Severity: Warning
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Filename: drivers/Session_files_driver.php
Line Number: 177
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File: /var/www/html/index.php
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Function: require_once
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Filename: Session/Session.php
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File: /var/www/html/index.php
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Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
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Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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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
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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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
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Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
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Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Function: require_once
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Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated
Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary
File: /var/www/html/index.php
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Function: require_once
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Message: Undefined array key "choices"
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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Function: require_once
Severity: Warning
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
Line: 316
Function: require_once
Severity: Warning
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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Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
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
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Message: Undefined array key "usage"
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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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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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
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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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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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: file_get_contents
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Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedSearch_Global
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Function: pubMedGetRelatedKeyword
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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File: /var/www/html/application/controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: pubMedGetRelatedKeyword
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Function: require_once
Kidney fibrosis is considered the essential pathophysiological process for the progression of chronic kidney disease (CKD) toward renal failure. 20-Hydroxyeicosatetraenoic acid (20-HETE) has crucial roles in modulating the vascular response in the kidney and the progression of albuminuria. However, the roles of 20-HETE in kidney fibrosis are largely unexplored. In the current research, we hypothesized that if 20-HETE has important roles in the progression of kidney fibrosis, 20-HETE synthesis inhibitors might be effective against kidney fibrosis. To verify our hypothesis, this study investigated the effect of a novel and selective 20-HETE synthesis inhibitor, TP0472993, on the development of kidney fibrosis after folic acid- and obstructive-induced nephropathy in mice. Chronic treatment with TP0472993 at doses of 0.3 and 3 mg/kg twice a day attenuated the degree of kidney fibrosis in the folic acid nephropathy and the unilateral ureteral obstruction (UUO) mice, as demonstrated by reductions in Masson's trichrome staining and the renal collagen content. In addition, TP0472993 reduced renal inflammation, as demonstrated by markedly reducing interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-) levels in the renal tissue. Chronic treatment with TP0472993 also reduced the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) in the kidney of UUO mice. Our observations indicate that inhibition of 20-HETE production with TP0472993 suppresses the kidney fibrosis progression via a reduction in the ERK1/2 and STAT3 signaling pathway, suggesting that 20-HETE synthesis inhibitors might be a novel treatment option against CKD. SIGNIFICANCE STATEMENT: In this study, we demonstrate that the pharmacological blockade of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis using TP0472993 suppresses the progression of kidney fibrosis after folic acid- and obstructive-induced nephropathy in mice, indicating that 20-HETE might have key roles in the pathogenesis of kidney fibrosis. TP0472993 has the potential to be a novel therapeutic approach against chronic kidney disease.
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Source |
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http://dx.doi.org/10.1124/jpet.122.001521 | DOI Listing |
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