Extracellular proteins as potential biomarkers in Sepsis-related cerebral injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37901226", "kind": "science-record", "revision": 3, "content_hash": "sha256:4bf527af393ddaf63da7a112e8fd42b473a3d3f3bd891e2e3903366bfe61b6bc", "created_at": "2026-11-01T19:02:46Z", "updated_at": "2026-11-01T22:10:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Extracellular proteins as potential biomarkers in Sepsis-related cerebral injury.", "doi": "10.3389/fimmu.2023.1128476", "pmid": "37901226", "authors": ["Jinlan Dong", "Shuang Wang", "Zhonghua Hu", "Li Gong"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: Sepsis can cause brain damage known as septic encephalopathy (SAE), which is linked to higher mortality and poorer outcomes. Objective clinical markers for SAE diagnosis and prognosis are lacking. This study aimed to identify biomarkers of SAE by investigating genes and extracellular proteins involved in sepsis-induced brain injury.\nMethods: Extracellular protein differentially expressed genes (EP-DEGs) from sepsis patients' brain tissue (GSE135838) were obtained from Gene Expression Omnibus (GEO) and evaluated by protein annotation database. The function and pathways of EP-DEGs were examined using GO and KEGG. Protein-protein interaction (PPI) networks were built and crucial EP-DEGs were screened using STRING, Cytoscape, MCODE, and Cytohubba. The diagnostic and prognostic accuracy of key EP-DEGs was assessed in 31 sepsis patients' blood samples and a rat cecal ligation and puncture (CLP)-induced sepsis model. Cognitive and spatial memory impairment was evaluated 7-11 days post-CLP using behavioral tests. Blood and cerebrospinal fluid from 26 rats (SHAM n=14, CLP n=12) were collected 6 days after CLP to analyze key EP-DEGs.\nResults: Thirty-one EP-DEGs from DEGs were examined. Bone marrow leukocytes, neutrophil movement, leukocyte migration, and reactions to molecules with bacterial origin were all enhanced in EP-DEGs. In comparison to the sham-operated group, sepsis rats had higher levels of MMP8 and S100A8 proteins in their venous blood (both p<0.05) and cerebrospinal fluid (p=0.0506, p<0.0001, respectively). Four important extracellular proteins, MMP8, CSF3, IL-6, and S100A8, were identified in clinical peripheral blood samples. MMP8 and S100A8 levels in the peripheral blood of sepsis patients were higher in SAE than in non-SAE. In comparison to MMP8, S100A8 had a higher area under the curve (AUC: 0.962, p<0.05) and a higher sensitivity and specificity (80% and 100%, respectively) than MMP8 (AUC: 0.790, p<0.05). High levels of S100A8 strongly correlated with 28-day mortality and the Glasgow Coma Scale (GCS) scores.\nConclusion: The extracellular proteins MMP8, CSF3, IL-6, and S100A8 may be crucial in the pathophysiology of SAE. S100A8 and MMP8 are possible biomarkers for SAE's onset and progression. This research may help to clarify the pathogenesis of SAE and improve the diagnosis and prognosis of the disease.", "claims": [{"id": "claim-method", "statement": "Receiver operating characteristic (ROC) curves were used to obtain the performance characteristics of diagnostic SAEs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37901226", "locator": "sections[9] \"Statistical methods\" paragraph 2", "quote": "Receiver operating characteristic (ROC) curves were used to obtain the performance characteristics of diagnostic SAEs."}], "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/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37901226", "locator": "sections[17] \"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/s."}], "state": "complete"}, {"id": "claim-target-result", "statement": "S100A8 showed the strongest diagnostic performance for identifying sepsis-associated encephalopathy, with an AUC of 0.962, 80% sensitivity, and 100% specificity at a cutoff of 82.29 pg/ml.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37901226", "locator": "sections[15] \"MMP8 and S100A8 diagnostic and prognostic efficacy\" paragraph 2", "quote": "Both S100A8 (AUC = 0.962, 95% CI = 0.9001-1.000) and MMP8(AUC = 0.791, 95% CI = 0.625-0.956) demonstrated high diagnostic accuracy for the diagnosis of SAE, with S100A8 having the highest AUC ( Figure 6B )."}, {"asset": "source:pmid:37901226", "locator": "sections[15] \"MMP8 and S100A8 diagnostic and prognostic efficacy\" paragraph 2", "quote": "S100A8 had a cut-off value of 82.29 pg/ml and corresponding sensitivity and specificity of 80% and 100%, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "S100A8 showed the strongest diagnostic performance for identifying sepsis-associated encephalopathy, with an AUC of 0.962, 80% sensitivity, and 100% specificity at a cutoff of 82.29 pg/ml.", "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:37901226"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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