Epigenetic modifications determine phenotypic characteristics in a reversible, stable and genotype-independent manner. Epigenetic modifications mainly encompass CpG island methylation and histone modifications, both being important in the pathogenesis of malignancies. The reversibility of epigenetic phenomenon provides a suitable therapeutic option that is reactivation of epigenetically silenced tumor-suppressor genes. Inhibition of DNA methyltransferase, histone deacetylase and Aurora B kinase, individually or collectively, could feasibly prevent or reverse the impact of epigenetic silencing. MicroRNAs [miRNAs] are an important layer of epigenetic controlling of gene expression, and serve as diagnostic and prognostic biomarkers as well as treatment targets for several types of cancer. miRNAs are involved inepigenetically silencing or activation of genes, tumor suppressor genes and oncogenes, and their modulation opens new horizons for designing novel cancer therapeutic agents.

Background: The previously established methods for type 2 diabetes (T2D) have mainly concentrated on overt diabetes model development. Here, our intention was to create an animal model passing through distinct phases such as obesity with insulin resistance, prediabetes, and gradual progress to the overt diabetes stage. A high-fat high-carbohydrate diet formulation was prescribed combined with multiple low-dose streptozotocin (STZ) injections after obesity establishment. Materials and Methods: Sixteen male Wistar rats were separated randomly into two groups and fed a normal diet for 1 week after which the body weight and biochemical indices of each rat were measured and recorded. Subsequently, one group (n = 8) switched to the high-fat high-carbohydrate diet formulated by us for 10 weeks, whereas the other group (n = 8) continued with the normal diet. Body weight and biochemical indices of the rats in the high-fat diet (HFD) group were measured at the end of 10 weeks, and each rat received 30 mg/kg intraperitoneal STZ injections with 1-week intervals in two steps and was continued on a high-fat high-carbohydrate diet. The differences between the groups were analyzed using the Student's t-test or one-way analysis of variance and by post hoc multiple comparisons. Results: A significant change in weight, fasting blood glucose, and triglyceride was observed in rats fed with a HFD after 10 weeks. The HFD rats showed typical characteristics of T2D mellitus (T2DM) such as insulin resistance and hyperglycemia following 30 mg/kg STZ. Conclusions: The novel high-fat high-carbohydrate formulation we used, along with multiple low doses of STZ, can mimic peculiar characteristics of T2DM development.

Background: Grape exosome-like nanovesicles (GELNs) have the advantage of inherent biocompatibility and biodegradability, the potential to be used as oral delivery vehicles. The objective of this research was to evaluate the efficiency of Syrah GELN purification and their effects on the intestinal stem cells when orally administrated to the rats. Materials and Methods: In this experimental study, Syrah GELN isolated by differential centrifugation and sucrose gradient ultracentrifugation method, then the concentration of protein, size, and zeta potential were measured as well as nanoparticles morphology. The stability of nanoparticles was investigated in the solution that mimicked the condition encountered in the stomach and intestine. To demonstrate transfection efficiency of intestinal stem cells, real-time PCR was carried out using rat leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-specific primers on cDNA derived from total RNA extracted from the upper part of the small intestine of GELN-treated rats and their controls. Results: The mean size, zeta potential, and concentration of nanoparticles were 205.1 nm, −12.5 mV, and 250 μg/ml, respectively. The result of stability test demonstrated that Syrah GELN were resistant to the harsh environment of the stomach. Lgr5 gene expression was increased by tenfold in GELN-treated rats compared with the controls. Conclusions: As intestinal stem cells are poorly accessible by common exogenous agents in vivo, oral delivery of GELNs provides a new approach to modulate the stem cell microenvironment for intestinal remodeling. This novel and effective method would help to overcome conditions such as inflammatory bowel disease, colorectal cancer, and applicable in regenerative medicine.