Similar Datasets
Project description:Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n=14) and matched sedentary controls (n=11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing oxygen consumption (V̇O2) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P=0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.
2019-03-09 | GSE128078 | GEO
Project description:Ulcerative colitis is a chronic inflammatory disorder for which a definitive cure is still missing. This is characterized by an overwhelming inflammatory milieu in the colonic tract where a composite set of immune and non-immune cells orchestrate its pathogenesis. Over the last years, a growing body of evidence has been pinpointing gut virome dysbiosis as underlying its progression. Nonetheless, its role during the early phases of chronic inflammation is far from being fully defined. Here we show the gut virome-associated Hepatitis B virus protein X, most likely acquired after an event of zoonotic spillover, to be associated with the early stages of ulcerative colitis and to induce colonic inflammation in mice. It acts as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering mucosal immunity at the level of both innate and adaptive immunity. This study paves the way to the comprehension of the aetiopathogenesis of intestinal inflammation and encourages further investigations of the virome as a trigger also in other scenarios. Moreover, it provides a brand-new standpoint that looks at the virome as a target for tailored treatments, blocking the early phases of chronic inflammation and possibly leading to better disease management.
2023-02-20 | GSE204665 | GEO
Project description:Comprehensive profiling of the human gut virome in ME/CFS (II)
| PRJEB57953 | ENA
Project description:Comprehensive profiling of the human gut virome in ME/CFS (I)
| PRJEB57952 | ENA
Project description:Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Genomic DNA from 24 peripheral blood mononuclear cells (PBMC) samples (12 CFS, 12 controls) were bisulfite-converted and hybridised to the Illumina Infinium HumanMethylation450 BeadChip. GenomeStudio files were generated and the data was analyzed using the Illumina Methylation Analyzer R package.
2014-08-12 | E-GEOD-59489 | biostudies-arrayexpress
Project description:Salmonella enterica serovar Typhimurium is known to synthesize and respond to the cell signaling molecule, autoinducer-2 (AI-2). The luxS gene is involved in the synthesis of AI-2. We have previously shown that luxS controls a variety of bacterial processes in S. Typhimurium. In this study we identified the genes regulated by AI-2 in the Cell-Free supernatant of S. Typhimurium using mRNA samples from isogenic luxS gene mutant of S. Typhimurium strain 87-26254 grown in LB media in the presence of S. Typhimurium wild type CFS / absence AI-2 (mutant CFS of S. Typhimurium). In the presence of AI-2 in CFS, 758 genes were significantly regulated. Interstingly, AI-2 in CFS caused the down-regulation of 39 genes in Salmonella Pathogenicity Island-1 (SPI-1). Purified cDNAs from the mutant supplemented with CFS containing AI-2 and mutant without AI-2 (Mutant CFS) were each labeled with Cy-3 mono-Reactive Dye and Cy-5 mono-Reactive Dye (GE Health Care, Piscataway, NJ) and were processed using a dye-swapping design. A total of 5 microarray arrays, each with duplicate spots for each gene.
2015-07-31 | E-GEOD-23761 | biostudies-arrayexpress
Project description:Direct conversion of cardiac fibroblasts (CFs) to cardiomyocytes (CMs) in vivo to regenerate heart tissue is an attractive approach. After myocardial infarction (MI), heart repair proceeds with an inflammation stage initiated by monocytes infiltration of the infarct zone establishing an immune microenvironment. However, whether and how the MI microenvironment influences the reprogramming of CFs remains unclear. Here, we found that in comparison with cardiac fibroblasts (CFs) cultured in vitro, CFs that transplanted into infarct region of MI mouse models resisted to cardiac reprogramming. RNA-seq analysis revealed upregulation of interferon (IFN) response genes in transplanted CFs, and subsequent inhibition of the IFN receptors increased reprogramming efficiency in vivo. Macrophage-secreted IFN-β was identified as the dominant upstream signaling factor after MI. CFs treated with macrophage-conditioned medium containing IFN-β displayed reduced reprogramming efficiency, while macrophage depletion or blocking the IFN signaling pathway after MI increased reprogramming efficiency in vivo. Co-IP, BiFC and Cut-tag assays showed that phosphorylated STAT1 downstream of IFN signaling in CFs could interact with the reprogramming factor GATA4 and inhibit the GATA4 chromatin occupancy in cardiac genes. Furthermore, upregulation of IFN-IFNAR-pSTAT1 signaling could stimulate CFs secretion of CCL2/7/12 chemokines, subsequently recruiting IFN-β-secreting macrophages. Together, these immune cells further activate STAT1 phosphorylation, enhancing CCL2/7/12 secretion and immune cell recruitment, ultimately forming a self-reinforcing positive feedback loop between CFs and macrophages via IFN-IFNAR-pSTAT1 that inhibits cardiac reprogramming in vivo. Cumulatively, our findings uncover an intercellular self-stimulating inflammatory circuit as a microenvironmental molecular barrier of in situ cardiac reprogramming that needs to be overcome for regenerative medicine applications.
2024-03-15 | GSE261308 | GEO
Project description:Post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with a yet unresolved pathophysiology and sparse diagnostic options. Extracellular vesicles (EVs) serve as carriers of disease-specific protein and microRNA (miRNA) signatures. We aim to identify novel miRNA markers as potential biomarker in isolated plasma EVs from female post-COVID-19 ME/CFS patients in comparison to healthy controls (HCs). EVs were isolated from plasma of post-infectious ME/CFS patients and HCs by size exclusion chromatography, and characterized for their number, size, morphology and surface marker expression. Small RNA sequencing identifed four small RNAs, which are significantly differential expressed between ME/CFS patients and healthy donors. Subsequently performed qPCR studies revealed significant downregulation exclusively for the hsa-let-7b-5p miRNA in EVs from ME/CFS patients versus HCs. Notably, reduced hsa-let-7b-5p expression correlated with impaired physical functioning as well as increased fatigue, pain, and immune activation scores. Our data indicate, that hsa-let-7b-5p could serve as a promising candidate for development as diagnostic and stratification marker of ME/CFS.
2026-03-18 | GSE317067 | GEO
Project description:Background: Cardiac fibroblasts (CFs) play a vital role in the physiological and pathological processes of the heart. Previous studies have demonstrated that high glucose stimulation induces the transformation of CFs into myofibroblasts, contributing to cardiac fibrogenesis. However, in vivo experiments have predominantly utilized adult animals, whereas most in vitro studies have focused on CFs derived from neonatal animals. The responses of CFs from different age groups to high glucose levels remain unclear. This study aimed to investigate transcriptional alterations in CFs at distinct developmental stages in response to high glucose exposure. Methods: CFs were isolated from neonatal (S1, 0–3 days), juvenile (S2, 3–4 weeks), adult (S3, 10–13 weeks), and aged (S4, 20 months) rats. CFs were exposed to normal (5.5 mM, NG) or high glucose (33 mM, HG). The cellular RNA was extracted for sequencing and analysis. Differentially expressed genes (DEGs) were validated by quantitative real-time PCR. Results: After NG treatment, fibrosis and inflammation-related gene expression in CFs (e.g., Col8a1, Col8a2, IL-6, Ccl2, Ccl20, Mmp2 and Mmp9) increased with age, while proliferation-related genes (MCM family, Sox10, Sox11) decreased. HG treatment most affected S3-CFs, showing 228 DEGs; it suppressed growth-related genes (Adra1d, Htr2b) and enhanced inflammatory genes (IL-6, Olr1). In S1-CFs, 197 inflammation-rich genes were upregulated under HG. S4-CFs displayed 166 DEGs, mostly metabolic downregulation (G6pc). S2-CFs had the fewest DEGs (112), focusing on cell metabolism. Conclusions: Fibrosis- and inflammation-associated gene expression in CFs showed an age-dependent stepwise elevation. CFs from distinct developmental stages responded differently to HG stimulation, with S3-CFs exhibiting the most pronounced response. These findings highlight the developmental characteristics of CFs and provide implications for the selection of appropriate CFs to investigate diabetes-associated cardiac fibrosis.
2025-02-04 | GSE269896 | GEO
Project description:Here report ME/CFS-related plasma proteome analysis using untargeted ultra-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS). We identified differing profiles between ME/CFS patients, as well as ME/CFS subgroups based on their IBS co-morbidity status, and controls. In addition, we identify a set of proteins that may predict ME/CFS status.
2020-07-07 | PXD016622 | Pride