Circulating signals of ME/CFS

项目2总结。ME/CFS的循环信号 ME/CFS患者会经历多种致残症状，如疲劳、疼痛、 睡眠不佳、认知困难、直立不耐受和运动后不适 （PEM）。PEM是指无法增加身体或精神努力而不加重症状 并且极大地限制了ME/CFS患者的生活质量。在这个项目中，我们将了解更多 关于ME/CFS患者在运动期间和运动后受到影响的组织和器官， 体验PEM我们进行了一项研究，其中ME/CFS和健康的久坐对照 受试者经历了两次连续的心肺运动试验（CPH）。以及 获得广泛的临床和运动生理学数据，我们收集了血液样本， 这些受试者在四个时间点：运动前（基线），第一次CPET后立即， 24小时恢复期后，以及第二次CPET后立即。我们已经 测量了这些样本中的数千种代谢物和蛋白质， 在免疫细胞亚群中的表达。在这个项目中，使用相同的血浆样本 从纵向运动研究中，我们将研究在运动中循环的新型信号， 血液：无细胞核糖核酸（RNA）和细胞外囊泡（EV）。无细胞RNA 从循环中的垂死细胞或从整个组织中的各种组织释放到血液中。 身体EV是膜封闭的身体，从不同组织穿过血液 并且可以传递蛋白质、RNA和其他信号分子。电动汽车提供有关 组织，如大脑，如果没有侵入性活检就无法获得。我们将 确定哪些组织将无细胞RNA和EV释放到循环中。了解 与对照组相比，ME/CFS患者中这些信号的内容和来源如何变化 运动前后可能揭示导致PEM的通路中断， 关于PEM中涉及的其他组织的线索。我们还将量化蛋白质和RNA货物 在电动汽车内部，这可以告诉我们电动汽车可能对接受者产生的调节作用， 细胞最近的研究还表明， （内皮）。我们将用来自ME/CFS患者的血浆和EV培养内皮细胞， 基线对照，以了解ME/CFS中引起内皮功能障碍的分子是否来源于 车内或车外我们将从相同的主题中获得丰富的数据， 寻找生物标志物来开发ME/CFS的诊断测试。我们还将整合这些 不同类型的数据，看看我们是否可以定义ME/CFS患者的临床相关子集。

Project 2 Summary. Circulating Signals of ME/CFS Individuals with ME/CFS experience a multitude of disabling symptoms such as fatigue, pain, unrefreshing sleep, cognitive difficulties, orthostatic intolerance, and post-exertional malaise (PEM). PEM is the inability to increase physical or mental effort without symptom exacerbation and it greatly limits the quality of life of ME/CFS patients. In this project, we will learn more about the tissues and organs affected during and after exercise when ME/CFS patients are experiencing PEM. We have conducted a study in which ME/CFS and healthy sedentary control subjects have undergone two successive cardiopulmonary exercise tests (CPETs). As well as obtaining extensive clinical and exercise physiology data, we have collected blood samples from these subjects at four time points: before exercise (baseline), immediately after the first CPET, after a 24 hour recovery period, and immediately after the second CPET. We have already measured thousands of metabolites and proteins in these samples and measured gene expression in subpopulations of immune cells. In this project, using the same plasma samples from the longitudinal exercise study, we will examine novel types of signals that circulate in blood: Cell-free ribonucleic acid (RNA) and extracellular vesicles (EVs). Cell-free RNA is released into the blood from dying cells in circulation or from various tissues throughout the body. EVs are membrane-enclosed bodies that travel through the blood from different tissues and can deliver protein, RNA, and other signaling molecules. EVs provide information about tissues such as the brain that could otherwise not be obtained without invasive biopsy. We will determine which tissues released the cell-free RNA and the EVs into circulation. Learning about how the content and origin of these signals changes in ME/CFS patients compared to controls before and after exercise may reveal disruptions in pathways that lead to PEM and provide clues about additional tissues involved in PEM. We will also quantify the protein and RNA cargo inside EVs, which can inform us about the modulatory effect the EVs may have in recipient cells. Recent work also implicates disruption of the tissue that lines the inside of blood vessels (endothelium). We will culture endothelial cells with plasma and EVs from ME/CFS patients and controls at baseline to learn if molecules causing endothelial dysfunction in ME/CFS originate inside or outside EVs. The wealth of data we will have from the same subjects will be used to look for biomarkers to develop a diagnostic test for ME/CFS. We will also integrate these different types of data to see if we can define clinically relevant subsets of ME/CFS patients.