scholarly journals PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels

Biomedicines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 85 ◽  
Author(s):  
Domenico De Rasmo ◽  
Anna Ferretta ◽  
Silvia Russo ◽  
Maddalena Ruggieri ◽  
Piergiorgio Lasorella ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Mitochondrial Dynamics ◽  
H2o2 Production ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Healthy Control ◽  
The Central Nervous System ◽  
Student’S T ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is an autoimmune disease in which activated lymphocytes affect the central nervous system. Increase of reactive oxygen species (ROS), impairment of mitochondria-mediated apoptosis and mitochondrial alterations have been reported in peripheral lymphocytes of MS patients. Mitochondria-mediated apoptosis is regulated by several mechanisms and proteins. Among others, optic atrophy 1 (OPA1) protein plays a key role in the regulating mitochondrial dynamics, cristae architecture and release of pro-apoptotic factors. Very interesting, mutations in OPA1 gene, have been associated with multiple sclerosis-like disorder. We have analyzed OPA1 and some factors involved in its regulation. Fifteen patients with MS and fifteen healthy control subjects (HC) were enrolled into the study and peripheral blood mononuclear cells (PBMCs) were isolated. H2O2 level was measured spectrofluorimetrically, OPA1, PHB2, SIRT3, and OMA1 were analyzed by western blotting. Statistical analysis was performed using Student’s t-test. The results showed that PBMC of MS patients were characterized by a deregulation of OPA1 processing associated with increased H2O2 production, inactivation of OMA1 and increase of PHB2 protein level. The presented data suggest that the alteration of PHB2, OMA1, and OPA1 processing could be involved in resistance towards apoptosis. These molecular parameters could also be useful to assess disease activity.

scholarly journals TGF-β Isoforms and Receptors: A Gene Expression Analysis in Multiple Sclerosis Patients and Normal Individuals

2021 ◽  
Author(s):  
Zeinab Shirvani-Farsani ◽  
Mehrdad Behmanesh ◽  
Mohammad Ali Sahraian
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Lymphocytic Infiltration ◽  
Chronic Inflammatory Disease ◽  
Expression Level ◽  
Peripheral Blood Mononuclear ◽  
Normal Individuals ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients ◽  
Tgf Β1

Abstract Objective: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), depicted by lymphocytic infiltration and demyelination. MS is associated with the up-regulation of pro-inflammatory and down-regulation of anti-inflammatory cytokines. The purpose of this experimental study was to evaluate the expression level of TGF-β1, TGF-β 2, TGF-β-R1 and TGF-β-R2 mRNAs in peripheral blood mononuclear cells (PBMCs) from MS patients and healthy controls using Real-Time PCR. Results: Our findings indicated that the TGF-β-R1 expression level was 2.25 times higher in controls than MS patients. Also, a significant correlation between normalized expression of TGF-β-R1 and TGF-β1, or TGF-β2 was observed. Therefore, these genes could likely play an important role in the etiology of MS.

scholarly journals Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies

2021 ◽  
Vol 22 (14) ◽  
pp. 7536
Author(s):  
Inez Wens ◽  
Ibo Janssens ◽  
Judith Derdelinckx ◽  
Megha Meena ◽  
Barbara Willekens ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Treatment Options ◽  
Cell Types ◽  
Peripheral Blood Mononuclear ◽  
Tailored Treatment ◽  
Key Issues ◽  
The Central Nervous System

Currently, there is still no cure for multiple sclerosis (MS), which is an autoimmune and neurodegenerative disease of the central nervous system. Treatment options predominantly consist of drugs that affect adaptive immunity and lead to a reduction of the inflammatory disease activity. A broad range of possible cell-based therapeutic options are being explored in the treatment of autoimmune diseases, including MS. This review aims to provide an overview of recent and future advances in the development of cell-based treatment options for the induction of tolerance in MS. Here, we will focus on haematopoietic stem cells, mesenchymal stromal cells, regulatory T cells and dendritic cells. We will also focus on less familiar cell types that are used in cell therapy, including B cells, natural killer cells and peripheral blood mononuclear cells. We will address key issues regarding the depicted therapies and highlight the major challenges that lie ahead to successfully reverse autoimmune diseases, such as MS, while minimising the side effects. Although cell-based therapies are well known and used in the treatment of several cancers, cell-based treatment options hold promise for the future treatment of autoimmune diseases in general, and MS in particular.

scholarly journals Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

2021 ◽  
Vol 11 (8) ◽  
pp. 721
Author(s):  
Afshin Derakhshani ◽  
Zahra Asadzadeh ◽  
Hossein Safarpour ◽  
Patrizia Leone ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

scholarly journals In Vitro Effects of Olive Vegetation Water on IFN-γ and IL-10 Secretion in Multiple Sclerosis Patients

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Mahboubeh Baheri ◽  
Mohammadreza Dayer ◽  
Narges Baharifar ◽  
Abdolkarim Sheikhi ◽  
Abolfazl Sheikh
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Inhibitory Effect ◽  
Inflammatory Disorder ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Reactions ◽  
Ifn Γ ◽  
Vegetation Water ◽  
Multiple Sclerosis Patients

Background: Multiple Sclerosis (MS) is an autoimmune and inflammatory disorder of the central nervous system (CNS), which is associated with the imbalance of pro- and anti-inflammatory cytokines. Evidence indicates that nutritional interventions have some immunomodulatory impacts. Objectives: In this study, we investigated the effect of olive vegetation water (OVW) on IFN-γ and IL-10 secretion by peripheral blood mononuclear cells (PBMCs) of MS patients. Methods: In this study, PBMCs of MS patients were separated by Ficoll-Hypaque centrifugation. The cytotoxicity of OVW was assessed by the MTT assay. The treatments were performed for 48 and 72 hours, and IFN-γ and IL-10 were measured by ELISA. Results: No cytotoxicity was observed for OVW. Besides, OVW showed a significant inhibitory effect on IFN-γ secretion but augmenting effect on IL-10 secretion by PBMCs dose-dependently. Conclusions: This study indicated that OVW could have immunoregulatory effects on inflammatory reactions in MS patients.

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