• Camacho Korsholm posted an update 6 months, 1 week ago

    To explore contractile actions of angiotensin II (ATII) on the muscularis mucosae (MM) of the bladder, ATII-induced contractions were compared between MM and the detrusor smooth muscle (DSM) of the pig bladder by isometric tension recordings. Effects of ATII on spontaneous Ca2+ transients in MM were visualized using Cal-520 fluorescence. ATII receptor type 1 (ATR1) expression in MM and DSM was also examined by immunohistochemistry. ATII (1 nM-1 μM) caused phasic contractions of MM in a concentration-dependent manner, while ATII (10 nM-10 μM) had no or marginal effects on DSM contractility. ATII (100 nM)-induced MM contractions had an amplitude of approximately 70% of carbachol (1 μM)-induced or 90% of U46619 (100 nM)-induced contractions. Candesartan (10 nM), an ATR1 blocker, prevented the contractile effects of ATII (1 nM) in MM, while ATR1 immunofluorescence was greater in MM than DSM. ATII (10-100 pM) increased the frequency but not the amplitude of spontaneous Ca2+ transients in MM. Both urothelium-intact and -denuded MM strips developed comparable spontaneous phasic contractions, but ATII, carbachol and U46619-induced contractions were significantly larger in urothelium-denuded than urothelium-intact MM strips. In conclusion, the MM appears to have a much greater sensitivity to ATII compared with DSM that could well sense circulating ATII, suggesting that MM may be the predominant target of contractile actions induced by ATII in the bladder while the urothelium appears to inhibit MM contractility.Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. The high expression of BART-miRNAs (miR-BARTs) during latent EBV infection in NPC strongly supports their pathological importance in cancer progression. Recently, we found that several BART-miRNAs work co-operatively to modulate the DNA damage response (DDR) by reducing Ataxia-telangiectasia-mutated (ATM) activity. In this study, we further investigated the role of miR-BARTs on DDR. The immunohistochemical study showed that the DNA repair gene, BRCA1, is consistently down-regulated in primary NPCs. Using computer prediction programs and a series of reporter assays, we subsequently identified the negative regulatory role of BART2-3p, BART12, BART17-5p and BART19-3p in BRCA1 expression. The ectopic expression of these four miR-BARTs suppressed endogenous BRCA1 expression in EBV-negative epithelial cell lines, whereas BRCA1 expression was enhanced by repressing endogenous miR-BARTs activities in C666-1 cells. More importantly, suppressing BRCA1 expression in nasopharyngeal epithelial cell lines using miR-BART17-5p and miR-BART19-3p mimics reduced the DNA repair capability and increased the cell sensitivity to the DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. Our findings suggest that miR-BARTs play a novel role in DDR and may facilitate the development of effective NPC therapies.

    The association of ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C ratio) change trajectory with risk of type 2 diabetes mellitus (T2DM) remains unknown. The aim of this study was to evaluate the association between risk of T2DM and TG/HDL-C ratio change trajectory.

    A total of 18 444 participants aged 18-80 years old were included in this cohort study. read more Linear regression and quadratic regression models were used to determine the TG/HDL-C ratio change trajectory. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TG/HDL-C ratio change trajectory and probability of T2DM.

    T2DM developed in 714 participants during a median follow-up of 5.74 years (92 076.23 person-years of follow-up). After adjusting for baseline potential confounders, odds of T2DM were greater for participants with the increasing, U-shape, bell-shape, and other shape change vs decreasing change (adjusted OR 2.01, 95% CI 1.42-2.81; 1.56, 1.15-2.13; 1.60, 1.17-2.20; and 1.49, 1.13-2.00, respectively). The results were robust in the sensitivity analyses on excluding baseline participants with T2DM. Moreover, the associations remained significant with male sex, age <60 years and body mass index <24 kg/m

    .

    This retrospective study revealed increased probability of T2DM with increasing, U-shape, bell-shape, and other-shape TG/HDL-C ratio change trajectories, especially with male sex, age <60 years and body mass index <24 kg/m

    .

    This retrospective study revealed increased probability of T2DM with increasing, U-shape, bell-shape, and other-shape TG/HDL-C ratio change trajectories, especially with male sex, age less then 60 years and body mass index less then 24 kg/m2 .Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.

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