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1/16/2018 12:25:31 AM | Browse: 695 | Download: 627
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Received |
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2017-10-24 04:03 |
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Peer-Review Started |
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2017-10-25 02:40 |
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To Make the First Decision |
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2017-11-15 01:26 |
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Return for Revision |
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2017-11-17 01:11 |
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Revised |
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2017-11-24 18:34 |
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Second Decision |
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2017-12-04 08:48 |
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Accepted by Journal Editor-in-Chief |
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Accepted by Company Editor-in-Chief |
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2017-12-04 19:57 |
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Articles in Press |
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2017-12-04 19:57 |
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Publication Fee Transferred |
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Edit the Manuscript by Language Editor |
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Typeset the Manuscript |
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2018-01-08 07:29 |
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Publish the Manuscript Online |
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2018-01-14 05:07 |
| ISSN |
1007-9327 (print) and 2219-2840 (online) |
| Open Access |
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
| Copyright |
© The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. |
| Article Reprints |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/247
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| Permissions |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
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| Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
| Website |
http://www.wjgnet.com |
| Category |
Gastroenterology & Hepatology |
| Manuscript Type |
Basic Study |
| Article Title |
INT-767 improves histopathological features in a diet-induced ob/ob mouse model of biopsy-confirmed non-alcoholic steatohepatitis
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| Manuscript Source |
Invited Manuscript |
| All Author List |
Jonathan D Roth, Michael Feigh, Sanne S Veidal, Louise K D Fensholdt, Kristoffer T G Rigbolt, Henrik H Hansen, Li Chen, Mathieu Petitjean, Weslyn W Friley, Niels Vrang, Jacob Jelsing and Mark Young |
| Funding Agency and Grant Number |
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| Corresponding Author |
Henrik H Hansen, PhD, Senior Scientist, Pharmacology, Gubra, Kongevej 11B, Hoersholm DK-2970, Denmark. hbh@gubra.dk |
| Key Words |
Non-alcoholic steatohepatitis; INT-767; Obeticholic acid; Liver biopsy; FXR; TGR5; Mouse model |
| Core Tip |
The studies contained herein evaluated the preclinical efficacy of INT-767, a dual FXR/TGR5 agonist, in a mouse model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis (NASH). Rigorous analyses for NASH histological endpoints and markers were conducted including blinded qualitative and quantitative scoring using standard microscopy as well as advanced morphometric fibrosis and steatosis features using second harmonic generation imaging and two-photon fluorescence excitation. INT-767 promoted dose-dependent improvements in fibrosis, steatosis, inflammation and ballooning degeneration. The effects of INT-767 and obeticholic acid (OCA) were also compared for histological efficacy, gene expression and tissue distribution. The nonclinical data suggest that INT-767 is a more potent FXR receptor agonist, and is expected to have therapeutic effect at lower doses than OCA. |
| Publish Date |
2018-01-14 05:07 |
| Citation |
Roth JD, Feigh M, Veidal SS, Fensholdt LKD, Rigbolt KT, Hansen HH, Chen LC, Petitjean M, Friley W, Vrang N, Jelsing J, Young M. INT-767 improves histopathological features in a diet-induced ob/ob mouse model of biopsy-confirmed non-alcoholic steatohepatitis. World J Gastroenterol 2018; 24(2): 195-210 |
| URL |
http://www.wjgnet.com/1007-9327/full/v24/i2/195.htm |
| DOI |
http://dx.doi.org/10.3748/wjg.v24.i2.195 |
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