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Diabetic cardiomyopathy (DCM) is a specific myocardial alteration in patients with diabetics. RAD1901 cell line LncRNA KCNQ1OT1 has been previously demonstrated to be involved in various diabetic complications. Our aims are to further investigate the underlying regulatory mechanisms/pathways of KCNQ1OT1 in DCM.
In vitro and in vivo models of DCM were established in high glucose (HG)-treated human cardiomyocytes and in streptozotocin (STZ)-induced diabetic mice, respectively. Gene and protein expressions were examined by qPCR, western blotting and ELISA. Cell proliferation and apoptosis were determined by CCK8 assay, flow cytometry and TUNEL staining. The association between KCNQ1OT1and miR-181a-5p, miR-181a-5p and PDCD4 was predicted using bioinformatics methods and subsequently confirmed by dual luciferase reporter and RNA immunoprecipitation assays. Mouse cardiac tissues were collected and analysed using HE staining, Masson's staining and immunohistochemical analysis.
KCNQ1OT1 and PDCD4 were upregulated in HG-treated human cardiomyocytes, while miR-181a-5p was downregulated. In addition, KCNQ1OT1 could negatively regulate miR-181a-5p expression; meanwhile, miR-181a-5p also negatively regulated PDCD4 expression. KCNQ1OT1 silencing suppressed the expression of inflammatory cytokines and cell apoptosis in vitro, whereas inhibition of miR-181a-5p abrogated those effects of KCNQ1OT1 knockdown. Moreover, overexpressed PDCD4 abolished the inhibition on inflammation and apoptosis caused by miR-181a-5p overexpression. Finally, KCNQ1OT1 knockdown reduced the expression of PDCD4 via regulating miR-181a-5p and inhibited myocardial inflammation and cardiomyocyte apoptosis in the in vivo DCM model.
Our findings suggest that KCNQ1OT1 and its target gene miR-181a-5p regulate myocardial inflammation and cardiomyocyte apoptosis by modulating PDCD4 in DCM.
Our findings suggest that KCNQ1OT1 and its target gene miR-181a-5p regulate myocardial inflammation and cardiomyocyte apoptosis by modulating PDCD4 in DCM.Focal segmental glomerulosclerosis (FSGS) represents a glomerular scar formation downstream of various different mechanisms leading to podocytopathy and podocyte loss. Recently, significant advances were made in understanding genetic factors, podocyte intrinsic mechanisms, and adaptive mechanisms causing FSGS. However, while most cases of nephrotic FSGS are being treated with immunosuppressants, the underlying immune dysregulation, involved immune cells, and soluble factors are only incompletely understood. Thus, we here summarize the current knowledge of proposed immune effector cells, secreted soluble factors, and podocyte response in immune-mediated (primary) FSGS.
Women meet criteria for substance use disorder after fewer years of drug use than men; this accelerated time course, or telescoping effect, has been observed for multiple drugs, including cocaine. Preclinical findings similarly indicate an enhanced vulnerability in females to developing an addiction-like phenotype; however, it is not yet known if this phenotype develops faster in females versus males.
The goal of this study was to determine using a rat model whether two key features of addiction in humans, an enhanced motivation for cocaine and compulsive use, emerge sooner during withdrawal from extended access cocaine self-administration in females versus males.
Motivation for cocaine, as assessed under a progressive-ratio reinforcement schedule, was determined prior to and following extended access cocaine self-administration (24h/day, 96 infusions/day, 10days) and after 7, 14, or 60days of withdrawal. Compulsive use, or use despite punishment, was evaluated once progressive-ratio responding stabilize use incubate over withdrawal.Due to the advantages of single-nucleotide polymorphisms (SNPs) in forensic science, many forensic SNP panels have been developed. However, the existing SNP panels have a problem that they do not reflect allele frequencies in Koreans or the number of markers is not sufficient to perform paternity testing. Here, we filtered candidate SNPs from the Ansan-Ansung cohort data and selected 200 SNPs with high allele frequencies. To reduce the risk of false inclusion and false exclusion, we calculated likelihood ratios of alleged father-child pairs from simulated families when the alleged father is the true father, the close relative of the true father, and the random man. As a result, we estimated that 160 SNPs were needed to perform paternity testing. Furthermore, we performed validation using Twin-Family cohort data. When 160 selected SNPs were used to calculate the likelihood ratio, paternity and non-paternity were accurately distinguished. Our set of 160 SNPs could be useful for paternity testing in Koreans.Y-Chromosomal short-tandem repeats (Y-STRs) could provide highly valuable information for forensic investigation and demographic studies. However, there is still no systematic Y-STR information on Tibetan as obtained from different regions of the broad Qinghai-Tibet Plateau. In this study, an analysis was conducted on 585 male individuals, classed into 3 different dialect branches as Ü-Tsang, Amdo, and Khams and originating from 11 scattered regions of the Qinghai-Tibet Plateau. The gene diversity values of the 41 Y-STRs in Tibetan ranged from 0.3636 to 0.9322. Additionally, a total of 563 distinct haplotypes were obtained with an overall haplotype diversity of 0.9999 and a discrimination capacity of 0.9624. As suggested by the inter-population diversity analysis, there were two main separated clades of Tibetan subgroups. The visualization of pairwise genetic distances between 11 Tibetan subgroups and 59 reference populations using cladogram revealed the distribution of various populations, which was basically consistent with the patterns of geographic origin and linguistic affinity.Most of insertion/deletion polymorphisms are diallelic molecular markers characterized as small amplicon sizes, high inter-population diversities, and low mutation rates, which make them the promising genetic markers in biogeographic ancestor inference field. The developmental validations of a 39 ancestry informative marker-insertion/deletion (AIM-InDel) panel and the genetic polymorphic investigations of this panel were performed in the Shaanxi Han population of China. The developmental validation included the optimizations of PCR-related indicators, repeatability, reproducibility, precision, accuracy, sensitivity, species specificity, stability of the panel, and the abilities in analyzing degraded, casework, and mixture samples, and the present results demonstrated that this 39 AIM-InDel panel was robust, sensitive, and accurate. For the population diversity analyses, the combined discrimination power value of 38 AIM-InDel loci except for rs36038238 locus was 0.999999999931257, indicating that this novel panel was highly polymorphic, biogeographic informative, and could be also used in individual identifications in the Shaanxi Han population.
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