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AimsRan GTPase is involved in nucleocytoplasmic shuttling of proteins and is overexpressed in several cancers. The expression of Ran in malignant melanoma (MM) and its functional activity have not been described and were investigated in this study.MethodsThe prognostic value of Ran expression was tested in a series of 185 primary cutaneous MM cases using immunohistochemistry. The functional activity of Ran was investigated in the two melanoma cell lines. Ran expression was knocked down using two siRNAs and the effect on the expression of the c-Met oncogene, a potential downstream target of Ran, was tested. Functional effects of Ran knockdown on cell motility and cell proliferation were also assessed.ResultsPositive Ran expression was seen in 12.4% of MM and was associated with advanced clinical stage and greater Breslow thickness. Positive expression was an independent marker of shorter overall survival (p=0.023). Knockdown of Ran results in decreased expression of c-Met and the downstream c-met signalling targets ERK1/2. There was a significant reduction in cell migration (p<0.001) and cell invasion (p<0.001). c-Met knockdown decreased the expression of Ran through MAPK and PI3K-AKT in A375 cell line, inhibited the cell viability and migration of both A375 and G361 melanoma cell lines while invasion was enhanced.ConclusionRan is a poor prognostic marker in cutaneous MM. It upregulates expression of the oncogene c-Met and, possibly through this, it promotes cell motility which may in turn promote metastasis.

Background: Atherosclerosis is known as a serious cardiovascular condition that causes human mortality worldwide. Atherosclerosis is a significant progressive condition of inflammation. Atherosclerosis of the cerebellar arteries affects voice, balance and fine motor control. Coenzyme-Q10 vitamin soluble in fat that used for heart failure and angina treatment protocol. It has the potential to influence cellular bioenergetics, and counteract free radical damage. This has proven success in treating many neurodegenerative diseases. Silymarin is a flavonoid extract of the herb Silybum marianum. It has been reported as the gold medicine in liver disorders and evaluated recently as a neuroprotective. Objective: Comparison of potential neuroprotective effects of Co Q10 and Silymarin on adult male albino rats cerebellar cortex suffering from atherosclerosis. Materials and Methods: Sixty adult male albino rats were divided randomly into equal four classes: Group I (control group) subdivided into three subgroups: Subgroup IA: provided ordinary diet. Subgroup IB (Co enzyme Q10 treated): obtained ordinary diet and co-enzyme Q10 Subgroup IC (Silymarin treated): obtained ordinary diet and Silymarin. Group II (atherosclerotic group), Group III (atherosclerotic Co Q10 treated group) and Group IV (atherosclerotic Silymarin treated group). After three months, lipid profile was assessed in blood samples taken from all classes. Cerebellar cortices were processed for histological, biochemical, immunohistochemical and electron microscopic studies. Results: Atherosclerotic rats showed loss and disruption of Purkinje cell layer with pyknotic nuclei, dilated cisternae of rough endoplasmic reticulum, prominent perineural spaces and spongiosis of granular and molecular layers. Significant increase in GFAP, Cox-2 immunoreactivity was also found. However, concomitant administration of Co Q10 or Silymarin had ameliorating effect on these changes. Conclusion: Co Q10 or Silymarin supplementation had a neurological protective role in atherosclerosis. Silymarin may be the ideal neuroprotective agent and new approach for reduction of many neurological diseases in high risk population.

Background: Penconazole is widely used triazole fungicide. It is used in agriculture, in human and veterinary medicine. High doses of penconazole causing nephrotoxicity and renal damage. Nigella sativa (black seed) is one of the native plants.It has anti-inflammatory, antidiabetic and anti-cancerous properties. Aim: This work aimed to evaluate the effect of Nigella sativa oil on Penconazole induced renal toxicity in a rat model. Material and Methods: Sixty male adult albino rats were used . They were divided into equal four groups. Group I (control): rats were received distilled water Group II (N. sativa): rats were given orally 0.2ml N. sativa oil /100 g b. wt. three days/ week for four weeks. Group III(PEN -treated): the animals were received intraperitoneally 67 mg penconazole /kg b. wt. three days/week for four weeks. Group IV(PEN+ N.sativa): rats were given penconazole (67 mg/kg b.w) and N. sativa oil (0.2ml/100 g) simultaneously three days weekly for four weeks. At the end of the experiment, kidney tissues were prepared for biochemical, immunohistochemical, light and electron microscopic studies. Results: Histological examination of penconazole treated group revealed glomerular atrophy, widening of the subcapsular space and hypercellularity of the glomerular cells. Detachment of podocytes and disruption of their processes resulted in impairment of the blood renal barrier. Tubular degeneration and necrosis were confirmed by significant decrease in Bcl2 immune marker. An increase in activity of intercalated cells of cortical collecting tubules was an indication of metabolic acidosis. Renal fibrosis was confirmed by an significant increase in α SMA and collagen fibers. Biochemical study revealed an increase in MDA level, decrease in both superoxide dismutase (SOD) and catalase (CAT).These changes were reserved by concomitant administration of Nigella sativa oil. Conclusion:The antioxidant properties of Nigella sativa could be attributed in ameliorating penconazole-induced nephrotoxicity in rats.

Introduction: Diabetes Mellitusi is a common endocrine and metabolic disease. It ischaracterized by hyperglycemia and abnormal metabolism of the lipid, carbohydrate, and protein that are caused bydeficiency of insulin or defective insulin action or both. Today,it is considered as one of the major health problems in the world. Ocimum basilicum (Basil) is one of the most widely grownpopular herbs in the world. It contains a large number of phytochemicals which have many significant health and nutritionalbenefits. It belongs to Lamiaceae (Mint family)and possesses marked anti-hyperlipidemic, anticancer and antioxidant activity. Objective: The aim of this work is to evaluate the possible protective effect of Ocimum basilicum administration on the induceddiabetic colon of adult male albino rats. Materials and Methods: Sixty adult male albino rats were used in the present study. They were divided into four groups, Group I (control group), Group II (ocimum basilicum received group), Group III (diabetic group) and Group IV (diabetic with ocimum basilicum group). After four weeks, the animals from all groups were anaesthetized and the blood samples were collected for biochemical study. The colon was dissected and the specimens were subjected to histological, histochemical, immunohistochemical and scanning electron microscopic studies. Results: Diabetic colon revealed a significant increase in the depth of intestinal crypts and number of goblet cells with marked biochemical and histological alterationsas increase in plasma level of MDA, shedding of the surface mucosa and small size Aeurbach's myenteric plexus. Administration of Ocimum basilicum in rats with diabetes mellitus has ameliorating effect on the histological, biochemical and morphometric abnormalities of the colonic tissue. Conclusion:Ocimum basilicum has a protective effect on the histological, biochemical and morphometric changes of the colon of diabetic rats. It has also a protective effect on the intestinal myenteric nerve plexus.