Revealing oxidative stress-related genes in osteoporosis and advanced structural biological study for novel natural material discovery regarding MAPKAPK2.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36479222", "kind": "science-record", "revision": 4, "content_hash": "sha256:1d47747440df88a6decb85eb80a5bb774f8b3a046e235e32aaea1eb2fa668ce2", "created_at": "2026-11-01T19:00:58Z", "updated_at": "2026-11-01T22:50:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Revealing oxidative stress-related genes in osteoporosis and advanced structural biological study for novel natural material discovery regarding MAPKAPK2.", "doi": "10.3389/fendo.2022.1052721", "pmid": "36479222", "authors": ["Yingjing Zhao", "Weihang Li", "Kuo Zhang", "Meng Xu", "Yujia Zou", "Xiaotong Qiu", "Tianxing Lu", "Bo Gao"], "journal": "Frontiers in endocrinology", "year": 2022, "abstract": "Objectives: This study aimed to find novel oxidative stress (OS)-related biomarkers of osteoporosis (OP), together with targeting the macromolecule Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) protein to further discover potential novel materials based on an advanced structural biology approach.\nMethods: Gene expression profiles of GSE35958 were obtained from the Gene Expression Omnibus (GEO) database, which were included for weighted gene co-expression network analysis (WGCNA) and differential analysis to identify the most correlated module, to identify OS-related hub genes in the progression of OP. Functional annotations were also analyzed on the interested module to get a comprehensive understanding of these genes. Then, a series of advanced structural biology methods, including high-throughput screening, pharmacological characteristic prediction, precise molecular docking, molecular dynamics simulation, etc., was implemented to discover novel natural inhibitor materials against the MAPKAPK2 protein.\nResults: The brown module containing 720 genes was identified as the interested module, and a group set of genes was determined as the hub OS-related genes, including PPP1R15A, CYB5R3, BCL2L1, ABCD1, MAPKAPK2, HSP90AB1, CSF1, RELA, P4HB, AKT1, HSP90B1, and CTNNB1. Functional analysis demonstrated that these genes were primarily enriched in response to chemical stress and several OS-related functions. Then, Novel Materials Discovery demonstrated that two compounds, ZINC000014951634 and ZINC000040976869, were found binding to MAPKAPK2 with a favorable interaction energy together with a high binding affinity, relatively low hepatoxicity and carcinogenicity, high aqueous solubility and intestinal absorption levels, etc., indicating that the two compounds were ideal potential inhibitor materials targeting MAPKAPK2.\nConclusion: This study found a group set of OS-related biomarkers of OP, providing further insights for OS functions in the development of OP. This study then focused on one of the macromolecules, MAPKAPK2, to further discover potential novel materials, which was of great significance in guiding the screening of MAPKAPK2 potential materials.", "claims": [{"id": "claim-method", "statement": "WGCNA was performed based on R environment (version 4.1.3) based on the “WGCNA” package (26). The DEGs between normal and primary OP patients were analyzed and identified according to the gene expression matrix from GSE35958 using R (“limma” package).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36479222", "locator": "sections[5] \"Weighted gene co-expression network analysis\" paragraph 2", "quote": "WGCNA was performed based on R environment (version 4.1.3) based on the “WGCNA” package (26)."}, {"asset": "source:pmid:36479222", "locator": "sections[6] \"Analysis of the differentially expressed genes\" paragraph 2", "quote": "The DEGs between normal and primary OP patients were analyzed and identified according to the gene expression matrix from GSE35958 using R (“limma” package)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE35958.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36479222", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE35958."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The brown module containing 720 genes was identified as the interested module, and a group set of genes was determined as the hub OS-related genes, including PPP1R15A, CYB5R3, BCL2L1, ABCD1, MAPKAPK2, HSP90AB1, CSF1, RELA, P4HB, AKT1, HSP90B1, and CTNNB1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36479222", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The brown module containing 720 genes was identified as the interested module, and a group set of genes was determined as the hub OS-related genes, including PPP1R15A, CYB5R3, BCL2L1, ABCD1, MAPKAPK2, HSP90AB1, CSF1, RELA, P4HB, AKT1, HSP90B1, and CTNNB1."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The brown module containing 720 genes was identified as the interested module, and a group set of genes was determined as the hub OS-related genes, including PPP1R15A, CYB5R3, BCL2L1, ABCD1, MAPKAPK2, HSP90AB1, CSF1, RELA, P4HB, AKT1, HSP90B1, and CTNNB1.", "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:36479222"], "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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