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: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
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
Background: Ferroptosis, an iron-dependent form of cell death, plays a pivotal role in the pathologic progression of asthma. Electroacupuncture (EA) has demonstrated considerable efficacy in mitigating asthma airway inflammation, although its underlying mechanisms remain partially elucidated.
Methods: We investigated the regulatory effect of NLRP3 on ferroptosis using a lipopolysaccharide (LPS)-induced inflammation model in BEAS-2B cells, where NLRP3 expression was modulated with si-RNA and overexpression plasmids. The levels of inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified. We also assessed NLRP3 and JAK2/STAT3 pathway-related proteins, and evaluated lipid peroxidation, mitochondrial membrane potential (ΔΨm), and antioxidant system functionality. In vivo, we examined the impact of EA on ferroptosis and airway inflammation by modulating NLRP3 activation. Asthma inflammation severity was evaluated using H&E, Masson, and PAS staining, alongside ELISA. NLRP3 and JAK2/STAT3 pathway-related proteins, as well as ferroptosis indicators, were also analyzed. The mechanism by which NLRP3 activates ferroptosis was investigated through in vitro assays.
Results: LPS exposure resulted in increased intracellular inflammatory cytokines, and activation of the NLRP3 and JAK2/STAT3 pathways, leading to enhanced lipid peroxidation, decreased ΔΨm, and disruption of antioxidant system balance, ultimately inducing ferroptosis. Si-NLRP3 countered the effects of LPS, whereas oe-NLRP3 exacerbated symptoms. In vivo studies revealed that EA reduced airway inflammation, inhibited NLRP3 activation, and decreased phosphorylation of JAK2/STAT3, effectively lowering ferroptosis-related indicators. Utilizing JAK2/STAT3 activators and inhibitors, we confirmed that NLRP3 mediates ferroptosis via the JAK2/STAT3 pathway.
Conclusions: EA alleviates HDM-induced asthma, primarily through the inhibition of NLRP3 activation, which modulates the JAK2/STAT3 pathway and mediates ferroptosis.
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http://dx.doi.org/10.1016/j.intimp.2024.113416 | DOI Listing |
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