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Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system

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Burns & Trauma 2021年第1期9卷 558-572页

作者： Jon Hazeldine Robert J.Dinsdale David N.Naumann Animesh Acharjee Jonathan R.B.Bishop Janet M.Lord Paul Harrison Institute of Inflammation and Ageing University of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre Heritage BuildingQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Scar Free Foundation Birmingham Centre for Burns Research University Hospital Birmingham Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Academic Department of Military Surgery and Trauma Royal Centre for Defence MedicineQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Institute of Cancer and Genomic Sciences Centre for Computational BiologyUniversity of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom

Background:Traumatic injury is associated with increased concentrations of cell-free DNA(cfDNA)in the circulation,which contribute to post-injury *** endonuclease deoxyribonuclease 1(DNase-1)is responsible for removing 90%of circulating ***,DNase activity was reported to be significantly reduced following major non-traumatic brain injury(TBI),but the processes responsible were not ***,it is not known how quickly following injury DNase activity is reduced and whether this also occurs after ***:At 3 post-injury time points(≤1,4–12 and 48–72 hours),blood samples were obtained from 155 adult trauma patients that had sustained an isolated TBI(n=21),TBI with accompanying extracranial injury(TBI^(+))(n=53)or an extracranial injury only(ECI)(n=81).In addition to measuring cfDNA levels and the activity and expression of DNase,circulating concentrations of monomeric globular action(G-actin),an inhibitor of DNase-1,and the actin scavenging proteins gelsolin(GSN)and vitamin D binding protein(VDBP)were determined and values compared to a cohort of healthy ***:Significantly elevated concentrations of plasma cfDNA were seen in TBI,TBI^(+)and ECI patients at all study time points when compared to healthy *** levels were significantly higher at≤1 hour post-injury in ECI patients who subsequently developed multiple organ dysfunction syndrome when compared to those who did *** DNase-1 protein was significantly elevated in all patient groups at all sampling time *** contrast,DNase enzyme activity was significantly reduced,with this impaired function evident in TBI^(+)patients within minutes of *** concentrations of G-actin were elevated in all patient cohorts in the immediate aftermath of injury and this was accompanied by a significant reduction in the levels of GSN and ***:The post-traumatic increase in circulating cfDNA that occurs following extracranial trauma and TBI

关键词： Cell-free DNA Deoxyribonuclease extracellular actin scavenging system Pre-hospital Trauma

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