Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37348034", "kind": "science-record", "revision": 4, "content_hash": "sha256:1f73d3d6e103bc5736df34555da1ba46dc6a1dfaf5d12ddb5e8c82360987f3c0", "created_at": "2026-11-01T19:02:05Z", "updated_at": "2026-11-01T22:52:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus.", "doi": "10.18632/aging.204822", "pmid": "37348034", "authors": ["Shuai Li", "Qi Hou", "Runjia Wang", "Yu Hou", "Qiang Wang", "Bo Zhang", "Cheng Ni", "Hui Zheng"], "journal": "Aging", "year": 2023, "abstract": "Postoperative cognitive dysfunction (POCD) is a serious and common complication induced by anesthesia and surgery. Neuronal apoptosis induced by general anesthetic neurotoxicity is a high-risk factor. However, a comprehensive analysis of general anesthesia-regulated gene expression patterns and further research on molecular mechanisms are lacking. Here, we performed bioinformatics analysis of gene expression in the hippocampus of aged rats that received sevoflurane anesthesia in GSE139220 from the GEO database, found a total of 226 differentially expressed genes (DEGs) and investigated hub genes according to the number of biological processes in which the genes were enriched and performed screening by 12 algorithms with cytoHubba in Cytoscape. Among the screened hub genes, Agt, Cdkn1a, Ddit4, and Rhob are related to the neuronal death process. We further confirmed that these genes, especially Ddit4, were upregulated in the hippocampus of aged mice that received sevoflurane anesthesia. NMDAR, the core target receptor of sevoflurane, rather than GABAAR, mediates the sevoflurane regulation of DDIT4 expression. Our study screened sevoflurane-regulated DEGs and focused on the neuronal death process to reveal DDIT4 as a potential target mediated by NMDAR, which may provide a new target for the treatment of sevoflurane neurotoxicity.", "claims": [{"id": "claim-method", "statement": "Then, the Limma package for the R environment was used to detect the differentially expressed genes (DEGs) in hippocampal tissue between the control group rats and the sevoflurane-treated rats [70].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37348034", "locator": "sections[9] \"Microarray data analysis\" paragraph 2", "quote": "Then, the Limma package for the R environment was used to detect the differentially expressed genes (DEGs) in hippocampal tissue between the control group rats and the sevoflurane-treated rats [70]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE139220 is available from the NCBI-GEO database with the link- https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139220. The datasets analyzed during this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37348034", "locator": "sections[16] \"Data availability statement\" paragraph 2", "quote": "GSE139220 is available from the NCBI-GEO database with the link- https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139220. The datasets analyzed during this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "NMDAR, the core target receptor of sevoflurane, rather than GABAAR, mediates the sevoflurane regulation of DDIT4 expression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37348034", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "NMDAR, the core target receptor of sevoflurane, rather than GABAAR, mediates the sevoflurane regulation of DDIT4 expression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "NMDAR, the core target receptor of sevoflurane, rather than GABAAR, mediates the sevoflurane regulation of DDIT4 expression.", "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:37348034"], "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:GSE139220"], "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:GSE139220"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37348034", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.204822", "sha256": "sha256:ac855172a8216f843f670bd06fe7bbc10fbc0ca00e7633573571e35dd01c332a", "bytes": 44863, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/aging.204822", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10333074", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE139220", "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=GSE139220", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE139220", "version": null, "note": "GSE139220 is available from the NCBI-GEO database with the link- https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139220. The datasets analyzed during this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE139220 is available from the NCBI-GEO database with the link- https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139220. The datasets analyzed during this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4134285", "GSM4134286", "GSM4134287", "GSM4134288", "GSM4134289", "GSM4134290"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "22388", "taxon": "Rattus norvegicus", "title": "Expression data from sevoflurane anesthesia treated rat", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE139220 not downloaded", "asset:data:geo:GSE139220 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": "Then, the Limma package for the R environment was used to detect the differentially expressed genes (DEGs) in hippocampal tissue between the control group rats and the sevoflurane-treated rats [70]."}}], "targets": [], "gaps": []}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE139220"], "resolved_accessions": ["GSE139220"], "statements": ["GSE139220 is available from the NCBI-GEO database with the link- https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139220. The datasets analyzed during this study are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE139220 in NCBI-GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37348034", "data:geo:GSE139220"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE139220"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:44:28Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13885, "completion_tokens": 1240, "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:37348034", "type": "paper", "label": "pmid:37348034"}, {"id": "source:pmid:37348034", "type": "manuscript", "label": "PMID 37348034 full text"}, {"id": "data:geo:GSE139220", "type": "dataset", "label": "GEO GSE139220"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37348034", "type": "paper", "label": "pmid:37348034"}, {"id": "source:pmid:37348034", "type": "manuscript", "label": "PMID 37348034 full text"}, {"id": "data:geo:GSE139220", "type": "dataset", "label": "GEO GSE139220"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37348034", "type": "extraction", "used": ["source:pmid:37348034"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE139220", "type": "accession_resolution", "used": ["data:geo:GSE139220"], "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:37348034", "parent_hash": "sha256:9854cdd287157e4b07d9fbfabd06b246a36ca3eb6b2fba831592ab05543564c3", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE139220 licence not read", "asset:data:geo:GSE139220 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["induced by anesthesia and surgery. Neuronal apoptosis induced by general anesthetic neurotoxicity", "antly enriched in the regulation of neuronal apoptosis (Figure 2B). Next, we screened the biologica", "antly enriched in the regulation of neuronal apoptosis. (F) Seven differentially expressed genes (6", "iched in the negative regulation of neuronal apoptosis. (Red: up regulated DEGs; blue: down regulat"], "order_basis": "paper_text_order:179", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.962, "evidence": ["f gene expression in the hippocampus of aged rats that received sevoflurane anesthesia in GSE1", "ed as the mean ± SD. The microarray data and in vivo PCR validations are displayed with boxplots."], "order_basis": "paper_text_order:493", "id": "assay:2"}, {"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": ["ive data are presented as the mean ± SD. The microarray data and in vivo PCR validations are display"], "order_basis": "paper_text_order:4531", "id": "assay:3"}, {"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": ["Then, the Limma package for the R environment was used to detect the differentially expressed genes (DEGs) in hippocampal tissue between the control group rats and the sevoflurane-treated rats [70]."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}