|
|
|
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 | The design of systems to control actively periodic sound transmission into enclosed spaces, Part II: Mechanisms and trends显示文摘 | Snyder S D Hansen C H | 1994 | J Sound and Vibration1994，170，4： | 1 |
| 3 | Active control of vibration transmission in a cylindrical shell显示文摘 | Pan X Hansen C H | 1997 | Journal of Sound and Vibration1997，203，3： | 1 |
| 4 | A modified filtered-x LMS algorithm for active control of periodic noise on-line cancellation path modeling显示文摘 | Qiu Xiaojun Hansen C H | 2000 | Journal of Low Frequency Noise Vibration and Active Control2000，19，1： | 1 |
| 5 | Persistent intrathecal antibody synthesis 15 years after recovering from anti-N-methyl-D- aspartate receptor encephalitis 显示文摘 | Hansen H C Klingbeil C Dalmau J | 2013 | JAMA Neurol2013，70，1： | 1 |
| 6 | Active control of vibration transmission in a cylindrical Shell 显示文摘 | PAN X HANSEN C H | 1997 | Journal of Sound and Vibration1997，203，： | 1 |
| 7 | The response of a Duffing-van derPol oscillator under delayed feedback control显示文摘 | Li Xinye Ji J C Hansen C H | 2006 | Journal of Sound and Vibration2006，291，3： | 1 |
| 8 | Power transmission from a vibrating body to a circular cylin drical shell through passive and active isolators显示文摘 | Howard C Q Hansen C H Pan Jiaqiang | 1997 | Journal of the Aeoustical Society of America1997，101，3： | 1 |
| 9 | Rapid quantification of viable Campylobacter bacteria on chicken carcasses,using real-time PCR and propidium monoazide treatment,as a tool for quantitative risk assessment显示文摘 | JOSEF SEN M H LOFSTROM C HANSEN T B | 2010 | Appl Environ Microbiol2010，76，15： | 1 |
| 10 | Strength of recycled concrete made fromcrushed concrete coarse aggregate显示文摘 | HANSEN T C NARU D H | 1983 | Concrete International1983，1，1： | 1 |
| 11 | Active control of vibration transmission in a cylindrical shell显示文摘 | Pan X Hansen C H | 1997 | Journal of Sound and Vibration1997，203，3： | 1 |
| 12 | Silicate pneumoconiosis in camels显示文摘 | Hansen H J Jama F M Nilsson C | 1989 | J Vet Med series A1989，36，10： | 1 |
| 13 | Distribution of multiple pesticide residues in apple segments after home processing显示文摘 | Rasmusssen R R Poulsen M E Hansen H C B | 2003 | Food Additives and Contaminants2003，20，11： | 1 |
| 14 | Proper- ties of magnetocaloric La(Fe, Co, Si)13 produced by powder metallurgy 显示文摘 | Hansen B R Theil-Kuhn L Bahl C R H | 2010 | Journal of Magnetism and Magnetic Materials2010，322，12： | 1 |
| 15 | Power transmission from a vibrating source through an intermediate flexible panel to a flexible cylinder显示文摘 | Pan Jiaqiang Hansen C H | 1994 | Journal of Vibration and Acoustics1994，116，4： | 1 |
| 16 | Tikhonov regularization and total least squares显示文摘 | Golub G H Hansen P C O'Leary D P | 1999 | SIAM Journal on Matrix Analysis and Applications1999，21，1： | 1 |
| 17 | Wave propagation through cylinder/plate junctions显示文摘 | Tso Y K Hansen C H | 1995 | J Sound Vib1995，186，3： | 1 |
| 18 | Synthesis and pharmacological evaluatin of 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide and N-(2-cyanomethyl-Sulfonyl penyl) acylamide derivatives as potential activators of ATP sensitive potassium channels显示文摘 | SCHOU S C HANSEN H C TAGMOSE T M | 2005 | Bioorg Med Chem2005，13，： | 1 |
| 19 | A modified filtered-x LMS Algorithm for active control of periodic noise with on-line cancellation path modeling,Journal of Low Frequency Noise显示文摘 | C H Hansen | 2000 | Vibration and Active Control2000，，19： | 1 |
| 20 | Identification of omentin as a novel depot specific adipokine in human adipose tissue: possible role in modulating insulin action 显示文摘 | Yang R Z Lee M J Hu H Pray J Wu H B Hansen B C | 2006 | Am J Physiol Endocrinol Metab2006，290，： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员