Differentiation of multipotent stem cells to insulin-producing cells for treatment of diabetes mellitus: bone marrow- and adipose tissue-derived cells comparison.

BACKGROUND: Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together. METHODS AND RESULTS: MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit. The differentiated cells were evaluated by immunocytochemistry staining for Insulin and PDX-1. Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose. CONCLUSIONS: Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their higher potency.

Regulation of autophagy by some natural products as a potential therapeutic strategy for cardiovascular disorders.

Autophagy is a lysosomal degradation process through which long-lived and misfolded proteins and organelles are sequestered, degraded by lysosomes, and recycled. Autophagy is an essential part of cardiomyocyte homeostasis and increases the survival of cells following cellular stress and starvation. Recent studies made clear that dysregulation of autophagy in the cardiovascular system leads to heart hypertrophy and failure. In this manner, autophagy seems to be an attractive target in the new treatment of cardiovascular diseases. Although limited activation of autophagy is generally considered to be cardioprotective, excessive autophagy leads to cell death and cardiac atrophy. Natural products such as resveratrol, berberine, and curcumin that are present in our diet, can trigger autophagy via canonical (Beclin-1-dependent) and non-canonical (Beclin-1-independent) pathways. The autophagy-modifying capacity of these compounds should be taken into consideration for designing novel therapeutic agents. This review focuses on the role of autophagy in the cardioprotective effects of these compounds.

Surveillance of Antibiotic Consumption Point Prevalence Survey 2014: Antimicrobial Prescribing in Pediatrics Wards of 16 Iranian Hospitals.

BACKGROUND: Antibiotics are among the most commonly prescribed drugs in pediatrics. Due to lack of uniformity in pediatric antimicrobial prescribing and the emergence of antibiotic resistance, appropriate drug utilization studies have been found to be crucial to evaluate whether these drugs are properly used. METHODS: Data were collected between January 2014 and February 2014 in 16 Iranian pediatric hospitals using a standardized method. The point prevalence survey included all inpatient beds. RESULTS: Of 858 children, 571 (66.6%) received one or more antimicrobials. The indications were therapeutic in 60.6%. The parenteral route was used in 92.5% of therapeutic indications. Ceftriaxone was the most prescribed antimicrobials for therapeutic indications (32.4%) and combination-therapy was the most type of therapy in pediatric intelligent care unit (PICU). CONCLUSION: According to results of this study, antibiotics' prescribing in pediatrics wards of Iranian hospitals is empirical. Therefore, for quality improvement of antimicrobial use in children continuous audit process and antibiotic prescriptions require further investigation.

Novel selective Cox-2 inhibitors induce apoptosis in Caco-2 colorectal carcinoma cell line.

The cyclooxygenase-2 (COX-2) inhibitors including celecoxib inhibit cell growth and induce apoptosis in cancer cells. As COX-2 is over expressed in solid tumors such as colorectal cancer, it can be a suitable target for cancer treatment studies. In this study we designed and synthesized 4,5-bisaryl imidazolyl imidazoles as novel COX-2 inhibitors and evaluated their apoptosis inducing activities. The ability of our synthetic compounds to inhibit ovine COX-1 and COX-2 was determined using a colorimetric method. The effects of these COX-2 inhibitors and celecoxib on the proliferation of Caco-2 cells were evaluated by MTT assay. Cell apoptosis was determined by flow cytometry and DNA fragmentation assay. cDNA microarray technique was used to evaluate the effects of these synthetic compounds on 112 genes involved in apoptosis pathways. The expression of five apoptosis-related genes Bak-1, Bcl-x, BIRC (Survivin), TNFSF10 and CASP3 were evaluated by quantitative real-time PCR. Among our synthetic compounds (3a-c), 4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl derivative (compound 3c) exhibited the highest COX-1/COX-2 selectivity index (SI=262.9) and lowest growth inhibitory concentration (IC(50)=21.20µM). In addition, compounds 3a-c could up-regulate pro-apoptotic genes and down-regulate anti-apoptotic genes. So, these synthetic compounds seem to be inducers of apoptosis in Caco-2 cell line. This study indicates that 4,5-bisaryl imidazolyl imidazole is a suitable scaffold to design COX-2 inhibitors and 4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl derivative exhibited highly COX-2 inhibitory potency and selectivity even more than celecoxib. It seems that it could induce apoptosis in Caco-2 colorectal carcinoma cell line.

Association of the colorectal cancer and MDR1 gene polymorphism in an Iranian population.

The human multidrug resistance (MDR1) gene product P-glycoprotein is highly expressed in intestinal epithelial cells, where it constitutes a barrier against xenobiotics, bacterial toxins, drugs and other biologically active compounds, possibly carcinogens. In this study, an association of MDR1 gene polymorphism and the occurrence of colorectal cancer were evaluated. In this case-control-designed 118 unrelated colorectal cancer and 137 sex-and-ages matched healthy controls were enrolled. The C3435T MDR1 gene polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism method. Significantly increased frequencies of the 3435T allele and the 3435TT were observed in patients with colorectal cancer compared with controls (P = 0.03; OR, 95% CI; 1.46 for 3435T allele and P = 0.003; OR, 95% CI; 2.2 for 3435TT genotype). In contrast, frequency of genotype TT was significantly higher in controls compared to colorectal cancer (P = 0.006; OR, 95% CI; 0.49 for TC genotype). In this study suggest that C3435T MDR1 polymorphism has an association with colorectal cancer. The results support that the presence of allele C results in decreased susceptibility to colorectal cancer.