{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:04:26Z","timestamp":1791929066260,"version":"4.3.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Sterile inflammation is a major clinical concern during ischemia\u2010reperfusion injury (IRI) triggered by traumatic events, including stroke, myocardial infarction, and solid organ transplantation. Despite high\u2010mobility group box 1 (HMGB1) clearly being involved in sterile inflammation, its role is controversial because of a paucity of patient\u2010focused research.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Here, we examined the role of HMGB1 oxidation states in human IRI following liver transplantation. Portal blood immediately following allograft reperfusion (liver flush; LF) had increased total HMGB1, but only LF from patients with histopathological IRI had increased disulfide\u2010HMGB1 and induced Toll\u2010like receptor 4\u2013dependent tumor necrosis factor alpha production by macrophages. Disulfide HMGB1 levels increased concomitantly with IRI severity. IRI<jats:sup>+<\/jats:sup> prereperfusion biopsies contained macrophages with hyperacetylated, lysosomal disulfide\u2010HMGB1 that increased postreperfusion at sites of injury, paralleling increased histone acetyltransferase general transcription factor IIIC subunit 4 and decreased histone deacetylase 5 expression. Purified disulfide\u2010HMGB1 or IRI<jats:sup>+<\/jats:sup> blood stimulated further production of disulfide\u2010HMGB1 and increased proinflammatory molecule and cytokine expression in macrophages through a positive feedback loop.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These data identify disulfide\u2010HMGB1 as a mechanistic biomarker of, and therapeutic target for, minimizing sterile inflammation during human liver IRI.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31324","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T08:50:47Z","timestamp":1589878247000},"page":"1158-1175","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":74,"title":["Disulfide High\u2010Mobility Group Box 1 Drives Ischemia\u2010Reperfusion Injury in Human Liver Transplantation"],"prefix":"10.1097","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-6830","authenticated-orcid":false,"given":"Rebecca A.","family":"Sosa","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4156-991X","authenticated-orcid":false,"given":"Allyson Q.","family":"Terry","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fady M.","family":"Kaldas","sequence":"additional","affiliation":[{"name":"Dumont\u2010UCLA Transplantation Center,Department of Surgery,David Geffen School of Medicine at UCLA,Los 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Laboratory Medicine,David Geffen School of Medicine at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-2752","authenticated-orcid":false,"given":"Richard S.","family":"Ahn","sequence":"additional","affiliation":[{"name":"Institute of Quantitative and Computational Biosciences,David Geffen School of Medicine at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bita V.","family":"Naini","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria M.","family":"Groysberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA,Los 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Transplantation Center,Department of Surgery,David Geffen School of Medicine at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-1531","authenticated-orcid":false,"given":"Ronald W.","family":"Busuttil","sequence":"additional","affiliation":[{"name":"Dumont\u2010UCLA Transplantation Center,Department of Surgery,David Geffen School of Medicine at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Gjertson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA,Los Angeles,CA"},{"name":"Department of Biostatistics,School of Public Health at UCLA,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy W.","family":"Kupiec\u2010Weglinski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,David Geffen School of 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