Benzo[a]pyrene and Rheumatoid Arthritis: An Integrated Computational Investigation.

Polycyclic aromatic hydrocarbons (PAHs), ubiquitous environmental pollutants, are considered significant environmental factors contributing to the pathogenesis of RA. Benzo[a]pyrene (BaP), a key component of PAHs, may be associated with RA onset; however, the underlying toxicological mechanism remains to be fully elucidated. In this study, we systematically addressed this knowledge gap using an integrated approach combining network toxicology, machine learning, and molecular docking. Initially, a network toxicology analysis was conducted based on the molecular structure of BaP. By integrating and screening target information from multiple databases, 15 potential RA-related target genes of BaP were ultimately identified, and their interaction network was constructed. GO and KEGG enrichment analyses revealed that these genes were significantly enriched in biological processes such as leukocyte migration and immune cell signal transduction and were associated with the NF-κB and T cell receptor signaling pathways, among others. Subsequent topological analysis using the STRING database and Cytoscape software screened out five core genes (LCK, ZAP70, ITK, GZMA, and ITGAL), whose importance was further validated through machine learning. Molecular docking and molecular dynamics simulation results indicated that BaP exhibits strong binding affinity for the protein products of these target genes, resulting in the formation of conformationally stable complexes. In summary, this study employs an integrated computational approach to elucidate the potential mechanisms by which BaP may contribute to RA development, thereby offering a theoretical foundation for future investigations into the prevention and treatment of RA associated with environmental pollutants.