Exploring the complex interplay: gut microbiome, stress, and leptospirosis.

Leptospirosis, a re-emerging zoonotic disease, remains a significant global health concern, especially amid floods and disasters such as the Kakhovka Dam destruction. As is known, the stress that occurs in the conditions of military conflicts among civilian and military personnel significantly affects susceptibility to infectious diseases and possibly even influences their course. This review aims to explore how the gut microbiome and stress mediators (such as catecholamines and corticosteroids) might impact the leptospirosis disease course. The review opens new horizons for research by elucidating the connections between the gut microbiome, stress, and leptospirosis.

Exploring Leptospira interrogans FDAARGOS_203: Insights into AMR and Anti-Phage Defense.

Leptospira, which are known to be important disease-causing agents transmitted between animals and humans, result in significant illness and, in some cases, significant death in human populations. This purpose of this study was to examine the genomic structure of Leptospira interrogans serovar Copenhageni strain FDAARGOS_203 to identify the specific genetic factors that contribute to antimicrobial resistance (AMR) and defense against phages. The genome, consisting of two contigs totaling 4,630,574 base pairs, underwent thorough examination for protein-coding sequences, transfer RNA genes, and ribosomal RNA genes. A total of twenty-two antibiotic resistance genes that specifically target essential cellular processes such as cell wall synthesis, DNA replication, and protein synthesis have been identified. Significant among these were gidB, gdpD, and ggsA, each involved in separate aspects of antibiotic resistance. In addition, the investigation explored the defense mechanisms of bacteriophages, revealing the presence of defense islands that contain a range of anti-phage systems, including RM_Type_IV, PrrC, Borvo, CAS_Class1-Subtype-IC, and CAS_Class1-Subtype-IB. This comprehensive genomic analysis enhances our understanding of the molecular mechanisms that determine Leptospira's ability to adapt to various environments. The identified genetic factors linked to AMR and defense against phages not only enhance our scientific comprehension, but also provide a basis for focused interventions to reduce the impact of leptospirosis.

The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants.

Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro. We identified several novel, synergistic two-drug and three-drug combinations that demonstrated significant inhibition of enterovirus infections in vitro. Specifically, the triple-drug combination of pleconaril, rupintrivir, and remdesivir exhibited remarkable efficacy against echovirus (EV) 1, EV6, EV11, and coxsackievirus (CV) B5, in human lung epithelial A549 cells. This combination surpassed the effectiveness of single-agent or dual-drug treatments, as evidenced by its ability to protect A549 cells from EV1-induced cytotoxicity across seven passages. Additionally, this triple-drug cocktail showed potent antiviral activity against EV-A71 in human intestinal organoids. Thus, our findings highlight the therapeutic potential of the pleconaril-rupintrivir-remdesivir combination as a broad-spectrum treatment option against a range of enterovirus infections. The study also paves the way towards development of strategic antiviral drug combinations with virus family coverage and high-resistance barriers.

Exploring the interplay between posttraumatic stress disorder, gut microbiota, and inflammatory biomarkers: a comprehensive meta-analysis.

Introduction: Posttraumatic stress disorder (PTSD) is the most common mental health disorder to develop following exposure to trauma. Studies have reported conflicting results regarding changes in immune biomarkers and alterations in the abundance of bacterial taxa and microbial diversity in patients with PTSD. Aim: The purpose of this meta-analysis is to summarize existing studies examining gut microbiota characteristics and changes in immune biomarkers in patients with PTSD. Methods: Relevant studies were systematically searched in PubMed, Scopus, and Embase, published in English between January 1, 1960, and December 1, 2023. The outcomes included changes in abundance and diversity in gut microbiota (gut microbiota part) and changes in immune biomarkers (immune part). Results: The meta-analysis included a total of 15 studies, with 9 focusing on changes in inflammatory biomarkers and 6 focusing on changes in gut microbiota composition in patients with PTSD. No differences were observed between groups for all inflammatory biomarkers (P≥0.05). Two of the six studies found that people with PTSD had less alpha diversity. However, the overall Standardized Mean Difference (SMD) for the Shannon Diversity Index was not significant (SMD 0.27, 95% CI -0.62-0.609, p = 0.110). Regarding changes in abundance, in two of the studies, a significant decrease in Lachnospiraceae bacteria was observed. Conclusion: This meta-analysis provides a comprehensive overview of gut microbiota characteristics in PTSD, suggesting potential associations with immune dysregulation. Future research should address study limitations, explore causal relationships, and consider additional factors influencing immune function in individuals with PTSD. Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42023476590.

Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes.

COVID-19 remains a significant global concern, particularly for individuals with type 2 diabetes who face an elevated risk of hospitalization and mortality. Metformin, a primary treatment for type 2 diabetes, demonstrates promising pleiotropic properties that may substantially mitigate disease severity and expedite recovery. Our study of the gut microbiota and the mRNA expression of pro-inflammatory and anti-inflammatory T-lymphocyte subpopulations showed that metformin increases bacterial diversity while modulating gene expression related to T-lymphocytes. This study found that people who did not take metformin had a downregulated expression of FOXP3 by 6.62-fold, upregulated expression of RORC by 29.0-fold, and upregulated TBX21 by 1.78-fold, compared to the control group. On the other hand, metformin patients showed a 1.96-fold upregulation in FOXP3 expression compared to the control group, along with a 1.84-fold downregulation in RORC expression and an 11.4-fold downregulation in TBX21 expression. Additionally, we found a correlation with gut microbiota (F/B ratio and alpha-diversity index) and pro-inflammatory biomarkers. This novel observation of metformin's impact on T-cells and gut microbiota opens new horizons for further exploration through clinical trials to validate and confirm our data. The potential of metformin to modulate immune responses and enhance gut microbiota diversity suggests a promising avenue for therapeutic interventions in individuals with type 2 diabetes facing an increased risk of severe outcomes from COVID-19.

Exploring Paxlovid Efficacy in COVID-19 Patients with MAFLD: Insights from a Single-Center Prospective Cohort Study.

This study investigates the intricate interplay between Metabolic-associated Fatty Liver Disease (MAFLD) and COVID-19, exploring the impact of MAFLD on disease severity, outcomes, and the efficacy of the antiviral agent Paxlovid (nirmatrelvir/ritonavir). MAFLD, affecting a quarter of the global population, emerges as a potential risk factor for severe COVID-19, yet the underlying pathophysiological mechanisms remain elusive. This study focuses on the clinical significance of Paxlovid, the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States. Notably, outcomes from phase II/III trials exhibit an 88% relative risk reduction in COVID-19-associated hospitalization or mortality among high-risk patients. Despite conflicting data on the association between MAFLD and COVID-19 severity, this research strives to bridge the gap by evaluating the effectiveness of Paxlovid in MAFLD patients with COVID-19, addressing the scarcity of relevant studies.

Altered Blood Molecular Markers of Cardiovascular Function in Rats after Intrauterine Hypoxia and Drug Therapy.

Many children and adults who have suffered prenatal hypoxia at an early age develop many serious diseases. This disease is an actual problem of pediatric cardiology and little studied. The aim was to analyze the cardioprotective effect of L-arginine, Thiotriazoline, Angioline, and Mildronate on the cardiovascular system of rats after prenatal hypoxia. Methods: The experiments were carried out on 50 female white rats; intraperitoneal sodium nitrite solution was administered daily to pregnant female rats after 16 days at a dose of 50 mg/kg. Control pregnant rats received saline. The offspring were divided into groups: 1-intact; 2-the control group of rat pups after PH, treated daily with physiological saline; 3-six groups of rat pups after PH, treated daily from the 1st to the 30th day after birth. Heat shock protein HSP70 was determined by enzyme immunoassay, ST2 Nitrotyrosine, and eNOS was observed by ELISA. Results: Angiolin showed a high cardioprotective effect even a month after discontinuation of the drug, and after introduction, the highest decrease in ST2 nitrotyrosine was revealed. Thiotriazoline and L-arginine have an antioxidant effect and a positive effect on eNOS expression, increasing the concentration of HSP70. Mildronate increased the expression of eNOS and the concentration of HSP70 in the blood of experimental rats after a course of administration, but did not show an antioxidant effect and did not reduce the concentration of nitrotyrosine. The results obtained indicate the cardioprotective effect of modulators of the NO system with different mechanisms of action of drugs after prenatal hypoxia.

Cardioprotective Activity of Pharmacological Agents Affecting NO Production and Bioavailability in the Early Postnatal Period after Intrauterine Hypoxia in Rats.

Intrauterine hypoxia in newborns leads to a multifaceted array of alterations that exert a detrimental impact on the cardiovascular system. The aim of this research was to assess the cardioprotective effects of modulators of the nitric oxide (NO) system, including L-arginine, Thiotriazoline, Angiolin, and Mildronate, during the early postnatal period following intrauterine hypoxia. Methods: The study involved 50 female white rats. Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy. A control group of pregnant rats received saline instead. The resulting offspring were divided into the following groups: Group 1-intact rats; Group 2-rat pups subjected to prenatal hypoxia (PH) and daily treated with physiological saline; and Groups 3 to 6-rat pups exposed to prenatal hypoxia and treated daily from the 1st to the 30th day after birth. Nitrotyrosine levels, eNOS, iNOS, and NO metabolites were evaluated using ELISA; to measure the expression levels of iNOS mRNA and eNOS mRNA, a PCR test was utilized. Results: Angiolin enhances the expression of eNOS mRNA and boosts eNOS activity in the myocardium of rats with ischemic conditions. Arginine and particularly Thiotriazoline exhibited a consistent impact in restoring normal parameters of the cardiac nitroxidergic system following PH. Mildronate notably raised iNOS mRNA levels and notably reduced nitrotyrosine levels, providing further support for its antioxidative characteristics.

Boosted production of antibodies that neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following messenger RNA vaccination - a case study.

Vaccinated convalescents do not develop severe COVID-19 after infection with new SARS-CoV-2 variants. We questioned how messenger RNA (mRNA) vaccination of convalescents provides protection from emerging virus variants. From the cohort of 71 convalescent plasma donors, we identified a patient who developed immune response to infection with SARS-CoV-2 variant of 20A clade and who subsequently received mRNA vaccine encoding spike (S) protein of strain of 19A clade. We showed that vaccination increased the production of immune cells and anti-S antibodies in the serum. Serum antibodies neutralized not only 19A and 20A, but also 20B, 20H, 21J, and 21K virus variants. One of the serum antibodies (100F8) completely neutralized 20A, 21J, and partially 21K strains. 100F8 was structurally similar to published Ab188 antibody, which recognized non-conserved epitope on the S protein. We proposed that 100F8 and other serum antibodies of the patient which recognized non- and conserved epitopes of the S protein, could have additive or synergistic effects to neutralize various virus variants. Thus, mRNA vaccination could be beneficial for convalescents because it boosts production of neutralizing antibodies with broad-spectrum activity.

Association of Myocardial Changes and Gene Expression of the NFATC1 and NFATC4-Calcineurin Signaling Pathway in Children with Bicuspid Aortic Valve.

BACKGROUND: The role of NFATC gene expression in bicuspid aortic valve (BAV) progression is not fully understood. The aim of this study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV. METHODS: In 47 children with BAV, the standard Doppler echocardiographic characteristics were detected, and the expression of the NFATC1 and NFATC4 genes was studied. RESULTS: Posterior wall thickness in diastole (PWTd) and aortic valve peak pressure gradient (AoPPG) in BAV patients were significantly higher compared to healthy controls (PWTd median (min-max), 9 (7-10) mm vs. 7 (6-8) mm; and AoPPG median (min-max), 7.79 (2.98-15.09) mm Hg vs. 2.94 (2.42-3.72) mm Hg). The expression of the NFATC1 gene in BAV children was significantly higher compared to NFATC4 (NFATC1 median (min-max); 70.88 (8.79-106.51) e.u. vs. 7.72 (1.74-22.67) e.u., respectively p < 0.05). A significant correlation of NFATC1 expression with Ao found (R = +0.53, p < 0.05). In BAV patients with PWTd > 8 mm and Ao > 21 mm the NFATC1 expression was significantly higher compared to those with PWTd ≤ 8 mm and Ao ≤ 21 mm (NFATC1 median (min-max); 45.49 (5.01-101.52) e.u. vs. 15.53 (2.36-44.40) e.u., p < 0.05 and 81.11 (20.27-101.10) e.u. mm vs. 12.16 (2.40-45.49) e.u., p < 0.05, respectively). CONCLUSION: In children with BAV the high expression of the NFATC1 calcineurin signaling pathway gene is associated with elevated PWTd and Ao.

Genetic Predictors of Comorbid Course of COVID-19 and MAFLD: A Comprehensive Analysis.

Metabolic-associated fatty liver disease (MAFLD) and its potential impact on the severity of COVID-19 have gained significant attention during the pandemic. This review aimed to explore the genetic determinants associated with MAFLD, previously recognized as non-alcoholic fatty liver disease (NAFLD), and their potential influence on COVID-19 outcomes. Various genetic polymorphisms, including PNPLA3 (rs738409), GCKR (rs780094), TM6SF2 (rs58542926), and LYPLAL1 (rs12137855), have been investigated in relation to MAFLD susceptibility and progression. Genome-wide association studies and meta-analyses have revealed associations between these genetic variants and MAFLD risk, as well as their effects on lipid metabolism, glucose regulation, and liver function. Furthermore, emerging evidence suggests a possible connection between these MAFLD-associated polymorphisms and the severity of COVID-19. Studies exploring the association between indicated genetic variants and COVID-19 outcomes have shown conflicting results. Some studies observed a potential protective effect of certain variants against severe COVID-19, while others reported no significant associations. This review highlights the importance of understanding the genetic determinants of MAFLD and its potential implications for COVID-19 outcomes. Further research is needed to elucidate the precise mechanisms linking these genetic variants to disease severity and to develop gene profiling tools for the early prediction of COVID-19 outcomes. If confirmed as determinants of disease severity, these genetic polymorphisms could aid in the identification of high-risk individuals and in improving the management of COVID-19.

Metformin Therapy Changes Gut Microbiota Alpha-Diversity in COVID-19 Patients with Type 2 Diabetes: The Role of SARS-CoV-2 Variants and Antibiotic Treatment.

The gut microbiota play a crucial role in maintaining host health and have a significant impact on human health and disease. In this study, we investigated the alpha diversity of gut microbiota in COVID-19 patients and analyzed the impact of COVID-19 variants, antibiotic treatment, type 2 diabetes (T2D), and metformin therapy on gut microbiota composition and diversity. We used a culture-based method to analyze the gut microbiota and calculated alpha-diversity using the Shannon H' and Simpson 1/D indices. We collected clinical data, such as the length of hospital stay (LoS), C-reactive protein (CRP) levels, and neutrophil-to-lymphocyte ratio. We found that patients with T2D had significantly lower alpha-diversity than those without T2D. Antibiotic use was associated with a reduction in alpha-diversity, while metformin therapy was associated with an increase. We did not find significant differences in alpha-diversity between the Delta and Omicron groups. The length of hospital stay, CRP levels, and NLR showed weak to moderate correlations with alpha diversity. Our findings suggest that maintaining a diverse gut microbiota may benefit COVID-19 patients with T2D. Interventions to preserve or restore gut microbiota diversity, such as avoiding unnecessary antibiotic use, promoting metformin therapy, and incorporating probiotics, may improve patient outcomes.

The F/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin.

The pandemic of COVID-19 has highlighted the intricate relationship between gut microbiome and overall health. Recent studies have shown that the Firmicutes/Bacteroidetes ratio in the gut microbiome may be linked to various diseases including COVID-19 and type 2 diabetes (T2D). Understanding the link between gut microbiome and these diseases is essential for developing strategies for prevention and treatment. In this study, 115 participants were recruited and divided into three groups: 1st group: T2D patients and healthy controls, 2nd group: COVID-19 patients with and without T2D, 3rd group: T2D patients with COVID-19 treated with or without metformin. Gut microbial composition at the phylum level was assessed using qRT-PCR with universal primers targeting the bacterial 16 S rRNA gene and specific primers for Firmicutes and Bacteroidetes. Data was analyzed using one-way ANOVA, logistic regression, and Spearman's rank correlation coefficient. The study found that the ratio of Firmicutes to Bacteroidetes (F/B) was higher in patients with both T2D and COVID-19 compared to those with only T2D or COVID-19. Additionally, the F/B ratio was positively correlated with C-reactive protein (CRP) in T2D and COVID-19 patients. The study also suggests that metformin treatment may affect this correlation. Logistic regression analysis showed that the F/B ratio was significantly associated with CRP. These findings suggest that the F/B ratio may be a potential biomarker for inflammation in T2D and COVID-19 patients and metformin treatment may have an effect on the correlation between F/B and CRP levels.

The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence.

The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. With our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a pervasive public health concern intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and MAFLD is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among MAFLD patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of MAFLD on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.

Therapeutic Effectiveness of Interferon-α2b against COVID-19 with Community-Acquired Pneumonia: The Ukrainian Experience.

Despite several targeted antiviral drugs against SARS-CoV-2 currently being available, the application of type I interferons (IFNs) still deserves attention as an alternative antiviral strategy. This study aimed to assess the therapeutic effectiveness of IFN-α in hospitalized patients with COVID-19-associated pneumonia. The prospective cohort study included 130 adult patients with coronavirus disease (COVID-19). A dose of 80,000 IU of IFN-α2b was administered daily intranasally for 10 days. Adding IFN-α2b to standard therapy reduces the length of the hospital stay by 3 days (p < 0.001). The level of CT-diagnosed lung injuries was reduced from 35% to 15% (p = 0.011) and CT injuries decreased from 50% to 15% (p = 0.017) by discharge. In the group of patients receiving IFN-α2b, the SpO2 index before and after treatment increased from 94 (92-96, Q1-Q3) to 96 (96-98, Q1-Q3) (p < 0.001), while the percentage of patients with normal saturation increased (from 33.9% to 74.6%, p < 0.05), but the level of SpO2 decreased in the low (from 52.5% to 16.9%) and very low (from 13.6% to 8.5%) categories. The addition of IFN-α2b to standard therapy has a positive effect on the course of severe COVID-19.

Tyrosine Kinase Inhibitors Target B Lymphocytes.

Autoimmune disorders and some types of blood cancer originate when B lymphocytes malfunction. In particular, when B cells produce antibodies recognizing the body's proteins, it leads to various autoimmune disorders. Additionally, when B cells of various developmental stages transform into cancer cells, it results in blood cancers, including multiple myeloma, lymphoma, and leukemia. Thus, new methods of targeting B cells are required for various patient groups. Here, we used protein kinase inhibitors alectinib, brigatinib, ceritinib, crizotinib, entrectinib, and lorlatinib previously approved as drugs treating anaplastic lymphoma kinase (ALK)-positive lung cancer cells. We hypothesized that the same inhibitors will efficiently target leukocyte tyrosine kinase (LTK)-positive, actively protein-secreting mature B lymphocytes, including plasma cells. We isolated CD19-positive human B cells from the blood of healthy donors and used two alternative methods to stimulate cell maturation toward plasma cells. Using cell proliferation and flow cytometry assays, we found that ceritinib and entrectinib eliminate plasma cells from B cell populations. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. More generally, we concluded that several drugs previously developed to treat ALK-positive malignant cells can be also used to treat LTK-positive B cells.

Efficacy of interferon alpha for the treatment of hospitalized patients with COVID-19: A meta-analysis.

Introduction: IFN-α intervention may block SARS-CoV-2 replication and normalize the deregulated innate immunity of COVID-19. Aim: This meta-analysis aimed to investigate the efficacy of interferon IFN-α-containing regimens when treating patients with moderate-to-severe COVID-19. Material and methods: PubMed, SCOPUS, and ClinicalTrials.gov were searched from inception to 15 January 2022. A systematic literature search was conducted by applying relevant terms for 'COVID-19' and 'interferon-α'. The primary outcome enclosed the all-cause hospital mortality. The secondary outcomes constituted the length of hospital stay; hospital discharge; nucleic acid negative conversion. Results: Eleven studies are enclosed in the meta-analysis. No significant difference in the all-cause mortality rate was found between the study and control groups (OR 0.2; 95% CI 0.05-1.2; I2 = 96%). The implementation of interferon did not influence such outcomes as the length of hospital stay (OR 0.9; 95% CІ, 0.3-2.6; I2 = 91%), nucleic acid negative conversion (OR 0.8; 95% CI, 0.04-17.2; I2 = 94%). Nevertheless, IFN-α treatment resulted in a higher number of patients discharged from the hospital (OR 26.6; 95% CІ, 2.7-254.3; I2 = 95%). Conclusions: Thus, IFN-α does not benefit the survival of hospitalized COVID-19 patients but may increase the number of patients discharged from the hospital. Systematic review registration: www.crd.york.ac.uk/prospero, identifier (CRD42022374589).

Weil's Disease-Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota.

Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. In this review, we have described in detail the immunopathogenesis of leptospirosis, the influence of cytokines, genetic susceptibility on the course of the disease, and the evasion of the immune response. These data are combined with information about immunological and pathomorphological changes in the kidneys, liver, and lungs, which are most affected by Weil's disease. The review also suggests a possible role of the gut microbiota in the clinical course of leptospirosis, the main mechanisms of the influence of gut dysbiosis on damage in the liver, kidneys, and lungs through several axes, i.e., gut-liver, gut-kidney, and gut-lungs. Modulation of gut microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.

Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses.

Multiple Sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group, received PBS orally; prevention group, oral administration of MOG35-55 two weeks before EAE induction; treatment group, oral administration of MOG35-55 after EAE induction). MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, and reduction in pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-ß, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.