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File: /var/www/html/index.php
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Function: require_once
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File: /var/www/html/index.php
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Function: require_once
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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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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
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Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: GetPubMedArticleOutput_2016
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
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Function: require_once
Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.
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Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030564 | PMC |
http://dx.doi.org/10.3390/toxins14040263 | DOI Listing |
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