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Senescent CD4+ T cells and autoimmune diseases: mechanisms and therapeutic prospects.

Senescent CD4⁺ T cells exhibit classical features of T-cell senescence-including telomere attrition, reduced proliferative capacity, and an upregulated senescence-associated secretory phenotype (SASP)-while also displaying unique characteristics. Notably, they maintain relatively healthy mitochondrial mass compared with senescent CD8⁺ T cells, a distinction that influences their roles in immune regulation and tissue pathology. Multiple signaling pathways, such as the ATM-DDR-p53 axis, AMPK-TAB1-p38 cascade, mTOR signaling, mitochondrial-ROS axis, and IL-7/IL-2 cytokine networks, are dysregulat

7-Nitroindazole, an nNOS inhibitor, reduces migraine-like nociception, demyelination, and anxiety-like behavior in a mouse model of relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a complex neuroinflammatory disease often associated with migraine and anxiety, both of which impair quality of life. MS pathology involves intense inflammatory and oxidative processes, including increased nitric oxide (NO) production. However, the role of NO in MS-related migraine symptoms remains unclear. This study evaluated whether repeated administration of 7-nitroindazole (7-NI), a selective neuronal nitric oxide synthase (nNOS) inhibitor, could alleviate migraine-like nociception, anxiety-like behavior, and neuroinflammatory biomarkers in a relapsing-remitting…

Офатумумаб в педиатрическом множественном склерозе: серия дел.

Педиатрический множественный склероз (POMS), на который приходится ~5% всех случаев заболевания MS, является хроническим имунизированным демиелинирующим расстройством центральной нервной системы. Одной из задач по-прежнему является предотвращение реанимации, а в патогенезе центральную роль играют клетки B. Ofatumumab (OFA) — полностью человеческая антиCD20 моноклональная антитела, утвержденная для взрослых MS. Оценка безопасности и эффективности использования не помеченной марки OFA у пациентов педиатрии MS. Мы ретроспективно проанализировали клинические данные четырёх педиатрических пациентов

Совпадение в аннотации оригинала
Pediatric-onset multiple sclerosis (POMS), accounting for ~5% of all MS cases, is a chronic immune-mediated demyelinating disorder of the central nervous system. Relapse prevention remains a challenge, and B cells play a central role in the pathogenesis. Ofatumumab (OFA), a fully human anti-CD20 monoclonal antibody, is approved for adult MS. To assess the sa…

Irilone и Lupinisoflavone C как потенциальные методы регулирования на основе растений S1PR1 для нейроиммунной модуляции при мультипликационном склерозе: Отличения от молекулярного допинга и динамических процессов.

Ген S1PR1 кодирует рецептор 1 фингозина-1-фосфата, который является членом семейства G-белковых рецепторов (GCR), сильно выраженных в эндотелиальных клетках. Протеин S1PR1 играет ключевую роль в регулировании миграции клеток, поддержании сосудистой целостности и посредничении нейронных сигналов посредством активации нижних эффекторов, включая RAC1, SRC, PTK2/FAK1 и MAP cinases. Его важнейшая роль в нейроинфламмации и гомеостазисе центральной нервной системы (СНС) связывает S1PR1 с патофизиологией нейродегенеративных расстройств, в частности множественным склерозом (МС). Чрезмерная активация S1

Совпадение в аннотации оригинала
The S1PR1 gene encodes the sphingosine-1-phosphate receptor 1, a member of the G protein-coupled receptor (GPCR) family that is highly expre … m (CNS) homeostasis links S1PR1 to the pathophysiology of neurodegenerative disorders, particularly multiple sclerosis (MS). Overactivation of S1PR1 can trigger chronic inflammation, neuronal injury, and synaptic dysfunction, thereby promoting disease progression. Given its central role in neuroimmune modulation, S1PR1 represents a compelling therapeutic target in M …

Nutritional status and taste impairment in adult patients with multiple sclerosis and dysphagia. A pilot study.

INTRODUCTION: Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune, and demyelinating disease of the central nervous system. Disease progression increases dysphagia, raising risks of malnutrition, dehydration, and respiratory complications, directly impacting nutrition management. OBJECTIVES: (I) To analyse the anthropometric profiles and body composition of adults with MS; (II) to determine the prevalence of dysphagia according to disease duration; (III) to examine dietary intake and eating habits; (IV) to identify potential alterations in taste perception. METHODOLOGY: A descript…

Расследовать внеклеточные везы Т в качестве биомаркеров активности заболеваний, аксоновых травм и инвалидности при множественном склерозе.

ВВЕДЕНИЕ: Множественный склероз (MS) представляет собой хроническое иммунопосредованное демиелионирующее заболевание центральной нервной системы, при котором активность клинических заболеваний контролируется главным образом с помощью магнитного резонансного изображения. МЕТОДЫ: С учетом ограничений, связанных с внедрением и приобретением новых и новейших биомаркеров изображений в обычной клинической практике, открытие биомаркеров с биофильтром может стать более простой и эффективной с точки зрения затрат мерой, которая позволит улучшить доступность, стандартизацию и уход за пациентами. Внешнек

Совпадение в аннотации оригинала
INTRODUCTION: Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system, whereby clinical disease activity is primarily monitored by magnetic resonance imaging. METHODS: Given the limitations associated with implementing and acquiring novel and emerging imaging biomarkers in routine clinical practice, the disco…

The janus face of astrocytes in multiple sclerosis: Balancing protection and pathology.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neurodegeneration in the central nervous system (CNS), predominantly affecting young adults with a notable female predominance. While the pathogenesis of MS involves complex interactions between peripheral immune cells and CNS glia, astrocytes-the most abundant glial cells-play a dual role in disease progression. Traditionally classified into pro-inflammatory A1 and neuroprotective A2 phenotypes, recent single-cell and spatial transcriptomics reveal that human astrocytes exhibit a continuum of states be…

Внеклеточные нуклеотиды являются посредником в вирусных инфекциях центральной нервной системы: ключи от нейроинфламмации и нейродегенерации.

Недавний рост инфекционных заболеваний, затрагивающих центральную нервную систему, вызвал обеспокоенность по поводу их роли в нейроинфламмации и нейродегенерации. Вирусные патогены или их продукты могут вторгаться в центральную нервную систему и вызывать повреждения, ведущие к менингиту, энцефалиту, менингоэнцефалиту, миелиту или постинфекционным демиелинизирующим заболеваниям. Хотя изначально нейроинфламмация имеет защитную функцию, хроническое воспаление может способствовать развитию нейродегенеративных заболеваний. Такие механизмы, как агрегация белков и клеточные расстройства, связаны с ко

Совпадение в аннотации оригинала
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and … as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis, respectively. Extracellular nucleotides, particularly adenosine triphosphate and its metabolites are released from activated, infected, and dying cells, acting as alarmins mediating neuroinflammation and neurodegeneration. When viruses infect centr …

Потенциальный потенциал визуального видения, вызывающий запоздалость и амплитуду, является субклиническим прогнозом клинического прогноза в множестве склерозов.

Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, характеризующимся поражением мозга, аксонной дисфункцией/дегенерацией и глиозом, что может привести к различным клиническим расстройствам. Визуальный потенциал (ВЭП) представляет собой чувствительные и повторяющиеся методы, способные отслеживать значительные краткосрочные изменения в нейроаксональной целостности и изменения в нервном проводе, вызываемые острым оптическим невритом. АИМ: Цель данного исследования состоит в том, чтобы оценить, могут ли ПВП запоздалость и амплитуда служить в ка

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by focal demyelinating lesions, axonal dysfunction/degeneration, and gliosis, which can lead to various clinical disabilities. Visual evoked potentials (VEP) is sensitive and repeatable techniques capable of monitoring significant short-term chan…

Decreased functional mobility in individuals with mild to moderate expanded disability status from relapsing multiple sclerosis: Analysis of the Glittre-ADL test.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease that significantly limits an individual's activities of daily living (ADLs) and negatively affects their social participation as it progresses. The impact of activities and participation must be continuously assessed, and the Glittre-ADL is a validated test for MS to assess functional capacity in tasks similar to ADLs. OBJECTIVE: To evaluate whether the Glittre-ADL test is a valid method for assessing functional mobility in individuals with MS and moderate disability or those who use assistive devices. MET…

Multiple sclerosis under the age of ten: the challenge of a rare diagnosis in a special population - a case series.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system which, when it begins before the age of 18, is defined as paediatric MS. Most common clinical presentations include long tract involvement, brainstem/cerebellum syndromes, optic neuritis and acute disseminated encephalomyelitis. Paediatric-onset MS typically has a more inflammatory-active course and a higher lesion burden in imaging studies, but an extensive post-relapse recovery, with a slower long-term disability progression. The first demyelinating clinical at…

Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors.

Multiple sclerosis (MS) is a heterogeneous autoimmune disease whereby the pathological sequelae evolve from oligodendrocytes (OLs) within the central nervous system and are targeted by the immune system, which causes widespread white matter pathology and results in neuronal dysfunction and neurological impairment. The progression of this disease is facilitated by a failure in remyelination following chronic demyelination. One mediator of remyelination is thyroid hormone (TH), whose reliance on monocarboxylate transporter 8 (MCT8) was recently defined. MCT8 facilitates the entry of THs into oli…

Cellular and molecular regulation of the programmed death-1/programmed death ligand system and its role in multiple sclerosis and other autoimmune diseases.

Programmed Cell Death 1 (PD-1) receptor and its ligands (PD-Ls) are essential to maintain peripheral immune tolerance and to avoid tissue da … as been less explored despite being a potential target of treatment for neurodegenerative diseases. Multiple Sclerosis (MS) is the most prevalent, chronic, inflammatory, and autoimmune disease of the central nervous system that leads to demyelination and axonal damage in young adults. Recent studies have highlighted the key role of the PD-1/PD-Ls pathway in inducing …

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue d-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus.

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized … have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels o …

Gray matter integrity predicts white matter network reorganization in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease leading to gray matter atrophy and brain network reconfiguration as a response to increasing tissue damage. We evaluated whether white matter network reconfiguration appears subsequently to gray matter damage, or whether the gray matter degenerates following alterations in white matter networks. MRI data from 83 patients with clinically isolated syndrome and early relapsing-remitting MS were acquired at two time points with a follow-up after 1 year. White matter network integrity was assessed based on probabilistic…

Epigenetics in Multiple Sclerosis: Molecular Mechanisms and Dietary Intervention.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic, inflammatory, neurodegenerative demyelinating disease of the central nervous system (CNS). Unfortunately, MS causes important disability in young adults and its prevalence is increasing. While the etiology of MS etiology is not completely understood, it seems to be a multifactorial entity that is influenced by both genetic and epigenetic modifications. Epigenetic mechanisms add or remove different chemical groups for the activation or inhibition of gene expression to block the production of proinflammatory proteins. It is truly important to i…

B Cell-Directed Therapeutics in Multiple Sclerosis: Rationale and Clinical Evidence.

Over the last decade, evidence condensed that B cells, B cell-derived plasma cells and antibodies play a key role in the pathogenesis and progression of multiple sclerosis (MS). In many patients with MS, peripheral B cells show signs of chronic activation; within the cerebrospinal fluid clonally expanded plasma cells produce oligoclonal immunoglobulins, which remain a hallmark diagnostic finding. Confirming the clinical relevance of these immunological alterations, recent trials testing anti-CD20-mediated depletion of peripheral B cells showed an instantaneous halt in development of new centra…

Modeling the Chronic Loss of Optic Nerve Axons and the Effects on the Retinal Nerve Fiber Layer Structure in Primary Disorder of Myelin.

PURPOSE: We determined whether the chronic lack of optic nerve myelination and subsequent axon loss is associated with optical coherence tomography (OCT) changes in the retinal nerve fiber layer (RNFL), and whether this models what occurs in multiple sclerosis (MS) and confers its use as a surrogate marker for axon degeneration. METHODS: Using an animal model of Pelizaeus-Merzbacher disease (shp) bilateral longitudinal measurements of the peripapillary RNFL (spectral-domain OCT), electroretinograms (ERG), and visual evoked potentials (VEP) were performed in affected and control animals from 5…

Evidence from Human and Animal Studies: Pathological Roles of CD8(+) T Cells in Autoimmune Peripheral Neuropathies.

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect … mainly by CD4(+) T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8(+) T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8(+) T cells in a …

Инвалидность у пациентов с множественным склерозом: влияние инсулинового сопротивления, адипозитивности и окислительного стресса.

ЦЕЛЬ: Цели настоящего исследования заключались в том, чтобы сообщить о распространенности инсулиновой резистентности (ИР) у пациентов с множественным склерозом (МС); проверить различия в метаболических и подстрекательских биомаркерах и окислительном стрессе у пациентов с ОР или без них; и определить, связаны ли ИП и адипозитивность с инвалидностью у этих пациентов. МЕТОДЫ: Записанное исследование 110 больные с синдромом MS и 175 здоровые люди. Пациенты с MS были разделены на пациенты с IR (n = 44) и без (n = 66). Метаболические и подстрекательские маркеры, окислительный стресс и инвалидность б

Совпадение в аннотации оригинала
OBJECTIVE: The aims of the present study were to report the prevalence of insulin resistance (IR) in patients with multiple sclerosis (MS); to verify differences in metabolic and inflammatory biomarkers, and oxidative stress in patients with MS with or without IR; and to assess if IR and adiposity are associated with disability in these patients. METHODS: Th…