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HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammat...

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Autores principales: Yang, Zhangsheng, Simovic, Milomir O., Edsall, Peter R., Liu, Bin, Cancio, Tomas S., Batchinsky, Andriy I., Cancio, Leopoldo C., Li, Yansong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773879/
https://www.ncbi.nlm.nih.gov/pubmed/35053249
http://dx.doi.org/10.3390/biom12010101
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author Yang, Zhangsheng
Simovic, Milomir O.
Edsall, Peter R.
Liu, Bin
Cancio, Tomas S.
Batchinsky, Andriy I.
Cancio, Leopoldo C.
Li, Yansong
author_facet Yang, Zhangsheng
Simovic, Milomir O.
Edsall, Peter R.
Liu, Bin
Cancio, Tomas S.
Batchinsky, Andriy I.
Cancio, Leopoldo C.
Li, Yansong
author_sort Yang, Zhangsheng
collection PubMed
description Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 h after admission. In total, 45 (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 h after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01 (2-O, 3-O desulfated heparin). Animals were cannulated, then recovered for 5–7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels along with severe tissue damage and high mortality. CX-01 inhibited systemic HMGB1 activity, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.
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spelling pubmed-87738792022-01-21 HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma Yang, Zhangsheng Simovic, Milomir O. Edsall, Peter R. Liu, Bin Cancio, Tomas S. Batchinsky, Andriy I. Cancio, Leopoldo C. Li, Yansong Biomolecules Article Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 h after admission. In total, 45 (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 h after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01 (2-O, 3-O desulfated heparin). Animals were cannulated, then recovered for 5–7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels along with severe tissue damage and high mortality. CX-01 inhibited systemic HMGB1 activity, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage. MDPI 2022-01-08 /pmc/articles/PMC8773879/ /pubmed/35053249 http://dx.doi.org/10.3390/biom12010101 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Zhangsheng
Simovic, Milomir O.
Edsall, Peter R.
Liu, Bin
Cancio, Tomas S.
Batchinsky, Andriy I.
Cancio, Leopoldo C.
Li, Yansong
HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma
title HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma
title_full HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma
title_fullStr HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma
title_full_unstemmed HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma
title_short HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma
title_sort hmgb1 inhibition to ameliorate organ failure and increase survival in trauma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773879/
https://www.ncbi.nlm.nih.gov/pubmed/35053249
http://dx.doi.org/10.3390/biom12010101
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