Mitigating psychological stress-induced cardiac injury: The impact of CB2R agonists on endoplasmic reticulum stress and mitophagy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41550502", "kind": "science-record", "revision": 3, "content_hash": "sha256:da10ed5b3e494e53b8852dd13f6801c2b3034fdcdcd9390a9793a79a35e58dc0", "created_at": "2026-11-01T20:31:31Z", "updated_at": "2026-11-01T22:15:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mitigating psychological stress-induced cardiac injury: The impact of CB2R agonists on endoplasmic reticulum stress and mitophagy.", "doi": "10.1016/j.bbrep.2025.102425", "pmid": "41550502", "authors": ["Chenke Ma", "Wenbin Gai", "Kan Zhang", "Cheng Qin"], "journal": "Biochemistry and biophysics reports", "year": 2026, "abstract": "Background: Psychological stress is a recognized contributor to cardiac injury and disease; however, the molecular mechanisms underlying this relationship remain incompletely understood, and effective therapeutic strategies are still limited.\nMaterials and methods: DEGs were identified from our sequencing data and GEO datasets, intersected with ER stress/mitophagy-related genes, and then prioritized by machine-learning and network analyses; pathway activity, immune signatures, molecular subtypes, and miRNA-mRNA interactions (DIANA-TarBase) were further characterized and experimentally validated.\nResults: In cardiac injury induced by psychological stress, 38 differentially expressed ER stress- and mitophagy-related genes were identified. Through methods such as LASSO regression, four key genes-Foxo3, Pparg, Sirt1, and Stat3-were selected. ROC analysis of the four-gene phenotype score showed strong discrimination in the test dataset (AUC = 0.917 for control vs. stress; AUC = 0.938 for stress vs. CB2R-agonist treatment) and moderate discrimination in the external validation cohort GSE68077 for the comparison of controls versus 5dayStress-1dayRest samples (AUC = 0.720). Correlation analysis revealed that Sirt1 exhibited significant positive correlations with CD56bright natural killer cells, MDSCs, and Type 1 T helper cells. Pparg showed a notable positive association with Type 1 T helper cells, while γδ T cells showed significant negative correlations with Stat3, Sirt1, Pparg, anRd Foxo3. Treatment with a cannabinoid type 2 receptor (CB2R) agonist notably downregulated the expression of these four key genes.\nConclusion: This study provides mechanistic insight into molecular processes underlying psychological stress-induced cardiac injury. The identified four-gene module may serve as an exploratory molecular signature and a starting point for evaluating CB2R agonism as a modulator of ER stress and mitophagy.", "claims": [{"id": "claim-method", "statement": "To construct a diagnostic model based on phenotype-associated differentially expressed genes within the test set, we performed Least Absolute Shrinkage and Selection Operator (LASSO) regression modeling conducted with the glmnet package in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41550502", "locator": "sections[7] \"LASSO analysis\" paragraph 2", "quote": "To construct a diagnostic model based on phenotype-associated differentially expressed genes within the test set, we performed Least Absolute Shrinkage and Selection Operator (LASSO) regression modeling conducted with the glmnet package in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data relevant to this study are publicly available through the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The specific datasets analyzed include GSE210820 and GSE68077. No additional proprietary or confidential data were utilized.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41550502", "locator": "sections[36] \"Data availability\" paragraph 2", "quote": "All data relevant to this study are publicly available through the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The specific datasets analyzed include GSE210820 and GSE68077. No additional proprietary or confidential data were utilized."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ROC analysis of the four-gene phenotype score showed strong discrimination in the test dataset (AUC = 0.917 for control vs. stress; AUC = 0.938 for stress vs. CB2R-agonist treatment) and moderate discrimination in the external validation cohort GSE68077 for the comparison of controls versus 5dayStress-1dayRest samples (AUC = 0.720).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41550502", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "ROC analysis of the four-gene phenotype score showed strong discrimination in the test dataset (AUC = 0.917 for control vs. stress; AUC = 0.938 for stress vs. CB2R-agonist treatment) and moderate discrimination in the external validation cohort GSE68077 for the comparison of controls versus 5dayStress-1dayRest samples (AUC = 0.720)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "ROC analysis of the four-gene phenotype score showed strong discrimination in the test dataset (AUC = 0.917 for control vs. stress; AUC = 0.938 for stress vs. CB2R-agonist treatment) and moderate discrimination in the external validation cohort GSE68077 for the comparison of controls versus 5dayStress-1dayRest samples (AUC = 0.720).", "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:41550502"], "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:GSE210820"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE210820"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41550502", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.bbrep.2025.102425", "sha256": "sha256:4010bf51ef2363f8b33ff07289d6bd0e8ae8a5817ce5da59f48bab7024481be2", "bytes": 63051, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.bbrep.2025.102425", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12808523", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE210820", "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=GSE210820", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE210820", "version": null, "note": "All data relevant to this study are publicly available through the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). 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