Unraveling the mechanisms of nicotine-induced osteoporosis via network toxicology, bioinformatics, and molecular docking.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41568086", "kind": "science-record", "revision": 4, "content_hash": "sha256:2df03d788c336b439dca51e1b91ee769782a80f6b0d5a6f66ad95d979929519a", "created_at": "2026-11-01T20:31:32Z", "updated_at": "2026-11-01T22:57:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unraveling the mechanisms of nicotine-induced osteoporosis via network toxicology, bioinformatics, and molecular docking.", "doi": "10.18332/tid/215177", "pmid": "41568086", "authors": ["Song Xu", "Guozhu Wang", "Jiaxin Liu", "Xiongwen Zhang", "Xie Dong", "Jin Liang", "Tao Bai"], "journal": "Tobacco induced diseases", "year": 2026, "abstract": "INTRODUCTION: Osteoporosis (OP) is linked to smoking. Nicotine may disrupt bone homeostasis through various pathways, but its molecular mechanisms are unclear. This study aims to explore the molecular networks and key regulatory factors underlying nicotine-induced OP.\nMETHODS: Nicotine toxicity was assessed via ProTox-3.0, with its Simplified Molecular Input Line Entry System (SMILES) structure retrieved from PubChem. Potential targets were predicted using five databases, including SuperPred. OP-related gene data (GSE56815) were extracted from Gene Expression Omnibus (GEO) and combined with GeneCards and Comparative Toxicogenomics Database (CTD) for target screening. Overlapping genes were identified by Venn diagram analysis, followed by protein-protein interaction (PPI) network construction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using HipLot, while Hallmark Gene Sets provided insights into key biological pathways. Core targets were screened via Cytoscape 3.9.1, and molecular docking was conducted using AutoDockTools 1.5.7.\nRESULTS: In all, 388 nicotine-associated targets and 1777 OP genes were predicted, with 116 overlapping. Enrichment analyses revealed associations with multiple signaling pathways, particularly those involving apoptosis and estrogen. Eight core targets, including SRC, BCL2, and CASP3, were identified. Molecular docking showed strong binding affinity (approximately -5 kcal/mol), with enhanced binding stability through hydrophobic interactions and hydrogen bonding.\nCONCLUSIONS: This study suggests nicotine exacerbates OP by regulating key targets, such as CASP3 and ESR1, and pathways like apoptosis and estrogen signaling. These findings provide insights into the molecular mechanisms underlying nicotine's role in OP and potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "Differential expression between the osteoporosis and normal groups was evaluated using the limma package, with p-values adjusted for multiple testing by the Benjamini-Hochberg method to control the false discovery rate (FDR <0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41568086", "locator": "sections[4] \"Osteoporosis-related target screening\" paragraph 2", "quote": "Differential expression between the osteoporosis and normal groups was evaluated using the limma package, with p-values adjusted for multiple testing by the Benjamini-Hochberg method to control the false discovery rate (FDR <0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data supporting this research are available from the authors on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41568086", "locator": "sections[24] \"DATA AVAILABILITY\" paragraph 2", "quote": "The data supporting this research are available from the authors on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Among 388 nicotine-related targets and 1777 osteoporosis genes, 116 overlapped, eight core targets were identified, and molecular docking indicated favorable binding, particularly for CASP3, ESR1, and SRC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41568086", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In all, 388 nicotine-associated targets and 1777 OP genes were predicted, with 116 overlapping."}, {"asset": "source:pmid:41568086", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Eight core targets, including SRC, BCL2, and CASP3, were identified."}, {"asset": "source:pmid:41568086", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Molecular docking showed strong binding affinity (approximately -5 kcal/mol), with enhanced binding stability through hydrophobic interactions and hydrogen bonding."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Among 388 nicotine-related targets and 1777 osteoporosis genes, 116 overlapped, eight core targets were identified, and molecular docking indicated favorable binding, particularly for CASP3, ESR1, and SRC.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41568086"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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