Are levels of adipokines and micronutrients different in male adult smokers and non-smokers? A case-control study.

OBJECTIVE: Smoking is a common public problem leading to increases in oxidative stress and decreases in the levels of some micronutrients, finally affecting adipokine levels. The aim of this study was to compare the serum levels of omentin (intelectin-1), chemerin, TNF-α, and some micronutrient intakes in male smokers and non-smokers. METHODS: 40 male smokers and 40 male non-smokers with a mean age of 38.6±14.1 years were included in this study. Serum levels of omentin, chemerin, and TNF-α were measured. To calculate the daily intake of energy, carbohydrate, protein, fat, and some of the micronutrients, the 24-h recall and semi-quantitative food frequency questionnaire (FFQ) was used. RESULTS: Omentin, chemerin, and TNF-α levels in male smokers were lower than non-smokers, but these differences were not statistically significant. However, after adjustment for total and saturated fat intakes and age, omentin (ß=138.4, p=0.027) and TNF-α (ß=144.5, p=0.015) revealed significant differences. CONCLUSION: The serum levels of omentin, chemerin, TNF-α, and some micronutrient intakes were not significantly different between smokers and non-smokers. Further population studies are needed to clarify this subject.

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

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.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences.

OBJECTIVE: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer's, Parkinson's, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. METHODS: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. RESULTS: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1ß, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. CONCLUSION: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

A Novel Combination of ω-3 Fatty Acids and Nano-Curcumin Modulates Interleukin-6 Gene Expression and High Sensitivity C-reactive Protein Serum Levels in Patients with Migraine: A Randomized Clinical Trial Study.

BACKGROUND: Migraine is a disabling neuroinflammatory condition characterized by increasing the levels of interleukin (IL)-6, a proinflammatory cytokine and C-reactive protein (CRP) which considered as a vascular inflammatory mediator, disrupting the integrity of blood-brain barrier and contributing to neurogenic inflammation, and disease progression. Curcumin and ω-3 fatty acids can exert neuroprotective effects through modulation of IL-6 gene expression and CRP levels. The aim of present study is the evaluation of combined effects of ω-3 fatty acids and nano-curcumin supplementation on IL-6 gene expression and serum level and hs-CRP levels in migraine patients. METHODS: Eighty episodic migraine patients enrolled in the trial and were divided into four groups as 1) combination of ω-3 fatty acids (2500 mg) plus nano-curcumin (80 mg), 2) ω-3 (2500 mg), 3) nanocurcumin (80 mg), and 4) the control (ω-3 and nano-curcumin placebo included oral paraffin oil) over a two-month period. At the beginning and the end of the study, the expression of IL-6 from peripheral blood mononuclear cells and IL-6 and hs-CRP serum levels were measured, using a real-time PCR and ELISA methods, respectively. RESULTS: The results showed that both of ω-3 and nano-curcumin down-regulated IL-6 mRAN and significantly decreased the serum concentration. hs-CRP serum levels significantly decrease in combination and nano-curcumin within groups (P<0.05). An additive greater reduction of IL-6 and hs-CRP was observed in the combination group suggested a possible synergetic relation. CONCLUSION: It seems that ω-3 fatty acids and curcumin supplementation can be considered a new promising target in migraine prevention.

Vitamin D's Molecular Action Mechanism in Attention-Deficit/ Hyperactivity Disorder: A Review of Evidence.

BACKGROUND & OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder characterized by hyperactivity, impulsivity and inattention. Children with ADHD have challenges with learning, behavior and psychosocial adjustments, sometimes retained into adulthood. The exact etiology of ADHD is unknown, and the pathophysiology of this disease is complex. Several hypotheses have been raised regarding ADHD pathogenesis, including serotonergic and catecholaminergic signalling pathway dysfunction, neurotropic-related factors, oxidative stress, or neuroinflammation. Vitamin D has an important protective effect against inflammation, oxidative stress and certain neurotrophic factors and neurotransmitter, as well as facilitating dopaminergic and serotonergic functions. Vitamin D levels in children with ADHD are lower than in healthy children, and thus may be involved in the pathogenesis of ADHD. These observations, therefore, confirm the neuroprotective role of vitamin D through multiple molecular mechanisms and can be considered as a promising target in understanding ADHD pathology. CONCLUSION: In this context, the present study reviews the molecular pathways of vitamin D in ADHD patients.

Worldwide prevalence of familial multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Several studies have suggested that the existence of a history of multiple sclerosis (MS) in family, is one of the predisposing factors for MS. Based on our knowledge, the review and estimation of the prevalence of familial multiple sclerosis (FMS) in the world has not been reported up to now. This study is a systematic review and a meta-analysis of FMS prevalence in the world. METHODS: Two researchers searched "epidemiology" or "prevalence" or "incidence" and "familial multiple sclerosis" as relevant keywords in international databases such as PubMed, web of science and Scopus up to 2016. MedCalc Version 15.8 was used to estimate the pooled prevalence of FMS. (PROSPERO ID = CRD42016033016) RESULTS: From the 184 total articles found from 1954 to 2016, we pooled and analyzed the data of 17 final eligible studies, according to the inclusion criteria. The prevalence of FMS was estimated as 12.6% within a total sample size of 14,619 MS patients in the world as of 95% confidence interval (CI: 9.6-15.9). CONCLUSION: We detected significant heterogeneity from Hungary to Saskatchewan for FMS prevalence that was not latitude and ethnicity dependent. This highlighted the accumulation effects of genetic and environment on FMS prevalence. Pooled prevalence of FMS in MS population was calculated 12.6% by random effect in the world.

The Combined Effects of ω -3 Fatty Acids and Nano-Curcumin Supplementation on Intercellular Adhesion Molecule-1 (ICAM-1) Gene Expression and Serum Levels in Migraine Patients.

BACKGROUND: Migraine is an episodic headache, which is an endothelial disorder with neurological inflammation. Intercellular Adhesion Molecule-1 (ICAM-1), as an endothelial factor, leads to the adhesion of leukocytes to the walls of the cerebral blood vessels, which is an important step in the inflammation process. Curcumin and omega-3 fatty acids, by affecting transcription factors, can regulate the gene expression and serum levels of ICAM-1. Thus, this study aimed to evaluate the synergistic effects of ω-3 fatty acids and nano-curcumin on ICAM-1 gene expression and serum levels in migraine patients. METHOD: This clinical trial study was conducted on 72 episodic migraine patients in 4 groups for 2 months, with patients receiving ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo during the study. At the beginning and end of the study, the gene expression and serum level of ICAM-1 were measured by real-time PCR and ELISA. RESULT: The results showed no significant change in ICAM-1 gene expression in any of the 4 groups. The ICAM-1 serum concentration in the combination group, and omega-3 alone, showed a significant reduction at the end of the study compared to the beginning. In addition, a significant reduction in attack frequency was observed in the combination group. CONCLUSION: Considering the results of supplementation with omega-3 fatty acids plus curcumin led to reductions of both attack frequency and ICAM-1 serum level in patients, it seems that supplementation with these two nutrients not only can lead to improvements in the function of metabolic pathways, but can also be used effectively as a treatment or prevention of migraine complications.

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

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.

Dietary Intake and Serum Level of Carotenoids in Lung Cancer Patients: A Case-Control Study.

The aim of this study was to compare the dietary intake and serum levels of some selected carotenoids of lung cancer patients with healthy subjects. Thirty-five lung cancer patients and 33 healthy people were enrolled into this case-control study. Daily intake of nutrients was estimated using a semiquantitative food frequency questionnaire and a 3-day 24-h food recall questionnaire. The concentration of serum beta-carotene and lycopene were analyzed using a high performance liquid chromatography method. Case and control groups did not differ by the means of age, gender, smoking habits, weight, body mass index, mean daily energy intake, mean daily fat intake, and the percentage of daily energy provided by fat to total daily energy intake. The beta-carotene and lycopene intake of the case subjects was 96% and 195% greater than that of the control subjects. Daily intake of fruits and vegetables in the cancer group was higher than the control group. However, the serum concentration of 118% beta-carotene and 60% lycopene were higher in the control group. Despite a higher daily dietary intake of beta-carotene and lycopene by lung cancer patients, serum beta-carotene and lycopene concentrations were significantly lower than the group without cancer.

Dietary intake of nutrients and its correlation with fatigue in multiple sclerosis patients.

BACKGROUND: The role of nutrition in the progression of multiple sclerosis (MS) and related complications such as fatigue has been reported by several studies. The aim of this study is the assessment of nutritional status and its relationship with fatigue in multiple sclerosis patients. METHODS: This is a cross-sectional study, in which 101 relapsing-remitting MS patients were enrolled. The fatigue status was determined using the validated Persian version of of the Modified Fatigue Impact Scale (MFIS). Dietary intake was assessed using a 3-day food record questionnaire and compared to dietary reference intake (DRI) values. Association between variables was determined using Pearson Correlation Coefficient. RESULTS: In the preset study, 25 men and 76 women (total = 101) were enrolled. Analysis of dietary intake showed that daily intake of vitamin D, folate, calcium, and magnesium were significantly lower than DRI in all of patients. In men, zinc intake was significantly lower than DRI; while, in women, iron was significantly below the DRI level. After adjusting for energy, MFIS and its physical subscale were highly correlated with intake of folate and magnesium. CONCLUSION: Our findings support that lower magnesium and folate diets are correlated with higher fatigue scores in MS patients.

In vitro effect of human serum and fetal calf serum on CD4+ T cells proliferation in response to myelin oligodendrocyte glycoprotein (MOG) in correlation with RBP/TTR ratio in multiple sclerotic patients.

Myelin oligodendrocyte glycoprotein (MOG) is one of the autoantigens used in evaluation of the CD4(+) T cells proliferation response in multiple sclerotic patients. In cell culture, human serum (HS) is one of the promising substitutions for fetal calf serum (FCS) that can induce different autoreactivity of T cells and fluctuation of autoantibody production from B cells. Because of immunomodulatory function of vitamin A, we examined the effect of HS and FCS on CD4(+) T cells proliferation in response to MOG in correlation with serum retinol-binding protein (RBP)/transthyretin (TTR) ratio, as an indirect way to assess vitamin A status in multiple sclerotic patients. Patients' peripheral blood mononuclear cells were isolated and cultured in the presence of MOG as well as FCS and HS both separately and together. Cell proliferation was evaluated using BrdU kit. Serum RBP and TTR levels were measured by ELISA kit. FCS and HS increase CD4(+) T cell proliferation. RBP/TTR ratio has significant negative correlation with cell proliferation in the presence of MOG, HS, and FCS. HS with FCS provides an appropriate medium for autoreactivity and proliferation of CD4(+) T cells. Vitamin A has a crucial role in regulation of this pathway.