{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:20:09Z","timestamp":1792167609041,"version":"4.4.0"},"reference-count":92,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219","award":["170\/1\/09.01.2024"],"award-info":[{"award-number":["170\/1\/09.01.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Sepsis is a major medical emergency, characterized by a dysfunctional immune response to infection, which often progresses to multiple organ failure and death. Early diagnosis and prognostic evaluation present significant challenges due to limitations in the specificity and sensitivity of traditional biomarkers. This narrative review summarizes recent evidence on the potential of circulating microRNAs (miRNAs) such as miR-150, miR-146a, miR-223, miR-155, miR-122, and miR-4772-5p and plasma gelsolin (pGSN) as diagnostic and prognostic markers in sepsis. We discuss mechanisms involved and their potential for integration with artificial intelligence (AI) in personalized medicine. PubMed, Embase, and Web of Science databases were searched for relevant literature. Original research, systematic reviews, and meta-analyses focused on the diagnostic or prognostic value of circulating miRNAs or pGSN in sepsis were included; opinion papers and case reports were excluded. Altered expression of certain circulating microRNAs correlates with disease severity and mortality. Among circulating microRNAs (miRNAs), miR-122 and miR-150 have become the most consistently validated biomarkers in clinical studies, associated with sepsis severity and death rates. Additionally, other miRNAs such as miR-146a, miR-155, and miR-223 play roles in modulating immune and endothelial responses, highlighting the complex regulation of sepsis pathophysiology. Low pGSN concentrations at admission are associated with severe sepsis and acute respiratory distress syndrome, and serve as an independent predictor of mortality. Preclinical studies suggest that supplementation with exogenous pGSN could increase survival. AI algorithms show promising results for early sepsis detection and optimization of therapeutic decisions. However, combining circulating miRNAs and plasma gelsolin (pGSN) into AI-based models is still an exploratory idea that needs prospective validation, assay standardization, and multicenter studies before it can be used clinically.<\/jats:p>","DOI":"10.3390\/biom15111621","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T16:49:51Z","timestamp":1763484591000},"page":"1621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Circulating microRNAs and Plasma Gelsolin as Biomarkers of Sepsis: Molecular Insights and Prospects for Precision Medicine"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6297-0378","authenticated-orcid":false,"given":"Mircea","family":"Stoian","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219, 540103 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-2267","authenticated-orcid":false,"given":"Leonard","family":"Azamfirei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219, 540103 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4126-9339","authenticated-orcid":false,"given":"Sergio Rares","family":"Bandila","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery and Traumatology Service, Marina Baixa Hospital, Av. Alcade En Jaume Botella Mayor, 03570 Villajoyosa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-4926","authenticated-orcid":false,"given":"Adina","family":"Stoian","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4004-9648","authenticated-orcid":false,"given":"Drago\u0219-Florin","family":"Bab\u0103","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mure\u0219, 540142 Targu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-524X","authenticated-orcid":false,"given":"Claudia","family":"B\u0103nescu","sequence":"additional","affiliation":[{"name":"Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154096","DOI":"10.1016\/j.jcrc.2022.154096","article-title":"Hospital-related costs of sepsis around the world: A systematic review exploring the economic burden of sepsis","volume":"71","author":"Bouma","year":"2022","journal-title":"J. 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