Comparison Log
2024-05-26 06:05:54.150546
mwtab Python Library Version: 1.2.5
Source:      https://www.metabolomicsworkbench.org/rest/study/analysis_id/AN004473/mwtab/...
Study ID:    ST002756
Analysis ID: AN004473
Status:      Inconsistent

Sections "PROJECT" contain missmatched items: {('PROJECT_SUMMARY', 'The aryl hydrocarbon receptor (AhR) is a transcription factor activated by  structurally diverse chemicals, endogenous metabolites, and natural products.  AhR activation causes the dissociation of chaperone proteins, followed by  translocation to the nucleus and dimerization with the AhR nuclear translocator  (ARNT). The complex binds dioxin response elements (DREs; 5’-GCGTG-3’) eliciting  changes in gene expression. AhR activation by its most potent ligand   2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotes the development and progression  of non-alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of pathologies  that spans simple, reversible, and benign lipid accumulation (hepatic steatosis),  to steatosis with inflammation (steatohepatitis) and collagen deposition  (fibrosis/cirrhosis) in the absence of excessive alcohol consumption. NAFLD prevalence  is projected to increase from ~83 million in 2015 to ~101 million by 2030 in the US  alone, while increasing the risk for more complex disorders including Metabolic Syndrome,  cardiovascular disease, diabetes, cirrhosis, end-stage liver disease and hepatocellular  carcinoma (HCC). The role of AhR-mediated metabolic dysregulation in hepatotoxicity and  the etiology of more complex metabolic diseases warrants further investigation. Therofore,  in this project on PND28 mice were orally gavaged at the start of the light cycle  (zeitgeber [ZT] 0-1) with 0.1 ml sesame oil vehicle or 0.01, 0.03, 0.1, 0.3, 1, 3, 10, and  30 ug/kg body weight TCDD every 4 days for 28 days for a total of 7 treatments. The first  gavage was administered on day 0, with the last gavage administered on day 24 of the 28-day  study. On day 28, tissue samples were harvested (ZT 0-3), immediately flash frozen in liquid  nitrogen and stored at -80°C until analysis. '), ('PROJECT_SUMMARY', 'The aryl hydrocarbon receptor (AhR) is a transcription factor activated by  structurally diverse chemicals, endogenous metabolites, and natural products.  AhR activation causes the dissociation of chaperone proteins, followed by  translocation to the nucleus and dimerization with the AhR nuclear translocator  (ARNT). The complex binds dioxin response elements (DREs; 5’-GCGTG-3’) eliciting  changes in gene expression. AhR activation by its most potent ligand   2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotes the development and progression  of non-alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of pathologies  that spans simple, reversible, and benign lipid accumulation (hepatic steatosis),  to steatosis with inflammation (steatohepatitis) and collagen deposition  (fibrosis/cirrhosis) in the absence of excessive alcohol consumption. NAFLD prevalence  is projected to increase from ~83 million in 2015 to ~101 million by 2030 in the US  alone, while increasing the risk for more complex disorders including Metabolic Syndrome,  cardiovascular disease, diabetes, cirrhosis, end-stage liver disease and hepatocellular  carcinoma (HCC). The role of AhR-mediated metabolic dysregulation in hepatotoxicity and  the etiology of more complex metabolic diseases warrants further investigation. Therofore,  in this project on PND28 mice were orally gavaged at the start of the light cycle  (zeitgeber [ZT] 0-1) with 0.1 ml sesame oil vehicle or 0.01, 0.03, 0.1, 0.3, 1, 3, 10, and  30 ug/kg body weight TCDD every 4 days for 28 days for a total of 7 treatments. The first  gavage was administered on day 0, with the last gavage administered on day 24 of the 28-day  study. On day 28, tissue samples were harvested (ZT 0-3), immediately flash frozen in liquid  nitrogen and stored at -80°C until analysis.')}
Sections "STUDY" contain missmatched items: {('STUDY_SUMMARY', 'In this study, we tested the hypothesis that the dose-dependent disruption of  propionyl-CoA metabolism produces toxic intermediates that contribute to TCDD  hepatotoxicity and progression of steatosis to steatohepatitis with fibrosis.  Our results suggest TCDD dose-dependently reduced cobalamin (Cbl aka vitamin B12)  levels compromising methylmalonyl-CoA mutase (MUT) activity and limiting the  metabolism of propionyl-CoA to succinyl-CoA using the canonical Cbl-dependent  carboxylation pathway. Consequently, accumulating propionyl-CoA was redirected to  the alternate Cbl-independent beta-oxidation-like pathway resulting in the dose-dependent  accumulation of acrylyl-CoA, as indicated by the increase in S-(2-carboxyethyl)-L-cysteine,  a conjugate produced following the spontaneous reaction between the sulfhydryl group  of cysteine and highly reactive acrylyl-CoA.'), ('STUDY_SUMMARY', 'In this study, we tested the hypothesis that the dose-dependent disruption of  propionyl-CoA metabolism produces toxic intermediates that contribute to TCDD  hepatotoxicity and progression of steatosis to steatohepatitis with fibrosis.  Our results suggest TCDD dose-dependently reduced cobalamin (Cbl aka vitamin B12)  levels compromising methylmalonyl-CoA mutase (MUT) activity and limiting the  metabolism of propionyl-CoA to succinyl-CoA using the canonical Cbl-dependent  carboxylation pathway. Consequently, accumulating propionyl-CoA was redirected to  the alternate Cbl-independent beta-oxidation-like pathway resulting in the dose-dependent  accumulation of acrylyl-CoA, as indicated by the increase in S-(2-carboxyethyl)-L-cysteine,  a conjugate produced following the spontaneous reaction between the sulfhydryl group  of cysteine and highly reactive acrylyl-CoA.    ')}