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| 1 | Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis显示文摘AIM To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis.METHODS Hepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone(nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry. Expression of type?Ⅰ?collagen was determined by quantitative PCR. Activation of hepatic stellate cells was assessed by alpha-smoothmuscle actin(SMA) levels. Liver peroxisome proliferator activated receptor-gamma coactivator 1 alpha(PGC1α) was determined by Western blotting.RESULTS Treatment of mice with CCl4 resulted in hepatic fibrosis as evidenced by increased liver enzyme levels(ALT and AST), and increased liver collagen and SMA. Monotherapy with either serelaxin or rosiglitazone for 2 wk was generally without effect. In contrast, the combination of serelaxin and rosiglitazone resulted in significantly improved ALT levels(P < 0.05). Total liver collagen content as determined by Sirius red staining revealed that only combination treatment was effective in reducing total liver collagen(P < 0.05). These results were supported by immunohistochemistry for type?Ⅰ?collagen, in which only combination treatment reduced fibrillar collagen levels(P < 0.05). The level of hepatic stellate cell activation was modestly, but significantly, reduced by serelaxin treatment alone, but combination treatment resulted in significantly lower SMA levels. Finally, while hepatic fibrosis reduced liver PGC1α levels, the combination of serelaxin and rosiglitazone resulted in restoration of PGC1α protein levels.CONCLUSION The combination of serelaxin and rosiglitazone treatment for 2 wk was effective in significantly reducing established hepatic fibrosis, providing a potential new treatment strategy. | Robert G Bennett Ronda L Simpson Frederick G Hamel | 2017 | World Journal of Gastroenterology2017，23，22： | 2 |
| 2 | The core competence of the corporation 显示文摘 | PRAHALAD C K HAMEL G | 1990 | Harvard Business Review1990，68，3： | 1 |
| 3 | The core competence of the corporation 显示文摘 | Prahalad C K Hamel G | 1990 | Harvard Business Review1990，68，3： | 1 |
| 4 | The Why,What and How of Management Innovation显示文摘 | HAMEL G | 2006 | Harvard Business Review2006，84，2： | 1 |
| 5 | Soil microbial dynamics in maize growing soil under different tillage and residue management systems显示文摘 | Spedding T A Hamel C Mehuys G R | 2004 | Soil Biology and Biochemistry2004，，36： | 1 |
| 6 | The core competence of the cerpomtion显示文摘 | Prahalad C K Hamel G | 1990 | Harvard Business Review1990，，3： | 1 |
| 7 | Collaborate with your customers and win显示文摘 | Hamel G Doz Y L Prahalad C K | 1989 | Harvard Business Review1989，，61： | 1 |
| 8 | The core competence of the corporations 显示文摘 | Prahalad C K hamel G | 1990 | Harvard Business Review1990，，： | 1 |
| 9 | Debate:duking it out over EVA显示文摘 | EHRBAR Al HAMEL G | 1997 | Fortune1997，，3： | 1 |
| 10 | The Core Compe-tency of the Corporation显示文摘 | Prahalad C.K Hamel G | | 0，，03： | 1 |
| 11 | Collaborate with Your Competitors and Win显示文摘 | Hamel G Doz Y Prahalad C K | 1989 | Harvard Business Review1989，67，1： | 1 |
| 12 | The Core Competence of the Corporation 显示文摘 | Prahalad C K Hamel G | 1990 | Harvard Business Review1990，68，3： | 1 |
| 13 | Competition for competence and inter partner learning with in international strategic alliances 显示文摘 | HAMEL G | 1991 | Strategic Management Journal1991，，12： | 1 |
| 14 | Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4 显示文摘 | PETTIT G R S1NGH S B HAMEL E | 1989 | Experientia1989，45，2： | 1 |
| 15 | NH3, N2O and CH4 emissions during passively aerated composting of straw-rich pig manure显示文摘 | Szanto G L Hamelers H M Rulkens W H | 2007 | Bioresource Technology2007，98，14： | 1 |
| 16 | The core competence of the corporation显示文摘 | Prahalad C K Hamel G | 1990 | Harvard Business Review1990，，3： | 1 |
| 17 | The core competence of the corporation显示文摘 | Prahalad C K Hamel G | 1990 | Harvard Business Review1990，3，： | 1 |
| 18 | Thrombolysis or heparin therapy or massive pulmonary embolism with right ventricular dilatation 显示文摘 | HAMEL E PACOURET G VINCENTELLI D | 2001 | Chest2001，120，： | 1 |
| 19 | The Core Competence of the corporation 显示文摘 | Pahalad C K & Hamel G | 1990 | Harvard Business Review1990，，3： | 1 |
| 20 | The core competence of the corporation 显示文摘 | Prahalad C K and Hamel G | 1990 | Harvard Business Review1990，，： | 1 |
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