Green synthesis of silver nanoparticles has gained great interest among scientists. In view of this data, we conducted this study to identify the ameliorative effect of green synthesis of silver nanoparticles using Nigella sativa extract in diabetic neuropathy induced experimentally. In this study, 50 adult male albino rats were used and they were randomly divided into five groups; the first group was the healthy control group, the second group were the diabetic neuropathy diabetic neuropathy induced, Groups (3-6) diabetic neuropathy induced group and treated with silver nanoparticles, Nigella sativa extract and green synthesized silver nanoparticles using Nigella sativa extract respectively. Biochemical parameters including diabetic, inflammatory and antioxidant biomarkers were evaluated. Brain histopathology was also performed. Results revealed substantial rise in glucose, AGE, aldose reductase with insulin reduction in diabetic neuropathy induced group as compared to healthy control. Also, inflammatory markers increased significantly in diabetic neuropathy induced group. A remarkable change in oxidative status was observed in the same group. Furthermore, significant decline in nitrotyrosin level was observed. Regarding gene expression, we found significant down regulation in brain TKr A accompanied by upregulation of nerve growth factor in diabetic neuropathy group comparing with healthy control. Several treatments for diabetic neuropathy remarkably ameliorate all the investigated biomarkers. Histological findings are greatly relied on for the results achieved in this study. Therefore, it can be established that green synthesis of silver nanoparticles in combination with Nigella sativa extract could be a newly neuroprotective agents against inflammation and oxidative stress characterizing diabetic neuropathy through their antidiabetic, anti-inflammatory and anti-oxidants effects.

Recombinant plasminogen kringle 5 (rK5) has been shown to induce apoptosis of dermal microvessel endothelial cells (MvEC) in a manner that requires glucose-regulated protein 78 (GRP78). As we are interested in antiangiogenic therapy for glioblastoma tumors, and the effectiveness of antiangiogenic therapy can be enhanced when combined with radiation, we investigated the proapoptotic effects of rK5 combined with radiation on brain MvEC. We found that rK5 treatment of brain MvEC induced apoptosis in a dose-and time-dependent manner and that prior irradiation significantly sensitized (500-fold) the cells to rK5-induced apoptosis. The rK5-induced apoptosis of both unirradiated and irradiated MvEC required expression of GRP78 and the low-density lipoprotein receptorrelated protein 1 (LRP1), a scavenger receptor, based on down-regulation studies with small interfering RNA, and blocking studies with either a GRP78 antibody or a competitive inhibitor of ligand binding to LRP1. Furthermore, p38 mitogen-activated protein kinase was found to be a necessary downstream effector for rK5-induced apoptosis. These data suggest that irradiation sensitizes brain MvEC to the rK5-induced apoptosis and that this signal requires LRP1 internalization of GRP78 and the activation of p38 mitogenactivated protein kinase. Our findings suggest that prior irradiation would have a dose-sparing effect on rK5 antiangiogenic therapy for brain tumors and further suggest that the effects of rK5 would be tumor specific, as the expression of GRP78 protein is up-regulated on the brain MvEC in glioblastoma tumor biopsies compared with the normal brain.

Background/Aims: Hepatic fibrosis is a wound-healing process in the chronically injured liver. Clinical application of platelet-rich plasma (PRP) is of considerable interest for wound healing and regeneration. In view of the regeneration effect of PRP, we designed this study to explore the hypothesis that PRP could play a role in improving the biochemical and molecular changes that occur in liver fibrosis induced by dimethylnitrosamine (DMN) in rats. Methods: Four groups were studied: control, PRP control, DMN (liver fibrosis), and DMN+PRP groups. Serum liver enzymes (alanine amino transferase ALT, aspartate amino transferase AST, gamma glutamyl transferase GGT, and lactate dehydrogenase LDH), and liver hydroxyproline content were measured colorimetrically.Interleukin-8 (IL-8) and B-cell lymphoma (Bcl2) were determined by enzyme-linked immunosorbent assay. And the expression levels of alpha-smooth muscle actin (α-SMA) ,transforming growth factor (TGF-β), and nuclear factor kappa B1(NF-қB1) were evaluated by quantitative real-time polymerase chain reaction. Results: Our results showed that PRP markedly improved the DMN-induced changes in liver enzymes accompanied by a significant decrease in liver hydroxyproline content and IL-8 level induced by DMN, and an increase in the anti-apoptotic marker Bcl-2. PRP also showed significant down-regulation of fibrosis-related genes α-SMA and TGF-β and a significant decrease in the inflammatory marker NF-қB1. Conclusion: Based on these encouraging results, we consider that PRP could be a promising new agent for liver regeneration and alleviation of fibrosis.