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Articles Published Processes
11/24/2020 12:41:21 PM | Browse: 714 | Download: 1671
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Received |
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2020-07-16 22:21 |
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Peer-Review Started |
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2020-07-16 22:22 |
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To Make the First Decision |
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Return for Revision |
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2020-09-14 20:58 |
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Revised |
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2020-09-16 17:24 |
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Second Decision |
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2020-09-30 08:41 |
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Accepted by Journal Editor-in-Chief |
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Accepted by Executive Editor-in-Chief |
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2020-10-05 17:50 |
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Articles in Press |
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2020-10-05 17:50 |
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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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2020-11-16 00:43 |
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Publish the Manuscript Online |
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2020-11-24 12:41 |
ISSN |
1948-5182 (online) |
Open Access |
This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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) 2020. 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 |
Obeticholic acid attenuates human immunodeficiency virus/alcohol metabolism-induced pro-fibrotic activation in liver cells
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Manuscript Source |
Invited Manuscript |
All Author List |
Moses New-Aaron, Murali Ganesan, Raghubendra Singh Dagur, Kusum K Kharbanda, Larisa Y Poluektova and Natalia A Osna |
ORCID |
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Funding Agency and Grant Number |
Funding Agency |
Grant Number |
National Institutes of Health |
R01AA027189-01A1 |
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Corresponding Author |
Natalia A Osna, MD, PhD, Associate Professor, Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, United States. nosna@unmc.edu |
Key Words |
Human immunodeficiency virus; Liver; Obeticholic acid; Alcohol; Hepatocytes; Fibrosis |
Core Tip |
We investigated the ability of obeticholic acid (OCA) to reverse pro-fibrotic effects of human immunodeficiency virus (HIV) and ethanol metabolism in liver cells. Based on our previous studies, hepatocyte apoptosis occurs under combined exposure of cells to HIV and ethanol metabolites. The subsequent engulfment of HIV-containing apoptotic hepatocytes by hepatic stellate cells induced pro-fibrotic activation in these cells, thereby promoting fibrosis development. Here, we demonstrated that OCA attenuates hepatocyte apoptosis by preventing accumulation of HIV components in liver cells exposed to HIV and acetaldehyde-generating system (AGS) mimicking natural ethanol metabolism in primary hepatocytes. These beneficial effects of OCA are attributed to suppression of oxidative stress leading to restoration of HIV-AGS-impaired proteasomal and lysosomal functions in liver cells. OCA also reduces activation of inflammasome in hepatic stellate cells and their pro-fibrotic activation. Thus, anti-fibrotic properties of OCA can be used for combined treatment of HIV-infected alcohol abusers with a high risk of liver fibrosis development. |
Publish Date |
2020-11-24 12:41 |
Citation |
New-Aaron M, Ganesan M, Dagur RS, Kharbanda KK, Poluektova LY, Osna NA. Obeticholic Acid attenuates human immunodeficiency virus/alcohol metabolism-induced pro-fibrotic activation in liver cells. World J Hepatol 2020; 12(11): 965-975 |
URL |
https://www.wjgnet.com/1948-5182/full/v12/i11/965.htm |
DOI |
https://dx.doi.org/10.4254/wjh.v12.i11.965 |
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