Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background: Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes. Recent evidence suggests chronic inflammation to be one of the causal factors of DKD. The mechanisms entailed are not completely elucidated except that a variety of cytokines play a major role in this process. High mobility group box 1 (HMGB1) is a pro-inflammatory toll-like receptor-4 (TLR4)-binding cytokine that is involved in inflammation-associated gene expression. This investigation was designed to assess the involvement of HMGB1, TLR-4, and nuclear factor (NF)-κB in the development of DKD and to evaluate that whether blocking HMGB1 by its natural inhibitor Glycyrrhizin (GLC) can reduce the progression of the disease.
Methods: Studies were carried out in 8-10-weeks old Zucker diabetic fatty (ZDF) and lean, age- and gender-matched rats. At 10 weeks of age, ZDF rats as compared to controls, showed hyperglycemia, without proteinuria. After 8-10 weeks of the development of diabetes, ZDF animals that showed proteinuria were treated with GLC for 4 weeks. In addition, normal rat kidney (NRK-52E) cells with epithelial-like morphology were comparatively treated with GLC under hyperglycemic condition in vitro.
Results: Substantial increase in the expression of HMGB1, TLR4, and NF-κB in vivo and in vitro under hyperglycemic conditions was observed as compared to normoglycemic conditions. The overexpression of HMGB1, TLR4, NF-κB, and glomerular injury marker nestin was significantly ameliorated by GLC administration.
Conclusion: Our findings suggest that hyperglycemia-induced HMGB1 activation in ZDF rats may contribute to the progression of DKD.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1159/000477820 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!