{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:01:54Z","timestamp":1792022514757,"version":"4.4.0"},"reference-count":87,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82302856"],"award-info":[{"award-number":["82302856"]}]},{"name":"National Natural Science Foundation of China","award":["GZC20241252"],"award-info":[{"award-number":["GZC20241252"]}]},{"name":"National Natural Science Foundation of China","award":["LQ21H170003"],"award-info":[{"award-number":["LQ21H170003"]}]},{"name":"Postdoctoral Fellowship program of CPSF","award":["82302856"],"award-info":[{"award-number":["82302856"]}]},{"name":"Postdoctoral Fellowship program of CPSF","award":["GZC20241252"],"award-info":[{"award-number":["GZC20241252"]}]},{"name":"Postdoctoral Fellowship program of CPSF","award":["LQ21H170003"],"award-info":[{"award-number":["LQ21H170003"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["82302856"],"award-info":[{"award-number":["82302856"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["GZC20241252"],"award-info":[{"award-number":["GZC20241252"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LQ21H170003"],"award-info":[{"award-number":["LQ21H170003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>This study explores how aristolochic acid I (AAI) drives hepatocellular carcinoma (HCC). We first employ network toxicology and machine learning to map the key molecular target genes. Next, our research utilizes molecular docking to evaluate how AAI binds to these targets, and finally confirms the stability and dynamics of the resulting complexes through molecular dynamics simulations. We identified 193 overlapping target genes between AAI and HCC through databases such as PubChem, OMIM, and ChEMBL. Machine learning algorithms (SVM-RFE, random forest, and LASSO regression) were employed to screen 11 core genes. LASSO serves as a rapid dimension-reduction tool, SVM-RFE recursively eliminates the features with the smallest weights, and Random Forest achieves ensemble learning through decision trees. Protein\u2013protein interaction networks were constructed using Cytoscape 3.9.1, and key genes were validated through GO and KEGG enrichment analyses, an immune infiltration analysis, a drug sensitivity analysis, and a survival analysis. Molecular-docking experiments showed that AAI binds to each of the core targets with a binding affinity stronger than \u22125 kcal mol\u22121, and subsequent molecular dynamics simulations verified that these complexes remain stable over time. This study determined the potential molecular mechanisms underlying AAI-induced HCC and identified key genes (CYP1A2, ESR1, and AURKA) as potential therapeutic targets, providing valuable insights for developing targeted strategies to mitigate the health risks associated with AAI exposure.<\/jats:p>","DOI":"10.3390\/toxins17080390","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T10:50:21Z","timestamp":1754391021000},"page":"390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1726-1761","authenticated-orcid":false,"given":"Tiantaixi","family":"Tu","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325035, China"},{"name":"Renji College, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Renji College, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangqi","family":"Lin","sequence":"additional","affiliation":[{"name":"The First School of Medicine, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peifeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yang","sequence":"additional","affiliation":[{"name":"Renji College, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolin","family":"Liu","sequence":"additional","affiliation":[{"name":"Chengdu Bayi Orthopedic Hospital, Chengdu 610031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwang","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105949","DOI":"10.1016\/j.fitote.2024.105949","article-title":"Effects of bioconversion by Battus polydamas on the chemical composition of Aristolochia spp. and evaluation of antimicrobial activity and biocompatibility","volume":"175","author":"Negri","year":"2024","journal-title":"Fitoterapia"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chan, C.K., Liu, Y., Pavlovi\u0107, N.M., and Chan, W. 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