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
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Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
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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
Background: Neuropathic pain (NP) is the primary symptom of various neurological conditions. Patients with NP often experience mood disorders, particularly depression and anxiety, that can severely affect their normal lives. Microglial cells are associated with NP. Excessive inflammatory responses, especially the secretion of large amounts of pro-inflammatory cytokines, ultimately lead to neuroinflammation. Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system.
Aim: To investigate the effects of botulinum toxin type A (BTX-A) on microglial pyroptosis in terms of NP and associated mechanisms.
Methods: Two models, an lipopolysaccharide (LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments, were used. Key proteins in the pyroptosis signaling pathway, NLRP3-GSDMD, were assessed using western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence. Inflammatory factors [interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α] were assessed using enzyme-linked immunosorbent assay. We also evaluated microglial cell proliferation and apoptosis. Furthermore, we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation.
Results: The expression levels of ACS and GSDMD-N and the mRNA expression of , , and were enhanced in LPS-treated microglia. Furthermore, expression was also induced in LPS-treated microglia. Notably, BTX-A inhibited mRNA and protein expression in the LPS-treated microglia. Additionally, depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia, whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin (sh)RNA in LPS-treated microglia. Finally, SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N, NLPRP3, and ASC and suppressed the production of inflammatory factors.
Conclusion: Notably, BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death. It improves pain perception and inhibits microglial activation in rats with selective nerve pain.
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Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331382 | PMC |
http://dx.doi.org/10.5498/wjp.v14.i8.1254 | DOI Listing |
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