{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:07:59Z","timestamp":1786406879401,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sepsis\u2010associated liver injury (SALI) plays a major role in aggravating disease progression and worsening prognosis in patients with sepsis. Macrophage polarization is a key factor in the modulation of SALI progression. Recent studies have shown that human breast milk\u2010derived exosomes (HBM\u2010Exos) regulate processes involved in macrophage polarization. Here, we investigated the function and mechanism of action of HBM\u2010Exos in a macrophage polarization model of SALI. The extracted HBM\u2010Exos were identified by morphological analysis and detection of marker proteins using flow cytometry. Human Kupffer cells were treated with lipopolysaccharide (LPS) to simulate macrophage polarization in SALI. Cell viability was measured using a CCK\u20108 kit. Protein and gene expression levels were evaluated using western blotting and RT\u2010qPCR, respectively. ELISA kits were used to assess the levels of inflammatory cytokines. The interactions between FP671120.4, ELAV Like RNA binding protein 1 (ELAVL1), and nuclear factor erythroid 2\u2010related factor 2 (Nrf2) were verified by RIP analysis. HBM\u2010Exos inhibited M1 macrophage polarization by promoting Nrf2 expression and phosphorylation via activation of the Nrf2\/Heme oxygenase\u20101 (HO\u20101) signaling pathway in LPS\u2010induced Kupffer cells. Furthermore, FP671120.4 reversed the HBM\u2010Exos\u2010mediated increase in Nrf2 mRNA stability. HBM\u2010Exos\u2010derived FP671120.4 enhanced the interaction between ELAVL1 and Nrf2. As a result, FP671120.4 inhibited M1 polarization by inducing Nrf2 expression via activation of the Nrf2\/HO\u20101 pathway. These findings suggest that HBM\u2010Exos\u2010derived FP671120.4 may inhibit M1 macrophage polarization through the ELVAL1\/Nrf2\/HO\u20101 signaling pathway in LPS\u2010induced Kupffer cells.<\/jats:p>","DOI":"10.1002\/kjm2.70108","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T10:25:23Z","timestamp":1758968723000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Human Breast Milk\u2010Derived Exosomal\n                    <scp>FP671120.4<\/scp>\n                    Inhibits Macrophage\n                    <scp>M1<\/scp>\n                    Polarization via Modulating the\n                    <scp>ELAVL1<\/scp>\n                    \/Nrf2 Axis in Sepsis\u2010Associated Liver Injury"],"prefix":"10.1002","volume":"42","author":[{"given":"Zhao\u2010Bin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine ICU Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou Municipal Hospital of Fujian Province  Zhangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine ICU Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou Municipal Hospital of Fujian Province  Zhangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Mei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine ICU Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou Municipal Hospital of Fujian Province  Zhangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4549-951X","authenticated-orcid":false,"given":"Lu\u2010Zhen","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine ICU Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou Municipal Hospital of Fujian Province  Zhangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","first-page":"67","article-title":"Sepsis Definition: What's New in the Treatment Guidelines","volume":"61","author":"Srzic I.","year":"2022","journal-title":"Acta Clinica 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