Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia-reperfusion rats by activating Prkaca-mediated cAMP/PKA-MAPK pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38856956", "kind": "science-record", "revision": 4, "content_hash": "sha256:d2b437501b715b53b3006e36d4c431cfb31a5c21547d66e02aa51148093ac5e7", "created_at": "2026-11-01T20:28:55Z", "updated_at": "2026-11-01T22:54:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia-reperfusion rats by activating Prkaca-mediated cAMP/PKA-MAPK pathway.", "doi": "10.1111/jcmm.18366", "pmid": "38856956", "authors": ["Tao Kang", "Lijuan Zhu", "Yanli Xue", "Qian Yang", "Qi Lei", "Qianqian Wang"], "journal": "Journal of cellular and molecular medicine", "year": 2024, "abstract": "Ischemic stroke is one of the main causes of disability and death. However, recanalization of occluded cerebral arteries is effective only within a very narrow time window. Therefore, it is particularly important to find neuroprotective biological targets for cerebral artery recanalization. Here, gene expression profiles of datasets GSE160500 and GSE97537 were downloaded from the GEO database, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened, and which highly associated with Calcium signalling pathway and MAPK pathway. Interacting protein of Olfr78, Prkaca, was predicted by STRING, and their interaction was validated by Co-IP analysis. Then, a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a neuronal cell model stimulated by oxygen-glucose deprivation/reoxygenation (OGD/R) were constructed, and the results showed that expression of Olfr78 and Prkaca was downregulated in MCAO rats and OGD/R-stimulated neurons. Overexpression of Olfr78 or Prkaca inhibited the secretion of inflammatory factors, Ca2+ overload, and OGD/R-induced neuronal apoptosis. Moreover, Overexpression of Prkaca increased protein levels of cAMP, PKA and phosphorylated p38 in OGD/R-stimulated neurons, while SB203580, a p38 inhibitor, treatment inhibited activation of the cAMP/PKA-MAPK pathway and counteracted the effect of Olfr78 overexpression on improvement of neuronal functions. Meanwhile, overexpression of Olfr78 or Prkaca markedly inhibited neuronal apoptosis and improved brain injury in MCAO/R rats. In conclusion, overexpression of Olfr78 inhibited Ca2+ overload and reduced neuronal apoptosis in MCAO/R rats by promoting Prkaca-mediated activation of the cAMP/PKA-MAPK pathway, thereby improving brain injury in cerebral ischaemia-reperfusion.", "claims": [{"id": "claim-method", "statement": "DESeq2 software (v1.30.1) was used to normalize and calculate the fold change and p‐value between two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38856956", "locator": "sections[3] \"Bioinformatics analyses for datasets from GEO\" paragraph 3", "quote": "DESeq2 software (v1.30.1) was used to normalize and calculate the fold change and p‐value between two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data and materials used and analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38856956", "locator": "sections[33] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data and materials used and analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Meanwhile, 291 overlapping MCAO/R‐related DEGs were screened from the GSE97573 and GSE160500 datasets by joint analysis, of which 168 were overlapping upregulated DEGs and 123 were overlapping downregulated DEGs (Figure 2A).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38856956", "locator": "sections[20] \"Olfr78 was screened as a potential regulator in progression of MCAO/R\" paragraph 2", "quote": "Meanwhile, 291 overlapping MCAO/R‐related DEGs were screened from the GSE97573 and GSE160500 datasets by joint analysis, of which 168 were overlapping upregulated DEGs and 123 were overlapping downregulated DEGs (Figure 2A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Meanwhile, 291 overlapping MCAO/R‐related DEGs were screened from the GSE97573 and GSE160500 datasets by joint analysis, of which 168 were overlapping upregulated DEGs and 123 were overlapping downregulated DEGs (Figure 2A).", "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:38856956"], "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:GSE160500"], "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:GSE160500"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38856956", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/jcmm.18366", "sha256": "sha256:b3eaa838423f65aeaeaca494d5634ba1489cc8a193864b1dd0b9cc2e0a7c66c7", "bytes": 52179, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1111/jcmm.18366", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11163950", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE160500", "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=GSE160500", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE160500", "version": null, "note": "The data and materials used and analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data and materials used and analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4874222", "GSM4874223", "GSM4874224", "GSM4874225", "GSM4874226", "GSM4874227", "GSM4874228", "GSM4874229", "GSM4874230"], "sample_count": 9, "group_sizes": null, "group_sizes_basis": null, "platform": "22396", "taxon": "Rattus norvegicus", "title": "Transcriptomic and metabolomic Profiling reveal the protective effect of Acanthopanax senticosus (Rupr. & Maxim.) Harms combined with Gastrodia elata Blume on cerebral ischemia-reperfusion injury", "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:GSE97537", "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=GSE97537", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE97537", "version": null, "note": "The data and materials used and analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data and materials used and analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2571735", "GSM2571736", "GSM2571737", "GSM2571738", "GSM2571739", "GSM2571740", "GSM2571741", "GSM2571742", "GSM2571743", "GSM2571744", "GSM2571745", "GSM2571746"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "1355", "taxon": "Rattus norvegicus", "title": "Expression data from MCAO or Sham operated rat brain [mRNA]", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE160500 not downloaded", "asset:data:geo:GSE160500 licence not read", "asset:data:geo:GSE97537 not downloaded", "asset:data:geo:GSE97537 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "deseq2", "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": "DESeq2 software (v1.30.1) was used to normalize and calculate the fold change and p‐value between 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": "analysis of variance"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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: deseq2."}, "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": ["GSE160500", "GSE97537"], "resolved_accessions": ["GSE160500", "GSE97537"], "statements": ["The data and materials used and analyzed during the current study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE160500, GSE97537 in 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:38856956", "data:geo:GSE160500"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE160500"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:20:49Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14483, "completion_tokens": 1192, "cached_tokens": 264}}, "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:38856956", "type": "paper", "label": "pmid:38856956"}, {"id": "source:pmid:38856956", "type": "manuscript", "label": "PMID 38856956 full text"}, {"id": "data:geo:GSE160500", "type": "dataset", "label": "GEO GSE160500"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38856956", "type": "paper", "label": "pmid:38856956"}, {"id": "source:pmid:38856956", "type": "manuscript", "label": "PMID 38856956 full text"}, {"id": "data:geo:GSE160500", "type": "dataset", "label": "GEO GSE160500"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38856956", "type": "extraction", "used": ["source:pmid:38856956"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE160500", "type": "accession_resolution", "used": ["data:geo:GSE160500"], "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:38856956", "parent_hash": "sha256:8a52573300386365cb997876d3d1246903e8eb298f70f93a231f1d1333c27426", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE160500 licence not read", "asset:data:geo:GSE160500 not downloaded", "asset:data:geo:GSE97537 licence not read", "asset:data:geo:GSE97537 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["ain injury in cerebral ischaemia-reperfusion rats by activating Prkaca-mediated cAMP/PKA-MAPK", "abase, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened", "se, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened", "ion was validated by Co-IP analysis. Then, a rat model of middle cerebral artery occlusion/re"], "order_basis": "paper_text_order:54", "id": "assay:1"}, {"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": ["s, Ca2+ overload, and OGD/R-induced neuronal apoptosis. Moreover, Overexpression of Prkaca increase", "Olfr78 or Prkaca markedly inhibited neuronal apoptosis and improved brain injury in MCAO/R rats. In", "inhibited Ca2+ overload and reduced neuronal apoptosis in MCAO/R rats by promoting Prkaca-mediated"], "order_basis": "paper_text_order:1227", "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": ["DESeq2 software (v1.30.1) was used to normalize and calculate the fold change and p‐value between two groups."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}