{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:54:20Z","timestamp":1788285260473,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Fujian Province","award":["2024J01013"],"award-info":[{"award-number":["2024J01013"]}]},{"name":"Natural Science Foundation of Fujian Province","award":["XAH23017"],"award-info":[{"award-number":["XAH23017"]}]},{"name":"Natural Science Foundation of Fujian Province","award":["2024GZL-CX08"],"award-info":[{"award-number":["2024GZL-CX08"]}]},{"name":"Xiang\u2019an Hospital of Xiamen University","award":["2024J01013"],"award-info":[{"award-number":["2024J01013"]}]},{"name":"Xiang\u2019an Hospital of Xiamen University","award":["XAH23017"],"award-info":[{"award-number":["XAH23017"]}]},{"name":"Xiang\u2019an Hospital of Xiamen University","award":["2024GZL-CX08"],"award-info":[{"award-number":["2024GZL-CX08"]}]},{"name":"Xiamen City Health High-Quality Development Science and Technology Program Medical Innovation Research Project","award":["2024J01013"],"award-info":[{"award-number":["2024J01013"]}]},{"name":"Xiamen City Health High-Quality Development Science and Technology Program Medical Innovation Research Project","award":["XAH23017"],"award-info":[{"award-number":["XAH23017"]}]},{"name":"Xiamen City Health High-Quality Development Science and Technology Program Medical Innovation Research Project","award":["2024GZL-CX08"],"award-info":[{"award-number":["2024GZL-CX08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study looked into the underlying mechanisms and causal relationship between alcoholic liver disease (ALD) and the blood metabolite uridine using a variety of analytical methods, such as Mendelian randomization and molecular dynamics simulations. We discovered uridine to be a possible hepatotoxic agent aggravating ALD by using Mendelian randomization (MR) analysis with genome-wide association study (GWAS) data from 1416 ALD cases and 217,376 controls, as well as with 1091 blood metabolites and 309 metabolite concentration ratios as exposure factors. According to network toxicology analysis, uridine interacts with important targets such as SRC, FYN, LYN, ADRB2, and GSK3B. The single-cell RNA sequencing analysis of ALD tissues revealed that SRC was upregulated in hepatocytes and activated hepatic stellate cells. Subsequently, we determined the stable binding between uridine and SRC through molecular docking and molecular dynamics simulation (RMSD = 1.5 \u00b1 0.3 \u00c5, binding energy &lt; \u22125.0 kcal\/mol). These targets were connected to tyrosine kinase activity, metabolic reprogramming, and GPCR signaling by Gene Ontology (GO) and KEGG studies. These findings elucidate uridine\u2019s role in ALD progression via immunometabolic pathways, offering novel therapeutic targets for precision intervention. These findings highlight the necessity of systems biology frameworks in drug safety evaluation, particularly for metabolites with dual therapeutic and toxicological roles.<\/jats:p>","DOI":"10.3390\/ijms26125473","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"5473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Uridine, a Therapeutic Nucleoside, Exacerbates Alcoholic Liver Disease via SRC Kinase Activation: A Network Toxicology and Molecular Dynamics Perspective"],"prefix":"10.3390","volume":"26","author":[{"given":"Zhenyu","family":"Liu","sequence":"first","affiliation":[{"name":"Organ Transplantation Institute of Xiamen University, Xiamen Human Organ Transplantation Quality Control Center, Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Wang","sequence":"additional","affiliation":[{"name":"Organ Transplantation Institute of Xiamen University, Xiamen Human Organ Transplantation Quality Control Center, Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Organ Transplantation Institute of Xiamen University, Xiamen Human Organ Transplantation Quality Control Center, Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiquan","family":"Xu","sequence":"additional","affiliation":[{"name":"Organ Transplantation Institute of Xiamen University, Xiamen Human Organ Transplantation Quality Control Center, Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7602-3856","authenticated-orcid":false,"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Organ Transplantation Institute of Xiamen University, Xiamen Human Organ Transplantation Quality Control Center, Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.14309\/ajg.0000000000000340","article-title":"Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review and Meta-Analysis","volume":"114","author":"Roerecke","year":"2019","journal-title":"Am. 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