Preoperative exercise therapy modulates neutrophil extracellular trap formation

术前运动疗法调节中性粒细胞胞外陷阱的形成

• 批准号: 10810353
• 负责人: Hai Huang
• 金额: $ 1.15万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-16 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10810353
• 关键词: Abdomen; Administrative Supplement; Anti-Inflammatory Agents; Award; Biogenesis; Biomedical Research; Cells; Development; Energy Metabolism; Environment; Excision; Exercise; Exercise Therapy; Foundations; Goals; Hepatic; Immune response; Immunity; Inflammation; Inflammatory; Inflammatory Response; Injury; Knowledge; Kupffer Cells; Liver; Macrophage; Medical Research; Mentors; Metabolic; Mitochondria; Morbidity - disease rate; Neutrophil Infiltration; Operative Surgical Procedures; Parents; Patients; Phenotype; Play; Postoperative Complications; Postoperative Period; Process; Recovery; Reperfusion Injury; Reperfusion Therapy; Research; Role; Serum; Stress; Training; Transaminases; career; chemokine; cost; cytokine; experience; extracellular; inflammatory milieu; innate immune function; ischemic injury; liver injury; liver ischemia; liver transplantation; mortality; neutrophil; novel; organ injury; parent grant; pharmacologic; prevent; programs; summer research; surgery outcome; systemic inflammatory response; therapeutic target; transcriptomics; undergraduate student

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.

项目描述：此行政补充申请的目的是支持 本科生通过确定 术前运动治疗调节中性粒细胞的能力的机制 细胞外陷阱（NETS），它与父母赠款高度相关（R01GM137203）标题为“术前 手术运动疗法引发炎症”。肝脏缺血和再灌注（I/R）是不可避免的 主要肝切除和肝移植的结果，导致显着的发病率，死亡率和 肝手术后的费用。但是，以前保护肝脏免受I/R损伤的策略重点是 特定的已知伤害机制，留下完整的其他有害过程。术前/术后练习 大腹手术后促进恢复。众所周知，锻炼对 通过调节多种机制的手术结果，包括先天数量和功能的改变 免疫细胞提供抗炎环境。我们发现术前练习 治疗（PET）显着降低了血清氨基转移酶水平（肝损伤）和细胞因子的表达 和肝I/R期间的趋化因子（炎症反应）通过代谢重编程kupffer细胞 炎症表型的炎症。但是，即使细胞能量代谢和 线粒体生物发生在免疫反应中起关键作用，宠物诱导的变化的影响 从未研究过形成嗜中性粒细胞细胞外陷阱（NET）的中性粒细胞。本科夏天 费恩斯坦医学研究所的研究计划是一项完善的研究计划 支持正在考虑从事生物医学研究职业的本科生 夏季的科学环境。我们提出的研究将由本科生进行 学生将通过询问两个新问题，从而大大扩大父母R01奖的范围 对于已经在父母R01奖中调查的人：1）宠物在转录组中的作用是什么 肝I/R后浸润性中性粒细胞的变化？ 2）在肝脏期间，受宠物训练的KC抑制净形成 i/r？总之，本科生在夏季研究中进行的指导研究 程序将通过 PET通过调节净形成并评估新颖 潜在的治疗靶标，并评估接受手术患者的有希望的新型治疗方法。