Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against neuropathy

A diabetic wound is the most frequent form of chronic wound. Because diabetic wounds have multiple factors contributing to their development, the best treatments involve using a combination of approaches. Herein we assessed whether bioactive and degradable bioengineered micro-porous collagen-based three-dimensional scaffold (CTS) encapsulated with adipose mesenchymal stem cells (ASCs)-derived exosomes could accelerate the wound healing process in diabetic rats. Diabetic animals were assigned to the control group, CTS group, Exo group, and CTS+Exo group. Tissue samples were collected on days 7, 14, and 21 for evaluations including stereological, molecular, and tensiometrical assessments. The findings showed that in the treatment groups, there was a notably increase in wound closure rate, total volumes of newly formed epidermis and dermis, numerical densities of fibroblasts and blood vessels, collagen density, and biomechanical parameters than the control group, with the most noticeable changes seen in the CTS+Exo group. Additionally, there was a notably increase in the transcript of miRNA-146a, TGF-β, bFGF, and VEGF genes in the treatment groups than the control group, with the highest expression observed in the CTS+Exo group. In the CTS+Exo group, there was a much greater decrease in TNF-α and IL-1β expression, as well as in the number of neutrophils, compared to the other groups. These results validated that the combination of CTS and ASCs-derived exosomes has a greater effect on improving diabetic wound healing.