Nrf2 functions as a pyroptosis-related mediator in traumatic brain injury and is correlated with cytokines and disease severity: a bioinformatics analysis and retrospective clinical study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38405399", "kind": "science-record", "revision": 4, "content_hash": "sha256:1600f0e07481166a60ba134d1291dca29df78c9b2dfec9990f4b9fe81ee3fb9b", "created_at": "2026-11-01T19:20:21Z", "updated_at": "2026-11-01T22:11:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Nrf2 functions as a pyroptosis-related mediator in traumatic brain injury and is correlated with cytokines and disease severity: a bioinformatics analysis and retrospective clinical study.", "doi": "10.3389/fneur.2024.1341342", "pmid": "38405399", "authors": ["Gengshui Zhao", "Jianfei Zhao", "Jiadong Lang", "Guozhu Sun"], "journal": "Frontiers in neurology", "year": 2024, "abstract": "Background: Traumatic brain injury (TBI) is a serious hazard to human health. Evidence has accumulated that pyroptosis plays an important role in brain trauma. The aim of this study is to screen potential key molecules between TBI and pyroptosis, and further explore their relationships with disease severity and cytokines.\nMethods: To acquire differentially expressed genes (DEGs) before and after brain injury, the GSE89866 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Meanwhile, pyroptosis-related genes were obtained from the GeneCards database, and the intersected genes were identified as differentially expressed pyroptosis-related genes (DEPGs). Moreover, the hub genes were screened via four algorithms (namely Maximum Clique Centrality, Edge Percolated Component, BottleNeck and EcCentricity) in Cytoscape software. Blood levels of Nrf2 were measured by ELISA using a commercially available kit. Finally, we further investigated the correlation between Nrf2 levels and medical indicators in TBI such as clinical characteristics, inflammatory cytokines, and severity.\nResults: Altogether, we found 1,795 DEGs in GSE89866 and 98 pyroptosis-related genes in the GeneCards database. Subsequently, four hub genes were obtained, and NFE2L2 was adopted for further clinical study. By using Kruskal-Wallis test and Spearman correlation test, we found that the serum Nrf2 levels in severe TBI patients were negatively correlated with GCS scores. On the contrary, there was a positive correlation between serum Nrf2 levels and pupil parameters, Helsinki CT scores, IL-1 β and IL-18.\nConclusions: In summary, bioinformatic analyses showed NFE2L2 plays a significant role in the pathology of TBI. The clinical research indicated the increase in serum Nrf2 levels was closely related to the severity of trauma and cytokines. We speculate that serum Nrf2 may serve as a promising biochemical marker for the assessment of TBI in clinical practice.", "claims": [{"id": "claim-method", "statement": "We utilized NetworkAnalyst to compare gene expression profiles between different groups in GSE89866.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38405399", "locator": "sections[4] \"2.2 Identification of differentially expressed pyroptosis-related genes\" paragraph 2", "quote": "We utilized NetworkAnalyst to compare gene expression profiles between different groups in GSE89866."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38405399", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:38405399"], "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:GSE89866"], "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:GSE89866"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38405399", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fneur.2024.1341342", "sha256": "sha256:1606cce9c5228363847ab0a31000affaa29a10068ee5f326179bc216df263293", "bytes": 26076, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fneur.2024.1341342", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10884226", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE89866", "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=GSE89866", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE89866", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2391756", "GSM2391757", "GSM2391758", "GSM2391759", "GSM2391760", "GSM2391761", "GSM2391762", "GSM2391763", "GSM2391764", "GSM2391765", "GSM2391766", "GSM2391767", "GSM2391768", "GSM2391769", "GSM2391770", "GSM2391771", "GSM2391772", "GSM2391773", "GSM2391774", "GSM2391775", "GSM2391776", "GSM2391777", "GSM2391778", "GSM2391779", "GSM2391780", "GSM2391781", "GSM2391782", "GSM2391783", "GSM2391784", "GSM2391785", "GSM2391786", "GSM2391787", "GSM2391788", "GSM2391789", "GSM2391790", "GSM2391791", "GSM2391792", "GSM2391793", "GSM2391794", "GSM2391795", "GSM2391796", "GSM2391797", "GSM2391798", "GSM2391799", "GSM2391800", "GSM2391801", "GSM2391802", "GSM2391803", "GSM2391804", "GSM2391805", "GSM2391806", "GSM2391807", "GSM2391808", "GSM2391809", "GSM2391810", "GSM2391811", "GSM2391812", "GSM2391813"], "sample_count": 58, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Moderate blast exposure alters gene expression and levels of amyloid precursor protein", "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:GSE89866 not downloaded", "asset:data:geo:GSE89866 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": "analysis of variance"}}, {"id": "method-2", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Spearman correlation"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "PPI"}}, {"id": "method-4", "family": "network_analysis", "specific": "centrality", "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": "Centrality"}}, {"id": "method-5", "family": null, "specific": null, "label": "NetworkAnalyst", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We utilized NetworkAnalyst to compare gene expression profiles between different groups in GSE89866."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE89866"], "resolved_accessions": ["GSE89866"], "statements": ["The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE89866 in National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:38405399", "data:geo:GSE89866"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE89866"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:10:03Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 7915, "completion_tokens": 1683, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:38405399", "type": "paper", "label": "pmid:38405399"}, {"id": "source:pmid:38405399", "type": "manuscript", "label": "PMID 38405399 full text"}, {"id": "data:geo:GSE89866", "type": "dataset", "label": "GEO GSE89866"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38405399", "type": "paper", "label": "pmid:38405399"}, {"id": "source:pmid:38405399", "type": "manuscript", "label": "PMID 38405399 full text"}, {"id": "data:geo:GSE89866", "type": "dataset", "label": "GEO GSE89866"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38405399", "type": "extraction", "used": ["source:pmid:38405399"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE89866", "type": "accession_resolution", "used": ["data:geo:GSE89866"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:38405399", "parent_hash": "sha256:bcf05597331ee0a21de2d95644e0a9a279df81ed3b33d8dda186b322549c9fee", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE89866 licence not read", "asset:data:geo:GSE89866 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["tware. Blood levels of Nrf2 were measured by ELISA using a commercially available kit. Finally,"], "order_basis": "paper_text_order:1035", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ets and study design The TBI gene expression microarray dataset was downloaded from the National Cen"], "order_basis": "paper_text_order:2178", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["analysis of variance"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}