{"title":"通过网络毒理学、分子对接和多层次生物信息学数据整合,分析环境污染物双酚 F 引发前列腺损伤的靶点和潜在机制。","authors":"Shujun Huang","doi":"10.1016/j.tox.2024.153847","DOIUrl":null,"url":null,"abstract":"<div><p>Bisphenol F (BPF) has gained prominence as an alternative to bisphenol A (BPA) in various manufacturing applications, yet being detected in diverse environments and posed potential public health risk. This research aims to elucidate the putative toxic targets and underlying molecular mechanisms of prostate injury induced by exposure to BPF through multi-level bioinformatics data, integrating network toxicology and molecular docking. Systematically leveraging multilevel databases, we determined 276 targets related to BPF and prostate injury. Subsequent screenings through STRING and Cytoscape tool highlighted 27 key targets, including <em>BCL2</em>, <em>HSP90AA1</em>, <em>MAPK3</em>, <em>ESR1</em>, and <em>CASP3</em>. GO and KEGG enrichment analyses demonstrated enrichment of targets involved in apoptosis, abnormal hormonal activities, as well as cancer-related signal transduction cascades, ligand-receptor interaction networks, and endocrine system signaling pathways. Molecular docking simulations conducted via Autodock corroborated high-affinity binding interaction between BPF and key targets. The results indicate that BPF exposure can contribute to the initiation and progression of prostate cancer and prostatic hyperplastic by modulating apoptosis and proliferation, altering nerve function in blood vessel endothelial cells, and disrupting androgen metabolism. This study offers theoretical underpinnings for comprehending the molecular mechanisms implicated in BPF-elicited prostatic toxicity, while concomitantly establishing foundational framework for the development of prophylactic and therapeutic strategies for prostatic injuries related to polycarbonate and epoxy resin plastics incorporated with BPF, as well as environments afflicted by elevated levels of these compounds.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Analysis of environmental pollutant Bisphenol F elicited prostate injury targets and underlying mechanisms through network toxicology, molecular docking, and multi-level bioinformatics data integration\",\"authors\":\"Shujun Huang\",\"doi\":\"10.1016/j.tox.2024.153847\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Bisphenol F (BPF) has gained prominence as an alternative to bisphenol A (BPA) in various manufacturing applications, yet being detected in diverse environments and posed potential public health risk. This research aims to elucidate the putative toxic targets and underlying molecular mechanisms of prostate injury induced by exposure to BPF through multi-level bioinformatics data, integrating network toxicology and molecular docking. Systematically leveraging multilevel databases, we determined 276 targets related to BPF and prostate injury. Subsequent screenings through STRING and Cytoscape tool highlighted 27 key targets, including <em>BCL2</em>, <em>HSP90AA1</em>, <em>MAPK3</em>, <em>ESR1</em>, and <em>CASP3</em>. GO and KEGG enrichment analyses demonstrated enrichment of targets involved in apoptosis, abnormal hormonal activities, as well as cancer-related signal transduction cascades, ligand-receptor interaction networks, and endocrine system signaling pathways. Molecular docking simulations conducted via Autodock corroborated high-affinity binding interaction between BPF and key targets. The results indicate that BPF exposure can contribute to the initiation and progression of prostate cancer and prostatic hyperplastic by modulating apoptosis and proliferation, altering nerve function in blood vessel endothelial cells, and disrupting androgen metabolism. This study offers theoretical underpinnings for comprehending the molecular mechanisms implicated in BPF-elicited prostatic toxicity, while concomitantly establishing foundational framework for the development of prophylactic and therapeutic strategies for prostatic injuries related to polycarbonate and epoxy resin plastics incorporated with BPF, as well as environments afflicted by elevated levels of these compounds.</p></div>\",\"PeriodicalId\":23159,\"journal\":{\"name\":\"Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-06-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0300483X24001288\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0300483X24001288","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Analysis of environmental pollutant Bisphenol F elicited prostate injury targets and underlying mechanisms through network toxicology, molecular docking, and multi-level bioinformatics data integration
Bisphenol F (BPF) has gained prominence as an alternative to bisphenol A (BPA) in various manufacturing applications, yet being detected in diverse environments and posed potential public health risk. This research aims to elucidate the putative toxic targets and underlying molecular mechanisms of prostate injury induced by exposure to BPF through multi-level bioinformatics data, integrating network toxicology and molecular docking. Systematically leveraging multilevel databases, we determined 276 targets related to BPF and prostate injury. Subsequent screenings through STRING and Cytoscape tool highlighted 27 key targets, including BCL2, HSP90AA1, MAPK3, ESR1, and CASP3. GO and KEGG enrichment analyses demonstrated enrichment of targets involved in apoptosis, abnormal hormonal activities, as well as cancer-related signal transduction cascades, ligand-receptor interaction networks, and endocrine system signaling pathways. Molecular docking simulations conducted via Autodock corroborated high-affinity binding interaction between BPF and key targets. The results indicate that BPF exposure can contribute to the initiation and progression of prostate cancer and prostatic hyperplastic by modulating apoptosis and proliferation, altering nerve function in blood vessel endothelial cells, and disrupting androgen metabolism. This study offers theoretical underpinnings for comprehending the molecular mechanisms implicated in BPF-elicited prostatic toxicity, while concomitantly establishing foundational framework for the development of prophylactic and therapeutic strategies for prostatic injuries related to polycarbonate and epoxy resin plastics incorporated with BPF, as well as environments afflicted by elevated levels of these compounds.
期刊介绍:
Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.