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Background The beneficial effects of polyphenols have been reported. This study aimed to investigate the effect of oral Ellagic acid (EA) supplement on insulin resistance (IR) and Fetuin-A and serum sirtuin1 (SIRT1) in type 2 diabetics. Methods In this double-blind, randomized clinical trial, 44 diabetic patients were selected. Patients were assigned to the intervention group (22 subjects) and placebo (22 subjects) and received a capsule containing 180 mg of EA per day or placebo for eight weeks, respectively. At the beginning and end of the study, anthropometric indices, fasting plasma glucose (FPG), plasma insulin level, IR, Fetuin-A, and SIRT1 were measured. Statistical analysis was performed using SPSS software. Results At the beginning and end of the study, there was no significant difference between the two groups regarding anthropometric indices (P > 0.05). At the end of the survey, EA supplementation significantly reduced FPG, insulin, IR, and Fetuin-A and increased SIRT1 levels compared with the placebo group (P 0.05). Conclusion EA with antioxidant properties plays an essential role in reducing the macrovascular and microvascular complications of diabetes by reducing inflammation and insulin resistance. Trial registration The protocol of this clinical trial is registered with the Iranian Registry of Clinical Trials (http://www.IRCT.IR, identifier: IRCT20141025019669N13)

Oxidative stress can worsen glycemic status. Considering the antioxidant properties of Ellagic acid (EA), this study was designed to evaluate the effect of EA on glycemic indices, lipid profile, oxidative stress, and inflammation status in type 2 diabetic patients. Overall, 44 patients were recruited and were randomly allocated consumed 180 mg of EA per day (n = 22) or placebo (n = 22) for 8 weeks. The blood sugar (BS), insulin, insulin resistance (IR), hemoglobin A1c (HbA1 c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total antioxidant capacity (TAC), malondialdehyde (MDA), the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), C-reactive protein (CRP), TNF-α and interleukin 6 (IL-6) were measured at the beginning and end of the study. At the end of the study, the mean of BS, insulin, IR, HbA1 c, TC, TG, LDL, MDA, CRP, TNF-α, and IL-6 were significantly decreased in the intervention group (p < .05). Also, the mean of TAC (+0.8 ± 0.01) and activity of GPx (+10.26 ± 0.22) and SOD enzymes (+459.6 ± 9.76) significantly increased in the intervention group (p < .05). EA supplementation can be helpful as a diet supplement in patients with type 2 diabetes through improvement in chronic adverse effects.

Background: MicroRNAs are a class of negative regulators of gene expression. Evidence indicates that miRNAs involved in the pathogenesis of New type 2 diabetes(NT2D) through decrease the expression of the genes secreting insulin and increase expression of insulin secretion suppressing ones, as well as exocytosis, incorporate in New type 2 diabetes. In this study, we evaluated the expression level of miR-135 in plasma sample of those prone to susceptible diabetes and New type 2 diabetes patients compared to the control group.Methods: Subsequently to evaluation of biochemical parameters such as (TG, TC, HDL, and LDL) in susceptible diabetes, New type 2 diabetes and control group, miR-135a level was measured by qRT-PCR in the plasma samples and results were analyzed by Stata and REST software.Results: We identified a significant increase in miR-135a expression in New type 2 diabetes and susceptible diabetes samples compared to the control group. AUC in ROC curve analysis was 1.1 respectively (confidence interval of 1.0-1.0) for NT2D and susceptible diabetes group, the best cut-off points for diagnostics in diabetics and susceptible diabetes were 2.00 and 1.02. The optimum sensitivity and specificity for both groups were 100 and 100. Results confirmed the test for 100% confidence in healthy, susceptible diabetes and New type 2 diabetes subjects.Conclusion: It seems that plasma level of miR-135a can be a desirable biomarker to differentiate T2DM diabetics from the control group.

This cohort intends to determine the sequential dynamic changes in Toll-like receptor (TLR)-4, TLR-2, and myeloid differentiation primary response gene 88 (MYD88) mRNA expressions in PBMCs and biopsy samples from kidney allograft recipients in relation to graft function. This study enrolled 52 renal transplant patients, 27 with well functioning graft (WFG) and 25 graft dysfunction (GD). Peripheral blood samples pre- and post-transplantation (days 2, 90 and 180) were collected to analyze mRNA expression levels of TLR-2, TLR-4, and MYD88 genes in relation to allograft function during one-year follow up. The mean dynamic changes of post-transplant TLR-2, TLR-4, and MYD88 mRNA expressions were significantly higher in GD compared to WFG patients (P = .001). ROC curve analysis based on glomerular filtration rate (GFR) index showed the area under curve (AUC) values for the genes: TLR-2(0.89;P < .001), TLR-4(0.86;P < .001), and MYD88(0.75;P = .003) in the third month post-transplantation for GD diagnosis. The calculated AUCs for the expressions of genes in allograft biopsies were 0.94(TLR-2), 0.95(TLR-4), and 0.98(MYD88) in the sixth month post-transplant based on pathology report (P < .001). Our results indicate that sequential monitoring of the expression patterns of TLR-2, TLR-4, and MYD88 in PBMCs and biopsy samples could be considered as predictive biomarkers for early and late kidney allograft function.

Objectives: Diabetes is one of the most important endocrine diseases caused by complex reactions between genetic and environmental factors. Recent studies have shown that microRNAs play an important role in the production, inhibition, and secretion of insulin. Identifying the relationship between key miRNAs that control the genes involved in the pathogenesis of diabetes is clinically important because it provides a way to identify preventive methods or treatments. In the present study, the expression of miR135a in serum samples between women with Gestational diabetes mellitus (GDM), non-pregnant type 2 diabetes, and healthy pregnant women were compared with the control group. Materials and methods: This study was a case-control study and non-random sampling method was used. The present study was conducted among four groups (healthy non-pregnant women (control), non-pregnant Diabetes type 2, GDM, and healthy pregnant). After serum separation, expression of miR-135a was measured using QRT-PCR technique and the results were analyzed by Stata and SPSS21 software. Results: The results show that the mean expression of miR-135a gene in control group was 0.9 ± 0.06, control of pregnancy was 1 ± 0.1, GDM group was 1.7 ± 0.3 and non-pregnant diabetic type 2 group was 6 ± 6 / 3. The results of analysis of variance showed that the mean difference of miR-135 gene expression was significant higher in the non- pregnant type 2 diabetes than GDM group (F = 2776.3, P

Background T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in alloimmune and autoimmune responses, as well as tolerance induction in kidney transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in epithelial cells of the injured proximal tubule. In this study, we have investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins in renal allograft recipients diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction (CAD), as well as those with well-functioning transplants (WFG). Methods We divided 85 patients into the following groups: AR (n = 24), CAD (n = 19), and WFG (n = 42). TIM-3 and KIM-1 mRNA expressions were quantified using real-time reverse-transcription TaqMan probe polymerase chain reaction (RT-PCR). An ELISA test was used to measure the amount of KIM-1 protein in serum and urine samples. Results AR and CAD patients had significantly greater urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins compared to WFG patients. Receiver operating characteristic (ROC) analysis showed that these molecules discriminated Allograft rejections from WFG. Conclusion Quantification of TIM-3 and KIM-1 mRNA expressions, along with KIM-1 protein measurements in urine and blood could be employed as promising tools for noninvasive diagnosis of allograft dysfunction.

Background It has been suggested that vitamin D and its receptors involve in suppressing fibrogenic signaling in non-alcoholic fatty liver disease (NAFLD). However, the effect of vitamin D supplementation on fibrogenic factors has not been investigated in NAFLD individuals with steatohepatitis. This study was designed to examine the effects on vitamin D supplementation on serum levels of vitamin D receptor (VDR), fibrogenic factors, and fibrogenic microRNAs (MiR) in NAFLD patients. Methods Forty-six NAFLD patients will be recruited in this study. After block matching for sex and BMI, they will be randomly assigned to receive 4000 IU/day vitamin D or placebo for 12 weeks. Weight, height, and waist circumference will be measured. Determination of serum fibrogenic MiRs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, calcium, blood glucose, serum insulin, lipid profile, liver markers (ALT, AST, total, direct, and indirect bilirubin) will be done at study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equation. Discussion This is the first randomized controlled trial that will determine the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors, and fibrogenic MiRs in NAFLD patients. The results of this trial will provide clinical evidence on the effectiveness of vitamin D supplementation in controlling liver fibrosis in NAFLD patients. Trial registration Iranian Registry of Clinical Trials, IRCT201405251485N13. Registered on 14 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3241-7) contains supplementary material, which is available to authorized users.

Background: Diagnosis of allograft dysfunction by noninvasive biomarker tests is preferable to invasive allograft biopsies and has been extensively considered in recent years. This study aims to evaluate blood and urinary forkhead box P3 (FOXP3) messenger RNA (mRNA) expression in renal transplant recipients in an attempt to determine whether differential diagnosis of graft dysfunction is feasible using mRNA profiles. Methods: We analyzed FOXP3 mRNA expression in paired urinary and peripheral blood mononuclear cell (PBMC) samples. A total of 91 kidney transplant recipients enrolled in this study that were classified into 3 groups: biopsy-proven acute rejection (AR; n = 27), chronic allograft nephropathy (n = 19), and well-functioning graft (n = 45). The FOXP3 mRNA expression was quantified by TaqMan probe real-time polymerase chain reaction. Results: Acute rejection patients had a higher expression level of transcription factor FOXP3 compared to the chronic nephropathy and control groups. Analysis of receiver operating characteristic curves showed that rejection could be diagnosed with 100% sensitivity and 96% specificity in urine, and 92% sensitivity and 86% specificity in PBMC samples using the optimal FOXP3 mRNA cutoff value. We subdivided the AR group into progressive and nonprogressive patients, which showed a significant difference in FOXP3 mRNA expression. This result confirmed the role of FOXP3 as a diagnostic marker in predicting transplantation outcomes. Conclusion: Our results suggested that elevated expression of FOXP3 in blood and urine samples from kidney transplant recipients could be a useful noninvasive biomarker to diagnose graft dysfunction.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to infections, autoimmunity and malignancies. This study was performed to analyze the Mannose-binding lectin (MBL) polymorphisms in Iranian patients with CVID. Thirty-five CVID patients who were treated at Children's Medical Center and 100 matched controls were enrolled in this study. Sixth single-nucleotide polymorphisms of the MBL gene were analyzed using PCR-SSP method. Comparison of MBL exon 1 coding alleles between patients and controls revealed that A allele (wild-type) was significantly decreased in CVID group, whereas B allele was overrepresented in the patient group. High frequency of heterozygous (A/O) in the patient group and high frequency of homozygous for wild-type coding regions in the control group were detected. Comparison of MBL haplotype promoters between CVID patients and controls showed that LYPB haplotype was significantly overrepresented in the CVID group. Mutant and low-producing MBL alleles and haplotypes might reflect as an associated genetic factor in CVID patients, which could play as a susceptibility factor in CVID.