Circulating signals of ME/CFS

ME/CFS 循环信号

• 批准号: 10627291
• 负责人: MAUREEN REBECCA HANSON
• 金额: $ 59.51万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10627291
• 关键词: Affect; Aptamer Technology; Biological Assay; Biological Markers; Biological Process; Biopsy; Blood; Blood - brain barrier anatomy; Blood Platelets; Blood Vessels; Blood specimen; Brain; Cardiopulmonary; Cell Death; Cell physiology; Cells; Chronic Fatigue Syndrome; Circulation; Classification; Clinical; Cluster Analysis; Cognitive; Collaborations; Collection; Data; Diagnostic; Diagnostic tests; Disease; Disease Marker; Endothelial Cells; Endothelium; Exercise; Exercise Physiology; Exercise Test; Exertion; Fatigue; Fluorescent Probes; Functional disorder; Gene Expression; Generations; Growth; Hormones; Hour; Immune; Incubated; Individual; Inflammatory; Learning; Lipids; Malaise; Measures; Mediating; Membrane; Metabolic; MicroRNAs; Molecular Profiling; Muscle; Nature; Neurons; Nitric Oxide; Organ; Pain; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Physical Efforts; Physiological; Plasma; Play; Preparation; Proteins; Proteomics; Psyche structure; Quality of life; RNA; Reactive Oxygen Species; Recovery; Research; Role; Sampling; Series; Signal Transduction; Signaling Molecule; Signaling Protein; Sleep; Source; Symptoms; System; Technology; Time; Tissue-Specific Gene Expression; Tissues; Travel; Vascular Endothelial Cell; Work; biomarker identification; biomarker signature; cell type; clinically relevant; cohort; comparison control; disabling symptom; endothelial dysfunction; experience; extracellular vesicles; immune activation; improved; insight; lipidomics; metabolomics; multiple omics; novel; orthostatic intolerance; predictive modeling; response; sedentary; time use; tissue injury; transcriptome sequencing; transcriptomics; treatment effect; vesicular release

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.

项目 2 摘要。 ME/CFS 循环信号 患有 ME/CFS 的人会经历多种残疾症状，例如疲劳、疼痛、 睡眠不佳、认知困难、体位不耐受和劳累后不适 （质子交换膜）。 PEM 是指无法在不加剧症状的情况下增加体力或脑力的努力 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 和健康的久坐控制 受试者接受了两次连续的心肺运动测试（CPET）。也 获得广泛的临床和运动生理学数据，我们收集了来自 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，并测量了基因 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，我们将研究在中循环的新型信号 血液：游离核糖核酸（RNA）和细胞外囊泡（EV）。游离RNA是 从循环中的垂死细胞或整个生命周期的各种组织释放到血液中 身体。 EV 是膜封闭体，通过来自不同组织的血液传播 并可以传递蛋白质、RNA 和其他信号分子。电动汽车提供以下信息 诸如大脑之类的组织，如果不进行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。学习有关 与对照组相比，ME/CFS 患者这些信号的内容和来源有何变化 运动前后的差异可能会揭示导致 PEM 的途径受到干扰，并提供 有关 PEM 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。最近的研究还表明血管内部的组织受到破坏 （内皮细胞）。我们将用 ME/CFS 患者的血浆和 EV 培养内皮细胞， 基线控制以了解导致 ME/CFS 内皮功能障碍的分子是否起源 电动汽车内部或外部。我们将从同一主题获得的大量数据将用于 寻找生物标志物来开发 ME/CFS 诊断测试。我们也会整合这些 不同类型的数据，看看我们是否可以定义临床相关的 ME/CFS 患者子集。