Publications by authors named "Mahmoud Djalali"

118 Publications

The effects of nano-curcumin supplementation on Th2/tregulatory axis in migraine patients: a randomized, double-blind, placebo-controlled trial.

Int J Neurosci 2021 Mar 16:1-7. Epub 2021 Mar 16.

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

Aim: In the present study we aimed to investigate the effects of nano-curcumin supplementation on gene expression and serum levels of IL-4 and TGF-β in migraine patients.

Methods: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin ( = 20) or placebo ( = 20) in a randomized double-blind clinical trial for two months. At the beginning and the end of the study, the interictal serum levels and gene expression of IL-4 and TGF-β in peripheral blood mononuclear cells (PBMCs) isolated from migraine patients were measured, using ELISA and real-time PCR methods, respectively.

Results: Intra-group assays showed a significant rise in the gene expression of both IL-4 and TGF-β ( < 0.05) in nano-curcumin group after two months of treatment, however the serum levels were only significantly changed for IL-4 ( < 0.05). On the contrast, inter-group assays revealed no statistical differences between nano-curcumin and placebo group in terms of IL-4 and TGF-β gene expression, while the serum levels of IL-4 was observed to be increased significantly ( 0.03) following two month nano-curcumin supplementation.

Conclusion: The findings of the present trial suggest that the treatment with nano-curcumin could induce significant levels of IL-4, in favour of anti-inflammatory effects, while has a minimal effects on the both gene expression and serum levels of TGF-β. Further studies are required to determine the exact mechanism of action of curcumin in patients with migraine.
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http://dx.doi.org/10.1080/00207454.2021.1897587DOI Listing
March 2021

The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial.

J Pharm Health Care Sci 2021 Mar 3;7(1). Epub 2021 Mar 3.

Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Although the exact mechanism involved in migraine pathogenesis remained uncertain, and different researches have been developed to address the role of neuroinflammation and immune dysfunction. Therefore, considering the immune protective functions of vitamin D3, we aimed to investigate the effects of daily administration of 2000 IU D3 supplements on serum status of immune markers in migraine patients.

Methods And Materials: Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000 IU/d or placebo for 12-week were enrolled in this placebo-controlled double-blind trial included. Serum concentrations of transforming growth factor-beta (TGF-β) and interleukin (IL)-17 were evaluated at baseline and after the trial via the ELISA method.

Results: Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that the serum level of TGF-β was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P-value = 0.012); on the other hand, vitamin D prevented the increment in IL-17 serum level in the intervention group after the trial (adjusted mean:37.84 ng/L) comparing to the controls (adjusted mean:70.09 ng/L; P-value = 0.039). The Pearson correlation analysis revealed a significant positive correlation between changes in serum 25-hydroxy-vitamin D (25(OH)D) and TGF-β (r = - 0.306, P-value = 0.008). In contrast, no significant correlations were noted between serum 25(OH) D and IL-17 changes throughout the study.

Conclusion: Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance the Th17/Treg related cytokines balance in episodic migraineurs. Although these findings are promising, it is needed to be extended.

Trial Registration: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6 ( https://www.irct.ir/trial/31246 ).
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http://dx.doi.org/10.1186/s40780-021-00192-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927391PMC
March 2021

The effects of nano-curcumin supplementation on Th1/Th17 balance in migraine patients: A randomized controlled clinical trial.

Complement Ther Clin Pract 2020 Nov 29;41:101256. Epub 2020 Oct 29.

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

Background: The present study was aimed to evaluate the nano-curcumin supplementation on Th1/Th17 balance by assessment of gene expression and serum level of interferon gamma (IFN-γ) and interleukin-17 (IL-17) in migraine patients.

Methods: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. The expression of IFN-γ and IL-17 from peripheral blood mononuclear cells and IFN-γ and IL-17 serum levels were measured, using a real-time PCR and ELISA methods, respectively.

Results: Compared to placebo group, two month nano-curcumin supplementation led to a significant reduction in serum levels and expression of IL-17 mRNA (P = 0.006 & 0.04, respectively), while there was no statistical difference regarding serum levels and expression of IFN-γ mRNA.

Conclusion: Nano-curcumin supplementation in migraine patients led to a significant reduction in gene expression and plasma levels of IL-17 compared to control group.
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http://dx.doi.org/10.1016/j.ctcp.2020.101256DOI Listing
November 2020

The Effect of Nano-Curcumin Supplementation on Pentraxin 3 Gene Expression and Serum Level in Migraine Patients.

Rep Biochem Mol Biol 2020 Apr;9(1):1-7

Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.

Background: This study was designed to investigate the effect of nano-curcumin supplementation on pentraxin 3 (PTX3) gene exp ression and serum level in migraine patients.

Methods: The present study, performed as a clinical trial, included 38 episodic migraine patients in two groups that received either nano-curcumin or placebo over a two-month period. At the start and the end of the study, PTX3 gene expression and serum levels were measured.

Results: After two months of treatment, PTX3 gene expression and serum levels were both significantly less in the nano-curcumin than in the placebo group (P= 0.01 and P< 0.001, respectively). No significant gene expression differences were found between the two groups.

Conclusion: Curcumin may have a potential inhibitory effect on PTX3 gene expression and serum levels in migraine disease and can be considered as an efficient therapy in migraine management.
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http://dx.doi.org/10.29252/rbmb.9.1.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424412PMC
April 2020

Quercetin Ameliorates Lipid and Apolipoprotein Profile in High-Dose Glucocorticoid Treated Rats.

Arq Bras Cardiol 2020 07 7;115(1):102-108. Epub 2020 Aug 7.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Irã.

Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.).
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http://dx.doi.org/10.36660/abc.20180397DOI Listing
July 2020

Anti-Neuroinflammatory Properties of n-3 Fatty Acids and Nano- Curcumin on Migraine Patients from Cellular to Clinical Insight: A Randomized, Double-Blind and Placebo-Controlled Trial.

Endocr Metab Immune Disord Drug Targets 2021 ;21(2):365-373

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.

Background And Objectives: Migraine is an exhausting neuro-inflammatory disorder recognized as recurrent headache attacks. Evidence has shown that Interleukin (IL)-1β plays a substantial role in the neuro-immunity pathogenicity of migraine. n-3 fatty acids and curcumin revealed neuromodulatory and anti-inflammatory effects through several pathways, of which the suppression of IL-1β gene expression is an important inflammatory pathway. The aim of this study was the investigation of synergistic relation of n -3 fatty acids and nano-curcumin on IL-1β gene expression and serum levels in migraine patients.

Methods: This study was performed as a randomized, double-blind, placebo-controlled trial in a period of two months. A total of 80 episodic migraines were assigned into 4 groups of 1) n-3 fatty acids and curcumin combination; 2) n -3 fatty acids; 3) nano-curcumin; and 4) n-3 fatty acids and curcumin placebo. The gene expression and serum level of IL-1β were measured by real-time PCR and ELISA methods respectively, at the beginning and the end of the interventions.

Results: Results showed the n-3 fatty acids and nano-curcumin combination significantly reduced the attack frequency in a synergistic status (P < 0.001). A significantly greater reduction in the serum level of IL-1β was observed in the combination group, and the differences in the other groups were not statistically significant. The IL-1β gene expression in the combination group showed a significant reduction for other treatment groups (P < 0.05), but these significant differences were absent after multiple testing Bonferroni corrections.

Conclusion: Present findings revealed that n -3 fatty acids and curcumin co-supplementation can be suggested as a promising new approach in migraine headache management, but further studies are needed to confirm these findings.
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http://dx.doi.org/10.2174/1871530320666200729144430DOI Listing
January 2021

Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies.

Aging Male 2020 Jun 8:1-9. Epub 2020 Jun 8.

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

Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection. Online databases including Web of Science, PubMed, Scopus, Cochrane Library and Google scholar were searched to detect relevant publications up to 1 May 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done. In total, 14 studies with 29,909 COVID-19 infected patients and 1445 cases of death were included in the current meta-analysis. Significant associations were found between older age (≥65 vs <65 years old) (pooled ORs = 4.59, 95%CIs = 2.61-8.04,  < .001), gender (male vs female) (pooled ORs = 1.50, 95%CIs = 1.06-2.12,  = .021) and risk of death from COVID-19 infection. In addition, hypertension (pooled ORs = 2.70, 95%CIs = 1.40-5.24,  = .003), cardiovascular diseases (CVDs) (pooled ORs = 3.72, 95%CIs = 1.77-7.83,  = .001), diabetes (pooled ORs = 2.41, 95%CIs = 1.05-5.51,  = .037), chronic obstructive pulmonary disease (COPD) (pooled ORs = 3.53, 95%CIs = 1.79-6.96,  < .001) and cancer (pooled ORs = 3.04, 95%CIs = 1.80-5.14,  < .001), were associated with higher risk of mortality. Older age (≥65 years old), male gender, hypertension, CVDs, diabetes, COPD and malignancies were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.
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http://dx.doi.org/10.1080/13685538.2020.1774748DOI Listing
June 2020

Effect of probiotic supplementation on migraine prophylaxis: a systematic review and meta-analysis of randomized controlled trials.

Nutr Neurosci 2020 May 18:1-8. Epub 2020 May 18.

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

The prevalence of migraine is higher in patients with gastrointestinal disorders. Possible underlying mechanisms could be increased intestinal permeability and systemic inflammation. Probiotics may reduce gut permeability as well as inflammation, and therefore may improve the clinical features of migraine. This systematic review and meta-analysis aimed to evaluate the impact of probiotic supplementation on the frequency and severity of migraine attacks. A systematic review of the literature was conducted using ISI Web of Science, PubMed/Medline, Scopus, Cochrane Library, EMBASE, Google Scholar, Magiran.com and Sid.ir to identify eligible studies published up to October 2019. A meta-analysis of eligible trials was performed using the random-effects model to estimate pooled effect size. Three randomized controlled trials with 179 patients (probiotic group = 94, placebo group = 85) were included. Probiotic supplementation had no significant effect on frequency (weighted mean difference (WMD) = -2.54 attacks/month, 95%CI: -5.31-0.22,  = 0.071) and severity of migraine attacks (WMD = -1.23 visual analog scale (VAS) score, 95%CI = -3.37-0.92,  = 0.262) with significant heterogeneity among the studies ( = 98%,  < 0.001). A pooled analysis of available randomized controlled clinical trials showed that probiotic supplementation had no significant effect on the frequency and severity of episodic migraine attacks.
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http://dx.doi.org/10.1080/1028415X.2020.1764292DOI Listing
May 2020

Effect of vitamin D supplementation on CREB-TrkB-BDNF pathway in the hippocampus of diabetic rats.

Iran J Basic Med Sci 2020 Jan;23(1):117-123

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

Objectives: Cyclic AMP (adenosine monophosphate) response element-binding protein (CREB) and Brain-derived neurotrophic factor (BDNF) are reported to broadly involve in learning capacity and memory. BDNF exerts its functions via tropomyosin receptor kinase B (TrkB). BDNF transcription is regulated by stimulating CREB phosphorylation. The CREB-TrkB-BDNF pathway is reported to be affected by diabetes, which may contribute to its cognitive deficits. This study was conducted to investigate the effect of vitamin D supplementation on the hippocampal fraction of this pathway in an animal model of type-1 diabetes mellitus (T1DM).

Materials And Methods: Thirty-six adult male Sprague-Dawley rats were randomly divided into 4 groups as follows: Group 1: normal healthy rats (n=8); group 2: normal healthy rats receiving sesame oil supplementation as placebo (n=8); Group 3: diabetic rats receiving sesame oil (n=10); and Group 4: diabetic rats treated with 4300 IU/kg/week vitamin D dissolved in sesame oil (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Blood and hippocampal samples were acquired at the end of the experiment. RNA was extracted from the hippocampus, and real-time PCR (polymerase chain reaction) was performed for BDNF and TrkB gene expression.

Results: Administration of vitamin D (4300 IU/kg/week) in a T1DM animal model increased CREB phosphorylation in the hippocampus, but the serum and hippocampal BDNF levels and TrkB and BDNF gene expression did not change significantly.

Conclusion: Vitamin D increased hippocampal CREB phosphorylation in a T1DM animal model. Our findings showed that vitamin D might be protective against central nervous system complications in diabetes. However, future studies are warranted.
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http://dx.doi.org/10.22038/IJBMS.2019.38170.9068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206842PMC
January 2020

The Effect of Vitamin D Supplementation on Serum and Muscle Irisin Levels, and FNDC5 Expression in Diabetic Rats.

Rep Biochem Mol Biol 2019 Oct;8(3):236-243

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

Background: Diabetes mellitus and metabolic disorders are a major burden on the healthcare system. Irisin is a novel myokine reported to have beneficial effects on glucose and lipid metabolism. Vitamin D deficiency has been implicated in the development of diabetes and hold a critical role in diabetes-related complications. In the present study, we examined the efficacy of vitamin D supplementation on serum irisin levels, skeletal muscle irisin levels, and the expression of the irisin precursor, FNDC5 (fibronectin-type III domain-containing 5) in type I diabetes mellitus rats.

Methods: Thirty-six adult male Sprague-Dawley rats (150 - 250 g) were randomly divided into four groups: group I: healthy control rats with no treatment (n=8), group II: healthy control rats receiving sesame oil as a placebo (n=8), group III: diabetic rats receiving sesame oil as placebo (n=10), group IV: diabetic rats treated with 4300 IU/kg/week vitamin D (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. At the end of the vitamin D intervention blood and triceps muscle samples were collected. RNA was extracted from muscle and real-time PCR was performed to examine FNDC5 gene expression.

Results: Our study showed that the administration of vitamin D (4300 IU/kg/week) in a streptozotocin-diabetic rat model resulted in increased serum vitamin D levels, FNDC5 gene expression and muscle irisin levels. However, the levels of serum irisin were not significantly changed by the administration of vitamin D.

Conclusion: In conclusion, we show that vitamin D supplementation enhances serum vitamin D levels, FDNC5 gene expression and muscle irisin levels in the streptozotocin-diabetic rat model. Our study highlights the potential therapeutic effect of vitamin D supplementation for diabetes mellitus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103079PMC
October 2019

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial.

J Headache Pain 2020 Feb 24;21(1):22. Epub 2020 Feb 24.

Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects.

Methods: The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method.

Results: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022).

Conclusion: According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings.

Trial Registration: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.
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http://dx.doi.org/10.1186/s10194-020-01090-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041277PMC
February 2020

Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial.

Neurol Sci 2020 May 2;41(5):1183-1192. Epub 2020 Jan 2.

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

Introduction: Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs.

Methods And Materials: This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 μg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method.

Results: At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055).

Conclusion: Based on the results of this study, we found that 2000 IU (50 μg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.
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http://dx.doi.org/10.1007/s10072-019-04220-8DOI Listing
May 2020

Retinol and α-Tocopherol Levels in the Serum and Subcutaneous Adipose Tissue of Newly Diagnosed Basal Cell Carcinoma Patients.

Iran J Public Health 2019 Oct;48(10):1838-1846

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

Background: Nonmelanoma skin cancers are the most frequently occurring skin cancers. Vitamin A is involved in epithelial cell differentiation and may control skin tumor development. Vitamin E is a powerful lipophilic antioxidant that can quench and scavenge reactive oxygen species. However, there is little consistent evidence considering micronutrients and the development of basal cell carcinoma (BCC). Therefore, we aimed to investigate the possible difference between retinol and α-tocopherol in BCC patients and controls in Iranian population.

Methods: This case-control study was conducted on adults with newly diagnosed BCC referred to Razi Hospital, Tehran, Iran in 2015. Serum and subcutaneous fat tissue retinol and α-tochopherol were measured by HPLC method.

Results: Overall, serum retinol level was lower significantly in BCC patients (0.237±0.01 μg/ml) in comparison with control group (0.27±0.02 μg/ml, -value: 0.038). However serum α-tocopherol level was not significantly different between BCC patients (4.41±0.33 μg/ml) and control subjects (4.06±0.35 μg/ml, -value=0.18). Sub-cutaneous adipose tissue retinol was lower significantly in BCC patients (38.60±3.30 ng/mg) compared with control group (54.78±3.49 ng/mg, -value=0.002). Furthermore, results revealed lower subcutaneous adipose tissue α-tocopherol in BCC patients (4.41±0.33 μg/ml) in comparison with control group (4.06±0.35 μg/ml, -value=0.18).

Conclusion: Skin tissue concentration of retinol and α-tocopherol and serum retinol level was lower in BCC patients in comparison with control group but serum α-tocopherol was not different between groups.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908907PMC
October 2019

The effect of l-carnitine supplementation on serum levels of omentin-1, visfatin and SFRP5 and glycemic indices in patients with pemphigus vulgaris: A randomized, double-blind, placebo-controlled clinical trial.

Phytother Res 2020 Apr 18;34(4):859-866. Epub 2019 Dec 18.

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

Pemphigus vulgaris (PV) is a chronic autoimmune disorder with potentially fatal outcomes. The aim of this study was to investigate the effect of l-carnitine (LC) on secreted frizzled-related protein-5 (SFRP5), omentin, visfatin, and glycemic indices in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 52 patients with PV were divided randomly into two groups to receive 2 g of LC or a placebo for 8 weeks. Serum levels of SFRP5, omentin, visfatin, and also glycemic indices were evaluated at the baseline and end of the study. LC supplementation significantly decreased the serum level of visfatin (95% CI [-14.718, -0.877], p = .05) and increased the serum levels of SFRP5 (95%CI [1.637, 11.380], p < .006) and omentin (95% CI [9.014, 65.286], p < .01). However, LC supplementation had no significant effects on the serum levels of glycemic factors such as insulin (95% CI [-1.125, 3.056], p = .426), fasting blood sugar (95% CI [-4.743, 3.642], p = .894), homeostatic model assessment of insulin resistance (95% CI [-0.305, 0.528], p = .729), and quantitative insulin-sensitivity check index (95% CI [-0.016, -0.010], p = .81). LC supplementation decreased visfatin serum level and increased omentin-1 and SFRP5 serum levels in patients with PV. However, it has no significant effect on the serum levels of insulin and glycemic indices.
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http://dx.doi.org/10.1002/ptr.6568DOI Listing
April 2020

Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial.

Diabetol Metab Syndr 2019 26;11:86. Epub 2019 Oct 26.

1Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poorsina Street, Enghelab Avenue, PO Box: 14155-6446, Tehran, Iran.

Background: Several researches have recommended vitamin D possible health benefits on diabetic complications development, but a few number of studies have been accomplished on the molecular and cellular mechanisms. Certain cellular pathways modification and also some transcription factors activation may protect cells from hyperglycemia condition induced damages. This study purpose was to determine the vitamin D supplementation effect on some key factors [advanced glycation end products (AGEs) signaling pathway] that were involved in the diabetic complications occurrence and progression for type-2 diabetes participants.

Methodology: 48 type-2 diabetic patients (T2DM) randomly divided into two groups (n = 24 per group), receiving: 100-µg vitamin D or placebo for 3 months. At this study beginning and the end, the receptor expression for advanced glycation end products (RAGE) and glyoxalase I (GLO1) enzyme from peripheral blood mononuclear cells (PBMCs) and AGEs and tumor necrosis factor-α (TNF-α) serum levels were measured by the use of real-time PCR and ELISA methods, respectively.

Results: This study results demonstrated that vitamin D supplementation could down-regulate RAGE mRNA [fold change = 0.72 in vitamin D vs. 0.95 in placebo) P = 0.001)]. In addition, no significant changes were observed for GLO1 enzyme expression (P = 0.06). This study results also indicated that vitamin D serum level significantly increased in vitamin D group (P < 0.001). Moreover, AGES and TNF-α serum levels significantly reduced in vitamin D group, but they were remained unchanged in the placebo group.

Conclusion: In conclusion, vascular complications are more frequent in diabetic patients, and vitamin D treatment may prevent or delay the complications onset in these patients by AGEs serum level and RAGE gene expression reducing. NCT03008057. Registered December 2016.
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http://dx.doi.org/10.1186/s13098-019-0479-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814978PMC
October 2019

Effects of vitamin D supplementation on circulatory YKL-40 and MCP-1 biomarkers associated with vascular diabetic complications: A randomized, placebo-controlled, double-blind clinical trial.

Diabetes Metab Syndr 2019 Sep - Oct;13(5):2873-2877. Epub 2019 Jul 29.

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

Aim: Diabetic patients predispose to vascular diseases such as nephropathy, and retinopathy. Poor adherence to medical treatment and dietary recommendations in uncontrolled diabetes leads to vascular damages. Vitamin D has been extensively studied and found to be protective against diabetes mellitus. YKL-40 and Monocyte chemoattractant protein-1 (MCP-1) are considered to exert crucial role in diabetes and its complications. Therefore, this study was designed to investigate effects of vitamin D supplementation on serum levels of YKL-40 and MCP-1 involved in the development of diabetic complications.

Methods: For 12 weeks, 48 type 2 diabetic patients enrolled in the trial and randomly were divided into two groups (n = 24 per group), receiving one of the following: 100 μg (4000 IU) vitamin D or placebo. Before and after intervention, serumYKL-40, MCP-1, insulin, IL-6, TNF-α, 25- (OH) vitamin D and HbA1c were measured.

Results: Our results revealed that serum levels of 25 (OH) vitamin D significantly increased in vitamin D group (p < 0.001). Vitamin D supplementation also significantly reduced serum YKL-40 levels (-22.7 vs. -2.4 ng/ml; (p-value = 0.003)). There was a significant decline in MCP-1 concentration in intervention group at the end of the study (-45.7 vs. -0.9 pg/ml; (p = 0.001)). Furthermore, there was a significant decrease in IL-6, fasting insulin and HOMA-IR in intervention group after 3 months supplementation.

Conclusions: Daily vitamin D supplementation effectively reduced circulatory YKL-40 and MCP-1 levels in patients with type-2 diabetes and vitamin D deficiency. Vitamin D might contribute in reducing diabetic complications via modulating YKL-40 and MCP-1 signaling pathways.
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http://dx.doi.org/10.1016/j.dsx.2019.07.047DOI Listing
February 2020

Effects of vitamin D supplementation on depressive symptoms in type 2 diabetes mellitus patients: Randomized placebo-controlled double-blind clinical trial.

Diabetes Metab Syndr 2019 Jul - Aug;13(4):2375-2380. Epub 2019 Jun 11.

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

Aim: Diabetes increases the odds of depression and depression is often associated with poor glycemic control and complications of diabetes. Vitamin D is also believed to improve glycemic control and ameliorate depressive symptoms. Therefore, we examined effects of vitamin D monotherapy (without antidepressant drugs) on depressive symptoms in Type 2 diabetic patients with mild to moderate depressive symptoms.

Methods: We conducted 12 weeks, placebo-controlled, double-blind, randomized trial on 68 subjects with T2DM and mild to moderate depressive symptoms. Subjects received 100 μg (4000 IU) vitamin D (n = 32) or placebo (n = 34) daily. Beck Depression Inventory-II (BDI-II-PERSIAN) was applied for assessment of the severity of depression. Depression scores and metabolic profiles were measured at the beginning and end of trail.

Results: after 3 months of vitamin D supplementation, mean values of 25(OH) D increased from 15.5 ± 8.8 to 32.2 ± 8.9 ng/ml (p-value <0.001) in the vitamin D group. Moreover, BDI-II scores decreased from 15.2 ± 9.6 to 9.8 ± 7.2 (p-value <0.001) in the vitamin D group and 15.5 ± 11.2 to 13.7 ± 11.5 (p-value = 0.03) in placebo group. This decrease in BDI-II scores were significant (27.6% vs 10.8%) compared with placebo (p-value = 0.02). In term of metabolic profiles, mean change in level of Hemoglobin A1c (HbA1c), insulin and triglycerides (TG) were significantly higher in response to the treatment with vitamin D compared to placebo (p-value <0.02).

Conclusions: In conclusion, supplementation of vitamin D in T2DM patients may protect these patients against the onset of major depressive disorder (MDD), with noticeable favorable effects on measures of metabolic profiles.

Trial Registration: NCT03008057.
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http://dx.doi.org/10.1016/j.dsx.2019.06.011DOI Listing
January 2020

Effects of l-carnitine supplementation on cardiovascular and bone turnover markers in patients with pemphigus vulgaris under corticosteroids treatment: A randomized, double-blind, controlled trial.

Dermatol Ther 2019 09 28;32(5):e13049. Epub 2019 Aug 28.

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

Pemphigus vulgaris (PV) is a severe, bullous, autoimmune disease of the skin and mucous membranes. Corticosteroids are usually the main core treatment for controlling PV, which could lead to several side effects such as insulin resistance, osteoporosis, and cardiovascular disorders. The aim of this study is to evaluate the protective effects of l-carnitine (LC) supplementation in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 48 patients with PV were divided randomly into two groups to receive 2 g LC (n = 24) or a placebo (n = 24) for 8 weeks, respectively. Serum levels of osteopontin (OPN), bone morphogenic protein 4 (BMP4), cystatin C, systolic and diastolic blood pressure, 25 hydroxyvitamin D3, and LC were evaluated at the beginning and at the end of the study. LC supplementation demonstrated a significant increase in serum carnitine (p < .001). In addition, at the end of the trial, LC supplementation significantly decreased serum BMP4 (p = .003), OPN (p = .03), and cystatin C (p = .001) levels. There was no significant effect on blood pressure in comparison with the placebo. During study, no harmful side effects were reported by patients. These findings indicate that LC supplementation significantly leads to favorable changes in OPN, BMP4, and cystatin C in PV patients under corticosteroid therapy. However, further investigations are required to confirm these results.
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http://dx.doi.org/10.1111/dth.13049DOI Listing
September 2019

Short-term curcumin supplementation enhances serum brain-derived neurotrophic factor in adult men and women: a systematic review and dose-response meta-analysis of randomized controlled trials.

Nutr Res 2019 09 9;69:1-8. Epub 2019 May 9.

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

The reduction of brain-derived neurotrophic factor (BDNF) affects cognitive function, learning, and memory and also causes behavioral disorders. Several randomized controlled trials have examined the neuroprotective effects of curcumin and its ability to increase BDNF levels, with inconclusive results. The aim of this systematic review was to evaluate the impact of curcumin supplementation on serum BDNF levels. A systematic review of the literature was conducted using PubMed, Scopus, ISI Web of Science, Cochrane library, and Google scholar to identify eligible studies up to January 2019. The studies included were randomized control trials of curcumin supplementation that reported the serum BDNF level as a primary outcome. A dose-response meta-analysis of eligible studies was performed using the random-effects model to estimate pooled effect size. Four randomized control trials with 139 participants were included. Curcumin supplementation dose and duration ranged from 200 to 1820 mg/d and 8 to 12 weeks, respectively. Curcumin supplementation significantly increased serum BDNF levels (weighted mean difference: 1789.38 pg/mL, 95% confidence interval: 722.04-2856.71, P < .01) with significant heterogeneity among the studies (I = 83.5%, P < .001). Subgroup analysis showed that sex, mean age of participants, curcumin dosage, and trial duration were potential sources of heterogeneity. The significant positive impact of curcumin supplementation on BDNF levels indicates its potential use for neurological disorders that are associated with low BDNF levels.
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http://dx.doi.org/10.1016/j.nutres.2019.05.001DOI Listing
September 2019

The Effect of Vitamin D3 Supplementation on Serum BDNF, Dopamine, and Serotonin in Children with Attention-Deficit/Hyperactivity Disorder.

CNS Neurol Disord Drug Targets 2019 ;18(6):496-501

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

Background & Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders in childhood. The exact etiology of this disease is unknown, but it is believed to be related to the disorder of catecholaminergic and serotonergic systems. Also, serum vitamin D levels in patients with ADHD is lower. Several studies have also shown the effect of vitamin D on the synthesis pathways of dopamine, serotonin, and a number of neurotrophic factors. Therefore, this study aimed to investigate the effect of vitamin D3 supplementation on serum levels of Brain-Derived Neurotrophic Factor (BDNF), dopamine, and serotonin in school-aged children with ADHD.

Methods: Eighty-six children with ADHD were divided into two groups, based on randomized permuted blocks. Patients received 2000 IU vitamin D/day or a placebo for 12 weeks. Serum levels of BDNF, dopamine, serotonin, and 25-hydroxyvitamin D [25(OH)D] were measured at baseline and at the end of the study.

Results: Serum levels of 25(OH)D and dopamine significantly increased in the vitamin D group, compared to the placebo group (p < 0.05). However, serum BDNF and serotonin levels did not change significantly.

Conclusion: Vitamin D3 supplementation in children with ADHD can increase serum dopamine levels, but further studies are needed to determine the effects of vitamin D on neurotrophic factors and serotonin.
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http://dx.doi.org/10.2174/1871527318666190703103709DOI Listing
September 2020

The synergistic effects of nano-curcumin and coenzyme Q10 supplementation in migraine prophylaxis: a randomized, placebo-controlled, double-blind trial.

Nutr Neurosci 2021 Apr 26;24(4):317-326. Epub 2019 Jun 26.

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

Migraine is a disabling neurovascular disorder characterized by increasing levels of pro-inflammatory cytokines and oxidative stress biomarkers. Curcumin and coenzyme Q10 (CoQ10) can exert neuroprotective effects through modulation of inflammation and oxidative stress. The aim of the present study was to evaluate the combined effects of nano-curcumin and CoQ10 supplementation on migraine symptoms and quality of life in migraine patients. One-hundred men and women (mean age 32 years) with episodic migraine based on the International Headache Society (IHS) criteria participated in this study. The subjects were randomly divided into four groups as (1) combination of nano-curcumin (80 mg) plus CoQ10 (300 mg), (2) nano-curcumin (80 mg), (3) CoQ10 (300 mg) and (4) the control (nano-curcumin and CoQ10 placebo included oral paraffin oil) beside usual prophylactic drugs for 8 weeks. Frequency, severity, duration of headache attacks, the headache diary results (HDR) and headache disability based on migraine-specific questionnaires were assessed at the baseline and end of the study. Ninety-one of 100 patients completed the study. The results showed a significant effect of nano-curcumin and CoQ10 supplementation on frequency, severity, duration of migraine attacks and HDR compared to other groups (All  < 0.001). Nano-curcumin and CoQ10 group also had better scores in migraine-specific questionnaires at the end of the study compared to other groups (All  < 0.001). There were no side effects reported by the participants. These findings suggest a possible synergistic effect of nano-curcumin and CoQ10 on clinical features of migraine. IRCT2017080135444N1.
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http://dx.doi.org/10.1080/1028415X.2019.1627770DOI Listing
April 2021

Vitamin D suppresses cellular pathways of diabetes complication in liver.

Iran J Basic Med Sci 2019 Jun;22(6):690-694

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

Objectives: The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.

Materials And Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group). The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes. Groups were treated for four weeks either with placebo or vitamin D (two injections of 20000 IU/kg). Thereafter, serum levels of glucose, insulin and HbA1c were assessed. Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).

Results: Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (=0.005). Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; = 0.01). Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake. Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (=0.04 and <0.001 respectively).

Conclusion: Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
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http://dx.doi.org/10.22038/ijbms.2019.36054.8584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570757PMC
June 2019

Vitamin D downregulates key genes of diabetes complications in cardiomyocyte.

J Cell Physiol 2019 11 7;234(11):21352-21358. Epub 2019 Jun 7.

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

Objective: Vitamin D deficiency has been reported to be associated with the incidence of type 1 and type 2 diabetes and worsening of diabetes complications. This study was designed to investigate the effect of vitamin D treatment on the expression of five key genes involved in the development of diabetic cardiomyopathy.

Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups. The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin (STZ) to develop diabetes. Then groups were treated for 4 weeks either with placebo or vitamin D (two injections of 20,000 IU/kg). Serum levels of glucose, insulin, HbA1c, and advanced glycation end products (AGEs), as well as the gene expression of AGE cellular receptor (RAGE), glyoxalase, aldose reductase, O-GlcNAc transferase (OGT), and glutamine-fructose-6-phosphate aminotransferase (GFAT) and nuclear factor-kB (NF-kB) activity of nuclear extracts were assessed at the end of experiment.

Results: Increment in serum cholecalciferol could improve hyperglycaemia and hypoinsulinemia in diabetic rats. In addition, a significant reduction was observed in RAGE, OGT, and GFAT gene expression and NF-kB activity in cardiac myocytes.

Conclusions: Vitamin D might contribute in reducing diabetic cardiomyopathy not only by improving blood glucose and insulin levels but also via downregulating AGE and hexosamine pathways and decreasing NF-kB activity in heart tissue.
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http://dx.doi.org/10.1002/jcp.28743DOI Listing
November 2019

Association between dietary intake of some antioxidant micronutrients with some inflammatory and antioxidant markers in active Rheumatoid Arthritis patients.

Int J Vitam Nutr Res 2019 Nov 1;89(5-6):238-245. Epub 2019 Apr 1.

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

Rheumatoid Arthritis (RA) is an autoimmune disease. Antioxidants intake and body antioxidants status are important in patients with RA. The aim of this study was to investigate the association between dietary intake of some antioxidant micronutrients with some inflammatory and antioxidant markers in patients with active rheumatoid arthritis and comparison with Recommended Dietary Allowance (RDA). In this cross-sectional study, eighty-seven patients with active rheumatoid arthritis were included. Dietary antioxidants intake was measured using 24-hour recall questionnaire and food record (3 days). Blood levels of inflammatory and antioxidant markers were determined by laboratory tests. The association between intake of antioxidants with inflammatory and antioxidant markers, and also with RDA were determined using Paired-Samples t-test and Pearson correlation by SPSS software. The findings showed that intakes of vitamin E, zinc, and magnesium in patients were significantly lower and intakes of copper and selenium were significantly higher than RDA (P < 0.05). Significant negative correlations were observed between vitamin A intake with PGE2 [R = -0.31], vitamin C intake with IL-1β [R = -0.25], zinc intake with PGE2 [R = -0.30], IL-2 [R = -0.23], and the activity of glutathione reductase enzyme [R = -0.21], magnesium intake with PGE2 [R = -0.24], IL-1β [R = -0.23] and IL-2 [R = -0.25], and selenium intake with PGE2 [R = -0.21] (P < 0.05). Also, significant positive correlations were observed between intakes of vitamin E and copper with catalase enzyme activity [R = 0.22 and R = 0.21 respectively] (P < 0.05). Some of the antioxidant micronutrients play important roles in the reduction of inflammatory conditions and improve the function of antioxidant enzymes in patients with rheumatoid arthritis.
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http://dx.doi.org/10.1024/0300-9831/a000255DOI Listing
November 2019

Vitamin D3 supplementation improves serum SFRP5 and Wnt5a levels in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

Int J Vitam Nutr Res 2018 Feb 10;88(1-2):73-79. Epub 2019 Apr 10.

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

To explore the effect of vitamin D3 on novel serum adipokines, secreted frizzled-related protein 5 (SFRP5) and Wingless-Type MMTV Integration Site Family Member 5a (Wnt5a) levels in Type 2 Diabetes Mellitus (T2DM) patients. Forty patients (16 women and 24 men) with type 2 diabetes participated in this double-blind, randomized, placebo-controlled clinical trial study. Participants were randomly assigned to receive 4000 IU vitamin D (n = 20) or placebo (n = 20) daily for 2 months. Anthropometric indices, fasting blood glucose (FBS), hemoglobin A1c (HbA1c), insulin, serum tumor necrosis factor (TNF)-α, Wnt5a, SFRP5, physical activity, lipid profile, dietary intake, and serum calcidiol were assessed at the baseline and after 8 weeks. In the group receiving Vitamin D, a significant increase in Calicidiol (15.03 ± 10.44 vs. 27.33 ± 11.2 ng/dl; P = < 0.001), SFRP5 (3.6 ± 0.46 vs. 3.98 ± 0.59 ng/ml; P = 0.01), and Wnt5a (0.33 ± 0.129 vs. 0.29 ± 0.047; P = 0.03) was observed. After two months supplementation, there were significant between-group differences in Calicidiol (27.33 ± 11.2 vs. 17.9 ± 12.95 ng/dl; P = 0.01), TNF-α (89.22 ± 34.28 vs. 164.93 ± 120.45 ng/ml; P = 0.006), Wnt5a (0.29 ± 0.047 vs. 0.33 ± 0.09; P = 0.04), and HbA1c (6.6 ± 0.96 % vs. 7.64 ± 1.15 %; = 0.002). Moreover, the net changes (end - baseline) of Calicidiol (P = < 0.001), SFRP5 (P = 0.04), Wnt5a (P = 0.005), TNF-α (P = 0.01), insulin (P = 0.03), and QUICKI (P = 0.01) was significant between the groups. There were no significant effects on FBS and homeostasis model of assessment-estimated insulin resistance (HOMA-IR). 8 weeks of vitamin D3 supplementation for patients with type 2 diabetes may increase serum anti-inflammatory adipokine SFRP5 but decrease serum pro-inflammatory Wnt5a and TNF-α.
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http://dx.doi.org/10.1024/0300-9831/a000509DOI Listing
February 2018

The Effect of Vitamin D on Cellular Pathways of Diabetic Nephropathy.

Rep Biochem Mol Biol 2019 Jan;7(2):217-222

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

Background: Diabetic nephropathy is one of the most important microvascular complications and a major cause of morbidity and mortality in diabetic patients. This study was designed to investigate the effect of vitamin D on the expression of three key genes involved in the development of diabetic nephropathy.

Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups. The first group served as control and the other two groups received intraperitoneal injections of 45 mg/kg STZ to develop diabetes. The groups were treated for four weeks either with placebo or two vitamin D injections of 20,000 IU/kg. Serum glucose, insulin, and HbA1c levels, and AGE cellular receptor (), aldose reductase () and glutamine: fructose-6-phosphate aminotransferase () gene expression were assessed in kidney tissue at the end of the experiment.

Results: Vitamin D treatment resulted in a significant increase in insulin concentration, which could improve hyperglycaemia in diabetic rats. Serum HbA1c decreased slightly but insignificantly following the vitamin D injections. In addition, expression of , a key regulatory enzyme in the hexosamine pathway, was significantly reduced following vitamin D administration.

Conclusion: Vitamin D may reduce diabetic nephropathy not only by improving blood glucose and insulin levels, but also by modulating hexosamine pathways in kidney.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374056PMC
January 2019

The Neuromodulatory Effects of ω-3 Fatty Acids and Nano-Curcumin on the COX-2/ iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms.

Endocr Metab Immune Disord Drug Targets 2019 ;19(6):874-884

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

Background: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine's neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of ω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients.

Methods: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded.

Results: The results of the present trial showed that ω-3 fatty acids and nano-curcumin can reinforce each other's effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05).

Conclusion: These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.
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http://dx.doi.org/10.2174/1871530319666190212170140DOI Listing
February 2020

Effect of Eicosapentaenoic Acid Supplementation on Paraoxonase 2 Gene Expression in Patients with Type 2 Diabetes Mellitus: a Randomized Double-blind Clinical Trial.

Clin Nutr Res 2019 Jan 28;8(1):17-27. Epub 2019 Jan 28.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14155-6446, Iran.

Type 2 diabetes mellitus (T2DM) is recognized as one of the most prevalent metabolic diseases, and it is mostly associated with oxidative stress, atherosclerosis and dyslipidemia. Paraoxonase 2 (PON2) due to its antioxidant properties may play a role in the atherosclerosis development. Although long-chain omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) have been shown to reduce the risk of cardiovascular disease, the exact mechanism of action is still unknown. Our goal in this study was to determine the effect of EPA administration on gene expression of PON2 in patients with T2DM. Present study was a randomized, controlled double-blind trial. Thirty-six patients with T2DM were randomly allocated to receive 2 g/day EPA (n = 18) or placebo (n = 18) for 8 weeks. There were no significant differences between 2 groups concerning demographic or biochemical variables, and dietary intakes as well (p > 0.05). However, patients received EPA showed a significant increase in the gene expression of PON2 compared with placebo group (p = 0.027). In addition, high-density lipoprotein cholesterol increased and fasting blood sugar decreased significantly after EPA supplementation compared with control group. Taken together, supplementation with 2 g/day EPA could be atheroprotective via the upregulation of PON2 in patients with T2DM.

Trial Registration: ClinicalTrials.gov Identifier: NCT03258840.
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http://dx.doi.org/10.7762/cnr.2019.8.1.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355950PMC
January 2019

Effect of coenzyme Q10 supplementation on clinical features of migraine: a systematic review and dose-response meta-analysis of randomized controlled trials.

Nutr Neurosci 2020 Nov 6;23(11):868-875. Epub 2019 Feb 6.

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

: Coenzyme Q10 is an antioxidant and an essential mitochondrial cofactor which has been suggested to improve the clinical features of migraine. Several randomized clinical trials have examined the effects of Coenzyme Q10 on migraine with inconclusive results. The aim of this systematic review and meta-analysis was to evaluate the impact of Coenzyme Q10 supplementation on the frequency, severity, and duration of migraine attacks. : A systematic review of the literature was conducted using ISI Web of Science, PubMed, Cochrane library and Scopus to identify eligible studies up to April 2018. Studies included were randomized clinical trials of Coenzyme Q10 supplementation that reported the frequency, severity, or duration of migraine attacks as a primary outcome. A meta-analysis of eligible studies was performed using the fixed effects model or the random effects model to estimate pooled effect size. : Four randomized clinical trials with 221 participants were included. Coenzyme Q10 supplementation significantly reduced the frequency of migraine attacks (weighted mean difference: -1.87 attacks/month, 95% CI: -2.69 to -1.05,  < 0.001) without significant heterogeneity among the studies ( = 36.6%,  = 0.192). Coenzyme Q10 supplementation had no significant effect on severity (weighted mean difference: -2.35 visual analog scale score, 95% CI: -5.19 to 0.49,  = 0.105) and duration of migraine attacks (weighted mean difference: -6.14 h, 95% CI: -13.14 to 0.87,  = 0.086) with high heterogeneity. : Pooled analyses of available randomized clinical trials suggest that Coenzyme Q10 supplementation may reduce the frequency of migraine attacks per month without affecting the severity or duration of migraine attacks.
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http://dx.doi.org/10.1080/1028415X.2019.1572940DOI Listing
November 2020

Resolvin D1 impacts on insulin resistance in women with polycystic ovary syndrome and healthy women.

Diabetes Metab Syndr 2019 Jan - Feb;13(1):660-664. Epub 2018 Nov 15.

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

Aims: The aim of this study was to determine the association between the intake of omega-3 PUFAs and the serum level of resolvin D1 and insulin resistance in women with Polycystic Ovary Syndrome (PCOS) compared to healthy women.

Methods: A cross-sectional study was conducted in 2015-2016 in Tehran, Iran, among females referred to the infertility clinic at Valie-Asr Reproductive Health Research Centre. Thirty-one patients with PCOS (according to the criteria of the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM)) and 29 healthy, normal cycling (NC) women of similar age, weight and height were enrolled. Anthropometric measurements, levels of resolvin D1, fasting insulin, glucose levels and insulin resistance index (HOMA) for each of the patients were determined.

Results: Intakes of macronutrients (protein, carbohydrates, and total fat) and omega-3 PUFAs were higher in the PCOS group compared to the control group; also, the PCOS group had significantly higher resolvin D1, fasting insulin, glucose levels and HOMA when compared with the control group. Moreover, resolvin D1 correlated negatively with HOMA and fasting insulin levels among both the PCOS and control women.

Conclusion: PCOS is associated with insulin resistance. We showed that omega-3 PUFAs can increase the synthesis of resolvin D1. Resolvin D1 is involved in insulin sensitivity by affecting insulin signaling and inflammatory pathways. Therefore, it can be a contributing factor in reducing insulin resistance in PCOS patients.
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http://dx.doi.org/10.1016/j.dsx.2018.11.018DOI Listing
May 2019