Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38539069", "kind": "science-record", "revision": 5, "content_hash": "sha256:ee8d14a86e3b41d5cd637a90d1caa157d81b97029d049b2aec586f253d9f6c7b", "created_at": "2026-11-01T19:20:29Z", "updated_at": "2026-11-01T22:53:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury.", "doi": "10.1186/s12872-024-03834-x", "pmid": "38539069", "authors": ["Zhian Chen", "Tianying Liu", "Hao Yuan", "Han Sun", "Sitong Liu", "Shuai Zhang", "Li Liu", "Shuang Jiang", "Yong Tang", "Zhi Liu"], "journal": "BMC cardiovascular disorders", "year": 2024, "abstract": "BACKGROUND: Myocardial ischemia is a prevalent cardiovascular disorder associated with significant morbidity and mortality. While prompt restoration of blood flow is essential for improving patient outcomes, the subsequent reperfusion process can result in myocardial ischemia-reperfusion injury (MIRI). Mitophagy, a specialized autophagic mechanism, has consistently been implicated in various cardiovascular disorders. However, the specific connection between ischemia-reperfusion and mitophagy remains elusive. This study aims to elucidate and validate central mitophagy-related genes associated with MIRI through comprehensive bioinformatics analysis.\nMETHODS: We acquired the microarray expression profile dataset (GSE108940) from the Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) using GEO2R. Subsequently, these DEGs were cross-referenced with the mitophagy database, and differential nucleotide sequence analysis was performed through enrichment analysis. Protein-protein interaction (PPI) network analysis was employed to identify hub genes, followed by clustering of these hub genes using cytoHubba and MCODE within Cytoscape software. Gene set enrichment analysis (GSEA) was conducted on central genes. Additionally, Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses were conducted to validate the expression patterns of pivotal genes in MIRI rat model and H9C2 cardiomyocytes.\nRESULTS: A total of 2719 DEGs and 61 mitophagy-DEGs were identified, followed by enrichment analyses and the construction of a PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1, HIF-1α, and BNIP3 emerged as the seven hub genes identified by cytoHubba and MCODE of Cytoscape software. Functional clustering analysis of HIF-1α and BNIP3 yielded a score of 9.647, as determined by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a significant elevation in the expression of HIF-1α and BNIP3, accompanied by a notable increase in the ratio of LC3II to LC3I. Subsequently, qPCR confirmed a significant upregulation of HIF-1α, BNIP3, and LC3 mRNA in the MIRI group. Activation of the HIF-1α/BNIP3 pathway mediates the regulation of the degree of Mitophagy, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes.\nCONCLUSIONS: This study has identified seven central genes among mitophagy-related DEGs that may play a pivotal role in MIRI, suggesting a correlation between the HIF-1α/BNIP3 pathway of mitophagy and the pathogenesis of MIRI. The findings highlight the potential importance of mitophagy in MIRI and provide valuable insights into underlying mechanisms and potential therapeutic targets for further exploration in future studies.", "claims": [{"id": "claim-method", "statement": "GEO2R (www.ncbi.nlm.nih.gov/geo/ge2r) is a online analysis tool that utilizes the GEO query and Limma packages. We used GEO2R with a P.adj < 0.05 and |logFC|> 0.58 to identify DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38539069", "locator": "sections[4] \"Identification of DEGs and mitophagy-DEGs\" paragraph 2", "quote": "GEO2R (www.ncbi.nlm.nih.gov/geo/ge2r) is a online analysis tool that utilizes the GEO query and Limma packages. We used GEO2R with a P.adj < 0.05 and |logFC|> 0.58 to identify DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The analysis in this study utilized publicly available datasets. The data can be accessed at the following links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108940 and https://www.genecards.org/Search/Keyword?queryString=mitophagy.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38539069", "locator": "sections[35] \"Availability of data and materials\" paragraph 2", "quote": "The analysis in this study utilized publicly available datasets. The data can be accessed at the following links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108940 and https://www.genecards.org/Search/Keyword?queryString=mitophagy."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:38539069"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE108940"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE108940"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38539069", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12872-024-03834-x", "sha256": "sha256:06dafb96ca2896c61d0e693acb1422532704ac6bba41e2ee2fe2f7f3a3381faa", "bytes": 63060, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12872-024-03834-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10967080", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE108940", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108940", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE108940", "version": null, "note": "The analysis in this study utilized publicly available datasets. 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The data can be accessed at the following links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108940 and https://www.genecards.org/Search/Keyword?queryString=mitophagy.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2916264", "GSM2916265", "GSM2916266", "GSM2916267", "GSM2916268", "GSM2916269", "GSM2916270", "GSM2916271", "GSM2916272", "GSM2916273", "GSM2916274", "GSM2916275", "GSM2916276", "GSM2916277", "GSM2916278", "GSM2916279", "GSM2916280", "GSM2916281", "GSM2916282", "GSM2916283", "GSM2916284", "GSM2916285", "GSM2916286", "GSM2916287"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "7202", "taxon": "Mus musculus", "title": "Cardiac Muscle Ring Finger-1 (MuRF1) and Transcriptional Regulation of Ischemia-Reperfusion Injury In Vivo", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE108940 not downloaded", "asset:data:geo:GSE108940 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "GEO2R (www.ncbi.nlm.nih.gov/geo/ge2r) is a online analysis tool that utilizes the GEO query and Limma packages. 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METHODS: We acquired the microarray expression profile dataset (GSE108940) from"], "order_basis": "paper_text_order:750", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["as conducted on central genes. Additionally, Western blotting, immunofluorescence, and quantitative polyme", "by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a"], "order_basis": "paper_text_order:1334", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ntral genes. Additionally, Western blotting, immunofluorescence, and quantitative polymerase chain reaction", "DE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a significant elevation i"], "order_basis": "paper_text_order:1352", "id": "assay:3"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and quantitative polymerase chain reaction (qPCR) analyses were conducted to validate the exp", "in the ratio of LC3II to LC3I. Subsequently, qPCR confirmed a significant upregulation of HIF-"], "order_basis": "paper_text_order:1417", "id": "assay:4"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["expression patterns of pivotal genes in MIRI rat model and H9C2 cardiomyocytes. RESULTS: A to", "determined by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence a", "y, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes. CONCLUSIONS: This study", "logy Co., Ltd., located in Wuhan, China. All rats were housed in the SPF-rated rat rearing room at"], "order_basis": "paper_text_order:1507", "id": "assay:5"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e of Mitophagy, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes. CONCLUSIONS: Thi", "n. Flow cytometric analysis of cardiomyocyte apoptosis Following cell culture supernatant collectio", "µL of cell suspension was added with 5 µL of Annexin V-PE (G1512-1, Servicebio, China) and 5 µL of"], "order_basis": "paper_text_order:2373", "id": "assay:6"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["el under the condition of HIF-1α inhibition. Flow cytometric analysis of cardiomyocyte apoptosis Followin", "ed, mixed gently, and analyzed within 1 h by flow cytometry or fluorescence microscopy. Validation and e"], "order_basis": "paper_text_order:5340", "id": "assay:7"}, {"role": "data_generation", "definition_id": "cell_imaging", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["within 1 h by flow cytometry or fluorescence microscopy. Validation and enrichment analysis of mitop"], "order_basis": "paper_text_order:6330", "id": "assay:8"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["GEO2R (www.ncbi.nlm.nih.gov/geo/ge2r) is a online analysis tool that utilizes the GEO query and Limma packages. We used GEO2R with a P.adj < 0.05 and |logFC|> 0.58 to identify DEGs."], "order_basis": "consumes_earlier_output", "id": "assay:9"}]}