{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T08:28:39Z","timestamp":1787128119083,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8P0341"],"award-info":[{"award-number":["CMRPG8P0341"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sepsis\u2010induced organ failure involves dysregulated neutrophil responses, including neutrophil extracellular trap (NET) formation, via NETosis. Exosomes generated from adipose\u2010derived stem cells (ADSCs) have shown potential in sepsis treatment. This study characterized organ\u2010specific NETosis in the kidney, liver, and lungs using a murine cecal ligation and puncture (CLP) model and assessed the modulatory effects of ADSC exosomes. Male C57BL\/6 mice were grouped as follows: control, CLP, and CLP with ADSC exosome therapy (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096 per group). Plasma cell\u2010free DNA (cfDNA) and tissue citrullinated histone H3 (CitH3) levels were measured at 16\u2009h postoperatively. Confocal immunofluorescence was performed by co\u2010staining for CitH3 and Ly6G. Organ\u2010derived Ly6G\u2010enriched neutrophils were subjected to quantitative reverse transcription polymerase chain reaction for seven NETosis\u2010related genes:\n                    <jats:italic>CYBB<\/jats:italic>\n                    ,\n                    <jats:italic>Padi4<\/jats:italic>\n                    ,\n                    <jats:italic>H2ac20<\/jats:italic>\n                    ,\n                    <jats:italic>H2bc21<\/jats:italic>\n                    ,\n                    <jats:italic>Nlrc4<\/jats:italic>\n                    ,\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    , and\n                    <jats:italic>Ripk3<\/jats:italic>\n                    . CLP significantly elevated plasma cfDNA and lung CitH3 levels, whereas ADSC exosome treatment reduced both. Kidney and liver CitH3 levels remained unchanged across the groups. Confocal imaging confirmed active NETosis predominantly in the lung, with minimal signals in the kidneys and liver. In kidney and liver neutrophils, only\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    and\n                    <jats:italic>Ripk3<\/jats:italic>\n                    were significantly upregulated by CLP. In the lungs, all seven genes were significantly elevated; ADSC exosomes significantly reduced\n                    <jats:italic>Padi4<\/jats:italic>\n                    ,\n                    <jats:italic>H2ac20<\/jats:italic>\n                    ,\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    , and\n                    <jats:italic>Ripk3<\/jats:italic>\n                    . CLP\u2010induced NETosis was more pronounced in the lungs at the protein and transcriptional levels, where ADSC exosomes broadly suppressed NETotic pathways. NETosis reduction by ADSC exosomes was not observed in renal and hepatic neutrophils, indicating their possible protective role in sepsis within the pulmonary system.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70273","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T08:19:41Z","timestamp":1787127581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>NETosis<\/scp>\n                    in the Kidney, Liver, and Lung of Mice With Cecal Ligation and Puncture\u2010Induced Sepsis and the Ameliorating Effects of Adipose\u2010Derived Stem Cell Exosomes"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0984-6921","authenticated-orcid":false,"given":"Shao\u2010Chun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsu\u2010Hsiang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Wen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-2746","authenticated-orcid":false,"given":"Ching\u2010Hua","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung Taiwan"},{"name":"Doctoral Program of Clinical and Experimental Medicine, College of Medicine National Sun Yat\u2010sen University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00138"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1377817"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2021.10.039"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1496966"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12081038"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-023-01204-y"},{"key":"e_1_2_10_11_1","article-title":"MPO\u2010DNA Complexes and 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