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Neuroprotective effects of rutin against cuprizone-induced multiple sclerosis in mice.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system that injures the myelin sheath, provoking progressive axonal degeneration and functional impairments. No efficient therapy is available at present to combat such insults, and hence, novel safe and effective alternatives for MS therapy are extremely required. Rutin (RUT) is a flavonoid that exhibits antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. The present study evaluated the potential beneficial effects of two doses of RUT in a model of pattern-III …

HB-EGF and EGF infusion following CNS demyelination mitigates age-related decline in regeneration of oligodendrocytes from neural precursor cells originating in the ventricular-subventricular zone.

In multiple sclerosis (MS), chronic demyelination initiated by immune-mediated destruction of myelin, leads to axonal damage and neuronal cell death, resulting in a progressive decline in neurological function. The development of interventions that potentiate remyelination could hold promise as a novel treatment strategy for MS. To this end, our group has demonstrated that neural precursor cells (NPCs) residing in the ventricular-subventricular zone (V-SVZ) of the adult mouse brain contribute significantly to remyelination in response to central nervous system (CNS) demyelination and can regen…

Analysis of changes in glomerular lesions in children diagnosed with IgA nephropathy following immunosuppressive therapy.

BACKGROUND: The European STOP study showed that glucocorticoids (with/without immunosuppressants) did not delay disease progression in adults with IgA nephropathy (IgAN). However, pediatric IgAN is characterized by more severe acute inflammatory lesions and milder chronic injuries. This study aimed to evaluate the effects of glucocorticoid‑based immunosuppressive therapy in children with IgAN using paired renal biopsy data. METHODS: A retrospective analysis was performed in 36 pediatric IgAN patients who underwent repeat renal biopsies. Patients were stratified by initial crescent status: Gro

A case of hemophagocytic lymphohistiocytosis after BNT162b2 COVID-19 (Comirnaty®) vaccination.

RATIONALE: Coronavirus disease (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was reported in Wuhan of China in December 2019. The world is still in a state of pandemic owing to COVID-19. COVID-19 vaccines help our bodies develop immunity against the virus that causes COVID-19 without having to get the illness. Herein, we describe a rare case of a critical disorder, hemophagocytic lymphohistiocytosis (HLH), in a patient with nephritic sclerosis associated with hypertension, following mRNA COVID-19 vaccination. HLH is a life-threatening hy

Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative disorders of the central nervous system: present and future prospects.

INTRODUCTION: Although IVIg is highly effective in several autoimmune neuromuscular disorders (neuropathies, myopathies and neuromuscular junction disorders), its effectiveness in autoimmune or neuroinflammatory CNS diseases, with the exception of multiple sclerosis, has not been explored. Emerging data suggest that IVIg may have a role not only in certain antibody-mediated CNS diseases but also in some neurodegenerative disorders associated with "neuroinflammation" mediated by proinflammatory cytokines. METHODS: Data from a previously reported controlled study conducted in patients with stif…

Structure and function of voltage-gated sodium channel Nav1.6: Involvement in the pathological process of neural injury.

The voltage-gated sodium channel Nav1.6, encoded by the sodium voltage-gated channel alpha subunit 8 gene, is a crucial regulator of neurona … neuron degeneration, with riluzole showing partial efficacy through sodium current modulation. (5) Multiple sclerosis pathophysiology features Nav1.6 redistribution in demyelinated axons, which drives calcium-dependent axonal injury via reverse Na + /Ca 2+ exchange. (6) Chronic pain mechanisms involve Nav1.6 overexpression in dorsal root ganglia neurons, regulated …

Development of a Diagnostic Autoantibody Assay to a Consensus Motif for the Risk Prediction of Epstein-Barr Virus-Related Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic progressive, demyelinating autoimmune CNS disease. Autoantibodies to the motif P-(SA)-x-(SGA)-R-(SN)-(LRKH) are a class of predictive markers specific to MS that could add to emerging diagnostic criteria for MS. In this study, we describe the discovery of an MS patient-derived monoclonal antibody (mAb) specific to this motif from memory B cells, and we develop a proof-of-principle autoantibody test to report the prevalence of seropositivity, predict MS early in disease, and identify underlying tolerance-breaking antigens in Epstei…

Clinical implications for the association of psoriasis and multiple sclerosis: an observational study.

BACKGROUND: Multiple sclerosis (MS) and psoriasis (PsO) are distinct chronic autoimmune conditions with varying impacts on patients' lives. While the co-occurrence of MS and PsO has been reported, the underlying pathogenic link remains unclear. This study aimed to investigate the prevalence of PsO in a MS outpatient clinic population and explore the potential interplay between these conditions. METHODS: 316 MS patients who had at least one visit at our MS center in the last year, were selected from our outpatient MS Clinic electronic database and were e-mailed in August 2023 and inquired abou…

Global, regional, and national burden of pulmonary arterial hypertension, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a vascular disease characterised by restricted flow and high pressure through the pulmo … YLLs attributed to PAH were similar to estimates for conditions such as chronic myeloid leukaemia, multiple sclerosis, and Crohn's disease. INTERPRETATION: PAH is a rare but fatal disease that accounts for a considerable health-associated burden worldwide. PAH is disproportionally diagnosed among females and older adults. FUNDING: Cardiovascular Medical Research …

Comparison of 2 Methods for Estimating Multiple Sclerosis-Related Mortality.

Background and objectivesDetermining whether multiple sclerosis (MS) causes death is challenging. Our objective was to contrast 2 frameworks to estimate probabilities of death attributed to MS (PMS) and other causes (Pother): the cause-specific framework (CSF), which requires the causes of death, and the excess mortality framework (EMF), which does not.MethodsWe used data from the Observatoire Français de la Sclérose en Plaques (OFSEP, n = 37,524) and from a comparative subset where causes of death were available (4,004 women with relapsing-onset MS [R-MS]). In CSF, the probabilities were esti…

Determinants of early working impairments in multiple sclerosis.

INTRODUCTION: Unemployment can directly affect social status and identity. Assessing and adjusting determinants of early working impairments in a chronic disease can thus reduce its long-term burden. Hereby, we aim to evaluate differences in occupational history and early working impairments between people with multiple sclerosis (MS) and healthy workers. METHODS: This is a cross-sectional study comparing 71 workers with MS [age 41.7 ± 9.4 years; females 59.1%; EDSS 2.0 (1.0-6.0)] and 71 controls (age 42.6 ± 11.9 years; females 33.8%). All participants filled in Work Ability Index (WAI), Work…

Human Polyomavirus JC monitoring and noncoding control region analysis in dynamic cohorts of individuals affected by immune-mediated diseases under treatment with biologics: an observational study.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) onset, caused by Polyomavirus JC (JCPyV) in patients affected by immune-mediate … ic diseases presented a JCPyV load in the urine significantly higher (p≤0.05) than in patients with multiple sclerosis (MS) and Crohn's disease (CD). It can also be observed a significant association between JC viruria and JCPyV antibodies after 1 year of natalizumab (p=0.04) in MS patients. Finally, NCCR analysis showed the presence of an archetype-like sequence in …

Epstein-Barr Virus-Specific CD8 T Cells Selectively Infiltrate the Brain in Multiple Sclerosis and Interact Locally with Virus-Infected Cells: Clue for a Virus-Driven Immunopathological Mechanism.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus strongly associated with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). However, the mechanisms linking EBV infection to MS pathology are uncertain. Neuropathological and immunological studies suggest that a persistent EBV infection in the CNS can stimulate a CD8 T-cell response aimed at clearing the virus but inadvertently causing CNS injury. Inasmuch as in situ demonstration of EBV-specific CD8 T cells and their effector function is missing, we searched for EBV-specific CD8 T cells in MS brain …

LMP2 deficiency causes abnormal metabolism, oxidative stress, neuroinflammation, myelin loss and neurobehavioral dysfunctions.

BACKGROUND: Substantial evidence suggests that immunoproteasome is implicated in the various neurological diseases such as stroke, multiple sclerosis and neurodegenerative diseases. However, whether the immunoproteasome itself deficiency causes brain disease is still unclear. Therefore, the aim of this study was to explore the contribution of the immunoproteasome subunit low molecular weight protein 2 (LMP2) in neurobehavioral functions. METHODS: Male LMP2 gene completed knockout (LMP2-KO) and littermate wild type (WT) Sprague-Dawley (SD) rats aged 12-month-old were used for neurobehavioral t…

Injury to a specific neural pathway detected by ultra-high-field MRI.

We present evidence for the potential of ultra-high-field MRI to reveal injury due to multiple sclerosis (MS) not appreciated using lower field imaging. Internuclear ophthalmoplegia (INO) is an eloquent ocular motor syndrome that frequently affects patients with MS. The medial longitudinal fasciculus (MLF) is a periventricular, dorsomedial brainstem tegmentum pathway that yokes the 2 eyes in many types of eye movements.1,2 Further, T2 lesions localized in the region containing the MLF strongly associate with INO.3 However, the small diameter of the MLF and lack of contrast between the MLF and …

Continued disease activity in a patient with multiple sclerosis after allogeneic hematopoietic cell transplantation.

OBJECTIVE: To examine the effect of allogeneic hematopoietic cell transplantation (HCT) on disease activity in a patient with multiple sclerosis (MS). DESIGN: Case report, prospective study, and autopsy. SETTING: Departments of Clinical Neurosciences, Internal Medicine, and Pathology at the University of Calgary, Alberta, Canada. PATIENT: A 39-year-old woman with chronic myelogenous leukemia and concurrent mild MS. INTERVENTIONS: Hematopoietic cell transplantation from a healthy unrelated donor. RESULTS: After HCT the patient developed graft-vs-host disease and experienced worsening, but …

Glatiramer Acetate Therapy вызывает изменения в метилировании ДНК в иммунных клетках пациентов с множественным склерозом: экспериментальное исследование.

Глатирамерная ацетат (GA) — это первая линия лечения склероза (MS) с умеренной эффективностью и высокой безопасностью, однако ее механизмы действий по-прежнему не до конца понятны. Метилирование ДНК играет важную роль в развитии НР и определяется различными экологическими факторами, включая терапевтические препараты. В этом экспериментальном исследовании мы сообщаем о первом перспективном анализе изменения метилации ДНК по всему геному в периферийных моноядерных клетках крови (ПБМК) с четырех женщин, вновь выделяющих MS, до начала ГА и после примерно четырех-восемь месяцев терапии. Мы выявили

Совпадение в аннотации оригинала
Glatiramer acetate (GA) is a first-line disease-modifying therapy for multiple sclerosis (MS) with well-established moderate efficacy and high safety, yet its mechanisms of action remain incompletely understood. DNA methylation plays a significant role in MS development and is modulated by various environmental factors, including therapeutic drugs. In this p…

Screening molecular recognition element-based SWCNT optical sensors for the inflammatory cytokine TNF-α.

TNF-α (Tumor Necrosis Factor) is a proinflammatory cytokine that amplifies inflammatory response and promotes leukocyte recruitment. TNF-α is primarily produced by activated macrophages, among others, in response to infection, inflammation, or tissue damage. Given its central role in normal and abnormal immune responses, it is the target of several therapeutics, such as adalimumab and etanercept. TNF-α is also a prognostic and diagnostic biomarker associated with rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, several kidney diseases, cancers, type 2 diabetes, sepsis, and others…

Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.

Glutathione is an abundant intracellular low-molecular-weight thiol that contributes importantly to cellular redox homeostasis. Besides its … and impaired cellular signaling in Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosis, Wilson's disease, type 2 diabetes, and nonalcoholic fatty liver disease. We also evaluate current translational interventions targeting restoration of glutathione balance through glutathione supplementation, precursor supplementation, pharmacologic …

Sp3 улучшила экспериментальный аутоиммунный энцефаломиэлит, спровоцировав Socs3 в клетках Th17.

ВВЕДЕНИЕ: Хотя считается, что хронические подстрекательские и дегенеративные заболевания центральной нервной системы поддерживаются аутоиммунными клетками ТТ17, основополагающие механизмы остаются в основном неисследованными. Недавние исследования и наши исследования показали, что Sp3 был заблокирован в нескольких склерозах (MS) и экспериментальном аутоиммунном энцефаломиелите (EAE). Вместе с тем остается неясным, почему в нем ничего не говорится и как он регулирует дифференциацию клеток TH17 в MS. ЦЕЛИ: Данное исследование было направлено на изучение воздействия Сп3 на ТХ17 в клетках EAE и ле

Совпадение в аннотации оригинала
INTRODUCTION: Although it is believed that chronic inflammatory and degenerative diseases of the central nervous system are mediated by autoimmune Th17 cells, the underlying mechanisms remain largely unexplored. Recent studies and our research have revealed that Sp3 was blocked in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis…