Project description:CyTOF data showed that 3-HAA significantly increased the percentage of F4/80hiCX3CR1loKi67loMHCIIhi macrophage and decreased the percentage of F4/80loCD64+PD-L1lo macrophages. scRNA-seq analyses demonstrated that 3-HAA administration was proved to regulate the function of M1 macrophages, M2 macrophages, and proliferating macrophages.
Project description:Purpose: Exosome-derived microRNAs (miRNAs) are potential diagnostic biomarkers. However, little is known about their effectiveness as diagnostic biomarkers of fulminant myocarditis (FM). This study aimed to explore miRNA levels in serum exosomes of patients with FM as potential biomarkers for FM diagnosis. Methods: 10 samples were screened with a exosomal small RNA sequencing platform (RiboBio). A Mann-Whitney test was performed to discover differentially expressed miRNAs in the two pairwise comparisons: FM versus HC. Results: From the differentially expressed miRNAs, fourteen candidate miRNAs discovered via small RNA sequencing with P<0.05 and fold expression change >2 were selected for further testing Conclusions: These data suggested that the miRNA panel in serum-derived exosomes provided excellent diagnostic capability for FM.
Project description:Fulminant myocarditis (FM) is the most serious type of childhood myocarditis. However, the molecular mechanism underlying the pathogenesis of FM has not been fully elucidated. Studies have shown that small extracellular vesicles (sEVs) play important roles in many diseases, but any potential role of sEVs in pediatric FM has not been reported. Here, the differential expression profiles of lncRNAs in plasma sEVs were studied in five children with FM and five healthy children using whole transcriptome sequencing, followed by functional analysis and screening of immune-related target genes. A total of 68 up-regulated and 11 down-regulated differentially expressed sEVs-lncRNAs were identified. Functional analysis showed that the differentially-expressed sEVs-lncRNAs were mainly involved in immune processes, apoptosis, and protein efflux. Further analysis of immune-related target genes revealed that differentially expressed sEVs-lncRNAs were closely related to immune activation, immune cell migration and cytokine pathway signal transduction in FM. Thus, sEVs-lncRNAs may play an important role in the pathogenesis of FM in children
Project description:Circulating miRNA expression profiles were detected by microarray analysis.qPCR arrays were performed to validate the potential miRNAs.KEGG pathway analysis was used to determine the critical roles of these circulating miRNAs in FM. Correlation analysis was employed between miRNAs and the parameters of cardiac functions in FM. The sensitivity and specificity of circulating lncRNA expression in FM diagnosis were evaluated using receiver operating characteristic curve analysis. Microarray and qPCR analysis showed that the expression of miR-4763-3p and miR-4281 were up-regulated in the plasma of FM at the onset, and their levels were restored as the clinical symptom recovered. The predicted target genes of miR-4763-3p and miR-4281 are involved in several pathways, mainly inflammatory and cardiac injury response. Moreover, the miRNAs enrichment was negatively correlated with the severity of FM. In addition, the expression levels of circulating miR-4763-3p was unchanged in MI and patients and miR-4281 showed high sensitivity and specificity for FM diagnosis.This study provides global profile of circulating miRNAs in patients with FM, among which miR-4763-3p and miR-4281 could serve as potential biomarkers.
Project description:Fulminant myocarditis (FM) is an acute fatal disease characterised by myocardial inflammation. Our previous study identified soluble growth stimulation- expressed gene 2 (sST2) as a sensitive and specific biomarker for early diagnosis of FM. However, its function in FM remains unclear.In the present study, we observed a marked elevation of sST2 in the plasma and hearts of mice with FM induced by coxsackievirus B3 (CVB3) and explored the main cellular sources of sST2 in FM. Moreover, using recombinant sST2 protein administration and unbiased transcriptomics analyses, we investigated the role and underlying mechanisms of sST2 in FM. Importantly, we found that sST2 has a novel non-classical function in cardiomyocytes, other than acting as an IL-33 decoy receptor. These findings reveal a novel role and action mechanism of sST2 in FM and suggest that sST2 may be a potential therapeutic target for FM.
Project description:We next asked whether RORgt-FM+ ILC are transcriptionally similar to the Tnfrsf9+ tILC that we identified in lupus-prone mice. To explore this, we isolated tissue RORgt-FM+ and RORgt-FM- NKp46+ ILC from RORgt-FM mice, some of which were treated with poly(I:C) and analyzed them by scRNA-seq