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Background: In the realm of diabetes treatment, various strategies have been tried, including islet transplantation and common drug therapies, but the limitations of these procedures and lack of responsive to the high number of patients have prompted researchers to develop a new method. In recent decades, the use of stem cells and three‐dimonsional (3D) scaffold to produce insulin‐secreting cells is one of the most promising new approaches. Meanwhile, human‐induced pluripotent stem cells (iPSCs) propose due to advantages such as autologousness and high pluripotency in cell therapy. This study aimed to evaluate the differentiation of iPSCs into pancreatic islet insuli‐producing cells (IPCs) on Silk/PES (polyethersulfone) nanofibers as a 3D scaffold and compare it with a two‐dimonsional (2D) cultured group. Methods: Investigating the functional, morphological, molecular, and cellular characteristics of differentiated iPSCs on control cultures (without differentiation medium), 2D and 3D were measured by various methods such as electron microscopy, Q‐PCR, immunofluorescence, western blot, and ELISA. Results: This investigation revealed that differentiated cells on the 3D Silk/PES scaffold expressed pancreatic specific‐markers such as insulin and pdx1 at higher levels than the control and 2D groups, with a significant difference between the two groups. All results of Q‐PCR, immunocytochemistry, and western blot showed that IPCs in the silk/PES 3D group was more efficient than in the 2D group. In the face of these cases, the release of insulin and C‐peptide in response to several concentrations of glucose in the 3D group was significantly higher than in the 2D culture. Conclusion: Finally, our findings displayed that optimized Silk/PES 3D scaffolds can enhance the differentiation of IPCs from iPSCs compared to the 2D culture group. [ABSTRACT FROM AUTHOR]

Wound healing is a complex but a fine‐tuned biological process in which human skin has the ability to regenerate itself following damage. However, in particular conditions such as deep burn or diabetes the process of wound healing is compromised. Despite investigations on the potency of a wide variety of stem cells for wound healing, adipose‐derived stem cells (ASCs) seem to possess the least limitations for clinical applications, and literature showed that ASCs can improve the process of wound healing very likely by promoting angiogenesis and/or vascularisation, modulating immune response, and inducing epithelialization in the wound. In the present review, advantages and disadvantages of various stem cells which can be used for promoting wound healing are discussed. In addition, potential mechanisms of action by which ASCs may accelerate wound healing are summarised. Finally, clinical studies applying ASCs for wound healing and the associated limitations are reviewed. Despite investigations on the potency of a wide variety of stem cells for wound healing, adipose‐derived stem cells (ASCs) seem to possess the least clinical limitations for clinical applications, and our review showed that ASCs can improve the process of wound healing very likely by promoting angiogenesis and/or vascularisation, modulating immune response, and inducing epithelialization in the wound. [ABSTRACT FROM AUTHOR]

Background: Diabetes caused by insulin production disturbance is considered as the most common metabolic disorder all over the world. Diabetes may outbreak because of low insulin secretion by Islets of Langerhans β-cells, insulin resistance or both of them. In this way, using stem cells, which have the capability to differentiate into Pancreatic β-cells, is one of novel methods in this field. MSCs are the most important candidates for cellular therapy. Materials and Methods: Insulin level was examined using ELIZA method. In order to examine the morphology of differentiated cells, they were stained by Dithizone. Insulin-producer cells are cells which turn into red as a result of staining. Specific gene involving insulin-producing cells was evaluated by Real Time-PCR method. Results: The ELISA results showed that the treated cells secreted more insulin than the control group. Moreover, we found differentiation of MSCs toward insulin-secreting cells. In order to evaluate insulin production in clusters on day 21 of differentiation, we used dithizone (DTZ) staining. PDX-1 gene was confirmed by RT- PCR analysis. Conclusion: In this study, we differentiated MSCs into insulin-producing cells in vitro. It is concluded that MSCs may be considered as an excellent candidate in β-cell therapy in diabetes patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Host genetic, environmental factors' and factors associated with hepatitis C virus (HCV) play critical roles in development of the hepatitis. This study was performed to investigate the association between Interleukin-28B (IL-28B) genetic variants and chronic hepatitis C. Materials and methods: This case-control study was conducted in 133 HCV-RNA positive patients attending to methadone treatment clinics, hemophilia center, thalassemia center and three dialysis center in Mazandaran province, Iran, during 2010-2011. In addition, 173 HCV negative subjects were recruited as the controls. The two groups were matched for age, sex and geographic region. The IL-28B genotype at polymorphic site rs12979860 was determined by Tetra-ARMS-PCR method. Quantitative and qualitative data were analyzed using Student t and Chi square tests, respectively. Results: The mean age of patients with HCV (96 male, 27 female) was 36.38 ± 12.49 years. The control group comprised 107 males and 66 females with the mean age of 38.27 ± 11.27 years. The distribution of IL-28B genotypes did not differ between two groups (P= 0.008). On the other hand, the frequency of C/C, C/T and T/T genotypes were 41.4, 41.6 and 17.3% in the pathents group and 42.5, 40.6, and 16.9% in the control group, respectively. The frequency of C and T alleles was not significantly different between the two groups (P= 0.84). Conclusion: No significant difference was observed in the frequency of the rs12979860 polymorphism in upstream of IL-28B among HCV patients and control groups. According to the proven role of C allele in association with HCV treatment response, it is assumed that genetic differences in IL-28B or IFN-? could predict HCV treatment outcome. [ABSTRACT FROM AUTHOR]

Background and purpose: Gastric cancer is one of the most common gastrointestinal cancers in the world. Gastric cancer is the most common cancer in north of Iran. Interleukin-17F (IL-17F) is a proinflammatory cytokine expressed by a novel subset of CD4+ Th cells (Th-17), and it causes the occurrence and strengthening the inflammatory response. This study aimed to assess the association between IL-17F- A7488G polymorphism and potential susceptibility to gastric cancer. Materials and methods: A case-control study consisting of 161 gastric cancer patients with mean age 62.14 ± 12.6 and 171 healthy controls with mean age 58.93 ± 14.2 was conducted. Genomic DNA was extracted and genotypes of - A7488G polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of G allele was higher in gastric cancer patients (12.1%) compared with the control group (9.15%), but these differences were not significant (P-0.22). In addition, the distribution of GG genotype was not significantly differed between the patients and the controls (4.3% vs. 1.8%, P=0.182). Furthermore, logistic regression analysis revealed no significant association between the presence of 7488G allele and clinical stages (P=0.28), tumor grade (P=0.36) and H. pylori infection (P=0.89). Conclusion: These results suggest that IL-17F A7488G polymorphism in the promoter of IL-17F gene is not directly assumed as a genetic risk factor in the predisposition to gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Deviation of host immune response by engagement of inhibitory receptors is one of the well-known mechanisms of tumor cells for immune evasion and survival. PD-1/PD-L1 and Tim-3/Gal-9 axes are two major pathways in this area which their contribution has been documented in a variety of malignancies. In this study, Gal-9 and PD-L1 expression was investigated in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL). Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 25 untreated CLL patients and 15 sex- and age-matched healthy controls. CLL patients were classified into different clinical stages based on the Rai staging system. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of Gal-9 and PD-L1 mRNA was determined by Real-Time PCR using β-actin as a housekeeping gene. Results: Gal-9 and PD-L1 mRNA was significantly more expressed in CLL patients compared to healthy controls (p<0.0001 and p=0.005, respectively). CLL patients in advanced clinical stages showed higher expression of Gal-9 and PD-L1 in comparison to patients in early clinical stages (p<0.0001 and p=0.004, respectively). Conclusion: Our promising results regarding over-expression of Gal-9 and PD-L1 in CLL patients call future complementary studies to more evaluate and confirm these pathways for immunotherapy approaches of this malignancy. Upregulation of both Gal-9 and PD-L1 in CLL patients with advanced clinical stages introduces them as useful prognostic biomarkers for disease progression., (Creative Commons Attribution License)

Aim: To investigate the association of the inducible nitric oxide synthetase (iNOS) C150T polymorphism with Helicobacter pylori (H. pylori) infection and gastric cancer (GC) risk in Iran., Methods: In order to determine whether there was a correlation between iNOS genotype and GC in Iran, we conducted a case-control study using samples from 329 individuals. For each sample, the C150T iNOS polymorphism was genotyped by polymerase chain reaction (PCR) and restriction digestion. Patients were grouped by cancer presence, demographic and behavior characteristics, and H. pylori infection status. Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population., Results: In this population, we found that smoking, hot beverage consumption, a familial history of GC and H. pylori infection status were significantly associated with GC development (P = 0.015, P < 0.001, P = 0.0034, and P < 0.015, respectively). The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone, but was impacted by H. pylori infection status. When compared to the non-H. pylori infected group, cancer patients who had a heterozygous CT genotype and were also infected with H. pylori were 2.1 times more at risk of developing GC [odds ratio (OR) = 2.1, P = 0.03] while those with a homozygous TT genotype and infected with H. pylori were 5.0 times more at risk of developing GC (OR = 5.0, P = 0.029). In contrast, this association was not seen in patients in the control group., Conclusion: A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility.

Unlabelled: Preeclampsia is a disease regarding with altered vascular reactivity leading to hypertension of the mother and metabolic alterations in the fetus. This study aimed to assess nitric oxide and bleeding time following administration of magnesium sulfate to preeclamtic patients compared to normotensive pregnant women. A total of 112 subjects (56 preeclamtic patients and 56 normotensive pregnant controls) were enrolled in this case-control study. Cases and controls were matched for age, BMI, gestational age, parity and gravidity. Total concentration of nitrite and nitrate (NOx) was measured before and during magnesium sulfate (MgSO4) treatment using a modified Griess-based method., Results: Systolic and diastolic blood pressures were significantly decreased during MgSO4 treatment in preeclamtic patients (p < 0.0001). NOx levels were significantly increased in preeclamtic women after MgSO4 administration (33.7 +/- 18.5 vs. 50.2 +/- 21.6, p < 0.0001) but it was not seen in normotensive parturients (52.4 +/- 28.9 vs. 57.3 +/- 21.7, p = 0.362). The bleeding time was scarcely increased following magnesium sulfate treatment in preeclamptic patients compared to normotensive pregnant women but it was not significant (p = 0.18). In addition, there was only a significantly reverse correlation between NOx levels and systolic or diastolic blood pressure in preeclamtic parturients after MgSO4 treatment (r = -0384; p = 0.003 and r = -0.29; p = 0.03, respectively). This study demonstrates that administrating MgSO4 to preeclamtic patients induced significant changes in NOx production which had a major role in modulating vasculature changes in preeclamsia.