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12/4/2017 7:57:42 PM | Browse: 1233 | Download: 1298
Publication Name World Journal of Gastroenterology
Manuscript ID 36729
Country/Territory United States
Category Gastroenterology and 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
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
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.
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
2017-10-24 04:03
Peer-Review Started
2017-10-25 02:40
To Make the First Decision
2017-11-15 01:26
Return for Revision
2017-11-17 01:11
2017-11-24 18:34
Second Decision
2017-12-04 08:48
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief
2017-12-04 19:57
Articles in Press
2017-12-04 19:57
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript
2018-01-08 07:29
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.
Permissions For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
Publisher Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Website http://www.wjgnet.com
Assistant Editor Xiang Li
Science Editor Ke Chen (Quit in 2017)
Reviewer Code 03648851, and 03022180
Editorial Director Jin-Lei Wang
Journal Chief Editor
Company Chief Editor Lian-Sheng Ma
Language Editor
Production Editor Yu-Jie Ma
Responsible Production Editor Yu-Jie Ma
Responsible Science Editor Ya-Juan Ma
Proofing Editorial Director Jin-Lei Wang
Proofing Editor-in-Chief Lian-Sheng Ma
Full Article (PDF) WJG-24-195.pdf
Full Article (Word) WJG-24-195.doc
Manuscript File 36729-Review.docx
Answering Reviewers 36729-Answering reviewers.pdf
Audio Core Tip 36729-Audio core tip.m4a
Conflict-of-Interest Disclosure Form 36729-Conflict-of-interest statement.pdf
Copyright License Agreement 36729-Copyright license agreement.pdf
Institutional Animal Care and Use Committee Approval Form or Document 36729-Institutional animal care and use committee statement.pdf
Institutional Review Board Approval Form or Document 36729 Approval and ethical review.pdf
Non-Native Speakers of English Editing Certificate 36729-Non-Native Speakers of English Editing Certificate.pdf
Peer-review Report 36729-Peer-review(s).pdf
Scientific Editor Work List 36729-Scientific editor work list.pdf