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Abstract This study aimed to investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and Remnant Cholesterol (Remnant-C) in relation to cardiovascular events and all-cause mortality in the general population. A population-based study. We conducted a retrospective cohort study analyzing data from the National Health and Nutrition Examination Survey (NHANES) spanning the years of 2011–2018, with follow-up for mortality status until December 31, 2019. Kaplan‒Meier and Cox proportional hazards regression analyses were used to evaluate the associations between NLR, Remnant-C, and cardiovascular events as well as all-cause mortality. Overall, 9409 individuals with both complete blood count and blood lipids were included in the analysis. Baseline NLR and Remnant-C were calculated. During the follow-up (median, 59.3 months), 177 cardiovascular events and 561 all-cause mortality occurred. In fully adjusted model, people with NLR > 2.26 were significantly associated with higher risk of cardiovascular events (HR 2.14, 95% CI 1.30–3.52, P

Abstract Epicardial adipose tissue (EAT) contributes to the pathophysiological process of coronary artery disease (CAD). The expression profiles of long non-coding RNAs (lncRNA) in EAT of patients with CAD have not been well characterized. We conducted high-throughput RNA sequencing to analyze the expression profiles of lncRNA in EAT of patients with CAD compared to patients without CAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were executed to investigate the principal functions of the significantly dysregulated mRNAs. We confirmed a dysregulated intergenic lncRNA (lincRNA) (LINC00968) by real-time quantitative PCR (RT-qPCR). Subsequently, we constructed a ceRNA network associated with LINC00968, which included 49 mRNAs. Compared with the control group, lncRNAs and genes of EAT in CAD were characterized as metabolic active and pro-inflammatory profiles. The sequencing analysis detected 2539 known and 1719 novel lncRNAs. Then, we depicted both lncRNA and gene signatures of EAT in CAD, featuring dysregulation of genes involved in metabolism, nuclear receptor transcriptional activity, antigen presentation, chemokine signaling, and inflammation. Finally, we identified a ceRNA network as candidate modulator in EAT and its potential role in CAD. We showed the expression profiles of specific EAT lncRNA and mRNA in CAD, and a selected non-coding associated ceRNA regulatory network, which taken together, may contribute to a better understanding of CAD mechanism and provide potential therapeutic targets. Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024782.

ObjectivesEpicardial adipose tissue (EAT) is closely adjacent to the coronary arteries and myocardium, its role as an endocrine organ to affect the pathophysiological processes of the coronary arteries and myocardium has been increasingly recognized. However, the specific gene expression profiles of EAT in coronary artery disease (CAD) has not been well characterized. Our aim was to investigate the role of EAT in CAD at the gene level.MethodsHere, we compared the histological and gene expression difference of EAT between CAD and non-CAD. We investigated the gene expression profiles in the EAT of patients with CAD through the high-throughput RNA sequencing. We performed bioinformatics analysis such as functional enrichment analysis and protein-protein interaction network construction to obtain and verify the hub differentially expressed genes (DEGs) in the EAT of CAD.ResultsOur results showed that the size of epicardial adipocytes in the CAD group was larger than in the control group. Our findings on the EAT gene expression profiles of CAD showed a total of 747 DEGs (fold change >2, p value

The roles of nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), and calcium-activated K+ (KCa) channels in diabetes-associated endothelial dysfunction of small renal arteries are not clear. The present study investigated acetylcholine (ACh)-induced vasorelaxation of renal arcuate arteries from obese Zucker (OZ) rats at different diabetes durations, and the relative contribution of NO, EDHF, and KCa channels to the endothelial dysfunction. OZ rats of 7 weeks (prediabetic stage), 12 weeks (early diabetic stage), and 20 weeks (late diabetic stage), and time-matched lean control rats, were studied. Segments of arcuate arteries (130 to 180 μm) were isolated, cannulated and pressurized. Vascular endothelial functions were tested using ACh-induced vasodilation. Our experiments demonstrated: (1) ACh-elicited vasodilation was impaired in OZ rats of 20 weeks, but not in rats of 7 and 12 weeks; (2) inhibition of NO or EDHF (contributed by epoxyeicosatrienoic acids [EETs]) production significantly decreased ACh-induced vasodilation in both lean and OZ rats of 20 weeks. The reduction of ACh-induced vasodilation by inhibition of NO or EDHF formation was less in OZ rats, as compared to lean rats; and (3) inhibition of KCa channels markedly reduced ACh-induced vasodilation in lean control rats, but not in OZ rats of 20 weeks. Our observations indicated that endothelium-dependent vasodilation in renal arcuate arteries is impaired in diabetes mellitus; NO and EDHF, mainly EETs, dominate the ACh-induced vasodilation in renal arcuate arteries; the contribution of NO and EETs is impaired in diabetic rats; KCa channels are involved in ACh-induced vasodilation; and the activity of KCa channels is downregulated in diabetes mellitus.

VEGFA administration has been explored as a pro-angiogenic therapy for cardiovascular diseases including heart failure for several years, but with little success. Here, we investigate a different approach to augment VEGFA bioavailability: by deleting the VEGFA decoy receptor VEGFR1 (also known as FLT1), one can achieve more physiological VEGFA concentrations. We find that after cryoinjury, zebrafish flt1 mutant hearts display enhanced coronary revascularization and endocardial expansion, increased cardiomyocyte dedifferentiation and proliferation, and decreased scarring. Suppressing Vegfa signaling in flt1 mutants abrogates these beneficial effects of flt1 deletion. Transcriptomic analyses of cryoinjured flt1 mutant hearts reveal enhanced endothelial MAPK/ERK signaling and downregulation of the transcription factor gene egr3. Using newly generated genetic tools, we observe egr3 upregulation in the regenerating endocardium, and find that Egr3 promotes myofibroblast differentiation. These data indicate that with enhanced Vegfa bioavailability, the endocardium limits myofibroblast differentiation via egr3 downregulation, thereby providing a more permissive microenvironment for cardiomyocyte replenishment after injury. [ABSTRACT FROM AUTHOR]

Birth defects have always been one of the most important diseases in medical research as they affect the quality of the birth population. Orofacial clefts (OFCs) are common birth defects that place a huge burden on families and society. Early screening and prevention of OFCs can promote better natal and prenatal care and help to solve the problem of birth defects. OFCs are the result of genetic and environmental interactions; many genes are involved, but the current research has not clarified the specific pathogenesis. The mouse animal model is commonly used for research into OFCs; common methods of constructing OFC mouse models include transgenic, chemical induction, gene knockout, gene knock-in and conditional gene knockout models. Several main signal pathways are involved in the pathogenesis of OFCs, including the Sonic hedgehog (SHH) and transforming growth factor (TGF)-β pathways. The genes and proteins in each molecular pathway form a complex network to jointly regulate the formation and development of the lip and palate. When one or more genes, proteins or interactions is abnormal, OFCs will form. This paper summarises the mouse models of OFCs formed by different modelling methods, as well as the key pathogenic genes from the SHH and TGF-β pathways, to help to clarify the pathogenesis of OFCs and develop targets for early screening and prevention. [ABSTRACT FROM AUTHOR]