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
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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
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Function: require_once
Paraquat (PQ) and diquat (DQ), two highly efficient herbicides sharing similar chemical backbone, both induce reactive oxygen species and are highly toxic to humans and livestock, however, PQ but not DQ poisoning result in pulmonary fibrosis, the leading cause of high mortality rate in patients suffering PQ toxicity. Understanding the unique mechanism of PQ different from DQ therefore would provide potential strategies to reduce PQ-induced pulmonary fibrosis. Here, we identified that PQ but not DQ continuously upregulates TGF-β expression in alveolar type II (AT II) cells. Importantly, such high expression of TGF-β increases cytosolic calcium levels and further promotes the activation of calcineurin-NFAT axis. TGF-β mainly activates NFATc1 and NFATc2, but not NFATc3 or NFATc4. Administration of the inhibitors targeting cytosolic calcium or calcineurin largely reverses PQ-induced epithelial-mesenchymal transition (EMT), whereas DQ has little effects on activation of NFAT and EMT. Ultimately, PQ poisoned patients exhibit significantly reduced blood calcium levels compared to DQ poisoning, possibly via the large usage of calcium by AT II cells. All in all, we found a vicious cycle that the upregulated TGF-β in PQ-induced EMT further aggravates EMT via promotion of the calcium-calcineurin axis, which could be potential drug targets for treating PQ-induced pulmonary fibrosis.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403590 | PMC |
http://dx.doi.org/10.1093/toxres/tfab055 | DOI Listing |
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