RESUMO
Diabetes mellitus (DM) is a major worldwide public health challenge, for which gene therapy offers a potential therapeutic approach. To date, no systematic review or meta-analysis has been published in this area, so we examined all relevant published studies on rodents to elucidate the overall effects of gene therapy on bodyweight, intraperitoneal glucose tolerance test (IPGTT), fasting blood glucose, and insulin in animals with type 1 DM. The Cochrane Library, PubMed, Embase, ISI Web of Science, SCOPUS, and Google Scholar were systematically searched for potentially relevant studies. Mean±standard deviation (SD) was pooled using a random-effects model. After the primary search, out of 528 studies identified, 16 studies were in concordance with predefined criteria and selected for the final assessment. Of these, 12 studies used viral manipulation, and 4 employed non-viral vectors for gene delivery. The meta-analysis showed gene therapy with a viral vector decreased mean IPGTT (-12.69 mmol/l, P<0.001), fasting blood glucose (-13.51 mmol/l, P<0.001), insulin (398.28 pmol/l, P<0.001), and bodyweight (24.22 g, P<0.001), whereas non-viral vectors reduced fasting glucose (-29.95 mmol/l, P<0.001) and elevated insulin (114.92 pmol/l, P<0.001). Gene therapy has favorable effects on alleviating type 1 DM related factors in diabetic rodents.
RESUMO
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.
