Computational Analysis of Naturally Occurring Aristolochic Acid Analogues and Their Biological Sources.

Aristolochic acids are known for nephrotoxicity, and implicated in multiple cancer types such as hepatocellular carcinomas demonstrated by recent studies. Natural products that are analogues to aristolochic acids have been constantly isolated from organisms; a larger chemical space of these compounds and a wider coverage of biological sources should be determined in consideration of the potential hazard of aristolochic acid analogues and the wide distribution of their biological sources in the nature. Therefore, we carried out an in silico research of naturally occurring aristolochic acid analogues and their biological sources, as a supplement to existing studies. The result shows a chemical space of 238 naturally occurring aristolochic acid analogues that are present in 175 species of biological sources including 44 traditional medicines. With the computational estimation for toxicity and the implication in hazard assessment of a biological source with the presence of aristolochic acid analogues, we propose that additional awareness should be raised to the public for avoidance of toxic species, especially those that are used as herbal medicines and easily accessible.

An In Vitro Study on Extracellular Vesicles From Adipose-Derived Mesenchymal Stem Cells in Protecting Stress Urinary Incontinence Through MicroRNA-93/F3 Axis.

Since the potential roles of extracellular vesicles secreted by adipose-derived mesenchymal stem cells (ADSCs) are not well understood in collagen metabolism, the purpose of this research was to evaluate the effects of ADSCs-extracellular vesicles in stress urinary incontinence and the regulatory mechanism of delivered microRNA-93 (miR-93). ADSCs were isolated and cultured, and ADSCs-extracellular vesicles were extracted and identified. Stress urinary incontinence primary fibroblasts or satellite cells were treated with ADSCs-extracellular vesicles to detect the expression of Elastin, Collagen I, and Collagen III in fibroblasts and Pax7 and MyoD in satellite cells. After transfecting ADSCs with miR-93 mimics or inhibitors, extracellular vesicles were isolated and treated with stress urinary incontinence primary fibroblasts or satellite cells to observe cell function changes. The online prediction and luciferase activity assay confirmed the targeting relationship between miR-93 and coagulation factor III (F3). The rescue experiment verified the role of ADSCs-extracellular vesicles carrying miR-93 in stress urinary incontinence primary fibroblasts and satellite cells by targeting F3. ADSCs-extracellular vesicles treatment upregulated expression of Elastin, Collagen I, and Collagen III in stress urinary incontinence primary fibroblasts and expression of Pax7 and MyoD in stress urinary incontinence primary satellite cells. miR-93 expression was increased in stress urinary incontinence primary fibroblasts or satellite cells treated with ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs could deliver miR-93 to fibroblasts and then negatively regulate F3 expression; ADSCs-extracellular vesicles could reverse the effect of F3 on extracellular matrix remodeling in stress urinary incontinence fibroblasts. miR-93 expression was also increased in stress urinary incontinence primary satellite cells treated by ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs were delivered to satellite cells through miR-93, which directly targets F3 expression and upregulates Pax7 and MyoD expression in satellite cells. Our study indicates that miR-93 delivered by ADSCs-extracellular vesicles could regulate extracellular matrix remodeling of stress urinary incontinence fibroblasts and promote activation of stress urinary incontinence satellite cells through targeting F3.

Interplay of microRNAs to genetic, epigenetic, copy number variations of cervical cancer related genes.

This study was to analyses the miRNAs role in cervical cancer and possibilities of microRNA-based markers as diagnostic tools. Genome wide analysis was performed for CNV detection using PennCNV and QuantiSNP. The associated mRNA qRT-PCR detection was used to measure quantities of microRNA gene expression. More than 10 CNV regions has a significant relationship with cervical cancer risk for both CNV detection algorithms. A total of 34 CNVs was detected by QuantiSNP while it was 27 in case of PennCNV, among which 22 CNVs was found to be overlapping between these two algorithms. the mRNA was analyzed for its expression on 36 carvical tumor normal tissue pairs of four targets i.e., MAP3K3, RIPK2, DIRAS3 and GAS7. These infers that there was a significant downregulation of all the four genes cervical tumor. Our results showed that miR-182 can modulate the expression of FAM83H, DIRAS3, RIPK2 and MAP3K3 in cervical cancer. Therefore, indicated that miR-182 can acts through these signaling pathway in proliferation of cervical cancer cells. The expression of tumor modulator miRNAs can be controlled by miRNA replacement therapy. Several miRNAs have been used for this purpose. The modulation of various signaling pathway and proteins in cervical cancer cells by miR-182 needs further clarification.