Neuroinflammation mediates the progression of neonate hypoxia-ischemia brain damage to Alzheimer's disease: a bioinformatics and experimental study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39872979", "kind": "science-record", "revision": 4, "content_hash": "sha256:69798c650ad9cc752fad68a392ea25b5ebe194042d933963876b502c5ed68096", "created_at": "2026-11-01T20:30:09Z", "updated_at": "2026-11-01T22:56:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Neuroinflammation mediates the progression of neonate hypoxia-ischemia brain damage to Alzheimer's disease: a bioinformatics and experimental study.", "doi": "10.3389/fnagi.2024.1511668", "pmid": "39872979", "authors": ["Shengjie Zhang", "Ruqiu Zhang", "Zhaoqin Chen", "Zihan Shao", "An Li", "Fan Li", "Fang Huang"], "journal": "Frontiers in aging neuroscience", "year": 2024, "abstract": "Background: Traumatic brain injury (TBI) can generally be divided into focal damage and diffuse damage, and neonate Hypoxia-Ischemia Brain Damage (nHIBD) is one of the causes of diffuse damage. Patients with nHIBD are at an increased risk of developing Alzheimer's disease (AD). However, the shared pathogenesis of patients affected with both neurological disorders has not been fully elucidated.\nPurpose: We here aim to identify the shared molecular signatures between nHIBD and AD. We used an integrated analysis of the cortex gene expression data, targeting differential expression of genes related to the mechanisms of neurodegeneration and cognitive impairment following traumatic brain injury.\nMethods: The gene expression profiles of Alzheimer's disease (GSE203206) and that of Neonate Hypoxia-Ischemia Brain Damage (GSE23317) were obtained from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of Alzheimer's disease and neonate Hypoxia-Ischemia Brain Damage by limma package analysis, five kinds of analyses were performed on them, namely Gene Ontology (GO) and pathway enrichment analysis, protein-protein interaction network, DEG-transcription factor interactions and DEG-microRNA interactions, protein-drug interactions and protein-disease association analysis, and gene-inflammation association analysis and protein-inflammation association analysis.\nResults: In total, 12 common DEGs were identified including HSPB1, VIM, MVD, TUBB4A, AACS, ANXA6, DIRAS2, RPH3A, CEND1, KALM, THOP1, AREL1. We also identified 11 hub proteins, three central regulatory transcription factors, and three microRNAs encoded by the DEGs. Protein-drug interaction analysis showed that CYC1 and UQCRFS1 are associated with different drugs. Gene-disease association analysis shows Mammary Neoplasms, Neoplasm Metastasis, Schizophrenia, and Brain Ischemia diseases are the most relevant to the hub proteins we identified. Gene-inflammation association analysis shows that the hub gene AREL1 is related to inflammatory response, while the protein-inflammation association analysis shows that the hub proteins AKT1 and MAPK14 are related to inflammatory response.\nConclusion: This study provides new insights into the shared molecular mechanisms between AD and nHIBD. These common pathways and hub genes could potentially be used to design therapeutic interventions, reducing the likelihood of Alzheimer's disease development in survivors of neonatal Hypoxic-Ischemia brain injury.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were identified using the “Limma” package of R software (Ritchie et al., 2015).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39872979", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were identified using the “Limma” package of R software (Ritchie et al., 2015)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203206 (GSE203206), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23317 (GSE23317).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39872979", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203206 (GSE203206), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23317 (GSE23317)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In total, 12 common DEGs were identified including HSPB1, VIM, MVD, TUBB4A, AACS, ANXA6, DIRAS2, RPH3A, CEND1, KALM, THOP1, AREL1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39872979", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "In total, 12 common DEGs were identified including HSPB1, VIM, MVD, TUBB4A, AACS, ANXA6, DIRAS2, RPH3A, CEND1, KALM, THOP1, AREL1."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In total, 12 common DEGs were identified including HSPB1, VIM, MVD, TUBB4A, AACS, ANXA6, DIRAS2, RPH3A, CEND1, KALM, THOP1, AREL1.", "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:39872979"], "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:GSE203206"], "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:GSE203206"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39872979", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fnagi.2024.1511668", "sha256": "sha256:17d460166f161c11e065f3413919c30d5376a56f64c1b184540b4489415cc419", "bytes": 50518, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fnagi.2024.1511668", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11770030", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE203206", "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=GSE203206", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE203206", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203206 (GSE203206), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23317 (GSE23317).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203206 (GSE203206), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23317 (GSE23317).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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For novel object recognition, the nHIBD mouse explored novel objects for less time than th", "occurrence of AD. It has been proved that SD rats after nHIBD developed cognitive impairment 1"], "order_basis": "paper_text_order:4632", "id": "assay:1"}, {"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": ["s of four DEGs in cortex tissues detected by RT-qPCR. (A-F), Open Filed test. (A) The number of f", "vels of DIRAS2 in cortex tissues detected by RT-qPCR. (J) The expression levels of VIM in cortex", "levels of VIM in cortex tissues detected by RT-qPCR. (K) The expression levels of AREL1 in corte", "evels of AREL1 in cortex tissues detected by RT-qPCR. (L) The expression levels of RPH3A in corte"], "order_basis": "paper_text_order:6031", "id": "assay:2"}, {"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": ["Differentially expressed genes (DEGs) were identified using the “Limma” package of R software (Ritchie et al., 2015)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}