Analysis and Identification of Therapeutic Targets for Neuronal Regeneration After Ischemic Stroke.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40320842", "kind": "science-record", "revision": 4, "content_hash": "sha256:396489f0ee2e42d38bc210b34ca2ac49c18a73103cbb470070a2e3bf373fff91", "created_at": "2026-11-01T20:30:29Z", "updated_at": "2026-11-01T22:56:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis and Identification of Therapeutic Targets for Neuronal Regeneration After Ischemic Stroke.", "doi": "10.1002/brb3.70377", "pmid": "40320842", "authors": ["Xiao-Li Min", "Li Guo", "Zhenyu Wang", "Lei Zhao", "Chenglong Shi", "Xiaoyong Liu", "Zhen Wang", "Fei-Fei Shang", "Jiaping Wang"], "journal": "Brain and behavior", "year": 2025, "abstract": "OBJECTIVE: The aim of this study is to analyze and identify genes associated with neuronal regeneration after ischemic stroke (IS) and to predict potential therapeutic targets for neuronal regeneration after IS using bioinformatics analysis methods.\nMETHODS: The GSE137482 and GSE208121 datasets were obtained from the Gene Expression Omnibus (GEO) database, and the differentially expressed hub genes that showed decreased expression in GEO and increased expression in neuronal regeneration after IS were identified as key genes. To identify the key genes, functional enrichment and Protein-Protein Interaction (PPI) network analysis were conducted. The expression levels of the key genes were characterized by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in neuron-induced cell models. Additionally, possible regulatory networks of the key genes were analyzed.\nRESULTS: The screening process yielded 24 differentially expressed pivotal genes, which were predominantly enriched in processes related to epithelial cell proliferation regulation and hormone response. The PPI analysis yielded five key genes (Npas4, Nr4a3, Nr4a1, Egr4, and Egr1), which may exert regulatory roles primarily through peptide and peptide hormone responses. RT-qPCR and western blot assays confirmed that the expression levels of the key genes were elevated in the neuron-like differentiated cell model. However, these findings were inhibited by additional treatment with hypoxia. The analysis of the key gene regulatory network revealed that EGR1 and NR4A1 might regulate hub genes by utilizing their transcription factor properties, with EGR1 being the predominant regulator. The validation results from our cellular model indicated that upregulating EGR1 promotes neuronal-like differentiation in SH-SY5Y cells.\nCONCLUSION: EGR1 could potentially serve as a therapeutic target for neuronal regeneration following IS.", "claims": [{"id": "claim-method", "statement": "Using the GEOquery V2.64.2 package (RRID: SCR000146) in R V4.3.3 software (RRID: SCR001905), we obtained the required data and performed differential analysis using the limma V3.52.2 package (RRID: SCR010943). A one‐way ANOVA was used for statistical differences, and Student's t‐test was used to analyze differences between the two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40320842", "locator": "sections[3] \"Analysis of Differentially Expressed Genes\" paragraph 2", "quote": "Using the GEOquery V2.64.2 package (RRID: SCR000146) in R V4.3.3 software (RRID: SCR001905), we obtained the required data and performed differential analysis using the limma V3.52.2 package (RRID: SCR010943)."}, {"asset": "source:pmid:40320842", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "A one‐way ANOVA was used for statistical differences, and Student's t‐test was used to analyze differences between the two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40320842", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Upregulating EGR1 promotes neuronal-like differentiation in SH-SY5Y cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40320842", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The validation results from our cellular model indicated that upregulating EGR1 promotes neuronal‐like differentiation in SH‐SY5Y cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Upregulating EGR1 promotes neuronal-like differentiation in SH-SY5Y cells.", "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:40320842"], "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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the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12050405", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE137482", "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=GSE137482", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE137482", "version": null, "note": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4080041", "GSM4080042", "GSM4080043", "GSM4080044", "GSM4080045", "GSM4080046", "GSM4080047", "GSM4080048", "GSM4080049", "GSM4080050", "GSM4080051", "GSM4080052", "GSM4080053", "GSM4080054", "GSM4080055", "GSM4080056", "GSM4080057", "GSM4080058", "GSM4080059", "GSM4080060", "GSM4080061", "GSM4080062", "GSM4080063", "GSM4080064"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "19057", "taxon": "Mus musculus", "title": "RNA-Seq of ischemic stroke in young and aged mice", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE208121", "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=GSE208121", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE208121", "version": null, "note": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM6337733", "GSM6337734", "GSM6337735", "GSM6337736", "GSM6337737", "GSM6337738", "GSM6337739", "GSM6337740", "GSM6337741", "GSM6337742", "GSM6337743", "GSM6337744"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "24247", "taxon": "Mus musculus", "title": "Erinacine S from Hericium erinaceus Mycelium Promotes Neuronal Regeneration by Inducing Neurosteroids Accumulation", "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:GSE137482 not downloaded", "asset:data:geo:GSE137482 licence not read", "asset:data:geo:GSE208121 not downloaded", "asset:data:geo:GSE208121 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "reordered", "quote": "Using the GEOquery V2.64.2 package (RRID: SCR000146) in R V4.3.3 software (RRID: SCR001905), we obtained the required data and performed differential analysis using the limma V3.52.2 package (RRID: SCR010943). A one‐way ANOVA was used for statistical differences, and Student's t‐test was used to analyze differences between the two groups."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-4", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Protein-Protein Interaction"}}, {"id": "method-5", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}], "targets": [], "gaps": ["method.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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