Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposure
Objective: This study elucidated the molecular mechanisms underlying chronic spontaneous urticaria (CSU), potentially induced by the food and environmental pollutant dioctyl terephthalate (DOTP), through the application of network toxicology and molecular dynamics simulations. Methods: The structura...
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Elsevier
2025-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325002003 |
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| author | Fang Cao Cui Guo Jing Guo |
| author_facet | Fang Cao Cui Guo Jing Guo |
| author_sort | Fang Cao |
| collection | DOAJ |
| description | Objective: This study elucidated the molecular mechanisms underlying chronic spontaneous urticaria (CSU), potentially induced by the food and environmental pollutant dioctyl terephthalate (DOTP), through the application of network toxicology and molecular dynamics simulations. Methods: The structural analysis of DOTP was conducted in PubChem, with target prediction executed via Swiss Target Prediction and SuperPred, and target identification standardized using UniProt. A PPI network analysis identified core disease-related targets using STRING and Cytoscape. GO and KEGG analyses were utilized to explore target functions, particularly in inflammation and immune response pathways. AutoDock was employed for molecular docking to predict DOTP's binding to core targets, followed by molecular dynamics simulations with Gromacs to observe detailed interactions and conformational changes in the target proteins. Results: The study identified 38 potential targets associated with CSU and highlighted six core targets—EGFR, BCL2, NFKB1, CASP3, ERBB2, and mTOR—through PPI network analysis. GO and KEGG analyses illuminated the roles of these targets in biological processes, cellular components, molecular functions, and signaling pathways, with a particular emphasis on the PI3K-Akt signaling pathway. Molecular docking demonstrated strong binding affinities between DOTP and the core targets, while molecular dynamics simulations confirmed the stable binding of DOTP to these targets, with exceptional stability observed in its interaction with the mTOR protein. Conclusion: This study clarifies the potential molecular mechanisms of DOTP-induced CSU and underscores the efficacy of network toxicology, molecular docking, and molecular dynamics simulations in assessing the toxicity of food and environmental pollutants and their related molecular biological mechanisms. These findings offer new insights for future research, enhance our comprehension of the potential health impacts of food and environmental pollutants, and establish a scientific foundation for the development of prevention and treatment strategies. |
| format | Article |
| id | doaj-art-1476ec73c92e401abedbe37301db93f3 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-1476ec73c92e401abedbe37301db93f32025-02-10T04:33:29ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-01291117864Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposureFang Cao0Cui Guo1Jing Guo2Chengdu University of Traditional Chinese Medicine, ChinaChengdu University of Traditional Chinese Medicine, ChinaHospital of Chengdu University of Traditional Chinese Medicine, China; Corresponding author.Objective: This study elucidated the molecular mechanisms underlying chronic spontaneous urticaria (CSU), potentially induced by the food and environmental pollutant dioctyl terephthalate (DOTP), through the application of network toxicology and molecular dynamics simulations. Methods: The structural analysis of DOTP was conducted in PubChem, with target prediction executed via Swiss Target Prediction and SuperPred, and target identification standardized using UniProt. A PPI network analysis identified core disease-related targets using STRING and Cytoscape. GO and KEGG analyses were utilized to explore target functions, particularly in inflammation and immune response pathways. AutoDock was employed for molecular docking to predict DOTP's binding to core targets, followed by molecular dynamics simulations with Gromacs to observe detailed interactions and conformational changes in the target proteins. Results: The study identified 38 potential targets associated with CSU and highlighted six core targets—EGFR, BCL2, NFKB1, CASP3, ERBB2, and mTOR—through PPI network analysis. GO and KEGG analyses illuminated the roles of these targets in biological processes, cellular components, molecular functions, and signaling pathways, with a particular emphasis on the PI3K-Akt signaling pathway. Molecular docking demonstrated strong binding affinities between DOTP and the core targets, while molecular dynamics simulations confirmed the stable binding of DOTP to these targets, with exceptional stability observed in its interaction with the mTOR protein. Conclusion: This study clarifies the potential molecular mechanisms of DOTP-induced CSU and underscores the efficacy of network toxicology, molecular docking, and molecular dynamics simulations in assessing the toxicity of food and environmental pollutants and their related molecular biological mechanisms. These findings offer new insights for future research, enhance our comprehension of the potential health impacts of food and environmental pollutants, and establish a scientific foundation for the development of prevention and treatment strategies.http://www.sciencedirect.com/science/article/pii/S0147651325002003Network toxicologyContaminantCSUMolecular dockingMolecular dynamics simulation |
| spellingShingle | Fang Cao Cui Guo Jing Guo Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposure Ecotoxicology and Environmental Safety Network toxicology Contaminant CSU Molecular docking Molecular dynamics simulation |
| title | Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposure |
| title_full | Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposure |
| title_fullStr | Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposure |
| title_full_unstemmed | Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposure |
| title_short | Deciphering CSU pathogenesis: Network toxicologyand molecular dynamics of DOTP exposure |
| title_sort | deciphering csu pathogenesis network toxicologyand molecular dynamics of dotp exposure |
| topic | Network toxicology Contaminant CSU Molecular docking Molecular dynamics simulation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325002003 |
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