The Mediating Effect of 3-Methoxytyrosine on TWEAK Levels and Primary Sclerosing Cholangitis: A Genetic Perspective DOI Creative Commons
Jie Zhou,

Yixin Xun,

Zhilin Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Abstract Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation, fibrosis, and bile stasis. Inflammatory proteins metabolites may be involved in PSC pathogenesis. However, comprehensive analysis currently lacking. In this study, we employed two-step Mendelian randomization (MR) to quantify the proportion of effect metabolites-mediated inflammation-related on PSC. The dataset includes information PSC, levels 91 proteins, 1400 plasma. data (n = 14,890) were obtained from International Study Group, while came study involving 14,824 participants. Metabolites sourced Genome-Wide Association with 8,299 individuals. Furthermore, After rigorous screening, found through MR that higher genetically predicted tumor necrosis factor ligand superfamily member 12 (TWEAK) (inverse-variance weighted method, odds ratio (OR) 1.53, 95% confidence interval (CI) 1.23–1.91) associated an increased risk There was no compelling evidence indicating had TWEAK (OR 1.004, CI 0.99–1.02). mediated 3-methoxytyrosine estimated 6.38%. Finally, we've shown causal relationship between some mediation 3-methoxytyrosine. TWEAK's pivotal role as protein highlights its potential critical therapeutic target.

Language: Английский

Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma DOI Creative Commons
Mahmoud Zhra, Muhammad Affan Elahi, Aamira Tariq

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 466 - 466

Published: March 20, 2025

Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The microbiome interacts with the via a bidirectional relationship gut–liver axis. Microbial metabolites, sirtuins, responses pivotal in different metabolic diseases. This extensive review explores complex multifaceted interrelationship between sirtuins microbiota, highlighting their importance health disease, particularly hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as group of NAD+-dependent deacetylases, serve crucial modulators wide spectrum cellular functions, including pathways, inflammatory response, process senescence. Their subcellular localization diverse functions link them various conditions, NAFLD cancer. Concurrently, comprising microorganisms, significantly influences host metabolism responses. Recent findings indicate modulate microbiota composition function, while can affect sirtuin activity. is relevant disorders, where dysbiosis contributes progression. highlights recent on roles specific maintaining implications HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked dysregulation pathology.

Language: Английский

Citations

0
The Mediating Effect of 3-Methoxytyrosine on TWEAK Levels and Primary Sclerosing Cholangitis: A Genetic Perspective DOI Creative Commons
Jie Zhou,

Yixin Xun,

Zhilin Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Abstract Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation, fibrosis, and bile stasis. Inflammatory proteins metabolites may be involved in PSC pathogenesis. However, comprehensive analysis currently lacking. In this study, we employed two-step Mendelian randomization (MR) to quantify the proportion of effect metabolites-mediated inflammation-related on PSC. The dataset includes information PSC, levels 91 proteins, 1400 plasma. data (n = 14,890) were obtained from International Study Group, while came study involving 14,824 participants. Metabolites sourced Genome-Wide Association with 8,299 individuals. Furthermore, After rigorous screening, found through MR that higher genetically predicted tumor necrosis factor ligand superfamily member 12 (TWEAK) (inverse-variance weighted method, odds ratio (OR) 1.53, 95% confidence interval (CI) 1.23–1.91) associated an increased risk There was no compelling evidence indicating had TWEAK (OR 1.004, CI 0.99–1.02). mediated 3-methoxytyrosine estimated 6.38%. Finally, we've shown causal relationship between some mediation 3-methoxytyrosine. TWEAK's pivotal role as protein highlights its potential critical therapeutic target.

Language: Английский

Citations

0