Julia Penatzer, Lisa Steele, Julie Breuer, Renata Fabia, Mark Hall, Rajan K Thakkar
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Subjects who went on to develop an NI had elevated high-mobility group box 1, heat shock protein 90 (HSP90), and FAS expression than those who did not develop an NI after injury (NoNI). Concurrently, phosphorylated (p-)AKT and mammalian target of rapamycin (p-mTOR) were elevated in those subjects who went on to develop an NI. Quadratic discriminant analysis revealed distinct differential profiles between NI and NoNI burn subjects using HSP90, FAS, and p-mTOR. The area under the receiver-operator characteristic curves displayed significant ability to distinguish between these 2 burn subject cohorts. These findings provide insight into predicting the signaling proteins involved in the development of NI in pediatric burn patients. 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引用次数: 0
摘要
小儿烧伤是发病的主要原因,感染是最常见的急性并发症。热损伤会引起细胞因子反应增强,同时抑制免疫功能;然而,导致这种功能障碍的机制仍不清楚。我们的目的是鉴定烧伤后血浆中的细胞外蛋白和循环磷蛋白表达,以预测院内感染(NI)的发生。我们在六十四名小儿烧伤患者受伤后 72 小时内采集了他们的血浆,其中十八人后来发生了 NI。对细胞外损伤相关分子蛋白(DAMPs)、FAS(APO)和蛋白激酶 b(AKT)信号磷酸蛋白进行了分析。与受伤后未出现 NI 的受试者(NoNI)相比,后来出现 NI 的受试者的高迁移率组盒 1(HMGB1)、热休克蛋白 90(HSP90)和 FAS 表达量更高。同时,在继续发展为 NI 的受试者中,磷酸化 (p-) AKT 和哺乳动物雷帕霉素靶标 (p-mTOR) 的表达也有所升高。利用 HSP90、FAS 和 p-mTOR 进行的二次判别分析显示,NI 和 NoNI 烧伤受试者之间存在明显的差异。接收器-操作者特征曲线下的面积显示了区分这两种烧伤受试者群组的显著能力。这些发现为预测参与小儿烧伤患者 NI 发展的信号蛋白提供了深入的见解。此外,这些蛋白质有望成为诊断有感染风险的小儿烧伤患者的工具,而进一步的研究可能会开发出预防 NI 的潜在疗法。
FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Pediatric Burn Injury.
Pediatric burn injuries are a leading cause of morbidity with infections being the most common acute complication. Thermal injuries elicit a heightened cytokine response while suppressing immune function; however, the mechanisms leading to this dysfunction are still unknown. Our aim was to identify extracellular proteins and circulating phosphoprotein expression in the plasma after burn injury to predict the development of nosocomial infection (NI). Plasma was collected within 72 hours after injury from 64 pediatric burn subjects; of these, 18 went on to develop an NI. Extracellular damage-associated molecular proteins, FAS(APO), and protein kinase b (AKT) signaling phosphoproteins were analyzed. Subjects who went on to develop an NI had elevated high-mobility group box 1, heat shock protein 90 (HSP90), and FAS expression than those who did not develop an NI after injury (NoNI). Concurrently, phosphorylated (p-)AKT and mammalian target of rapamycin (p-mTOR) were elevated in those subjects who went on to develop an NI. Quadratic discriminant analysis revealed distinct differential profiles between NI and NoNI burn subjects using HSP90, FAS, and p-mTOR. The area under the receiver-operator characteristic curves displayed significant ability to distinguish between these 2 burn subject cohorts. These findings provide insight into predicting the signaling proteins involved in the development of NI in pediatric burn patients. Further, these proteins show promise as a diagnostic tool for pediatric burn patients at risk of developing infection while additional investigation may lead to potential therapeutics to prevent NI.
期刊介绍:
Journal of Burn Care & Research provides the latest information on advances in burn prevention, research, education, delivery of acute care, and research to all members of the burn care team. As the official publication of the American Burn Association, this is the only U.S. journal devoted exclusively to the treatment and research of patients with burns. Original, peer-reviewed articles present the latest information on surgical procedures, acute care, reconstruction, burn prevention, and research and education. Other topics include physical therapy/occupational therapy, nutrition, current events in the evolving healthcare debate, and reports on the newest computer software for diagnostics and treatment. The Journal serves all burn care specialists, from physicians, nurses, and physical and occupational therapists to psychologists, counselors, and researchers.