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Filename: drivers/Session_files_driver.php
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Filename: Session/Session.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Filename: helpers/my_audit_helper.php
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Function: formatAIDetailSummary
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Function: require_once
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Filename: controllers/Detail.php
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
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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
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Function: file_get_contents
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Function: require_once
RIPK1/RIPK3/MLKL (Receptor-interacting protein kinase 1/Receptor-interacting protein kinase 3/Mixed lineage kinase domain-like protein) pathway-mediated necroptosis contributes to myocardial ischemia/reperfusion (I/R) injury, and Arctiin can prevent myocardial fibrosis and hypertrophy. This study aims to explore the effect of Arctiin on myocardial I/R injury and the underlying mechanisms. SD rat hearts or cardiomyocytes were subjected to I/R or hypoxia/reoxygenation (H/R) to establish the I/R or H/R injury model. The methods of biochemistry, PI/DAPI (propidium iodide/4',6-Diamidino-2-Phenylindole) and H&E (Hematoxylin & eosin) staining were used to evaluate the I/R or H/R injury. The effects of Arctiin on necroptosis in I/R-treated hearts or H/R-treated cardiomyocytes were assessed. The results showed that Arctiin reduced myocardial I/R injury (decreases in myocardial infarction and creatine kinase release), concomitant with a decrease in levels of necroptosis-associated proteins (RIPK1/p-RIPK1, RIPK3/p-RIPK3 and MLKL/p-MLKL) in I/R-treated rat hearts. Consistently, the necrosis and LDH release in H/R-treated cardiomyocytes were attenuated in the presence of Arctiin, accompanied by suppression of necroptosis-relevant proteins. Furthermore, H/R-induced reactive oxygen species (ROS) generation and mitochondrial dysfunctions (increase in mitochondrial membrane potential and decrease in ATP production) were impaired by Arctiin. Using the program of the Molecular Operating Environment (MOE), we predict that RIPK1 and MLKL (but not RIPK3) might be the potential targets of Arctiin. Based on these observations, we conclude that Arctiin can protect the rat heart from I/R injury, and its beneficial effect is related to reduction of necroptosis via scavenging reactive oxygen species and restoring mitochondrial functions or targeting RIPK1 and/or MLKL.
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Source |
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http://dx.doi.org/10.1016/j.ejphar.2020.173053 | DOI Listing |
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