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Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder characterized by an extremely elevated serum level of low-density lipoprotein cholesterol (LDL-C) and accelerated premature atherosclerotic cardiovascular diseases (ASCVD). https://www.selleckchem.com/products/peg300.html However, the detailed mechanism of how the pathogenic mutations of HoFH trigger the acceleration of ASCVD is not well understood. Therefore, we performed high-throughput RNA and small RNA sequencing on the peripheral blood RNA samples of six HoFH patients and three healthy controls. The gene and miRNA expression differences were analyzed, and seven miRNAs and six corresponding genes were screened out through regulatory network analysis. Validation through quantitative PCR of genes and miRNAs from 52 HoFH patients and 20 healthy controls revealed that the expression levels of hsa-miR-486-3p, hsa-miR-941, and BIRC5 were significantly upregulated in HoFH, while ID1, PLA2G4C, and CACNA2D2 were downregulated. Spearman correlation analysis found that the levels of ID1, hsa-miR-941, and hsa-miR-486-3p were significantly correlated with additional ASCVD risk factors in HoFH patients. This study represents the first integrated analysis of transcriptome and miRNA expression profiles in patients with HoFH, a rare disease, and as a result, six differentially expressed miRNAs/genes that may be related to atherosclerosis in HoFH are reported. The miRNA-mRNA regulatory network may be the critical regulation mechanism by which ASCVD is accelerated in HoFH.Both SETD2-mediated H3K36me3 and miRNAs play critical epigenetic roles in inflammatory bowel disease (IBD) and involve in the dysfunctional intestinal barrier. However, little is known about cross-talk between these two types of regulators in IBD progression. We performed small RNA sequencing of Setd2 epithelium-specific knockout mice (Setd2Vil-KO) and wild-type controls, both with DSS-induced colitis, and designed a framework for integrative analysis. Firstly, we integrated the downloaded ChIP-seq data with miRNA expression profiles and identified a significant intersection of pre-miRNA expression and H3K36me3 modification. A significant inverse correlation was detected between changes of H3K36me3 modification and expression of the 171 peak-covered miRNAs. We further integrated RNA-seq data with predicted miRNA targets to screen negatively regulated miRNA-mRNA pairs and found the H3K36me3-associated differentially expressed microRNAs significantly enriched in cell-cell junction and signaling pathways. Using network analysis, we identified ten hub miRNAs, among which six are H3K36me3-associated, suggesting therapeutic targets for IBD patients with SETD2-deficiency.Clavibacter michiganensis subsp. michiganensis (Cmm) is a gram-positive bacterium causing destructive bacterial wilt and canker disease in tomato. Herein, a comparative transcriptome analysis was performed on Cmm-resistant and -susceptible tomato lines. Tomato seedlings were inoculated with Cmm and harvested for transcriptome analysis after 4 and 8 day time-points. Twenty-four transcriptome libraries were profiled by RNA sequencing approach. Total of 545 million clean reads was generated. 1642 and 2715 differentially expressed genes (DEG) were identified in susceptible lines within 4 and 8 days after inoculation (DAI), respectively. In resistant lines, 1731 and 1281 DEGs were found following 4 and 8 DAI, respectively. Gene Ontology analysis resulted in a higher number of genes involved in biological processes and molecular functions in susceptible lines. On the other hand, such biological processes, "defense response", and "response to stress" were distinctly indicated in resistant lines which were not found in susceptible ones upon inoculation, according to the gene set enrichment analyses. Upon Cmm-inoculation, several defense responsive genes were found to be differentially expressed. Of which 26 genes were in the resistant line and three were in the susceptible line. This study helps to understand the transcriptome response of Cmm-resistant and -susceptible tomato lines. The results provide comprehensive data for molecular breeding studies, for the purpose to control of the pathogen in tomato.The genetic factors of tuberculosis (TB) susceptibility have been widely recognized. Here we performed a two-stage study in 616 TB patients and 709 healthy controls to systematically identify the genetic markers of TB susceptibility. In the discovery stage, we identified 93 single nucleotide polymorphisms (SNPs) and 3 human leucocyte antigen (HLA) class II alleles that had potential associations with TB susceptibility. In the validation stage, we confirmed that 6 nominally significant SNPs, including 2 novel missense variants at RAB17 and DCTN4 (odds ratio (OR) = 1.40, P = 4.98 × 10-3 and OR = 2.30, P = 3.17 × 10-2 respectively), were associated with the predisposition to TB. Moreover, our study found that HLA-II allele DQA1*0505 (P = 0.0011, OR = 1.44, 95%CI = 1.15-1.77) was a TB susceptibility locus for the first time. This study comprehensively investigated the genetic variants that were associated with TB susceptibility and provided insight into the tuberculosis pathogenesis.Right ventricular (RV) dysfunction and tricuspid regurgitation (TR) are known to be associated with adverse outcomes in patients undergoing percutaneous mitral valve repair (PMVR). Although the effect of PMVR on left ventricular function is well known, data on the response of the right ventricle to PMVR, and its impact on prognosis, are limited. In this review the authors summarize available data regarding the prognostic role of RV function and TR in PMVR recipients and the possible effects of PMVR on the right heart. Preprocedural tricuspid annular plane systolic excursion less then 15 mm, tricuspid annular tissue Doppler S' velocity less then 9.5 cm/sec, and moderate or severe TR are reported as predictors of adverse outcome after PMVR. Therefore, they should be carefully evaluated for patient selection. Moreover, emerging data show that the benefit of PMVR may go beyond the left heart, leading to an improvement in RV function and a reduction in TR severity. Among PMVR recipients, improvement in RV function and reduction of TR degree are observed mainly in patients with RV dysfunction at baseline.
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