Project description:Blood cell counts often fail to report on immune processes occurring in remote tissues. Here we use 25 immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying 26 human immune cell dynamics. We characterized cfDNA released from specific immune cell types in 27 healthy individuals (N=242), cross sectionally and longitudinally. Immune cfDNA levels had no 28 individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects 29 adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation 30 of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza 31 vaccination (N=92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and 32 predicted efficacy of antibody production. Patients with Eosinophilic Esophagitis (N=21) and B-cell 33 lymphoma (N=27) showed selective elevation of eosinophil and B-cell cfDNA respectively, which 34 were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for 35 monitoring immune responses to physiological and pathological processes that are not accessible using 36 conventional methods.
Project description:Blood cell counts often fail to report on immune processes occurring in remote tissues. Here, we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N = 242), cross sectionally and longitudinally. Immune cfDNA levels had no individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza vaccination (N = 92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and predicted efficacy of antibody production. Patients with eosinophilic esophagitis (N = 21) and B-cell lymphoma (N = 27) showed selective elevation of eosinophil and B-cell cfDNA, respectively, which were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for monitoring immune responses to physiological and pathological processes that are not accessible using conventional methods.
Project description:Remote ischemic conditioning (RIC) is a safely therapeutic strategy for a variety of ischemic diseases, with efficiency comparable to the classic in-situ ischemic methods. Recent evidence has shown that RIC could alter the content of circulating exosomes. microRNAs involves in numerous functionally different biological and physiological processes. The aim of this study is to identify the differentially expressed exosomal microRNAs in rat plasma with RIC and to further explore the functions in ischemic heart diseases. Five RIC rats and 5 control rats were enrolled in this study. We used microarray analysis to identify miRNA expression in their plasma exosomes.
Project description:Circulating immune cells play a role in the pathophysiology of diabetic retinopathy (DR). Our study focused on examining the exact role of circulating immune cells in the development of DR. Single-cell RNA sequencing (scRNA-seq) techniques revealed unique differentially-expressed genes and pathways in circulating immune cells among non-diabetic retinopathy (NDR) patients and DR patients. These findings highlight the notable alterations in the immunophenotypes of circulating immune cells in patients with type 1 DR.
Project description:AMPK is a regulator of cellular catabolism that is activated by AMP. Since AMP accumulates in cells with low ATP, AMPK is considered a stress activated kinase. Here, while studying organ growth during Drosophila development, we find that AMPK is activated by a signaling metabolite not related to stress. We find that the two main physiological inputs that regulate organ growth rates during development - the hormone ecdysone and dietary protein - both regulate expression in the intestine of an enzyme, adenosine deaminase. This leads to changes in the levels of adenosine in circulation. Circulating adenosine acts as a signaling molecule by entering into cells, becoming phosphorylated to adenosine mono-phosphate (AMP) and activating AMPK to inhibit organ growth. Thus AMPK activity is regulated developmentally, and AMPK in one tissue such as the wing can be remote-controlled by another tissue such as the intestine via circulating adenosine. Interestingly, this mechanism accounts for half of the effect of dietary protein on tissue growth rates in Drosophila.
Project description:Previous studies have shown that colorectal cancer patients’ prognosis and overall survival was related with immune cell expression in patients’ tissue. However, the circulating immune cell activity changes in patients’ blood has few studies. The purpose of this study is to analyze the variation of circulating immune cell activity in colorectal patients’ blood which is classed as clinical staging.
Project description:Background: Many circulating proteins are associated with risk of ESKD but their source and the biological pathways/disease processes they represent are unclear. Methods: Using OLINK proteomics platform, concentrations of 455 proteins were measured in plasma specimens obtained at baseline from 399 individuals with diabetes. Results: Elevated concentrations of 46 circulating proteins were associated (p <10-5) with development of ESKD (n=149) during 7-15 years of follow-up. Twenty of these proteins enriched apoptosis/TNF receptors signaling pathways. A subset (5-7), summarized as an apoptosis score, together with clinical variables accurately predicted risk of ESKD. Expression of genes encoding the 46 proteins in peripheral white blood cells showed no difference between cells from individuals who did or did not develop ESKD. In contrast, plasma concentration of many of the 46 proteins differed by this outcome. In snRNA-seq analysis of kidney biopsies, the majority of genes encoding for the 20 apoptosis/TNF receptors proteins were overexpressed in injured versus healthy proximal tubule cells. Expression of these 20 genes also correlated with the overall index of apoptosis in these cells. Conclusion: Elevated levels of circulating proteins flagging apoptotic processes/TNF receptors signaling pathways, and likely originating from injured/apoptotic proximal tubular cells, preceded the development of ESKD.
Project description:Remembrances of traumata range among the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that in mice successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes as revealed by whole genome RNA sequencing, which is accompanied by higher metabolic, synaptic and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. 3 biological replicates per group were analyzed. The material analyzed was whole hippocampi from one brain hemisphere, from which total RNA was extracted.