Molecular anti-inflammatory mechanisms of retinoids and carotenoids in Alzheimer's disease : a review of current evidence

Alzheimer’s disease (AD) is considered as one of the most prevalent neurodegenerative disorders characterized by progressive loss of mental function and ability to learn. AD is a multifactorial disorder. Various hypotheses are suggested for the pathophysiology of AD including “Aβ hypothesis,” “tau hypothesis,” and “cholinergic hypothesis.” Recently, it has been demonstrated that neuroinflammation is involved in the pathogenesis of AD. Neuroinflammation causes synaptic dysfunction and neuronal death within the brain. Excessive production of pro-inflammatory mediators induces Aβ peptide production/accumulation and hyperphosphorylated tau generating inflammatory molecules and cytokines. These inflammatory molecules disrupt blood–brain barrier integrity and increase the production of Aβ42 oligomers. Retinoids and carotenoids are potent antioxidants and anti-inflammatory agents having neuroprotective properties. They are able to prevent disease progression through several mechanisms such as suppression of Aβ peptide production/accumulation, oxidative stress, and pro-inflammatory mediator’s secretion as well as improvement of cognitive performance. These observations, therefore, confirm the neuroprotective role of retinoids and carotenoids through multiple pathways. Therefore, the administration of these nutrients is considered as a promising approach to the prevention and/or treatment of AD in the future. The aim of this review is to present existing evidences regarding the beneficial effects of retinoids and carotenoids on AD’s risk and outcomes, seeking the mechanism of their action

Mechanisms of action of ginger in nuclear factor-kappaB signaling pathways in diabetes

Diabetes mellitus is considered a metabolic disorder characterized by high blood sugar. Active disease is associated with low grade chronic inflammation resulting from the enhanced release of inflammatory mediators such as interleukin (IL)-1 β, IL-6, induced nitric oxide synthase, and cyclooxygenase-2 enzymes that lead to insulin resistance and disease progression. Nuclear factor kappa-B (NF-κB) is a key mediator involved in the inflammatory process which plays an important role in the inflammatory pathogenesis of diabetes. Based on recent evidence, ginger—which contains many phytochemicals—is believed to exert anti-inflammatory properties through multiple mechanisms, such as probably inhibiting the activation of NF-κB signaling pathway. It can thus be a target agent in the treatment and control of diabetes. It appears that ginger may be a complementary agent in diabetes treatment by targeting the NF-κB cascade pathway and exerting antioxidant or anti-inflammatory actions. In this context, this review aims to present the recent evidence regarding the mechanisms of action of ginger in NF-κB signaling pathways in diabetes mellitus

Comparison of Cytokine Expression in Multiple Sclerosis Patients and Healthy Volunteers

Multiple sclerosis (MS) is an autoimmune disease with the impaired balance of CD4+T cells. This trial is a descriptive study to evaluate the expression of CD4+T cell cytokines, interleukin (IL) ‑2, IL‑4, IL‑17, TGF‑β, and respectively related transcription factors, including T-bet, GATA3, RORγt and FoxP3 in MS patients. Sixteen relapsing-remitting MS (RRMS) patients receiving interferon beta (IFN-β)-1a in the stable phase of the disease and 14 healthy control volunteers (HCs) were enrolled in this study. The expression of cytokines and transcription factors was evaluated in peripheral blood mononuclear cells (PBMCs) of patients using real time PCR. The results of this study showed that the expression of IL-2 (P≤0.05), IL-4 (P≤0.05), IL-17 (P≤0.05) and RORγt (P≤0.01) in PBMCs of RRMS patients were significantly higher than those in HCs. The expression of TGF‑β, GATA3, and FoxP3 were higher but the RORγt expression was lower in the patients than HCs without reaching significant value. Observed results indicated differences in immune system cytokines of healthy volunteers and the patients that were in the stable phase and under immunomodulatory therapy especially in proinflammatory mediators. Therefore, any therapeutic strategy to restore the immune system balance is desirable in RRMS patients

The omega-3 and Nano-curcumin effects on vascular cell adhesion molecule (VCAM) in episodic migraine patients: a randomized clinical trial

Objective The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.Medicine, Faculty ofNon UBCCellular and Physiological Sciences, Department ofReviewedFacultyResearche

The Effect of Vitamin a Supplementation on Disease Progression, Cytokine Levels and Gene Expression in Multiple Sclerotic Patients: Study Protocol For a Randomized Controlled Trial

Multiple Sclerosis (MS) is a chronic inflammatory disease that leads to degeneration of the brain and spinal tissue. Imbalances of CD4+ T cells including Thelper1 (Th1)/Thelper2 (Th2) and Thelper17 (Th17)/Tregulatory (Treg), their secreted cytokines and gene expressions, are important aspects of in immunopathogenesis of MS. Vitamin A and its metabolites can regulate the immune system and appears to be effective in preventing progression of the autoimmune disease such as MS. Disease progression was evaluated By Magnetic Resonance Imaging (MRI), Expanded Disability States Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) tests. Cytokine levels were measured using ELISA kits and gene expression was quantified by Real time PCR (RT-PCR) system. According to the difference between the epidemiological and clinical data on the relationship between vitamin A and immune system regulation, this study of the first time assesses Immune function as well as gene expression and progression of the disease following administration of vitamin A supplement