Publications by authors named "Ali Akbar Saboor-Yaraghi"

55 Publications

Immunomodulatory Effects of Calcitriol through DNA Methylation Alteration of FOXP3 in the CD4+ T Cells of Mice.

Iran J Allergy Asthma Immunol 2020 Oct 18;19(5):509-516. Epub 2020 Oct 18.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.

Vitamin D plays a variety of physiological functions, such as regulating mineral homeostasis. More recently, it has emerged as an immunomodulator player, affecting several types of immune cells, such as regulatory T (Treg) cells. It has been reported that vitamin D exerts some mediatory effects through an epigenetic mechanism. In this study, the impacts of calcitriol, the active form of vitamin D, on the methylation of the conserved non-coding sequence 2 (CNS2) region of the forkhead box P3 (Foxp3) gene promoter, were evaluated. Fourteen C57BL/6 mice were recruited in this study and divided into two intervention and control groups. The CD4+ T cells were isolated from mice splenocytes. The expression of Foxp3, IL-10, and transforming growth factor-beta (TGF-β1) genes were relatively quantified by real-time PCR technique, and the DNA methylation percentage of every CpG site in the CNS2 region was measured individually by bisulfite-sequencing PCR. Vitamin D Intervention significantly (p<0.05) could increase the expression of Foxp3, IL-10, and TGF-β1 gene in the CD4+ T cells of mice comparing with the control group. Meanwhile, methylation of the CNS2 region of Foxp3 promoter was significantly decreased in three of ten CpG sites in the vitamin D group compared to the control group. The results of this study showed that vitamin D can engage the methylation process to induce Foxp3 gene expression and probably Treg cytokines profile. Further researches are needed to discover the precise epigenetic mechanisms by which vitamin D modulates the immune system.
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http://dx.doi.org/10.18502/ijaai.v19i5.4466DOI Listing
October 2020

Contraceptive and molecular function of a novel recombinant vaccine based human leukemia inhibitory factor on Balb/c mice: An experimental in vivo study.

J Reprod Immunol 2020 11 31;142:103195. Epub 2020 Aug 31.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The functional competence of leukemia inhibitory factor (LIF), as immunocontraceptive vaccine in mice, was investigated. Balb/c mice were divided into two groups of vaccinated and controls. The recombinant human LIF (rhLIF) protein and phosphate buffer saline was emulsified with Freund's adjuvant and injected into vaccinated and control groups, respectively. Theinhibition of implantation was evaluated in mice uterine. The concentration of secreted interferon-γ (IFN-γ) and interleukin (IL)-4 were measured in cultured splenocyte of mice stimulated by rhLIF. The expressions of immune responsive gene 1 (IRG-1), cochlin (COCH), amphiregulin(Ar), and heparin-binding EGF-like growth factor (HB-EGF) genes were determined. Mice were assessed for inhibition of fertility after delivery, reversibility of immune response against rhLIF, and survival rate. Active immunization of mice with rhLIF resulted in reduction of the implantation and fertility rate up to 80.49% and 75%, respectively. All mice produced a high titer of anti-rhLIF antibodies in serums and vaginal fluids washes after 16 weeks; however, these antibodies were cleared from vaginal fluid washes after six months. A significant down-regulation in mRNA levels of IRG-1, Ar and HB-EGF was observed in vaccinated group compared to controls; however, no significant change in the expression profile of cochlin gene was detected. The results showed that rhLIF prevented pregnancy in a high percentage of female mice. Although the immunization of female Balb/c mice with rhLIF inhibited fertility and expression of genes associated with this molecule, further studies are needed to support this protein as a suitable candidate for contraceptive vaccine in mammals.
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http://dx.doi.org/10.1016/j.jri.2020.103195DOI Listing
November 2020

The effect of calcitriol and all-trans retinoic acid on T-bet, IFN-γ, GATA3 and IL-4 genes expression in experimental autoimmune encephalomyelitis.

APMIS 2020 Nov 26;128(11):583-592. Epub 2020 Sep 26.

Department of Cellular and Molecular Nutrition, Tehran University of Medical Sciences, Tehran, Iran.

Multiple sclerosis (MS) is an immune-mediated inflammatory disease which affects the central nervous system (CNS). In the present study, the in vivo effects of ATRA, calcitriol, and their combinations on the expression of murine CD4+ T cell cytokines and their specific transcription factors in experimental autoimmune encephalomyelitis (EAE)-induced mice were explored. Thirty-two EAE induced inbred C57BL/6 female mice with an age ranged from 8 to 10 weeks were divided into four categories in a random manner. The first, second, and third groups received ATRA, calcitriol, ATRA+ calcitriol, respectively, and the fourth group received vehicle. The treatment started on the day prior to immunization and through the IP injections every other days for 21 days. The dosages of administration for calcitriol, ATRA, and calcitriol+ ATRA were 100 ng, 250 μg, and 50ng + 125 μg, respectively per mouse. An equal volume of excipient was administered for the vehicle group. T-bet, IFN-γ, GATA-3, and IL-4 genes expression were assessed in the splenocytes of EAE -induced mice. The expression of T-bet and IFN-γ genes in the splenocytes of ATRA, calcitriol and combination- treated mice were significantly reduced compared to vehicle group (p < 0.05). A significant decrease in T-bet expression was observed in the combination-treated group compared to the ATRA-treated group (p < 0.05). The expression of GATA3 and IL-4 genes was significantly increased in the ATRA-, calcitriol-, and combination-treated mice when compared with the control group (p < 0.05). Furthermore, the effect of calcitriol alone and in combination with ATRA was more considerable than that of ATRA alone. The nutraceutical approaches may be promising in the prevention and/or treatment of MS.
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http://dx.doi.org/10.1111/apm.13073DOI Listing
November 2020

Production and characterization of recombinant human leukemia inhibitory factor and evaluation of anti-fertility effects of rabbit anti-rhLIF in Balb/c mice.

Protein Expr Purif 2020 10 5;174:105684. Epub 2020 Jun 5.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Human leukemia inhibitory factor (hLIF) is a cytokine of interleukin-6 family. This study aimed to evaluate the recombinant production rate of active hLIF by different vector-host systems under various conditions. Moreover, a rabbit polyclonal antibody (pAb) against recombinant hLIF (rhLIF) was produced and its anti-fertility effects were explored in Balb/c mice. Four different constructs including pET22b/hLIF, pET28b/hLIF, pET32b/hLIF and pColdI/hLIF were designed and transformed into BL21-(DE3), Rosetta-(DE3), Origami-(DE3) and Shuffle T7-(DE3) host cells. The expression level and proliferative effect of rhLIF were measured by SDS-PAGE and MTT assays, respectively. Rabbit pAb to rhLIF was produced and characterized using enzyme-linked immunosorbent assay and western blot techniques. The Balb/c mice were divided into two intervention and control groups. Then, they were intraperitoneally injected by purified rabbit anti-rhLIF and non-immunized rabbit pAb, respectively. After sacrifice on day 7, the number of implantation sites was counted. The rhLIF was successfully expressed by pET32b/hLIF and pColdI/hLIF vectors in all hosts with no significant difference in the rate of their expression. The rhLIF was purified and checked for activity. The results showed that it is functionally active and the produced anti-rhLIF pAb could specifically bind to commercial rhLIF. Passive immunization results showed that anti-rhLIF antibody completely inhibited fertility in all injected Balb/c mice compared to controls. Although previous studies showed expression of rhLIF using various methods, using different vector-host systems ensures us of successful biological active expression of it. The pAb against rhLIF could be a powerful tool for inducing in vivo infertility.
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http://dx.doi.org/10.1016/j.pep.2020.105684DOI Listing
October 2020

Upregulation of FNDC5 gene expression in C2C12 cells after single and combined treatments of resveratrol and ATRA.

Lipids Health Dis 2019 Oct 22;18(1):181. Epub 2019 Oct 22.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Background: Irisin is a newly discovered myokine that secreted from skeletal muscle cells. Several studies showed that irisin involves in thermogenesis and increases the expression of browning markers such as uncoupling protein-1 that in turns induces the conversion of white adipose tissue to brown fat. Resveratrol (Res) and all-trans retinoic acid (ATRA) can also upregulate the expression of thermogenesis genes. In the present study, the effects of single and combined treatments of Res and ATRA on fibronectin type III domain containing 5 (FNDC5) gene expression was explored.

Methods: The mouse myoblasts, C2C12 cells, were seeded in 6-well plastic plates and cultured in DMEM media. After differentiation, in a pilot study, C2C12 myotubes were treated with different concentrations of Res and ATRA for 12 h. The best result was obtained by treatment of 1and 25 μM of Res and 1 μM of ATRA. Then the main study was continued by single and combined treatment of these compounds at chosen concentration. After treatments, total RNA was extracted from C2C12 cells. Complementary DNA (cDNA) was generated by the cDNA synthesis kit and FNDC5 mRNA expression was evaluated by the real-time PCR method.

Results: The FNDC5 gene expression in C2C12 myotubes of alone-treated with 1 μM, 25 μM Res and 10 μM ATRA did not change compared to vehicle group. However, in combination-treated the expression of FNDC5 gene was significantly increased compared to vehicle group.

Conclusion: This is the first evidence that Res and ATRA can regulate FNDC5 gene expression in C2C12 myotubes. More investigations are necessary to explore the therapeutic effects of these nutrients in obesity, diabetes, cardiac and neurovascular disease.
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http://dx.doi.org/10.1186/s12944-019-1128-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806552PMC
October 2019

Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial.

Horm Metab Res 2019 May 9;51(5):296-301. Epub 2019 May 9.

Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Caion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.
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http://dx.doi.org/10.1055/a-0856-1044DOI Listing
May 2019

Effects of vitamin D supplements on frequency of CD4 T-cell subsets in women with Hashimoto's thyroiditis: a double-blind placebo-controlled study.

Eur J Clin Nutr 2019 09 29;73(9):1236-1243. Epub 2019 Jan 29.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Vitamin D is a modulator of immune functions. Investigations on the mechanisms of vitamin D action and pathogenesis of Hashimoto's thyroiditis (HT) have revealed that vitamin D can reduce damages to thyroid cells caused by autoreactive immune cells.

Methods: Totally, 48 female patients with HT disease were introduced to the study by endocrinologists. Patients were divided into two major groups of 24 individuals and treated weekly with 50,000 IU of cholecalciferol (vitamin D group) or placebo (placebo group) using oral administration for 3 months. Eventually, 17 of the 24 patients in each group finished the study. Before and after supplementation, frequencies of Th1, Th17, Th2 and Tr1 cells and mean fluorescent intensity (MFI) of the associated cytokines, including IFN-γ, IL-17, IL-4 and IL-10, were assessed using flow cytometry. Furthermore, gene expression of IL-10 was assessed using real-time PCR.

Results: Results of this study showed that cholecalciferol supplementation caused a significant decrease in Th17/Tr1 ratio. The proportion and MFI of Th1, Th2, Tr1 and Th17 cells included no significant changes in vitamin D group, compared to those in placebo group. Expression rate and MFI of IL-10 increased in both groups. This increase was higher in vitamin D group than placebo group with no significance.

Conclusions: In this novel preliminary clinical trial study, supplementation with cholecalciferol in HT patients for 3 months changed the balance of CD4 T-cell subsets to improve the disease control. However, further studies are necessary to investigate effects of vitamin D on immune functions in HT patients.
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http://dx.doi.org/10.1038/s41430-019-0395-zDOI Listing
September 2019

The effect of retinyl-palmitate on the level of pro and anti-inflammatory cytokines in multiple sclerosis patients: A randomized double blind clinical trial.

Clin Neurol Neurosurg 2019 02 7;177:101-105. Epub 2019 Jan 7.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: Multiple sclerosis (MS) is an inflammatory and autoimmune disease associated with the imbalance of cytokines secreted from CD4 T cells. Studies have shown that vitamin A and its active derivatives are able to modulate the immune system in MS patients. The aim of the present study was to investigate the effect of supplementation of retinyl palmitate (RP), the dietary form of vitamin A, on pro- and anti-inflammatory cytokines in the plasma and supernatants of cultured peripheral blood mononuclear cells (PBMCs) of MS patients.

Patients And Methods: Thirty-six relapsing-remitting MS patients were enrolled in this double-blind randomized clinical trial. Participants received one capsule of 25,000 IU RP or a placebo per day for six months. Blood samples were taken before and after intervention. After intervention, the PBMCs were isolated and cultured. The levels of pro- and anti-inflammatory cytokines in the plasma and supernatant of cells stimulated with myelin oligodendrocyte glycoprotein, phytohemagglutinin or vehicle (media) were determined. The sample t-test and Mann Whitney U test were used to compare data between groups.

Results: The changes in pro-inflammatory cytokine levels (IL-1β, TNF-α, IFN- γ, IL-2, IL-6, and IL-17) in the serum and supernatant of MS patients were not significant (p > 0.05). There were also no significant changes in the levels of anti-inflammatory cytokines (IL-10, IL-13, IL-4, and TGF-β) (p > 0.05).

Conclusion: Unexpectedly, this study found no significant changes in cytokine levels after six months of RP supplementation in MS patients. The results of other studies by our team have shown significant changes in the gene expression of the cytokines in response to RP supplements. Therefore, we recommend that periodic follow-up of RP supplementation may be needed to reveal changes in the level of the cytokines in the plasma and PBMCs and to clarify the real effect of RP on the immune factor levels in the serum of MS patients.
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http://dx.doi.org/10.1016/j.clineuro.2019.01.003DOI Listing
February 2019

Immunotherapeutic Effects of β-D Mannuronic Acid on IL-4, GATA3, IL-17 and RORC Gene Expression in the PBMC of Patients with Inflammatory Bowel Diseases.

Iran J Allergy Asthma Immunol 2018 Aug 12;17(4):308-317. Epub 2018 Aug 12.

Department of Immunology, School of Public Health, International Campus, Tehran University of Medical Sciences, Tehran, Iran.

Inflammatory bowel diseases (IBD) are chronic relapsing immune-mediated disorders that result from an aberrant immunological response. IBD comprises of Crohn's disease (CD) and ulcerative colitis (UC). The precise aetiology of IBD has not been fully understood, however, recent studies support the hypothesis that patients with IBD have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract (GIT). The increasing number of hospitalisation coupled with the high economic burden faced by IBD patients, calls for more concerted research efforts, to design a potent and credible treatment option for these strata of patients. This research was designed to test the efficacy and potency of β-D Mannuronic acid (M2000) in the treatment of IBD. Ten ml of blood was aseptically collected from 24 IBD patients and 24 normal controls. PBMC was isolated and stimulated with 1 µg/mL of LPS and incubated for 4 hours. The cells were later treated with 10 µg/mL or 50 µg/mL of Mannuronic acid and incubated for 24 hours at 370C under 5% CO2 and 100% humidity. After the incubation, RNA was extracted from the cells, cDNA was synthesised, and the expression of the gene was evaluated using quantitative real-time PCR. The result indicated a significant down-regulation of RORC and IL-17 genes expression, while the expression of IL-4 and GATA3 genes were significantly up-regulated. These research findings have shown that M2000 a biocompatible agent, that has an immunotherapeutic, immunomodulatory and immunosuppressive effects on the PBMC of IBD patients.
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http://dx.doi.org/10.18502/ijaai.v17i4.90DOI Listing
August 2018

Resveratrol suppresses hyperglycemia-induced activation of NF-κB and AP-1 via c-Jun and RelA gene regulation.

Med J Islam Repub Iran 2018 10;32:10. Epub 2018 Feb 10.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran.

Resveratrol (RSV) provides several important biological functions in wide variety of cells. In this study, we investigated the molecular mechanisms underlying anti-inflammatory effect of RSV on HepG2 cells by assessing the gene expression of RelA and c-Jun- subunits of NF-κB and AP-1 transcription factors. HepG2 cells were settled in a serum- free medium with high concentrations of glucose (30 mM) and insulin (1 µM) overnight and were then incubated with RSV (5, 10, and 20 µM) for 24 and 48 hours. Real time quantitative polymerase chain reaction (qRT-PCR) was used to determine RelA and c-Jun expression. RSV diminished hyperglycemia/hyperinsulinemia stimulated expression of c-Jun dose- dependently after 24 and 48 hours (p<0.05). In addition, RelA gene expression was decreased dose-dependently in all RSV doses after 48-hour incubation (p<0.05). Our results indicated that RSV may reduce NF-κB and AP-1 activity via RelA and c-Jun gene regulation. The findings of the present study demonstrated that RSV may be considered as a preventative and therapeutic agent for antagonizing inflammation in Hepatocellular carcinoma (HCC).
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http://dx.doi.org/10.14196/mjiri.32.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108266PMC
February 2018

Enhancement of monoclonal antibody production after single and combination treatment of the hybridoma cells with all-trans retinoic acid and docosahexaenoic acid: An in vitro and in vivo study.

Int Immunopharmacol 2018 Jun 24;59:295-300. Epub 2018 Apr 24.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Murine hybridoma cells can produce monoclonal antibody (MAb) and the production of these antibodies in culture and peritoneum can be affected by different factors, including stimulants, inhibitors and supplements. Among these factors, the impact of micronutrients on the production of MAbs by mouse hybridoma cells has not fully been explored. In this study the murine hybridoma cells, M3C5, were cultured and treated with different concentrations of ATRA and DHA, alone, in combinations, and at different time of exposure. Then, changes in the production of MAb in culture medium were evaluated using ELISA. The hybridoma cells after single and combined treatment with ATRA, DHA and vehicles were IP injected to Balb/c mice and the changes in production of MAb in ascites were determined by ELISA. The results showed that single and combined treatment of ATRA and DHA elevated the production of MAb by hybridoma cells in both in vivo and in vitro. The production of MAb following in vitro single treatment with 1 μM of ATRA and 10 μM of DHA for 2 days was significantly increased. The in vitro effects of ATRA on increase of MAb production was obtained more than DHA. The MAb productions in combined treatment with 0.5 μΜ of ATRA plus 5 μΜ of DHA were significantly increased in in vivo and in vitro. However, the effect of DHA was obtained more significant in in vivo conditions. The results of this study showed for the first time that in vitro and in vivo treatments of ATRA and DHA could increase the production of MAb in mouse M3C5 hybridoma cells.
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http://dx.doi.org/10.1016/j.intimp.2018.03.008DOI Listing
June 2018

Combination treatment of docosahexaenoic acid (DHA) and all-trans-retinoic acid (ATRA) inhibit IL-17 and RORγt gene expression in PBMCs of patients with relapsing-remitting multiple sclerosis.

Neurol Res 2018 Jan 18;40(1):11-17. Epub 2017 Nov 18.

b Department of Immunology, School of Public Health , Tehran University of Medical Sciences , Tehran , Iran.

Objectives: Multiple sclerosis (MS) is a demyelinating disorder with a complex autoimmune pathophysiology. Its initiation and progression correlate with IL-17 and the related transcription factor, RORγt. All-trans retinoic acid (ATRA) is a bioactive derivative of vitamin A, and docosahexaenoic acid (DHA) is an active metabolite of omega-3 fatty acid; both have immunomodulatory effects in many immune disorders. This study investigated the effects of DHA and ATRA individually and in combination on IL-17 and RORγt gene expression in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting MS (RRMS) patients who were receiving interferon beta (IFN-β).

Methods: The PBMCs of 15 RRMS patients were treated in vitro with 1 μM of ATRA and 15 μM of DHA as single and combination treatments for assessing probable additive or synergistic effects.

Results: The results showed that single treatment of ATRA (p = 0.05) could significantly decrease the expression of IL-17 gene and single treatment of ATRA (p = 0.04) and single treatment of DHA (p = 0.05) induced significant inhibition on the expression of RORγt gene. The suppressive effect of combined treatment with ATRA and DHA on IL-17 (p = 0.02) and RORγt (p = 0.01) was also found significant showing that the combined treatments can have additive effects.

Discussion: These results indicate that both DHA and ATRA might help control disease progression in IFN-β treated RRMS patients with the strongest effects produced by a combination of the two compounds.
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http://dx.doi.org/10.1080/01616412.2017.1382800DOI Listing
January 2018

The Effect of Eicosapentaenoic Acid on the Serum Levels and Enzymatic Activity of Paraoxonase 1 in the Patients With Type 2 Diabetes Mellitus.

Acta Med Iran 2017 Aug;55(8):486-495

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Paraoxonase 1 is known as one of the most important ant oxidative enzymes associated with HDL-c, and because of its antioxidant and antiinflammatory activities. EPA has the antioxidant, anti inflammatory, antithrombogenic, and antiarteriosclerotic properties. Therefore, we investigated the effect of EPA supplementation on the serum levels and activity of PON1 in type 2 diabetic patients. This study was designed as a randomized, double-blind, and placebo-controlled clinical trial. Thirty-six patients with type 2 diabetes were given written; informed consent randomly was classified into 2 groups. They were supplemented with 2 g/day of the capsules of EPA or placebo for eight weeks. Blood sample was given for measurement of the serum levels of lipids, the activity of PON1, FBS and HbA1c. The patients supplemented with EPA showed a significant increase in the serum levels and activity of PON1 and the serum ratio of PON1/HDL-c. There were no significant differences between the two groups regarding any demographic, clinical or biochemical data, total energy intake, and macronutrient intake at the baseline during the intervention, except for a significant increase of protein intake and the levels of HbA1c in the placebo group, and a significant increase of HDL-c, as well as a slight reduction of total cholesterol, LDL-c, TG and FBS in the supplement group. EPA is atheroprotective via increase in the serum levels and activity of PON1, as well as change in the serum levels of lipids, FBS and HbA1c.
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August 2017

Combined effect of retinoic acid and calcium on the in vitro differentiation of human adipose-derived stem cells to adipocytes.

Arch Physiol Biochem 2018 May 29;124(2):109-118. Epub 2017 Aug 29.

f Department of Immunology, School of Public Health , Tehran University of Medical sciences , Tehran , Iran.

Context: It has been shown that adipogenesis can be modulated by factors such as all-trans retinoic acid (ATRA) and calcium.

Objective: To determine, the combined effect of ATRA and calcium on the differentiation of human adipose-derived stem cells (hADSCs).

Methods: Mesenchymal stem cells (MSCs) were differentiated into the adipocytes by 0.5 and 1 µM of ATRA and 5 and 10 mM calcium separately or in combination. After MTS assay the differentiation of MSCs to adipocyte was evaluated, Oil Red O staining, GLUT4 concentration and gene expression of PPARG2, adiponectin, and GLUT4 were measured by Real-Time PCR.

Results: Except 10 mM calcium treated group, other groups and more significantly combination treatments could reduce all adipocyte markers compared to the control.

Conclusion: These results suggest that ATRA and calcium together have significant inhibitory effect on adipogenesis that can be helpful for finding new mechanisms to prevent or control the adipogenesis.
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http://dx.doi.org/10.1080/13813455.2017.1367009DOI Listing
May 2018

Immunomodulatory effects of M2000 (β-D-Mannuronic acid) on TNF-α, IL-17 and FOXP3 gene expression in patients with inflammatory bowel disease.

Int Immunopharmacol 2017 Oct 17;51:107-113. Epub 2017 Aug 17.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-, IC, Tehran, Iran. Electronic address:

Introduction: Inflammatory bowel diseases (IBD) are immune-mediated disorders that result from an aberrant immunological response to the gut luminal antigen in genetically susceptible patients. IBD is categorized into two serotype, Crohn's diseases (CD) and ulcerative colitis (UC), both subtype are important cause of gastrointestinal diseases. The increasing rate of hospitalization, with the high economic burden experienced by the IBD patients, calls for more concerted research efforts to design a potent and affordable treatment option for the treatment of IBD.

Aims/objective: This research was designed to test the efficacy and potency of β-D Mannuronic acid (M2000) and assess if it could serve as a better therapeutic option in the treatment of IBD.

Methodology: Ten (10)ml of blood was aseptically collected into an EDTA container, from 24 IBD patients and 24 normal healthy controls. PBMC was isolated and stimulated with 1μg/ml of LPS in cell culture plate and incubated for 4h. The cells were later treated with 10μg/ml and 50μg/ml of β-D Mannuronic acid (M2000) and incubated for 24h at 37°C under 5% CO2 and 100% humidity. The RNA extractions, cDNA synthesis, and QRT-PCR were performed.

Results: Our findings showed a significant down-regulation of TNF-α and IL-17 gene expression, while the expression of FOXP3 gene was significantly up-regulated.

Conclusion: This result has indicated that β-D Mannuronic acid (M2000) have immunoregulatory and anti-inflammatory effects on these cytokines that are pivotal in the pathogenesis of IBD.
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http://dx.doi.org/10.1016/j.intimp.2017.08.011DOI Listing
October 2017

Epigenetic and gene expression alterations of FOXP3 in the T cells of EAE mouse model of multiple sclerosis.

J Neurol Sci 2017 Apr 24;375:203-208. Epub 2017 Jan 24.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells. In the current study, the expression of FOXP3 and BACH2 genes and FOXP3 promoter methylation were evaluated in T cells of the EAE-induced mice. The results of this study showed a prominent and significant hypermethylation of the FOXP3 gene promoter in the EAE-induced mice compared to the sham and control groups. The expression of FOXP3 and BACH2 genes was significantly decreased in the EAE group in comparison with the sham and control groups. This study suggests that the epigenetic modification of FOXP3 gene is involved in the pathogenesis of EAE and this could be important in therapy in an appropriate and logical statement.
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http://dx.doi.org/10.1016/j.jns.2017.01.060DOI Listing
April 2017

Synergistic induction of apoptosis in B-cell chronic lymphocytic leukemia cells after treatment with all-trans retinoic acid in combination with interleukin-21 and rituximab.

J Cancer Res Ther 2016 Oct-Dec;12(4):1278-1283

Department of Immunology, School of Public Health, Tehran University of Medical Sciences; Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Aim: B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world and characterized by the progressive expansion of malignant B lymphocytes in peripheral blood. In spite of advances in sciences to recognize the number of effective agents for the treatment of chronic lymphocytic leukemia (CLL), this leukemia is thought as incurable one. Introducing a new therapy that has a direct effect on B-CLL lymphocytes and no cytotoxic effects on the other cells is a great wish.

Materials And Methods: Twenty-one patients with B-CLL were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated from patients' blood samples and were further treated with all-tans retinoic acid (ATRA), interleukin (IL-21), and rituximab at concentrations of 30 ng/ml, 25 ng/ml, and 4 μg/ml, respectively. ATRA, IL21, and rituximab were used alone or in various combinations and their effects on apoptosis were measured using annexin V-fluorescein isothiocyanate apoptosis detection kit.

Result: Treatment of the patients' cells with IL21 and rituximab showed a synergistic effect on the induction of apoptosis, in comparison with untreated CLL cells (P < 0.05). The induction of apoptosis by ATRA in combination with IL21 and rituximab were significantly increased compared to untreated CLL cells as a negative control (P < 0.01).

Conclusion: Treatment of patients' PBMCs by ATRA in combination with IL21 and rituximab and also IL21 in combination with rituximab showed synergistic induction of apoptosis compared to untreated CLL cells as a negative control (P < 0.01). It seems that ATRA in combination with IL21 and rituximab activate different pathways of apoptosis (extrinsic pathway, intrinsic pathway, and granzyme B pathway).
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http://dx.doi.org/10.4103/0973-1482.184522DOI Listing
March 2017

Fibrinogen and Fibronectin Binding Activity and Immunogenic Nature of Choline Binding Protein M.

Iran J Public Health 2016 Dec;45(12):1610-1617

Dept. of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Choline-binding proteins (CBPs) are a group of surface-exposed proteins, which play crucial and physiological roles in . The novel member of CBPs, choline-binding protein M (CbpM) may have binding activity to plasma proteins. This study aimed to clone and express CbpM and demonstrate its interaction with plasma proteins and patients' sera.

Methods: The total length of M gene was cloned in ET21a vector and expressed in BL21 expression host. Verification of recombinant protein was evaluated by Western blot using anti-His tag monoclonal antibody. Binding ability of the recombinant protein to plasma proteins and the interaction with patients' sera were assessed by Western blot and ELISA methods.

Results: The M gene was successfully cloned into ET21a and expressed in BL21 host. Binding activity to fibronectin and fibrinogen and antibody reaction of CbpM to patients' sera was demonstrated by Western blot and ELISA methods, respectively.

Conclusion: CbpM is one of the pneumococcal surface-exposed proteins, which mediates pneumococcal binding to fibronectin and fibrinogen proteins.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207102PMC
December 2016

Various Effects of Omega 3 and Omega 3 Plus Vitamin E Supplementations on Serum Glucose Level and Insulin Resistance in Patients with Coronary Artery Disease.

Iran J Public Health 2016 Nov;45(11):1465-1472

Dept. of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Omega 3 and vitamin E are two critical nutrients which include beneficial effects in coronary artery disease (CAD). The aim of this study was to assess the effects of omega 3 alone supplementation or in combination with vitamin E on serum glucose and lipid levels and insulin resistance in CAD patients.

Methods: Participants of this clinical trial included 60 male patients with CAD who selected from Tehran Heart Center in Tehran, Iran in 2014. They received 4 g/day omega 3 plus 400 IU/day vitamin E (OE), 4 g/day omega 3 with vitamin E placebo (OP), or omega 3 and vitamin E placebo (PP) for two months. Serum glucose, lipids and insulin were assessed and HOMA-IR was calculated before and after the trial and effects of these nutrients on the highlighted parameters were compared within the study groups.

Results: Serum glucose level increased significantly in OP group (=0.004), but not in OE group. OE and OP groups showed a significant decrease in fasting serum TG (=0.020 and =0.001, respectively). Serum insulin and HOMA-IR decreased significantly in OE group (=0.044 and =0.039, respectively) but did not change significantly in OP group.

Conclusion: Although, omega 3 supplementation may include adverse effects on serum glucose level, co-administration of omega 3 and vitamin E can beneficially decrease serum insulin and insulin resistance in CAD patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5182255PMC
November 2016

Does Resveratrol Improve Insulin Signalling in HepG2 Cells?

Can J Diabetes 2017 Apr 23;41(2):211-216. Epub 2016 Dec 23.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objectives: Diabetes mellitus is a common metabolic disorder with high global prevalence. It is characterized by a decrease in insulin secretion or a decrease in insulin sensitivity or both. The aim of the present study was to investigate the effects of resveratrol treatment on the expression of the genes involved in insulin signalling cascade, such as Forkhead box protein O1 (FoxO1), 3-phosphoinositide-dependent protein kinase 1 (PDPK1) and mammalian target of rapamycin (mTOR).

Methods: HepG2 cells were cultured in serum-free medium with high concentrations of glucose and insulin and then were treated with resveratrol (5, 10 and 20 µM) for 24 and 48 hours. Complementary deoxyribonucleic acids (cDNAs) were synthesized followed by RNA extraction. Real-time quantitative reverse transcription polymerase chain reaction was used to analyze the expression of FoxO1, PDPK1 and mTOR.

Results: Resveratrol increased the expression of PDPK1, mTOR and FoxO1. No significant difference was seen among differing dosages of resveratrol, but treatments for 48 hours exerted the greatest effectiveness.

Conclusions: Our results were consistent with other studies showing the beneficial effects of resveratrol on diabetes. However, considering the effects of resveratrol in increasing FoxO1 and gluconeogenic gene expression, long-term usage of resveratrol should be investigated in greater depth in future studies.
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http://dx.doi.org/10.1016/j.jcjd.2016.09.015DOI Listing
April 2017

The effect of 1, 25(OH)2 D3 (calcitriol) alone and in combination with all-trans retinoic acid on ROR-γt, IL-17, TGF-β, and FOXP3 gene expression in experimental autoimmune encephalomyelitis.

Nutr Neurosci 2018 Apr 20;21(3):210-218. Epub 2016 Dec 20.

a Department of Cellular and Molecular Nutrition , School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.

Objectives: It has been shown that calcitriol and all-trans retinoic acid (ATRA) have modulatory effects on the immune system. The present study investigates the synergistic effects of combination treatment of calcitriol and ATRA in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).

Methods: The mice were allocated to four preventive groups, each consisting of eight animals, ATRA (250 μg/mouse), calcitriol (100 ng/mouse), combination of ATRA and calcitriol (125  μg/mouse and 50 ng/mouse) and vehicle groups. EAE was induced by MOG35-55 peptide in female C57BL/6 mice. Treatments were initiated at day 1 before immunization and continued every other day throughout the study until the day 21 post-immunization. Splenocytes were isolated from EAE-induced mice and the expression of retinoic acid receptor-related orphan receptor gamma t (ROR-γt), Interleukin-17 (IL-17), transforming growth factor beta (TGF-β), and forkhead box P3 (FOXP3) genes was measured using real-time polymerase chain reaction.

Results: The expression of FOXP3 and TGF-β genes in the splenocytes of combination-treated and calcitriol alone-treated mice was significantly increased compared to vehicle group (P < 0.05). The expression of ROR-γt and IL-17 genes in the splenocytes of ATRA, calcitriol and combination- treated mice was significantly reduced compared to those of vehicle- treated mice (P < 0.05). The relative expression level of ROR-γt was significantly (P < 0.05) lower in the combination group than in the mice treated by ATRA or calcitriol alone.

Discussion: This study demonstrated that treatment with combination of calcitriol and ATRA can be considered as a new strategy for MS prevention and treatment.
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http://dx.doi.org/10.1080/1028415X.2016.1263039DOI Listing
April 2018

A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis.

J Mol Neurosci 2016 Dec 19;60(4):498-508. Epub 2016 Sep 19.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, International Campus, Tehran University of Medical Sciences, Tehran, Iran.

Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the protective and ameliorative effects of novel combination of all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D (D), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]. Encephalomyelitis was induced in female C57BL/6 mice by subcutaneous immunization using commercial kits. Preceding day of EAE induction, combination of ATRA, D, and DHA was administered with a single IP injection every 48 h and continued until day 26. Findings of present study showed that administration of vitamins A, D, and DHA significantly decreased average clinical scores, cumulative EAE score, and EAE incidence in Group T, compared to Group E (p values <0.001). Interferon γ secretion in serum and T-bet mRNA expression in splenocytes were significantly reduced (p = 0.004, p = 0.029, respectively) while PPARγ mRNA expression was significantly increased in Group T compared to Group E (p = 0.021). These findings highlighted that ATRA, D, and DHA combination modulated PPARγ and T-bet gene expression and resulted in decrease in Th1 response and lymphocyte invasion into the central nervous system (CNS) and resultant inflammation. In conclusion, the results of this study suggested the potential use of this intervention in treatment and/or prevention of EAE/MS and probably other Th1 cell-mediated autoimmune diseases.
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http://dx.doi.org/10.1007/s12031-016-0834-4DOI Listing
December 2016

Retinyl Palmitate Supplementation Modulates T-bet and Interferon Gamma Gene Expression in Multiple Sclerosis Patients.

J Mol Neurosci 2016 Jul 28;59(3):360-5. Epub 2016 Apr 28.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Vitamin A derivatives such as retinoic acid may improve the impaired balance of CD4+ T cells in autoimmune and inflammatory diseases. This study is a double-blind randomized trial to evaluate the effect of vitamin A (as form of retinyl palmitate) supplementation on multiple sclerosis (MS) patients. Thirty-nine patients were enrolled and randomly assigned to two groups. Both groups were followed for 6 months. The experimental group received 25,000 IU of retinyl palmitate daily, while the control group received a placebo. Before and after the study, the expression of interferon gamma (IFN-γ) and T-bet genes was evaluated in peripheral blood mononuclear cells of patients by RT-PCR. The results showed that after 6 months of supplementation, expression of IFN-γ and T-bet was significantly decreased. These data suggest that retinyl palmitate supplementation can modulate the impaired balance of Th1 and Th2 cells and vitamin A products that may be involved in the therapeutic mechanism of vitamin A in MS patients. This study provides information regarding the decreased gene expression of IFN-γ and T-bet in MS by retinyl palmitate supplementation.
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http://dx.doi.org/10.1007/s12031-016-0747-2DOI Listing
July 2016

The combined effects of all-trans-retinoic acid and docosahexaenoic acid on the induction of apoptosis in human breast cancer MCF-7 cells.

J Cancer Res Ther 2016 Jan-Mar;12(1):204-8

Department of Cellular and Molecular Nutrition, Faculty of Nutritional Sciences and Dietetics; Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Breast cancer is one of the most women's cancers in the worldwide. In vivo and in vitro studies showed that all-trans-retinoic acid (ATRA) and docosahexaenoic acid (DHA) can modulate differentiation and apoptosis in both cancer and immune cells. Nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) activation in the presence of their ligands, plays a critical role in the proliferation, differentiation, and apoptosis of normal cells.

Aim Of Study: We hypothesized that ATRA and DHA, as ligands of RARs and RXRs respectively, may have synergistic effects on the induction of apoptosis in MCF-7 human mammary carcinoma cell lines.

Materials And Methods: MCF-7 cells were seeded in a 24-well plate at 3 × 105 cells per well. The cells were treated with 5 µM ATRA, 30 DHA, and various combinations of them over a 3-day trial. Apoptosis was measured by Annexin V-FITC kit and flow cytometery.

Results: Our results showed that the combination treatment of ATRA and DHA (5 µM and 30 µM and half dose at 2.5 µM and 15 µM, respectively) in a dose-dependent manner induced apoptosis rate in MCF-7 cells significantly more than single treatment of ATRA or DHA, as compared to control group (P < 0.05).

Conclusion: We conclude that the combination of ATRA and DHA at the well-balanced proportion may be effective in cancer cell apoptosis. Further studies provide details about the potential synergistically effects of combination treatment of ATRA and DHA in growth inhibition and differentiation of human mammary cancer cells.
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http://dx.doi.org/10.4103/0973-1482.154071DOI Listing
December 2016

Vitamin A supplementation reduces the Th17-Treg - Related cytokines in obese and non-obese women.

Arch Endocrinol Metab 2016 Feb;60(1):29-35

Department of Clinical Nutrition, School of Nutrition and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Objective: The objective of the present study was to investigate the effect of vitamin A supplementation on serum Th17 (IL-6, IL-17, IFNγ) and Treg (TGF-β, IL-10) related cytokines in obese and non-obese women.

Subjects And Methods: In a randomized double blind placebo controlled design, 56 obese women were randomly assigned to receive either an oral dose of 25,000 IU retinyl palmitate or placebo per day for 4 months. Twenty eight ages matched non-obese women were also received vitamin A. At the study entry, anthropometric variables were measured and serum Th17 and Treg related cytokine profile were determined at baseline and 4 months after intervention.

Results: Significantly higher baseline concentrations of IL-6 were observed in obese compared with non-obese women (P < 0.05). However, the initial concentrations of other cytokines were not significantly different between groups. The mean concentrations of IL-17 and TGF-β were significantly decreased after vitamin A supplementation in non-obese and obese women respectively. Positive relationships between IL-17 and IL-10 (r = 0.42, P < 0.001), TGF-β and IL-17 (r = 0.35, P < 0.001) and between IL-10 and IFN-γ (r = 0.41, P = 0.002) in total participants were also observed.

Conclusions: The results of the present study showed for the first time that vitamin A supplementation reduces serum concentrations of IL-17 and TGF-β in reproductive age women. Further studies are needed to explore the possible underlying mechanisms.
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http://dx.doi.org/10.1590/2359-3997000000125DOI Listing
February 2016

Vitamin A Decreases Cytotoxicity of Oxidized Low-Density Lipoprotein in Patients with Atherosclerosis.

Immunol Invest 2016 23;45(1):52-62. Epub 2015 Dec 23.

b Department of Cellular Molecular Nutrition , School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.

Background: Oxidized low-density lipoprotein (ox-LDL) is implicated in initiation and progression of atherosclerosis. Previously, we found that ox-LDL increases vulnerability of peripheral blood mononuclear cells (PBMCs) in atherosclerotic patients compared to controls. Vitamin A induces proliferation of PBMCs. The aim of this study was to determine the effect of vitamin A supplementation on PBMC survival against LDL and different doses of ox-LDL.

Method: In this double-blind placebo-controlled trial, we recruited 35 atherosclerotic patients and 38 healthy controls and randomly allocated them into placebo and vitamin A groups, which received either placebo or 25,000 IU/day of vitamin A for 3 months. PBMCs were isolated, cultured, and stimulated by 1 µg/mL LDL as well as 1 µg/mL and 50 µg/mL ox-LDL. The stimulation indexes (SIs) of PBMCs were calculated to identify cell viability. Additionally, the circulating ox-LDL levels were measured by ELISA.

Results: Viability of PBMCs stimulated by 50 µg/mL ox-LDL significantly increased following vitamin A supplementation in patients (p < 0.01). The levels of circulating ox-LDL were not changed by vitamin A treatment. Ox-LDL levels were strongly and positively correlated to SI of PBMCs stimulated by 1 µg/mL LDL and1 µg/mL ox-LDL in all groups.

Conclusion: Vitamin A decreases cytotoxicity of high-dose ox-LDL and improves PBMC viability. The protective effect of vitamin A is not mediated by an antioxidative mechanism, but may instead have been due to intracellular protection of the apoptotic machinery or induction of proliferation of the cells. Higher levels of ox-LDL increase PBMC irritability in all participants.
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http://dx.doi.org/10.3109/08820139.2015.1095208DOI Listing
October 2016

Molecular Mechanisms of the Action of Vitamin A in Th17/Treg Axis in Multiple Sclerosis.

J Mol Neurosci 2015 Dec 30;57(4):605-13. Epub 2015 Aug 30.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Multiple sclerosis (MS) is an autoinflammatory disease of the central nervous system (CNS). The immunopathogenesis of this disease involves an impaired balance of T helper (Th) 17 cells and regulatory T (Tregs) cells. MS is an autoinflammatory disease characterized by the degeneration of the CNS. For many years, MS has been considered to be an autoreactive Th1 and Th17 cell-dominated disease. The activity and number of Th17 cells are increased in MS; however, the function and number of Treg cells are reduced. Therefore, in MS, the balance between Th17 cells and Treg cells is impaired. Th17 cells produce pro-inflammatory cytokines, which play a role in experimental autoimmune encephalomyelitis (EAE) and MS. However, Treg cell-mediated production of cytokines maintains immune homeostasis and can ameliorate the progression of MS. These observations, therefore, confirm the pathogenic and protective role of Th17 and Treg cells, respectively, and highlight the importance of maintaining the balance of both of these cell types. Evidence suggests that vitamin A and its active metabolites (all-trans-retinoic acid and 9-cis-retinoic acid) modulate the imbalance of Th17 and Treg cells through multiple molecular pathways and can be considered as a promising target in the prevention and treatment of MS.
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http://dx.doi.org/10.1007/s12031-015-0643-1DOI Listing
December 2015

The Effects of Vitamin D Supplementation on Glucose Control and Insulin Resistance in Patients with Diabetes Type 2: A Randomized Clinical Trial Study.

Iran J Public Health 2014 Dec;43(12):1651-6

Dept. of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Background: Vitamin D deficiency is prevalent in diabetes type 2 and this vitamin may be related to insulin action. This randomized controlled trial study was done to evaluate the effect of vitamin D supplementation on glucose control and insulin resistance in patients with diabetes type 2.

Methods: Participants of this randomized clinical trial study consisted of 28 patients with type 2 diabetes who received 100 microgram (4000 IU) vitamin D and 30 diabetic patients who received placebo for 2 months between September 2012 and February 2013. The effect of vitamin D on glucose control was assessed by measuring HbA1c and insulin resistance as HOMA-IR at the baseline and the end of the intervention.

Results: The results showed a significant decrease in HbA1c (from 7.29 ± 0.22 % to 6.76 ± 0.18 %, P<0.001) and insulin concentration (from 8.24 ± 0.97 μIU/mL to 6.55 ± 0.28 μIU/mL, P=0.048), but a non-significant decrease in HOMA-IR in vitamin D group. Also, HDL-C level increased significantly in both of vitamin D (P=0.046) and placebo groups (P=0.028).

Conclusion: It seems that vitamin D supplementation has beneficial effects on glucose homeostasis and can increases insulin sensitivity in diabetic 2 patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499086PMC
December 2014

The immunomodulatory effects of fish-oil supplementation in elite paddlers: A pilot randomized double blind placebo-controlled trial.

Prostaglandins Leukot Essent Fatty Acids 2015 Aug 16;99:35-40. Epub 2015 May 16.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Physical exercise can induce imbalance of different cytokines by leading them towards an inflammatory and immunosuppressive milieu. Fish-oil (FO) supplementation may modulate the mentioned skewed balance following intense exercise. Therefore, we decided to investigate the effect of intense physical exercise and FO supplementation on cytokine production and helper T (Th) cell phenotype in male elite paddlers.

Subjects And Methods: Male elite paddlers consumed 6 g/day of either FO capsules (n=11) containing 3.6 g long chain n-3 polyunsaturated fatty acids (1.2 g docosahexaenoic acid and 2.4 g eicosapentaenoic acid) or placebo capsules (n=11) for 4 weeks. The paddlers simultaneously undertook a program of increasing exercise. Blood samples were taken from all the subjects 48 h before and after the 4 weeks of supplementation.

Results: Our results show that while FO supplementation decreases the production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the elite paddlers, it increases the production of IL-6. On the other hand, while there was no change in IL-4 secretion, the production of interferon (IFN)-γ was significantly decreased after 4 weeks FO consumption. We also showed that the production of IL-10 was significantly higher in the FO group compared to the placebo. Finally, we found that fish-oil consumption shifts the balance between Th cells towards Th2 phenotype during intensive exercise.

Conclusion: Our results suggest that the consumption of n-3 polyunsaturated fatty acids during intense exercise can induce the anti-inflammatory and immunosuppressive cytokine networks that are associated with a reduced Th1/Th2 ratio in elite paddlers.
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http://dx.doi.org/10.1016/j.plefa.2015.04.011DOI Listing
August 2015

The Effect of Vitamin A Supplementation on FoxP3 and TGF-β Gene Expression in Avonex-Treated Multiple Sclerosis Patients.

J Mol Neurosci 2015 Jul 19;56(3):608-12. Epub 2015 May 19.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran,

Multiple sclerosis (MS) is an autoinflammatory condition of the central nervous system with impaired T helper (Th)17 and regulatory T cell (Treg) balance that is involved in disease immunopathogenesis. The vitamin A active metabolite, retinoic acid, can re-establish this imbalance through the modulation of gene expression of specific nuclear receptors including Forkhead box P3 (FoxP3). At present, few data exist on the impact of vitamin A supplementation on T cell balance. This study reports the results of a clinical trial, over a 6-month period, of 36 relapsing-remitting MS (RRMS) patients that received vitamin A (25,000 IU retinyl palmitate) or placebo (one capsule of placebo per day). Peripheral blood mononuclear cells were isolated from patients, and the expression of FoxP3 and transforming growth factor (TGF)-β gene expression was measured using real-time PCR at the beginning and end of the study. The results of this study showed that vitamin A upregulated TGF-β and FoxP3 gene expression. Therefore, vitamin A supplementation can be considered as a new approach in MS prevention and treatment.
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http://dx.doi.org/10.1007/s12031-015-0549-yDOI Listing
July 2015