Crosstalk between septic shock and venous thromboembolism: a bioinformatics and immunoassay analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38029239", "kind": "science-record", "revision": 4, "content_hash": "sha256:810166f5caa5e1e49b1489d9f6c731b0238de706c5d5b2b2e0d25fe3a0fb0e53", "created_at": "2026-11-01T19:02:58Z", "updated_at": "2026-11-01T22:53:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Crosstalk between septic shock and venous thromboembolism: a bioinformatics and immunoassay analysis.", "doi": "10.3389/fcimb.2023.1235269", "pmid": "38029239", "authors": ["Zhishu Li", "Chaolan Wang", "Xu Zhang", "Xiaolin Xu", "Meng Wang", "Lixia Dong"], "journal": "Frontiers in cellular and infection microbiology", "year": 2023, "abstract": "Background: Herein, we applied bioinformatics methods to analyze the crosstalk between septic shock (SS) and venous thromboembolism (VTE), focusing on the correlation with immune infiltrating cells.\nMethods: Expression data were obtained from the Gene Expression Omnibus (GEO) database, including blood samples from SS patients (datasets GSE64457, GSE95233, and GSE57065) and VTE patients (GSE19151). We used the R package \"limma\" for differential expression analysis (p value<0.05,∣logFC∣≥1). Venn plots were generated to identify intersected differential genes between SS and VTE and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment analysis. The protein-protein interaction (PPI) network of intersected genes was constructed by Cytoscape software. The xCell analysis identified immune cells with significant changes in VTE and SS and correlated them with significant molecular pathways of crosstalk. Finally, we validated the mRNA expression of crosstalk genes by qPCR, while Matrix Metalloprotein-9 (MMP-9) protein levels were assessed through Western blotting (WB) and Immunohistochemistry (IHC) in human umbilical vein endothelial cells (HUVECs) and mice.\nResults: In the present study, we conducted a comparison between 88 patients with septic shock and 55 control subjects. Additionally, we compared 70 patients with venous thromboembolism to 63 control subjects. Twelve intersected genes and their corresponding three important molecular pathways were obtained: Metabolic, Estrogen, and FOXO signaling pathways. The resulting PPI network has 194 nodes and 388 edges. The immune microenvironment analysis of the two diseases showed that the infiltration levels of M2 macrophages and Class-switched memory B cells were correlated with the enrichment scores of metabolic, estrogen, and FOXO signaling pathways. Finally, qPCR confirmed that the expression of MMP9, S100A12, ARG1, SLPI, and ANXA3 mRNA in the SS with VTE group was significantly elevated. WB and IHC experiments revealed that MMP9 protein was significantly elevated in the experimental group.\nConclusion: Metabolic, estrogen, and FOXO pathways play important roles in both SS and VTE and are related to the immune cell microenvironment of M2 macrophages and Class-switched memory B cells. MMP9 shows promise as a biomarker for diagnosing sepsis with venous thrombosis and a potential molecular target for treating this patient population.", "claims": [{"id": "claim-method", "statement": "We used the R package “limma” for differential expression analysis of controls and patients with SS and VTE, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38029239", "locator": "sections[4] \"Data preprocessing and differential expression analysis\" paragraph 3", "quote": "We used the R package “limma” for differential expression analysis of controls and patients with SS and VTE, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38029239", "locator": "sections[18] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE19151"], "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:GSE19151"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38029239", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcimb.2023.1235269", "sha256": "sha256:e6ba6bfd93031a319efdb7038ba0fea2899057903dbb9074a2858caf2ba81c33", "bytes": 53810, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcimb.2023.1235269", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10666789", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE19151", "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=GSE19151", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE19151", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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Additi", "ntrol subjects. Additionally, we compared 70 patients with venous thromboembolism to 63 control subject", "Expression Omnibus (GEO) database, including blood samples from SS patients (datasets GSE64457, GSE95233, an"], "order_basis": "paper_text_order:354", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ed the mRNA expression of crosstalk genes by qPCR, while Matrix Metalloprotein-9 (MMP-9) prote", "rogen, and FOXO signaling pathways. Finally, qPCR confirmed that the expression of MMP9, S100A"], "order_basis": "paper_text_order:1066", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["(MMP-9) protein levels were assessed through Western blotting (WB) and Immunohistochemistry (IHC) in human"], "order_basis": "paper_text_order:1147", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e assessed through Western blotting (WB) and Immunohistochemistry (IHC) in human umbilical vein endothelial ce", "tern blotting (WB) and Immunohistochemistry (IHC) in human umbilical vein endothelial cells (", "VTE group was significantly elevated. 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