{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:08:47Z","timestamp":1792188527904,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":91,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108404h0001"],"award-info":[{"award-number":["20fk0108404h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acute Medicine &amp; Surgery"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Community\u2010acquired pneumonia is an acute lung infection in patients without recent healthcare exposure that can progress to severe sepsis. Despite the well\u2010established influence of miRNAs on inflammation, their specific roles in pneumonia\u2010associated sepsis remain underexplored. In this pilot study, we aimed to provide insights into the pathogenesis of community\u2010acquired pneumonia\u2010associated sepsis by performing an integrative mRNA\u2013miRNA analysis to identify key cellular signaling pathways and potential molecular targets for future research and treatment development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective, observational, single\u2010center study including 14 critically ill patients with community\u2010acquired pneumonia\u2010associated sepsis and 15 healthy controls (median age: 78 [interquartile range 67.3\u201383.5] and 55 [interquartile range 40.5\u201359.0] years, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven patients required ventilatory support, and six met the diagnostic criteria for septic shock. All patients survived. RNA sequencing revealed 1209 upregulated and 1461 downregulated differentially expressed genes for mRNAs (false discovery rate\u2009&lt;\u20090.05, |log\n                      <jats:sub>2<\/jats:sub>\n                      fold change| &gt;1.2), 51 upregulated and 21 downregulated genes for miRNAs, and 646 upregulated and 1274 downregulated for mRNA related to miRNAs. Canonical pathway analysis revealed activation of the programmed death\u20101\/programmed death\u2010ligand\u20101 cancer immunotherapy pathway and suppression of the Th1 pathway, indicating T\u2010cell exhaustion in the acute phase of community\u2010acquired pneumonia\u2010associated sepsis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides valuable insights into the molecular mechanisms underlying CAP\u2010associated sepsis, confirming the occurrence of immune dysregulation, particularly T\u2010cell exhaustion. Our findings suggest that specific miRNAs and signaling pathways identified here may serve as potential therapeutic targets or biomarkers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ams2.70054","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T07:45:23Z","timestamp":1743752723000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>mRNA<\/scp>\n                    \u2013\n                    <scp>miRNA<\/scp>\n                    integration analysis of T\u2010cell exhaustion in sepsis from community\u2010acquired pneumonia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2322-5423","authenticated-orcid":false,"given":"Sayaka","family":"Oda","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Osaka University Graduate School of Dentistry  Osaka 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