Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Non-alcoholic fatty liver disease (NAFLD) is currently a common chronic liver disease worldwide. By now, however, there isn't any FDA-approved specific drug for NAFLD treatment. It has been noticed that farnesoid X receptor (FXR), miR-34a and Sirtuin1 (SIRT1) is related to the occurrence and development of NAFLD. A oligochitosan-derivated nanovesicle (UBC) with esterase responsive degradability was designed to co-encapsulate FXR agonist (obeticholic acid, OCA) and miR-34a antagomir (anta-miR-34a) into the hydrophobic membrane and the center aqueous lumen of nanovesicles, respectively, by dialysis method. The action of UBC/OCA/anta-miR-34a loop on the regulation of lipid deposition via nanovesicles was evaluated on high-fat HepG2 cells and HFD-induced mice. The obtained dual drug-loaded nanovesicles UBC/OCA/anta-miR-34a could enhance the cellular uptake and intracellular release of OCA and anta-miR-34a, leading to the reduced lipid deposition in high-fat HepG2 cells. In NAFLD mice models, UBC/OCA/anta-miR-34a achieved the best curative effect on the recovery of body weight and hepatic function. Meanwhile, in vitro and vivo experiments validated that UBC/OCA/anta-miR-34a effectively activated the expression level of SIRT1 by enhancing the FXR/miR-34a/SIRT1 regulatory loop. This study provides a promising strategy for constructing oligochitosan-derivated nanovesicles to co-deliver OCA and anta-miR-34a for NAFLD treatment. STATEMENT OF SIGNIFICANCE: This study proposed a strategy to construct oligochitosan-derivated nanovesicles to co-deliver obeticholic acid and miR-34a antagomir for NAFLD treatment. Based on the FXR/miR-34a/SIRT1 action loop, this nanovesicle effectively exerted a synergetic effect of OCA and anta-miR-34a to significantly regulate lipid deposition and recover liver function in NAFLD mice.
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http://dx.doi.org/10.1016/j.actbio.2023.04.002 | DOI Listing |
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