{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T11:10:46Z","timestamp":1710933046149},"reference-count":63,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006020","name":"Center for Translational Molecular Medicine","doi-asserted-by":"publisher","award":["grant 04I\u2010201"],"award-info":[{"award-number":["grant 04I\u2010201"]}],"id":[{"id":"10.13039\/501100006020","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Community\u2010acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non\u2010coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP\u2010associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non\u2010infectious control participants. Plasma small RNA\u2010sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over\u2010represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to <jats:italic>Streptococcus pneumoniae<\/jats:italic> infection. Pathway analysis of plasma miRNA signatures unique to Influenza or <jats:italic>Streptococcus pneumoniae<\/jats:italic> infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways.<\/jats:p>","DOI":"10.1111\/jcmm.16406","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T07:43:27Z","timestamp":1626507807000},"page":"7621-7630","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The circulatory small non\u2010coding RNA landscape in community\u2010acquired pneumonia on intensive care unit admission"],"prefix":"10.1111","volume":"25","author":[{"given":"Hina N.","family":"Khan","sequence":"first","affiliation":[{"name":"Center for Experimental Molecular Medicine Amsterdam University Medical Centers location Academic Medical Center University of Amsterdam The Netherlands"},{"name":"Department of Clinical Epidemiology, Biostatistics and Bioinformatics Amsterdam University Medical Centers location Academic Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldo","family":"Jongejan","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Biostatistics and Bioinformatics Amsterdam University Medical Centers location Academic Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lonneke A.","family":"van Vught","sequence":"additional","affiliation":[{"name":"Center for Experimental Molecular Medicine Amsterdam University Medical Centers location Academic Medical Center University of Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janneke","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Intensive Care &amp; Laboratory of Experimental Intensive Care and Anesthesiology (L\u00b7E\u00b7I\u00b7C\u00b7A) Amsterdam 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