Preoperative exercise therapy modulates neutrophil extracellular trap formation

项目描述：此行政补充应用程序的目标是支持 本科生在今年暑假期间通过确定 术前运动疗法调节中性粒细胞形成中性粒细胞能力的机制 细胞外陷阱(NETs)，这与名为“术前”的父母拨款(R01GM137203)高度相关 手术运动疗法引发炎症“。肝脏缺血再灌注(I/R)是一个不可避免的问题。 大范围肝切除和肝移植的后果，导致显著的发病率、死亡率和 肝脏手术后的费用。然而，以前保护肝脏免受I/R损伤的策略主要集中在一个 特定的已知伤害机制，而不影响其他有害的过程。术前/术后锻炼 促进腹部大手术后的康复。众所周知，锻炼对身体健康有好处。 通过多种机制调节手术结果，包括改变先天的数量和功能 免疫细胞提供抗炎环境。我们发现，术前锻炼 治疗(PET)显著降低血清转氨酶水平(肝损伤)和细胞因子的表达 和趋化因子(炎症反应)在肝脏I/R期间通过代谢重新编程Kupffer细胞，从亲 炎症性到厌炎性表型。然而，即使细胞能量代谢和 线粒体的生物发生在免疫反应中起关键作用，PET诱导的改变的影响 形成中性粒细胞胞外陷阱(Net)的中性粒细胞从未被研究过。本科生的夏天 范斯坦医学研究所的研究计划是一个成熟的研究计划， 支持正在考虑从事尖端生物医学研究职业的本科生 夏季的科学环境。我们建议的研究将由本科生进行 学生将通过询问两个相关的新问题来显著扩大家长R01奖励的范围 对于那些已经在父母R01奖中进行研究的人：1)PET在转录中的作用是什么 肝脏I/R后浸润性中性粒细胞的变化2)PET训练的KCs是否抑制肝脏的净形成 I/R？综上所述，本科生在暑期研究中进行的指导研究 计划将通过以下方式显著扩展当前对潜在机械机制的理解 PET通过调节网状结构预防外科应激性器官损伤及评价新方法 潜在的治疗目标，并评估为接受手术的患者提供前景看好的新疗法。

PROJECT DESCRIPTION: The goal of this Administrative Supplement application is to support an undergraduate student to obtain the authentic research experience during this summer by determining the mechanism by which preoperative exercise therapy modulates the capability of neutrophils forming neutrophil extracellular traps (NETs), which is highly relevant to the parent grant (R01GM137203) entitled "Preoperative exercise therapy for surgery triggered inflammation". Liver ischemia and reperfusion (I/R) is an unavoidable consequence of major liver resection and liver transplantation that leads to significant morbidity, mortality, and costs after liver surgery. However, previous strategies to protect the liver from I/R injury have focused on one specific known injury mechanisms, leaving intact other detrimental processes. Pre/post-operative exercise facilitates recovery after major abdominal surgery. It is known that exercise confers beneficial effects on the surgical outcome by regulating multiple mechanisms, including alteration of quantity and function of innate immune cells to provide an anti-inflammatory environment. We have discovered that preoperative exercise therapy (PET) significantly reduced serum aminotransferase levels (liver damage) and expression of cytokines and chemokines (inflammatory responses) during liver I/R via metabolic reprogramming Kupffer cells from pro- inflammatory to ani-inflammatory phenotype. However, even though cellular energy metabolism and mitochondrial biogenesis play a critical role in the immune response, the effects of PET-induced changes in neutrophils forming neutrophil extracellular traps (NETs) have never been studied. The undergraduate summer research program at Feinstein Institutes for Medical Research is a well-established research program that support undergraduate students who are considering pursuing biomedical research careers in cutting-edge scientific environments during the summer. Our proposed studies which will be conducted by undergraduate student will significantly expand the scope of the parent R01 award by interrogating two new questions related to those already being investigated in the parent R01 award: 1) What is the role of PET in the transcriptomic changes of infiltrating neutrophils after liver I/R? 2) Do PET-trained KCs suppress NET formation during liver I/R? In summary, the mentored studies that performed by undergraduate student in the Summer Research Program will significantly expand the current understanding of the underlying mechanistic mechanisms by which PET prevent surgical stress-induced organ injury via modulating NET formation and evaluate novel potential therapeutic targets, and assess promising novel treatments for patients undergoing surgery.