcock H R Jonathan P T | 2007 | Polymer Engine ering and Science2007，40，： | 1 |
| 7 | Tensile-Reinforcement Effect on Bridge-Approach Settlement 显示文摘 | Jonathan T H Wu | 1993 | Journal of Geotechnical Engineering1993，119，4： | 1 |
| 8 | Soil resources heterogeneity in the Mojave Desert显示文摘 | Jonathan H T Robert S N Stanley D S | 2002 | Journal of Arid Environments2002，52，3： | 1 |
| 9 | Strand spaces:proving security protocols correct显示文摘 | Fdbrega J T Jonathan C H Joshua D G | 1999 | Journal of Computer Security1999，7，23： | 1 |
| 10 | Components for high speed atomic force microscopy显示文摘 | GEORG E GEORG S JOHANNES H TZVETAN I KATARINA I ROH P NIELS H JONATHAN A PHILIPP T IVO W PAUL K | 2006 | Ultramicroscopy2006，106，： | 1 |
| 11 | Bearing capacity of rectangular footings on geogrid–reinforcedsand显示文摘 | YETIMOGLU T JONATHAN T H W SAGLAMER A | 1994 | Journal of Geotechnical Engineering1994，120，20： | 1 |
| 12 | Paleoclimatic evidence for future ice-sheet instability and rapid sea-level rise显示文摘 | JONATHAN T O BETTE L O GIFFORD H M | 2006 | Science2006，311，5768： | 1 |
| 13 | A method for evaluating alternative landscape management scenarios in relation to the biodiversity conservation of habitats显示文摘 | Janet H Joseph T Jonathan M | 2007 | Ecological Economics2007，61，23： | 1 |
| 14 | A two-di- mensional Neighborhood Preserving Projection for appear- ance-based face recognition 显示文摘 | Zhang H Jonathan Wu Q M Chow T W S | 2012 | Pattern Recognition2012，45，5： | 1 |
| 15 | Model for end-stage liver disease score fails to predict perioperative outcome after hepatic resection for hepatocellular carcinoma in patients without cirrhosis显示文摘 | SWEE H T BRETT C S JONATHAN S | 2008 | The American Journal of Surgery2008，195，： | 1 |
| 16 | Soil resourcesheterogeneity in the Mojave Desert显示文摘 | Jonathan H T Robert S N Stanley D S | 2002 | Journal of AridEnvironments2002，52，3： | 1 |
| 17 | Defying Gravity显示文摘 | Jonathan H C Stephen F T | 1998 | Civil Engineering1998，68，2： | 1 |
| 18 | Synchronous primary cancers of the endometrium and ovary: a single institution review of 84 cases显示文摘 | Pamela T Soliman Brian M Slomovitz Russell R Broaddus Charlotte C Sun Jonathan C Oh Patricia J Eifel David M Gershenson Karen H Lu | 2004 | Gynecologic Oncology2004，，2： | 1 |
| 19 | GRS bridge abutments--an effective means to alleviate bridge approach settlement显示文摘 | Sam M B Helwany Jonathan T H Wu Burkhard Froessl | 2003 | Geotextiles and Geomembranes2003，，21： | 1 |
| 20 | Image segmentation by Dirichlet process mixture model with generalised mean 显示文摘 | ZHANG H JONATHAN W Q M NGUYEN T M | 2014 | Iet image processing2014，8，8： | 1 |
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