• Secher Trolle posted an update a month ago

    Cellular experiments revealed that the overexpression of miR-4636 inhibited GC cell proliferation, migration and invasion, while the knockdown of miR-4636 led to opposite effects on the biological function of GC. In summary, decreased miR-4636 expression may serve as a biomarker for the diagnosis and prognosis of GC. Furthermore, miR-4636 overexpression significantly inhibited GC cell proliferation, migration and invasion, indicating the potential of miR-4636 as a therapeutic target for GC treatment.Sesamin, the major furofuran lignan found in the seeds of Sesamum indicum L., has been investigated for its various medicinal properties. In the present study, the anti-leukemic effects of sesamin and its underlying mechanisms were investigated in MOLT-4 and NB4 acute leukemic cells. Leukemic cells were treated with various concentrations of sesamin. Cell viability was determined using an MTT assay. Flow cytometry using Annexin V-FITC/PI staining and anti-LC3/FITC antibodies was applied to detect the level of apoptosis and autophagy, respectively. Reverse transcription-quantitative PCR was performed to examine the alterations in the mRNA expression of apoptotic and autophagic genes. In addition, bioinformatics tools were used to predict the possible interactions between sesamin and its targets. The results revealed that sesamin inhibited MOLT-4 and NB4 cell proliferation in a dose-dependent manner. In addition, sesamin induced both apoptosis and autophagy. In sesamin-treated cells, the gene expression levels of caspase 3 and unc-51 like autophagy activating kinase 1 (ULK1) were upregulated, while those of mTOR were downregulated compared with in the control. Notably, the protein-chemical interaction network indicated that caspase 3, mTOR and ULK1 were the essential factors involved in the effects of sesamin treatment, as with anticancer agents, such as rapamycin, AZD8055, Torin1 and 2. Overall, the findings of the present study suggested that sesamin inhibited MOLT-4 and NB4 cell proliferation, and induced apoptosis and autophagy through the regulation of caspase 3 and mTOR/ULK1 signaling, respectively.Epithelial-mesenchymal transition (EMT) serves an important role in the formation and development of various types of cancer, including oral squamous cell carcinoma (OSCC). Metformin, used for treating type 2 diabetes, has been revealed to exert an anticancer effect in various types of cancer, including liver, breast and colorectal cancer. However, its role in the EMT of OSCC has been rarely reported. Therefore, the present study aimed to investigate the effects of metformin on EMT and to identify its underlying mechanism in OSCC. Firstly, EMT was induced in CAL-27 cells using CoCl2. Subsequently, the effects of metformin on cell viability, migration and xenograft growth were evaluated in vitro and in vivo. selleck compound Reverse transcription-quantitative PCR was performed to detect the expression levels of E-cadherin, vimentin, snail family transcriptional repressor 1, mTOR, hypoxia inducible factor 1α, pyruvate kinase M2 and STAT3. The results demonstrated that metformin abolished CoCl2-induced cell proliferation, migration, invasion and EMT. Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR-associated HIF-1α/PKM2/STAT3 signaling pathway. Overall, the present findings characterized a novel mechanism via which metformin modulated EMT in OSCC.MicroRNAs (miRs) play important roles in the protection against and development of congenital heart disease (CHD). However, the role and potential mechanisms of miR-219-5p in cyanotic CHD remains unclear. Reverse transcription-quantitative PCR (RT-qPCR) was used to measure miR-219-5p levels in cyanotic CHD and hypoxia-induced H9C2 cells. Dual luciferase reporter gene assay was used to confirm whether liver receptor homolog-1 (LRH-1) was a direct target of miR-219-5p. miR-219-5p inhibitor and LRH-1-small interfering RNA were transfected into H9C2 cells under hypoxic conditions to investigate the role of miR-219-5p in hypoxia-induced H9C2 cells. Subsequently, cell viability was detected using an MTT assay and cell apoptosis was detected using flow cytometry. In addition, RT-qPCR and western blotting assays were performed to detect the mRNA and protein expression of LRH-1, cyclin D1 and β-catenin, respectively. The data showed that miR-219-5p expression was higher in patients with cyanotic CHD compared with patients with acyanotic CHD gradually increased in H9C2 cells with prolonged hypoxia time. Dual luciferase reporter assay results showed that LRH-1 was a direct target gene of miR-219-5p. Inhibition of miR-219-5p reversed hypoxia-induced cell viability reduction and attenuated hypoxia-induced cell apoptosis. In addition, hypoxia induction inhibited the expression of LRH-1, cyclin D1 and β-catenin, which was reversed by miR-219-5p inhibitor. However, LRH-1 downregulation reversed the miR-219-5p inhibitor enhanced cell viability, decreased cell apoptosis and increased expression of LRH-1, cyclin D1 and β-catenin in hypoxia-treated cardiomyocytes. The present results demonstrated that downregulation of miR-219-5p promoted the expression of the LRH-1/Wnt/β-catenin signaling pathway-associated components, reduced cardiomyocyte apoptosis and increased cell growth under hypoxic conditions. miR-219-5p may be a potential therapeutic target for cyanotic CHD therapy.Chronic hepatitis B (CHB) and acquired immunodeficiency syndrome (AIDS) are global public health problems that pose a significant health burden. Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is common, as these viruses have similar transmission routes, such as blood transmission, sexual transmission and mother-to-child transmission. Coinfection frequently leads to accelerated disease progression. For individuals coinfected with HIV/HBV, combination antiretroviral therapy containing dual anti-HBV drugs is recommended. Certain studies have also indicated the benefits of antiretroviral drugs with anti-HBV activity in patients with coinfection. A total of four Food and Drug Administration-approved HIV drugs also have anti-HBV activity; namely, emtricitabine, lamivudine, tenofovir disoproxil fumarate and tenofovir alafenamide, which are all nucleoside reverse transcriptase inhibitors. However, various issues, including drug resistance and side effects, limit their application. Therefore, it is necessary to develop more drugs with dual activity against HBV and HIV.

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