فهرست مطالب behrouz robat jazi

Previous studies noted an imbalance in T helper (Th) 17 and regulatory T cells (Tregs) in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis animal model. calcitriol, vitamin D's active form, was found to ameliorate EAE symptoms by favoring Tregss over Th17 cells, suggesting immunomodulatory effects. This study aimed to assess calcitriol's impact on EAE manifestations and cytokine profile in mice. In this study, we recruited twenty-eight C57BL/6 mice and divided them into 4 groups: healthy controls, EAE, EAE with calcitriol treatment, and healthy mice with calcitriol treatment. CD4+ T cells were isolated from splenocytes using magnetic-activated cell sorting. Real-time polymerase chain reaction was employed to quantify the genes associated with Th9 cells (i.e., SPI1 encoding PU.1 and IL9 encoding interleukin [IL]-9). Moreover, the levels of IL-17 and transforming growth factor beta (TGF-β) were evaluated through enzyme-linked immunosorbent assay in the supernatant of CD4+ T cell culture stimulated by anti-CD3 and anti-CD28 antibodies for 72 hours. In the supernatant of CD4+ T cell cultures, the levels of interleukin-17 (IL-17) were significantly increased, while the levels of transforming growth factor beta (TGF-β) were decreased in the EAE Group compared to the healthy control group. Calcitriol treatment reversed these changes and attenuated EAE symptoms, as confirmed in hematoxylin and eosin, and luxol fast blue stains. Notably, calcitriol increased IL9 gene expression in both EAE and healthy mice.  This study provides further evidence of the anti-inflammatory effects of calcitriol and its role in attenuating EAE.

T cells play an important role in the development and progression of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the present study, the immunomodulatory impacts of two Lactobacillus strains, L paracasei DSM 13434 and L plantarum DSM 15312, on the frequency and cytokine production of CD4+ T cells in MS patients were explored. Thirty MS patients were enrolled in this study. The CD4+ T cells were isolated, cultured, and exposed to the media containing cell-free supernatants of L plantarum (group1), L paracasei (group 2), the mixture group of cell-free supernatants of both probiotics (group 3), and vehicle (control) group (group 4). The frequencies of T helper (Th) 1, Th17, Th2, and T regulatory type 1 (Tr1) cells and mean fluorescent intensity (MFI) of the associated cytokines were assessed using flow cytometry. The levels of interleukin 17 (IL-17), transforming growth factor β (TGF-β), and interferon-gamma (IFN-γ) cytokines in supernatants of all groups were measured by enzyme-linked immunosorbent assay. The percentage of Th1 cells and the MFI of IFN-γ in Th1 cells (CD4+ IFN-γ+) in all three probiotic treatment groups were significantly decreased compared to the control group. However, no significant changes were observed in the proportion and MFI of Th2, Th17, and Tr1 cells. A significant decrease was observed in IL-17 secretion in the supernatant of cultured CD4+ T cells in all three treatment groups in comparison with control. The levels of TGF-β and IFN-γ were not significantly different among any of the study groups.  Collectively, cell-free supernatants of the lactobacilli showed an in vitro anti-inflammatory effect. However, further studies are needed to prove the real effects of probiotics on MS.

coronavirus disease of 2019 (COVID-19) can be complicated by acute respiratory distress syndrome (ARDS) and may be associated with cytokine storm and multiorgan failure. Anti-inflammatory agents, such as systemic corticosteroids, monoclonal antibodies, and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used for this purpose. In this study, we evaluated the immunomodulatory effect of mannuronic acid (M2000), which is a novel NSAID, on COVID-19-related cytokine storms. This study was conducted in vitro on blood samples of 30 COVID-19 patients who presented with ARDS to a referral center. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and incubated with phorbol myristate acetate for 24 hours. M2000 was administered with the dosages of 25 µg/well and 50 µg/well after 4 hours of incubation at 37°C. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess mRNA gene expression. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the supernatant PBMC levels of interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Both mRNA expression and the supernatant PBMC levels of IL-17, TNF-α, IL‑6, and IFN‑γ were decreased in PBMCs of COVID-19 patients treated with M2000 compared with the control  group. For the first time, it was observed that M2000 could be effective in alleviating the inflammatory cascade of COVID-19 patients based on an in vitro model. After further studies in vitro and in animal models, M2000 could be considered a novel NSAID drug in COVID-19 patients.

Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group.  During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.

The novel coronavirus disease of 2019 (COVID-19) appeared almost two years ago in China and quickly created a pandemic and affected all aspects of human life. The virus, termed SARS-CoV-2, is generally asymptomatic but contagious and might have originated from bats. Nowadays, the mechanisms underlying the infection and the incidence of SARS-CoV-2 are distinguishable from previous coronaviruses. Early diagnosis and supportive treatment are necessary to cure the patients with COVID-19. Early evidence recommended that children are just likely as adults to become infected with this novel virus. It is now established that children are more often show gastrointestinal manifestations than adults do, and many children affected by SARS-CoV-2 are asymptomatic. Over 300 vaccine projects are recently developed by the scientific community to treat COVID-19 disease; however, these vaccines might lose efficacy by a number of unpredicted issues, including the emergence of new SARS-CoV-2 mutants.

Due to the high prevalence and worldwide widespread of COVID-19, many studies are underway to find treatment modalities and develop new vaccines or antiviral substances to fight the virus. The COVID-19 pandemic is not only a challenge to global health but also has globally affected mental, social, and economic health. Moreover, the post-corona pandemic condition will undoubtedly have many Socioeconomic Challenges. This review study has been focused on epidemiology, virology, transmission methods, clinical features, laboratory findings, and prevalent mutations of the SARS-CoV-2 virus. We hope that information provided within this article will significantly benefit researchers currently investigating COVID-19 patients.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that leads to myelin degradation and neuronal damage. MS symptoms detrimentally affect the quality of life and expectancy in MS patients. It affects frequently peoples, aged between 18 and 40 years, with an incidence 2–3 times higher in women. . MS can be arranged conforming to its clinical course in four various types of MS could be distinguished: relapsing remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS) and progressive-relapsing MS. Experimental animal pattern for the MS disease that commonly used is Experimental autoimmune encephalomyelitis (EAE) .inflammation, demyelination, axonal loss and gliosis in EAE associated with interaction among a variety of immunopathological mechanisms. The results of immunological, histopathological, and genetic studies on MS patients suggest that autoimmunity plays an important role in the pathogenesis of this disease. Th17 cells are thought to play an important role in the onset of the early phase of MS, while Th1 cells are involved in the late stages of CNS inflammation. Decreased number of regulatory T cells as well as dysfunction of these cells have been observed in MS patients. The results of previous studies showed a significant association between dietary supplements and the onset and progression of the MS disease. Researchers in last years, becoming more interest about relationship among the dietary MS and supplementation.  Supplementation with Vitamin D, vitamin A, Curcumin, Omega-3 and omega-6 fatty acids improve the patientchr('39')s physiological symptoms and increase life expectancy and reduce the symptoms of MS. Vitamin D establish an essential fat-soluble vitamin obtained through exposure to sunlight as well as dietary origin such as animal protein, fish liver oil, and fortified dairy and cereal products. The cellular mechanisms of vitamin D are mediated by the Vitamin D receptor (VDR). VDR is one of transcription factor that belong  steroid superfamily of nuclear receptors .heterodimer form of Ligand-bound VDR  and retinoid X receptor (RXR), together becomes translocated to the nucleus where it performs its functions on gene regulation. The vitamin D effects are associated with cell type-specific and depend on VDR/ RXR binding, which is influenced by the cellular chromatin condition and the availability of interacting DNA-binding protein component. VDR/RXR as nuclear receptors associated with a diversity of coactivators and corepressors in cells and resulting in local epigenetic changes that have either permissive or repressive effects on gene expression. DNA methylation, histone modifications and expression of noncoding RNAs (ncRNAs), which is important for cell survival and its physiological function are epigenetic condition comprises highly interconnected mechanisms. Vitamin D has impact on histone modifications and VDR/RXR associations with deacetylases, histone methyl transferases and histone acetyltransferases that its access on DNA methylation is just beginning to emerge. Curcumin (diferuloylmethane) origin turmeric plant Curcuma longa and its derivatives known as curcuminoids have been identified to be effective in experimental studies. In addition, curcumin has been tested as an anti-inflammatory agent for treatment of cancers and other diseases. Curcumin exerts its beneficial effects by anti-oxidative, anti-proliferative and anti-inflammatory properties and is commonly used in traditional medicine to treat inflammation and promote wound healing.  Moreover, curcumin has been gradually used as an auxiliary drug for various diseases, such as cancer, arthritis, and immune diseases. Curcumin exerts its beneficial effects by anti-oxidative, anti-proliferative and anti-inflammatory properties and is commonly used in traditional medicine to treat inflammation and promote wound healing .Curcumin inhibits EAE in association with the inhibition of neural antigen-specific Th1 and Th17 cell differentiation. Curcumin modulates Th1/Th17 responses by acting directly on T cells and indirectly by attenuating IL-12/IL-23 production by antigen presenting cells (APCs) in EAE and can improve the severity of symptoms in the Spinal Cord Injury (SCI) model by modulating the mammalian target of rapamycin (mTOR) Pathway signaling.  Curcumin enhances neurotrophic factors and repair mechanisms in CNS via repair of myelin. The proteins and cells involved in the immune system have specific actions and role. The role of T-helper 17(Th17) cells and T regulatory (Treg) cells in MS pathogenesis, the effect of vitamin A, and of its active metabolite retinoic acid (RA), as well as the management of inflammation, have been well analyzed, mainly in in vitro studies. Also it is known that in MS, the balance between Th17 cells and Treg cells is diminished. Vitamin A may amend MS pathogenesis via several mechanisms. Those mechanisms include the reduction of inflammatory processes by re-balancing pathogenic (Th1, Th17, Th9) and immune-protective (Th2, Treg) cells, modulating the B-cell and dendritic cell functions, as well as increasing autoimmunity and regeneration tolerance in the CNS . The aim of this study was to investigate the importance of micronutrients and dietary supplements on the immune system in MS. Thus, vitamin A could be considered as a potential co-treatment agent in MS disease management. Data of this review study were collected from PubMed, Science Direct, and Google Scholar databases from 2000 to 2019 and keywords like “Multiple Sclerosis, Vitamin D, Calcitriol, Retinoic acid, Vitamin A, Curcumin, Omega 3 and Omega 6 fatty acids” were used in this search.

Autism Spectrum Disorders (ASD) refers to a group of neurodevelopmental abnormalities characterized by impairment in communication, social skills and eye contacts with restrictive interests and repetitive behaviors. Individuals with autism show variable reactions in sensitive situations. Some children have normal intelligence and some have intellectual disability, macrocephaly, microcephaly, developmental delay and/or epilepsy. The symptoms appear in infancy and early childhood and affect daily functioning. Recent studies suggest that approximately 1 in 54 children are affected by an autism spectrum disorder. Autism spectrum disorder is notably four times more common in boys than in girls. Many types of research have revealed that genetic and environmental factors are linked to ASD. Major susceptibility factors can play a critical role in the development of autistic behaviors. It is well accepted that ASD have a strong genetic predisposition; however, genes that cause neuropsychiatric disorders are unknown and more than 100 genes are involved in ASD patients. Several genetic factors, such as mitochondrial DNA (mtDNA) variations, have been linked to autistic behaviors. We searched the PubMed, Science Direct, Elsevier, SID, HGMD, SFARI and AUTDB databases for mitochondrial dysfunction associated with the development of autistic behaviors published between 2010 and 2020. The purpose of the search strategy was to obtain relevant studies that provided appropriate information. In 1985, Coleman and Blass made the first hypothesis associating ASD with high levels of lactate in the plasma of individuals with autistic behaviors. Studies showed that various biomarkers of mitochondrial disruption (alanine-to-lysine ratio, acylcarnitine) are altered in some cases with ASD. So far, a great deal of research has been carried out in the field of genetics, perinatal factors, immune and environmental factors affecting autistic behaviors, so that in the latest update of genes involved in human and animal models of autism (on AutDB and SFARI.GENE databases), about 2000 genes involved in the etiology of autism and autistic behaviors have been classified. This list contains many genes including mTOR, MECP2 and genes involved in mitochondrial function or responsible for mtDNA maintenance. Several pathogenic variations that cause defects in mitochondrial metabolic pathways can lead to alterations in neuronal circuits and neurotransmitter systems. Protein coding genes of the mitochondria are components of the respiratory oxidative phosphorylation chain. Oxidative phosphorylation is vital to the growing nerve cells. Studies show that the capacity of oxidative phosphorylation in granulocytes is significantly lower in autistic children, in comparison with normal children. There is evidence of modified immune function in neural systems. The antigen-antibody complexes can induce immune cell migration and stimulate neuro-inflammation. Several investigations revealed that an immune abnormality during pregnancy or postnatal environment results in psychiatric disorders. Immune system irregularities, including defects in T cell responses or Th1/Th2 cytokines, have been reported in individuals with psychiatric disorders, proposing that unusual immune functions in the brain may play an important role in a significant subset of children with autism. Furthermore, Interferons can also induce the expression of more than 300 genes, some of which are mitochondrial genes and some are nuclear genes involved in regulating mitochondrial function. Glucocorticoids can inhibit the production of certain cytokines, such as TNF-α, IL-2, IL-6, IL1β and IL-8, and also can alter the production of anti-inflammatory cytokines, such as IL-10, IL-4, and growth factor-β. Besides, nuclear- or mitochondrial-encoded oxidative phosphorylation subunits (OXPHOS) are regulated by glucocorticoids that their receptors have been identified in the mitochondria. In summary, immune system disorders can impair prenatal brain development or postnatal brain function, so that they can create causality with the ASD phenotype. Also, some maternal allergies during pregnancy, such as exposure to infections, can cause persistent and long-term changes in mitochondrial functions that can lead to autism-like behaviors. This study focused on some clinical aspects of mitochondrial dysfunction in ASD. Most children with autistic behaviors indicate mitochondrial dysfunction and enhanced oxidative stress. Published findings have revealed broad alterations in the immune and nervous systems of children with autistic behaviors. Detection of dependent factors related to ASD can help in the early intervention of these children to address psychological requirements. This article tries to give a useful summary of critical pathways involved in mitochondrial dysfunction in autistic behaviors. Data of this review will give a wide perspective to genetic factors in autism.