Salib has completed his DVM and Ph.D. at age of 28 from faculty of veterinary medicine, department of Physiology he promoted to full professor at age of 39 at University of Cairo Egypt. He serves as the head of the department of physiology for 6 years, senior research director, University of Alberta Canada. He works as senior research fellow, department of medicine, haematology division, school of medicine, Ann Arber, MI. and research fellow, department of Pathology, University of Maryland, school of medicine, Baltimore, MD. He has published more than 70 papers in reputed national, international and serving as an editorial board member of reputed journals and also has Awards from NIH, USA and From QAAP, Egypt
Searching for insulin replacements or insulin-mimetic upon oral administration as diabetic patients still develop complications even with intensive insulin treatment.Rats were rendered diabetic by injection of streptozotocin (60 mg/kg body weight).After confirmation of diabetes, rats randomly allocated into 5 groups (15 rats/group): control(normal), diabetic, the treated groups daily received oral doses of100 mg/kg of Alpha lipoic acid ,vanadylacetylacetonate group were received 6 mg/kg of vanadylacetylacetonate and nigella sativa group were received oral doses of 500 mg/kg of Nigella Sativa via stomach tube for 6 weeks.After 2,4 and 6 weeks from onset of diabetes, serum and fluoride blood samples were obtained for evaluation of fasting blood glucose, lipid metabolism evaluation (total cholesterol ,triglyceride , HDL and LDL) , liver functions (ALT, AST, ALP activities and total bilirubin) and kidney functions ( urea , uric acid, total protein and albumin). After6weeks, histopathological samples were taken from the liver, kidney and pancreas. Administration of alpha lipoic Acid, nigella sativa and vanadylacetylacetonateto diabetic rats resulted in a significant decrease in blood glucose, triglycerides, cholesterol, LDL , ALT, AST, ALP, total bilirubin , urea , uric acid while HDL, total protein and albumin level were markedly increased compared tountreated diabetic rats. Also histopathological findings in liver, kidney of treated group showed improvement when compared with those of diabetic group while histopathological findings of pancreas in all treated group revealed regeneration in the islands of langerhans cells while those of diabetic groupshowedatrophy in islands of langerhans cells, degeneration in the acini and hyalinization in the wall of congested blood vessels.The results of this study indicate that the alpha lipoic Acid, nigella sativa and vanadylacetylacetonate possess hypoglycemic, hypolipidemic, improvement effects on kidney and liver functions and protective effects on beta cells of pancreasin STZ-induced diabetic rats.The improvement action of alpha lipoic may attributed to reducing the oxidative stress in diabetes and its hypoglycemic effect through decreasing hepatic glucose output and increase glucose uptake through increasing glucose transporter (GLUT) 1 and 4 translocation, moreover it has insulin mimetic actions. The effect of vanadyl may be due to its improvement action on hepatic glucose metabolism asits insulin mimic action while the action of nigella attributed to its antioxidant properties which decrease oxidative stress in diabetes and improves its complications through hypoglycemic actionand hepatic insulin sensitivity and decrease gluconeogenesis. Also nigella has insulin mimetic properties. The most improvement in diabetic state was seen in alpha lipoic group then vanadylacetylacetonate group however nigella sativa group significally improve kidney functions than vanadylacetylacetonate
Daniel Díaz obtained his Biology B.Sc. at the Universidad Juárez del Estado de Durango (México), he then obtained his PhD diploma at the Universidad Autónoma de Nuevo León where he was awarded with an Academic Excellence fellowship from the National Board for Science and Technology (CONACyT) and a fellowship granted by the Science and Technology Research Support Program (PAICyT). Dr. Díaz had the opportunity of undergoing extensive training in the Medical Center (Houston, TX) under the tutelage of several researchers in the University of Texas and M.D. Anderson Cancer Center and in the Institute of Biotechnology in Madrid, Spain. Currently, Dr. Díaz is a Post-Doctoral Fellow in the Faculty of Medicine of the Charles University at Prague, Czech Republic.
PI3K signaling cascade is often hyperactivated in human cancer and involved in both vertical and horizontal resistance to different targeted therapies. Inhibition of PI3K often show limited efficacy due to the reactivation of PI3K/AKT signaling. Kinases of the Janus family (JAKs) and their effector molecules (STATs) also play an important role in cancer. Since they are capable of stimulating cell proliferation, differentiation, migration, and survival. This pathway is activated upon binding of hormones and cytokines which are secreted by cancer cells and by cells from the tumor microenvironment. JAK2 is a known activator of PI3K and it is possible that JAK2 activation induced by PI3K inhibition contributes to AKT reactivation. Analyses of cytokine profiles after PI3K inhibition resulted in expression changes of several cytokines, IL-8 upregulation. Secreted IL-8 activates JAK2/STAT5 in breast cancer cells with a higher expression of CXCR receptors. It has been previously reported that activation of BIM and downregulation MCL1 are required for induction of cell death. The PI3K and JAK2 pathways activate the pro-survival protein MCL1 and suppress the pro-apoptotic protein BIM. Combined inhibition of PI3K/mTOR and JAK2 activates BIM and concomitantly downregulates MCL1, causing an increase in apoptosis, reduced tumor seeding and metastasis. Bcl-2 may serve as a target in the treatment of breast cancer as it is a known anti-apoptotic protein. Previous reports suggest that NF-kB and PI3K may contribute to Bcl-2 up-regulation in resistant cancers. Thus, IKK and PI3K inhibitors may potentially be used therapeutically in resistant breast cancers that have increased expression of Bcl-2. We propose that the knockdown of resistance molecules STAT5 and Bcl2 along with the chemical inhibition of PI3K will have a synergetic effect promoting an increased apoptotic rate of the treated breast cancer cells than by inhibiting only PI3K and JAK2. Project expenses are co-financed by the European Social Fund and the Czech Republic State Budget’s project no. CZ.1.07/2.3.00/30.0022.