Interaction of the Gut Microbiome and Immunity in Multiple Sclerosis: Impact of Diet and Immune Therapy.

The bidirectional communication between the gut and central nervous system (CNS) through microbiota is known as the microbiota-gut-brain axis. The brain, through the enteric neural innervation and the vagus nerve, influences the gut physiological activities (motility, mucin, and peptide secretion), as well as the development of the mucosal immune system. Conversely, the gut can influence the CNS via intestinal microbiota, its metabolites, and gut-homing immune cells.

Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis.

Multiple Sclerosis (MS) has been reported to be associated with intestinal inflammation and gut dysbiosis. To elucidate the underlying biology of MS-linked gut inflammation, we investigated gut infiltration of immune cells during the development of spontaneous experimental autoimmune encephalomyelitis (EAE) in humanized transgenic (Tg) mice expressing HLA-DR2a and human T cell receptor (TCR) specific for myelin basic protein peptide (MBP87-99)/HLA-DR2a complexes. Strikingly, we noted the simultaneous development of EAE and colitis, suggesting a link between autoimmune diseases of the central nervous system (CNS) and intestinal inflammation.

Effect of switching glatiramer acetate formulation from 20 mg daily to 40 mg three times weekly on immune function in multiple sclerosis.

Background: Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells.

Objective: To investigate the difference in immunological parameters in response to GA20 and GA40 treatments.

Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition.

Dimethyl fumarate (DMF) is an oral agent for relapsing-remitting multiple sclerosis (RRMS). In this study, we investigated the therapeutic mechanism of DMF using experimental autoimmune encephalomyelitis (EAE). DMF treatment decreased the proliferation of T cells and the production of IL-17A and GM-CSF.

Surface Layer Protein A Expressed in DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Recent studies suggest that migration of Th1 and Th17 cells specific for enteric bacteria from the gut to the CNS may lead to the initiation and/or exacerbation of autoimmune diseases including MS. Human leukocyte antigen (HLA)-DR15 is an MHC class II (MHCII) haplotype highly associated with the development of MS that contains the two HLA-DRB* genes, DRB1*1501 (DR2b) and DRB5*0101 (DR2a).

Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis.

Dimethyl fumarate (DMF) is an oral, disease-modifying agent for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, details regarding its mode of action are still emerging. It is believed that the mode of action of DMF involves both nuclear factor erythroid-derived 2-related factor (Nrf2)-dependent and independent pathways, which lead to an anti-inflammatory immune response due to type II myeloid cell and Th2 cell differentiation and neuroprotection.

Germanene Epitaxial Growth by Segregation through Ag(111) Thin Films on Ge(111).

Large-scale two-dimensional sheets of graphene-like germanium, namely, germanene, have been epitaxially prepared on Ag(111) thin films grown on Ge(111), using a segregation method, differing from molecular beam epitaxy used in previous reports. From the scanning tunneling microscopy (STM) images, the surface is completely covered with an atom-thin layer showing a highly ordered long-range superstructure in wide scale. Two types of protrusions, named hexagon and line, form a (7√7 × 7√7) R19.

[Growth Process of Cystic Lung Cancer Followed with Computed Tomography Findings Over 5 Years].

An estimated 2~16% of primary lung cancers form cavities with cases that form thin-walled cavities being comparatively rare. We treated a patient with squamous cell carcinoma of the lung with a small cystic shadow that showed no changes for 3 years. The cyst then suddenly grew larger, after which the cyst wall thickened over time and a thin-walled cavity was seen.

Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood.

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) mainly in young adults, and a breakage of immune tolerance to CNS self-antigens has been suggested to initiate CNS autoimmunity. Age and microbial infection are well-known factors involved in the development of autoimmune diseases, including MS. Recent studies have suggested that alterations in the gut microbiota, referred to as dysbiosis, are associated with MS.

IL-27: a potential biomarker for responders to glatiramer acetate therapy.

Glatiramer acetate (GA) is an FDA-approved efficacious drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, this treatment is not effective for all RRMS patients. Therefore, it is important to identify reliable biomarkers that can predict a beneficial clinical response to GA therapy.

Advances in the immunopathogenesis of multiple sclerosis.

Purpose Of Review: Recent studies indicate a role for immune dysregulation in the pathogenesis of multiple sclerosis, an inflammatory demyelinating and degenerative disease of the central nervous system. This review addresses the current mechanisms of immune dysregulation in the development of multiple sclerosis, including the impact of environmental risk factors on immunity in both multiple sclerosis and its animal models.

Recent Findings: CD4 T-helper (Th) cells have long been implicated as the main drivers of pathogenesis of multiple sclerosis.

Early treatment with anti-VLA-4 mAb can prevent the infiltration and/or development of pathogenic CD11b+CD4+ T cells in the CNS during progressive EAE.

Natalizumab is a humanized monoclonal antibody against the leukocyte adhesion molecule very late antigen (VLA)-4, and is currently an approved therapy for patients with relapsing-remitting multiple sclerosis (RRMS). However, it is unknown whether natalizumab is beneficial for progressive forms of MS. Therefore, we assessed the effects of anti-VLA-4 monoclonal antibody (mAb) therapy in a progressive experimental autoimmune encephalomyelitis (EAE) mouse model.

Comparison of IFN-β inducible gene expression in primary-progressive and relapsing-remitting multiple sclerosis.

Interferon (IFN)-β is a type I IFN commonly produced by the innate immune system in response to viral infection. IFN-β is also used for the treatment of patients with the relapsing-remitting form of multiple sclerosis (RRMS); however, IFN-β therapy is unable to confer a significant benefit for primary-progressive MS (PPMS) patients. In this study, we assessed the gene profiles of peripheral blood mononuclear cells (PBMCs) isolated from PPMS, RRMS, and healthy donors (HD) in response to IFN-β treatment in vitro to examine genetic mechanisms underlying the inadequate response of IFN-β therapy in PPMS patients.

HLA DR and DQ alleles and haplotypes associated with clinical response to glatiramer acetate in multiple sclerosis.

Objective: Clinical response to immunomodulatory therapies in multiple sclerosis (MS) is variable among patients. Currently, there are no validated biomarkers of clinical response to any of the approved treatments for MS. The objective of this study was to determine if HLA-class II alleles predict the clinical response to glatiramer acetate (GA).

Effect of interferon beta-1a on B7.1 and B7.2 B-cell expression and its impact on T-cell proliferation.

The effect of pharmacologically relevant doses of interferon (IFN) β-1a on B-cell expression of B7.1 and B7.2 was investigated.

Immune response during interferon beta-1b treatment in patients with multiple sclerosis who experienced relapses and those who were relapse-free in the START study.

We measured immune markers in subjects with multiple sclerosis (MS) treated with IFNβ-1b for 12 months. IL-17 levels were significantly higher at Month 6 (p=0.036) in relapsing subjects while BDNF levels were significantly higher at Month 3 (p=0.

Myelin basic protein-specific TCR/HLA-DRB5*01:01 transgenic mice support the etiologic role of DRB5*01:01 in multiple sclerosis.

Genetic susceptibility to multiple sclerosis (MS) has been linked to the HLA-DR15 haplotype consisting of DRB1*15:01(DR2b) and DRB5*01:01(DR2a) alleles. Given almost complete linkage disequilibrium of the two alleles, recent studies suggested differential roles in susceptibility (DR2b) or protection from MS (DR2a). Our objective was to assess the potential contribution of DR2a to disease etiology in MS using a humanized model of autoimmunity.

Immunologic aspects of multiple sclerosis.

Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system characterized by demyelination and axonal loss. Genetic and environmental factors contribute to the risk of immune dysregulation in multiple sclerosis. The review focuses on the immunopathogenic role played by various lymphocyte subsets and their cytokine products in the onset and disease progression, and the role of regulatory immune cells in disease remission.

Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery.

Myelin basic protein (MBP)-specific T cells are thought to play a role in the development of multiple sclerosis. MBP residues 111-129 compose an immunodominant epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of MBP (MBP(111-129)) differs in humans (MBP122:Arg) and mice (MBP122:Lys) at aa 122.

[Properties of commercial licorice extracts used as a food additive].

Properties of eight commercial licorice extracts used as a food additive (sweetener, listed in the List of Existing Food Additives in the Japanese Food Sanitation Law) were surveyed. Residue on ignition ranged from 0.3 to 12.

Fast cleanup method for the analysis of Sudan I-IV and para red in various foods and paprika color (oleoresin) by high-performance liquid chromatography/diode array detection: focus on removal of fat and oil as fatty acid methyl esters prepared by transesterification of acylglycerols.

A fast and effective cleanup method was developed for the analysis of Sudan I, II, III, IV, and Para Red (Sudan dyes) in various foods and paprika color (oleoresin) by high-performance liquid chromatography (LC) with a diode array detector (DAD). Removal of fat or oil in fatty sample was a critical point for reducing the volume of the final sample solution in order to obtain a sufficient level of the analytes. Separation of fat or oil from the dyes with a silica gel solid-phase extraction (SPE) column seemed unfeasible, because elution profiles of oil, fat, and the dyes were similar.

Growth-suppressive function of phosphatidylethanolamine-binding protein in anaplastic thyroid cancer.

Background: A cDNA microarray analysis of anaplastic thyroid cancer cell lines (ACL) was recently performed and the down-regulation of phosphatidylethanolamine-binding protein (PBP) [RAF kinase inhibitor protein (RKIP)] in ACL compared to normal thyroid tissues was identified.

Materials And Methods: The expression levels of PBP in primary anaplastic and papillary thyroid cancer, thyroid cancer cell lines (anaplastic, papillary and follicular) and several normal human organs were examined. To examine the function of PBP, cell-growth assays were performed.

Down-regulation of transcription elogation factor A (SII) like 4 (TCEAL4) in anaplastic thyroid cancer.

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and appears to arise mainly from transformation of pre-existing differentiated thyroid cancer (DTC). However, the carcinogenic mechanism of anaplastic transformation remains unclear. Previously, we investigated specific genes related to ATC based on gene expression profiling using cDNA microarray analysis.

Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.

We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes.