|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | 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 |
| 2 | Matrix metalloproteinase - 1, -3, - 13 and aggrecanase - 1 and -2 are differentially expressed in experimental osteoarthritis显示文摘 | Bluteau G Conrozier T Mathieu P | 2001 | Biochirn Biophy Act2001，1562，： | 1 |
| 3 | Empowerment and team effectiveness: An empirical test of an inte- grated model显示文摘 | Mathieu J E Gilson L L Ruddy T M | 2006 | Journal of Applied Psychology2006，91，1： | 1 |
| 4 | Team Effectiveness 1997-2007:A Review of Recent Advancements and a Glimpse into the Future显示文摘 | Mathieu J Maynard M.T Rapp T Gilson L | | 0，，3： | 1 |
| 5 | The influence of shared mental models on team process and performance显示文摘 | Mathieu J E Heffner T S Goodwin G F | 2000 | Journal of Applied Psychology2000，85，2： | 1 |
| 6 | An isotopic study (2H and ^18O) of water movements in clayey soils under a semiarid climate显示文摘 | MATHIEU R BARIAC T | 1996 | Water Resource Research1996，32，4： | 1 |
| 7 | Rheologic behavior of os- teoarthritic synovial fluid after addition of hyaluronic acid a pilot study 显示文摘 | Mathieu P Conrozier T Vignon E | 2009 | Clin Orthop Relat Res2009，467，11： | 1 |
| 8 | Team Effectiveness 1997--2007: A Review of Recent Advancements and a Glimpse into the Future 显示文摘 | Mathieu J Maynard T M Rapp T | 2008 | Journal of Management2008，34，3： | 1 |
| 9 | Matrix metalloproteinase - 1 ,- 3,- 13 and aggrecanase - 1 and - 2 are differentially expressed in experimental osteoarthritis显示文摘 | Bluteau G Conrozier T Mathieu P | 2001 | Biochim Biophy Acta(General Subjects)2001，1526，2： | 1 |
| 10 | Rheologic behavior of osteoar- thritic synovial fluid after addition of hyaluronic acid : a pilot study显示文摘 | Mathieu P Conrozier T Vignon E | 2009 | Clin Orthop Relat Res2009，467，11： | 1 |
| 11 | Intraluminal pressure increases vascular neuronal nitric oxide synthase expression显示文摘 | Ebrahimian T Mathieu E Silvestre JS | 2003 | J Hypertens2003，21，5： | 1 |
| 12 | Enzymatic Degradation of Etereocopolymers Derived from L -,DL-and Meso-Lactide显示文摘 | SUMING L MATHIEU T HENRI G | 2000 | Polymer Degradation and Stability2000，67，： | 1 |
| 13 | Recent advance in techniques for hyperspectral image processing显示文摘 | Antonio P Jon A B Joseph W B Jason B Lorenzo B Gustavo C V Jocelyn C Mathieu F Paolo G Anthony G Mattia M James C T Giovanna T | 2009 | Remote Sensing of Environment2009，113，： | 1 |
| 14 | Team Effectiveness 1997-2007: A review of recent advancements and a glimpse into the future 显示文摘 | Mathieu J Maynard M T Rapp T & Gilson L | 2008 | Journal of Management2008，34，： | 1 |
| 15 | Transformation of zearalenone to zearalenone-sulfate by Aspergillus spp 显示文摘 | JARD G LIBOZ T MATHIEU F | 2010 | World Mylotoxin J2010，3，2： | 1 |
| 16 | The influence of shared mental models on team process and performance显示文摘 | Mathieu J E Heffner T S Goodwin G F | 2000 | Journal of Applied Psychology2000，85，2： | 1 |
| 17 | Scaling the quality of teammates' mental models:equifinality and normative comparisons显示文摘 | Mathieu J E Heffner T S Goodwin G F | 2005 | Journal of Organizational Behavior2005，26，： | 1 |
| 18 | Enzymatic degradation of stereocopolymers derived from L-,DL-and meso-lactide显示文摘 | MATHIEU T HENRI G | 2000 | Polymer Degradation and Stability2000，67，2： | 1 |
| 19 | Factors predicting long-term efficacy of Hylan GF-20 viscosupplementatien in knee osteoarthritis显示文摘 | Mathieu P Schott AM | 2003 | J Bone Spine2003，70，2： | 1 |
| 20 | The Influence of Shared Mental Models on Team Process and Performance显示文摘 | Mathieu J E Heffner T S Goodwin G F | 2000 | Journal of Applied Psychology2000，85，2： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员