Background/Aims: Adenomyosis is a disease in which ectopic endometrial glands and stromal cells appear in the uterine myometrium. Despite its prevalence, the molecular mechanisms involved in the development of adenomyosis are largely unknown. The aim of this study was to investigate the role of miR-10b and its target genes ZEB1 and PIK3CA in adenomyosis. Methods: 1387 miRNAs in human normal endometrium and ectopic endometrial lesions of adenomyosis using a microarray screen assay. The significant differential expression of 10 miRNAs was confirmed by qRT-PCR. The expression of miR-10b in endometrial epithelial cells isolated from normal endometrium and paired eutopic and ectopic endometrium of adenomyosis was measured by qRT-PCR. Subsequently, the targets of miR-10b were predicted by bioinformatics and confirmed using a luciferase assay, and the mRNA and protein expression of ZEB1 and PIK3CA were assessed in the endometrium or endometrial epithelial cells by qRT-PCR and western blotting or immunohistochemical analysis. Cell migration and cell invasion of endometrial epithelial cells with different treatments by Transwell assays. The expression of p-AKT, Akt and E-cadherin proteins was determined by Western blot analysis. Results: MiR-10b expression was significantly downregulated in both adenomyotic lesions and adenomyotic epithelial cells. MiR-10b overexpression in adenomyotic epithelial cells inhibited cell migration and invasion. We then demonstrated that miR-10b directly targets the 3'-UTRs of ZEB1 and PIK3CA, and downregulates ZEB1 and PIK3CA in adenomyotic epithelial cells, leading to increased E-cadherin expression and decreased Akt phosphorylation. Conclusions: miR-10b directly targets ZEB1 and PIK3CA to curb adenomyotic epithelial cell invasiveness via upregulation of E-Cadherin and inhibition of Akt phosphorylation.
Background: Photodynamic therapy (PDT) is a new treatment for esophageal cancer which has been shown to be effective in the elimination of tumor. However, PDT could induce the activation of nuclear factor-kappa B (NF-κB) in many photosensitizers based PDT, which plays a negative role in PDT. In addition, our previous results have shown that dihydroartemisinin (DHA), which was the most potent one of artemisinin derivatives, has anticancer activity in esophageal cancer cells. Methods: Cell viability was determined by MTT analysis, and apoptosis was evaluated by flow cytometry. Nuclear extract was obtained for determining NF-κB DNA-binding activity, while total protein extract obtained for downstream gene expression by western blot. Results: We demonstrated DHA enhanced PDT-induced growth inhibition and apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vitro. The mechanism was at least partially due to DHA deactivated PDT-induced NF-κB activation, so as to decrease tremendously the expression of its target gene Bcl-2. Conclusion: Our results demonstrate that DHA augments PDT-induced growth inhibition and apoptosis in esophageal cancer cells, and that inactivation of NF-κB activity is a potential mechanism by which DHA sensitizes esophageal cancer cells to PDT-induced growth inhibition and apoptosis.
The aim of this study was to systematically search literature and conduct a meta-analysis comparing the clinical efficacy and safety of Evolut R and Sapien 3 valves for transcatheter aortic valve implantation (TAVI). The PubMed, Biomed Central, Scopus, Cochrane library and Google scholar databases were searched for articles published up to June, 2019. A total of 5 studies were included. In total, 795 patients underwent TAVI with Evolut R, while 665 patients received the Sapien 3 valve in the included studies. Overall device success with Evolut R was 95.7% and with Sapien 3 was 94.2%. Pooled data indicated no significant differences between the 2 valves (OR, 1.12; 95% CI, 0.66–1.89; P=0.68; I2=0%). No significant differences were observed in the incidence of none to mild paravalvular leakage between the 2 groups (OR, 1.71; 95% CI, 0.83–3.54; P=0.14; I2=0%). Both mean [random; mean difference (MD) = −3.96; 95% CI, −4.61 to −3.31; P<0.00001, I2=0%] and peak (random; MD = −6.85; 95% CI, −8.22 to −5.48; P<0.00001, I2=0%) aortic valve gradients were significantly lower with Evolut R. No significant differences were observed in the 30-day mortality (OR, 1.32; 95% CI, 0.45–3.87; P=0.62; I2=0%) or 30-day stroke outcomes (OR, 0.76; 95% CI, 0.32–1.81; P=0.54; I2=0%) between the 2 devices. On the whole, the findings of this study indicate that Evolut R and Sapien 3 valves may be comparable in terms of device success and short-term complications. The differences between the 2 devices for post-operative moderate to severe paravalvular leak and permanent pacemaker implantation remain unclear. There is thus a need for a large multi-center randomized controlled trial to provide stronger evidence on this subject.
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