MiR-196a-5p facilitates progression of estrogen-dependent endometrial cancer by regulating FOXO1

Background and Purpose. Estrogen-dependent endometrial cancer mainly occurs in younger pre-menopausal and post-menopausal women and threatens their health. Recently, microRNAs (miRNAs) have been considered as novel targets in endometrial cancer treatment. Therefore, we aimed to explore the effect of miRNA (miR)-196a-5p in estrogen-dependent endometrial cancer. Methods. 17β-estradiol (E2; 2.5, 5, 10 and 20 nM) was used to treat RL95-2, HEC-1B and ECC-1 cells followed by cell viability assessment using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The level of miR-196a-5p was measured by reverse transcription-quantitative PCR (RT-qPCR). We then transfected miR-196a-5p mimic/inhibitor and Forkhead box protein O1 (FOXO1) small interfering RNA (siRNA) into E2-treated cells. Apoptotic cells were measured by flow cytometry. Wound healing and Transwell assays were implemented to assess migration and invasion. Bioinformatics and luciferase reporter assays were applied to confirm the interaction between miR-196a-5p and FOXO1. Immunoblotting determined the levels of FOXO1, Bcl-2, Bax, Caspase 3. Results. E2 promoted cell viability and miR-196a-5p expression in RL95-2 and ECC-1 cells. miR-196a-5p mimic enhanced cell viability, migration and invasion but suppressed apoptosis and FOXO1, whilst miR-196a-5p inhibitor blocked these processes. In addition, miR-196a-5p upregulated Bcl-2, but down regulated Bax and Caspase 3 expression, an effect that was reversed by miR-196a-5p inhibitor. We determined that miR-196a-5p targeted FOXO1, and that si-FOXO1 blocked the effects of miR-196a-5p inhibitor on viability, apoptosis, migration and invasion of E2-treated RL95-2 and ECC-1 cells. Conclusions. Our findings suggested potential diagnostic and therapeutic applications for miR-196a-5p and its FOXO1 target in patients suffering from estrogen-dependent endometrial cancer

Vanishing viscosity limits for the degenerate lake equations with Navier boundary conditions

The paper is concerned with the vanishing viscosity limit of the two-dimensional degenerate viscous lake equations when the Navier slip conditions are prescribed on the impermeable boundary of a simply connected bounded regular domain. When the initial vorticity is in the Lebesgue space $L^q$ with $2<q\le\infty$, we show the degenerate viscous lake equations possess a unique global solution and the solution converges to a corresponding weak solution of the inviscid lake equations. In the special case when the vorticity is in $L^\infty$, an explicit convergence rate is obtained

miR-196a-2 Promotes Malignant Progression of Thyroid Carcinoma by Targeting NRXN1

Thyroid cancer (TC) is the most common endocrine malignant disease with a rising morbidity year by year. Accumulating studies have shown that microRNAs (miRNAs) play a regulatory role in the progression of various tumors, but the molecular regulatory mechanism of miR-196a-2 in TC is still unknown. qRT-PCR was employed to measure the expression of miR-196a-2 and NRXN1 mRNA in TC cells, while western blot was used to detect the protein expression of NRXN1. CCK-8, colony formation and flow cytometry assays were used to measure cell proliferation and apoptosis of TC cells. Dual-luciferase reporter gene assay was used to predict and verify the targeted binding relationship between miR-196a-2 and NRXN1. Our study results manifested that miR-196a-2 was dramatically overexpressed in cells of TC, while NRXN1 was lowly expressed. miR-196a-2 could promote cell proliferation and inhibit cell apoptosis of TC. Additionally, miR-196a-2 could also target and inhibit the expression of NRXN1. Silencing NRXN1 could reverse the inhibitory effect of miR-196a-2 downregulation on cell proliferation of TC, as well as the promoting effect on cell apoptosis. In a conclusion, we found that miR-196a-2 could promote cell proliferation and inhibit cell apoptosis of TC by targeting NRXN1. Therefore, miR-196a-2/NRXN1 is potential to be a molecular therapeutic target for TC

miR-301b-3p Regulates Breast Cancer Cell Proliferation, Migration, and Invasion by Targeting NR3C2

Objectives. Breast cancer is the most common malignant tumor among females, and miRNAs have been reported to play an important regulatory role in breast cancer progression. This study aimed to explore the function and underlying molecular mechanism of miR-301b-3p in breast cancer. Methods. Differential analysis and survival analysis were performed based on the data accessed from the TCGA-BRCA dataset for identification of the target miRNA. Bioinformatics analysis was conducted to predict the downstream target gene of the miRNA. Real-time quantitative PCR was carried out to detect the expression of miR-301b-3p and nuclear receptor subfamily 3 group C member 2 (NR3C2). Western blot was used to assess the protein expression of NR3C2. Cell counting kit-8 assay was performed to evaluate the proliferation of breast cancer cells. Transwell assay was conducted to determine the migratory and invasive abilities of breast cancer cells. Dual-luciferase reporter assay was employed to verify the targeting relationship between miR-301b-3p and NR3C2. Results. miR-301b-3p was elevated in breast cancer cell lines and promoted cell proliferation, migration, and invasion in terms of its biological function in breast cancer. NR3C2 was validated as a direct target of miR-301b-3p via bioinformatics analysis and dual-luciferase reporter assay, and NR3C2 was downregulated in breast cancer cell lines. The rescue experiment indicated that NR3C2 was involved in the mechanism by which miR-301b-3p regulated the malignant phenotype of breast cancer cells. Conclusion. The present study revealed for the first time that miR-301b-3p could foster breast cancer cell proliferation, migration, and invasion by targeting NR3C2, unveiling that miR-301b-3p is a novel carcinogen in breast cancer

Additional file 1: Figure S1. of Molluscicidal activity and mechanism of toxicity of a novel salicylanilide ester derivative against Biomphalaria species

The high resolution mass spectra analysis of salicylanilidate. (TIFF 1218 kb

Prediction of the potential global distribution for <i>Biomphalaria straminea</i>, an intermediate host for <i>Schistosoma mansoni</i>

<div><p>Background</p><p>Schistosomiasis is a snail-borne parasitic disease and is endemic in many tropical and subtropical countries. <i>Biomphalaria straminea</i>, an intermediate host for <i>Schistosoma mansoni</i>, is native to the southeastern part of South America and has established in other regions of South America, Central America and southern China during the last decades. <i>S</i>. <i>mansoni</i> is endemic in Africa, the Middle East, South America and the Caribbean. Knowledge of the potential global distribution of this snail is essential for risk assessment, monitoring, disease prevention and control.</p><p>Methods and findings</p><p>A comprehensive database of cross-continental occurrence for <i>B</i>. <i>straminea</i> was compiled to construct ecological models. We used several approaches to investigate the distribution of <i>B</i>. <i>straminea</i>, including direct comparison of climatic conditions, principal component analysis and niche overlap analyses to detect niche shifts. We also investigated the impacts of bioclimatic and human factors, and then used the bioclimatic and footprint layers to predict the potential distribution of <i>B</i>. <i>straminea</i> at global scale. We detected niche shifts accompanying the invasions of <i>B</i>. <i>straminea</i> in the Americas and China. The introduced populations had enlarged its habitats to subtropical regions where annual mean temperature is relatively low. Annual mean temperature, isothermality and temperature seasonality were identified as most important climatic features for the occurrence of <i>B</i>. <i>straminea</i>. Additionally, human factors improved the model prediction (<i>P</i><0.001). Our model showed that under current climate conditions the snail should mostly be confined to the tropic and subtropic regions, including South America, Central America, Sub-Saharan Africa and Southeast Asia.</p><p>Conclusions</p><p>Our results confirmed that niche shifts took place in the invasions of B. straminea, in which bioclimatic and human factors played an important role. Our model predicted the global distribution of <i>B</i>. <i>straminea</i> based on habitat suitability, which would help for prioritizing monitoring and management efforts for <i>B</i>. <i>straminea</i> control in the context of ongoing climate change and human disturbances.</p></div

Multimodality Imaging Evaluation of Functional and Clinical Benefits of Percutaneous Coronary Intervention in Patients with Chronic Total Occlusion Lesion

<p><b>Aims: </b>To determine the effects of percutaneous coronary intervention (PCI) on cardiac perfusion, cardiac function, and quality of life in patients with chronic total occlusion (CTO) lesion in left anterior descending (LAD) coronary artery.</p><p><b>Methods and Results: </b>Patients (n=99) with CTO lesion in the LAD coronary artery who had successfully undergone PCI were divided into three groups based on the SPECT/CTCA fusion imaging: (a) no severe cardiac perfusion defects (n=9); (b) reversible cardiac perfusion defects (n=40); or (c) fixed cardiac perfusion defects (n=50). No statistical difference of perfusion abnormality was observed at 6 months and 1 year after PCI in group (a). In group (b), SPECT/CTCA fusion imaging demonstrated that cardiac perfusion abnormality was significantly decreased 6 month and 1 year after PCI. Left ventricular ejection fraction (LVEF) increased significantly at 6 months and 1 year follow up. Quality of life improved at 6 months and 1 year after PCI procedure. Moreover, patients in group (c) also benefited from PCI therapy: a decrease in cardiac perfusion abnormality, an increase in LVEF, and an improvement in quality of life. PCI of coronary arteries in addition to LAD did not significantly affect cardiac function and quality of life improvement in each group.</p><p><b>Conclusions:</b> PCI exerts functional and clinical benefits in patients with CTO lesion in LAD coronary artery, particularly in patients with reversible cardiac perfusion defects. SPECT/CTCA fusion imaging may serve as a useful tool to evaluate the outcomes of patients with CTO lesion in LAD coronary artery.</p