Trimetazidine Preconditioning Potentiates the Effect of Mesenchymal Stem Cells Secretome on the Preservation of Rat Pancreatic Islet Survival and Function In Vitro.

Islet transplantation offers improved glycemic control in individuals with type 1 diabetes mellitus. However, in vitro islet culture is associated with islet apoptosis and eventually will lose their functionality prior to transplantation. In this study, we examined the effects of mesenchymal stem cells (MSCs) secretome preconditioned with diazoxide (DZ) and trimetazidine (TMZ) on rat islet cells during pre-transplant culture. With and without preconditioned hAD-MSCs' concentrated conditioned media (CCM) were added to the culture medium containing rat islets every 12 h for 24 and 48 h, after testing for selected cytokine concentrations (interleukin (IL)-4, IL-6, IL-13). Insulin content, glucose-stimulated insulin secretion, islet cell apoptosis, and mRNA expression of pro-apoptotic (BAX, BAK-1, and PUMA) and anti-apoptotic factors (BCL-2, BCL-xL, and XIAP) in rat islets were assessed after 24 and 48 h of culture. The protein level of IL-6 and IL-4 was significantly higher in TMZ-MSC-CM compared to MSC-non-CM. In rat isolated islets, normalized secreted insulin in the presence of 16.7 mM glucose was significantly higher in treated islet groups compared to control islets at both 24 and 48 h cultivation. Also, the percentage of apoptotic islet cells TMZ-MSC-CCM-treated islets was significantly lower compared to MSC-CM and MSC-CCM-treated islets in both 24 and 48 h cultivation. Consistent with the number of apoptotic cells, after 24 h culture, the expression of BCL-2 and BCL-xL genes in the control islets was lower than all treatment islet groups and in 48 h was lower than only TMZ-MSC-CM-treated islets. Also, the expression of the XIAP gene in control islets was significantly lower compared to the TMZ-MSC-CCM-treated islets at both at 24 and 48 h. In addition, mRNA level of the BAX gene in TMZ-MSC-CCM-treated islets was significantly lower compared to other groups at 48 h. Our findings revealed that TMZ proved to be more effective than DZ and could enhance the potential of hAD-MSCs-CM to improve the function and viability of islets prior to transplantation.

Association of the 12669G>A Apolipoprotein B Gene Polymorphism with Apo-B Serum Level and Lipid Profile in Patients with Coronary Artery Disease Comparing with Individuals Without Coronary Artery Disease in Zanjan Population of Iran.

Atherosclerosis is a pathologic disorder which has an important role in the occurrence of coronary heart disease. It is determined as a focal, inflammatory proliferative response to several types of endothelial damage. Apolipoprotein B which is a requirement in the sustenance of cholesterol homeostasis, and is the major protein component of low density lipoprotein, characterized by multitude polymorphic sites, one of which (12669G>A) is related to the levels of serum lipid profiles, coronary artery disease and/or myocardial infarction. One Common polymorphism which is more important in this process is 12669G>A that is appraised in this research. We recruited 80 patients from the Mousavi hospital, Zanjan, Iran, diagnosed with coronary artery disease by the clinician on the basis of clinical symptoms, echocardiogram result, and angiography. Seventy-seven healthy individuals without any evident symptoms of Coronary stenosis and any past history of the disease were taken as controls from the general population. We carried out PCR using specific primers. Then, we digested PCR product by RFLP. Lipid parameters by biochemical methods and Apolipoprotein B serum level by immunoturbidometry method were done. Genotype frequencies for 12669G>A polymorphism were determined: 55 % R+R+, 45 % R+R- in case group, and 55.8 R+R+, 44.2 % R+R- in controls. The R-R- genotype was not seen. There was no significant relationship between this polymorphism and the risk of Coronary stenosis (P = 0.6). In the present study, higher plasma levels of cholesterol and low density lipoproteins in the subjects with R+R- genotype were found while there was no association between this polymorphism and coronary stenosis with ≥50 % in the Zanjan population.