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Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture
Polychlorinated biphenyls (PCBs) are persistent and highly toxic pollutants, which can accumulate in organisms and produce toxic effects, especially damaging the function of thyroid hormones. So far, the molecular mechanism of PCBs mixture and their metabolites interfering with thyroid hormones has...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532094/ https://www.ncbi.nlm.nih.gov/pubmed/36203481 http://dx.doi.org/10.1155/2022/2394398 |
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author | Li, Chunxia Xing, Hong He, Qiaoyu Liu, Jing Liu, Hong Li, Yue Chen, Xiaopeng |
author_facet | Li, Chunxia Xing, Hong He, Qiaoyu Liu, Jing Liu, Hong Li, Yue Chen, Xiaopeng |
author_sort | Li, Chunxia |
collection | PubMed |
description | Polychlorinated biphenyls (PCBs) are persistent and highly toxic pollutants, which can accumulate in organisms and produce toxic effects, especially damaging the function of thyroid hormones. So far, the molecular mechanism of PCBs mixture and their metabolites interfering with thyroid hormones has not been studied thoroughly except for individual compounds. In this study, PubMed, Web of Science, and STITCH databases were used to search PCBs and their corresponding target proteins. The intersection of PCBs and thyroid hormone dysfunction target proteins was obtained from GeneCards. The “compounds-targets-pathways” network was constructed by Cytoscape software. And KEGG and Go analyses were performed for key targets. Finally, molecular docking was used to verify the binding effect. Four major active components, five key targets, and 10 kernel pathways were successfully screened by constructing the network. Functional enrichment analysis showed that the interference was mediated by cancer, proteoglycans, PI3K-Akt, thyroid hormone, and FoxO signaling pathways. The molecular docking results showed that the binding energies were less than -5 kcal·mol(−1). PCBs and their metabolites may act on the key targets of MAPK3, MAPK1, RXRA, PIK3R1, and TP53. The toxic effect of sulfated and methyl sulfone PCBs is greater. The method of screening targets based on the simultaneous action of multiple PCBs can provide a reference for other research. The targets were not found in previous metabolite toxicity studies. It also provides a bridge for the toxic effects and experimental research of PCBs and their metabolites in the future. |
format | Online Article Text |
id | pubmed-9532094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-95320942022-10-05 Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture Li, Chunxia Xing, Hong He, Qiaoyu Liu, Jing Liu, Hong Li, Yue Chen, Xiaopeng Biomed Res Int Research Article Polychlorinated biphenyls (PCBs) are persistent and highly toxic pollutants, which can accumulate in organisms and produce toxic effects, especially damaging the function of thyroid hormones. So far, the molecular mechanism of PCBs mixture and their metabolites interfering with thyroid hormones has not been studied thoroughly except for individual compounds. In this study, PubMed, Web of Science, and STITCH databases were used to search PCBs and their corresponding target proteins. The intersection of PCBs and thyroid hormone dysfunction target proteins was obtained from GeneCards. The “compounds-targets-pathways” network was constructed by Cytoscape software. And KEGG and Go analyses were performed for key targets. Finally, molecular docking was used to verify the binding effect. Four major active components, five key targets, and 10 kernel pathways were successfully screened by constructing the network. Functional enrichment analysis showed that the interference was mediated by cancer, proteoglycans, PI3K-Akt, thyroid hormone, and FoxO signaling pathways. The molecular docking results showed that the binding energies were less than -5 kcal·mol(−1). PCBs and their metabolites may act on the key targets of MAPK3, MAPK1, RXRA, PIK3R1, and TP53. The toxic effect of sulfated and methyl sulfone PCBs is greater. The method of screening targets based on the simultaneous action of multiple PCBs can provide a reference for other research. The targets were not found in previous metabolite toxicity studies. It also provides a bridge for the toxic effects and experimental research of PCBs and their metabolites in the future. Hindawi 2022-09-27 /pmc/articles/PMC9532094/ /pubmed/36203481 http://dx.doi.org/10.1155/2022/2394398 Text en Copyright © 2022 Chunxia Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Chunxia Xing, Hong He, Qiaoyu Liu, Jing Liu, Hong Li, Yue Chen, Xiaopeng Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture |
title | Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture |
title_full | Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture |
title_fullStr | Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture |
title_full_unstemmed | Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture |
title_short | Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture |
title_sort | network toxicology guided mechanism study on the association between thyroid function and exposures to polychlorinated biphenyls mixture |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532094/ https://www.ncbi.nlm.nih.gov/pubmed/36203481 http://dx.doi.org/10.1155/2022/2394398 |
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