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Protein phosphatase 6 regulates metabolic dysfunction-associated steatohepatitis via the mTORC1 pathway.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is a serious chronic liver disease for which therapeutic options are limited. Although fibroblast growth factor 21 (FGF21) analogs have shown therapeutic promise for MASH in multiple preclinical and clinical studies, their underlying mechanisms of action remain elusive. METHODS: Liver-specific PPP6C and βKlotho knockout mice and their wild-type littermates were fed an AMLN (Amylin liver NASH) diet for 16 weeks or a CDA-HFD (choline-deficient, L-amino acid-defined, high-fat diet) for 8 weeks, followed by daily subcutane

Bcl-2 as a Double-edged Sword for the Treatment of Multiple Sclerosis: A Systematic Review.

INTRODUCTION: Multiple sclerosis (MS) is a chronic immune-mediated neurodegenerative disease that involves inflammation, demyelination, and neuronal loss. The B-cell lymphoma 2 (Bcl-2) protein family regulates intrinsic apoptotic pathways and may impact disease progression via effects on immune cell survival and neuroprotection. METHODS: To review current evidence on the role of Bcl-2 and its modulators in MS. Englishlanguage, clinical and preclinical studies (1998-October 2025) were retrieved from PubMed, Google Scholar, and other databases. RESULTS: Clinical studies show that peripheral B …

Multimodal Neuroimaging and Electrophysiological Markers in Multiple Sclerosis: An Integrative Review of fMRI, EEG, and EMG Approaches : fMRI, EEG, EMG in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease marked by demyelination, neurodegeneration, and widespread network dysfunction. While conventional MRI remains central to diagnosis, advanced techniques such as functional MRI (fMRI), electroencephalography (EEG), and electromyography (EMG) are increasingly recognized for their ability to capture dynamic functional changes that underlie clinical symptoms. This review explores the individual and combined applications of fMRI, EEG, and EMG in MS, emphasizing recent clinical findings from 2019 to 2024. fMRI provides high-resolution mapping…

The Role of Vitamin C in Selected Autoimmune and Immune-Mediated Diseases: Exploring Potential Therapeutic Benefits.

Autoimmune diseases are characterized by immune response dysregulation against self-components, leading to chronic inflammation and tissue damage. Vitamin C (VitC), a water-soluble vitamin with established functions in antioxidant defence and collagen synthesis, has also been of interest based on its potential immunomodulatory effects. This review discusses the role of VitC in the course and progression of (A) autoimmune diseases (multiple sclerosis, rheumatoid arthritis, Sjögren's disease, type 1 diabetes, Hashimoto's thyroiditis, pernicious anaemia, antiphospholipid syndrome), (B) other immu…

NHE9 и Endosomal pH: Совпадающие механизмы нейроразвития, психиатрии и нейродегенеративных расстройств.

Na+(K+)/H+обменник NHE9 (SLC9A9), являющийся ключевым регулятором эндосомного рН, все чаще признается в качестве фактора, способствующего совместному возникновению патомеханизма-эндосомной дисфункции, пересекающей нейроразвитость, психические и нейродегенеративные расстройства. Обогащенный мозгом, NHE9 служит для протонов каналом утечки, позволяющим уравновешивать подкисление, вызванное вакулярной аттракционной системой, точный световой pH, необходимый для синаптических, цепных и поведенческих функций. Структурно NHE9 действует в качестве димера с помощью транспортного механизма типа лифта. Фу

Совпадение в аннотации оригинала
The Na+(K+)/H+ exchanger NHE9 (SLC9A9), a key regulator of endosomal pH, is increasingly recognized as a contributor to a shared pathomechan … and Alzheimer's disease. Genetic studies also associate NHE9 with interferon-β therapy response in multiple sclerosis and chronic pain, underscoring broader neurological significance. Despite growing evidence, mechanistic links between NHE9 dysfunction and clinical phenotypes across the neurodevelopmental-neurodegenerative continuum remain poorly defined. This narr …

Множественная функциональность ингибитора ткани металлической протеины-1 в заболеваниях центральной нервной системы.

Болезни центральной нервной системы (ЦНС) характеризуются высокой заболеваемостью, продолжительными заболеваниями и необратимыми неврологическими нарушениями, которые часто являются результатом повреждения нейроваскулярной единицы (НВБ). Ингибитор мешка металлической протеины-1 (TIMP-1), эндогенный ингибитор матрицы Metalloproteinase-9 (MMP-9), играет ключевую роль в поддержании гомеостазиса внеклеточной матрицы (ECM) и регулировании целостности NVU. Помимо своей канонической функции MMP-inhibory, TIMP-1 оказывает широкий спектр независимого воздействия MMP как многофункционального цитокина, к

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Central nervous system (CNS) diseases are characterized by high morbidity, long disease courses, and irreversible neurological impairment, o … the onset, progression, and prognosis of major CNS disorders, including ischemic stroke, epilepsy, multiple sclerosis, and neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Accumulating evidence highlights its dual, context-dependent roles-protective in acute neuroinflammatory and ischemic injury, yet potentially profibrotic or maladaptive und …

Гуманистический подход к совершенствованию: подход, основанный на постоянном склерозе и постоянном повышении качества сотрудничества в области координации.

Множественный склероз (MS) является дорогостоящим, хроническим, сложным заболеванием, которое требует индивидуализации ухода на системном уровне для достижения лучших результатов. Авторы описывают осуществляемое при поддержке тренеров мероприятие по совершенствованию качества (QI) в рамках постоянного сотрудничества в области QI (MS-CQI), которое представляет собой исследование по вопросам охраны здоровья в рамках многоцентральной системы обучения (LHS) в целях улучшения результатов MS (2018-2022 годы). МЕТОДЫ: Авторы разработали при поддержке тренера программу " QI " в рамках систем

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BACKGROUND: Multiple sclerosis (MS) is a costly, chronic, complex condition, which requires customization of care at the system level to achieve better outcomes. The authors describe a cluster-randomized, coach-supported quality improvement (QI) intervention in the MS continuous QI (MS-CQI) Collaborative, which was a multicenter learning health system (LHS) …

Может ли дополнение антиоксидантами улучшить когнитивные функции у пациентов с множественным склерозом? Обзор литературы.

Множественный склероз (MS) — хроническое нервно-воспалительное и нейродегенеративное заболевание центральной нервной системы (CNS), имеющее сложную и многофакторную патофизиологию. Хотя эти механизмы еще не полностью прояснились, установлено, что окислительный стресс (ОС) играет ключевую роль в вождении нейродегенерации в MS. Эти патологические механизмы способствуют возникновению широкого круга симптомов, включая моторные и сенсорные расстройства, а также когнитивное расстройство. Дефекты когнитивных функций могут создавать для этих пациентов тяжелое бремя и существенно влиять на качество их

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Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of the central nervous system (CNS) with a complex and multifactorial pathophysiology. Although these mechanisms are not yet fully elucidated, it is established that oxidative stress (OS) plays a key role in driving neurodegeneration in MS. These pathological mechanisms cont…

Изучение терапевтической роли видеоконференцсвязи тренера-руководителя с экспресс-конференцией в многоразовом склерозе: качественное исследование.

Справочная информация/цели: Эмоциональные изменения оказывают значительное воздействие на людей с множественным склерозом (PwMS), что часто приводит к негативным психологическим симптомам, включая горе. Эффективное управление этими симптомами может способствовать развитию личности, укрепить доверие и возродить надежду. Хотя экспрессивное письмо продемонстрировало психологические преимущества при обработке травм и хронических заболеваний, его воздействие на PwMS по-прежнему недостаточно изучено. Цель этого исследования заключалась в устранении этого пробела путем изучения опыта ПВМС, которые уч

Совпадение в аннотации оригинала
Background/Objectives: Emotional changes significantly affect people with multiple sclerosis (PwMS), often leading to negative psychological symptoms including grief. Effective management of these symptoms can foster personal growth, increase confidence, and renew hope. While expressive writing has demonstrated psychological benefits in processing trauma and…

The T1-dark-rim: A novel imaging sign for detecting smoldering inflammation in multiple sclerosis.

PURPOSE: Paramagnetic rim lesions (PRLs), usually identified in susceptibility-weighted imaging (SWI), are a promising prognostic biomarker of disability progression in multiple sclerosis (MS). However, SWI is not routinely performed in clinical practice. The objective of this study is to define a novel imaging sign, the T1-dark rim, identifiable in a standard 3DT1 gradient-echo inversion-recovery sequence, such as 3D T1 turbo field echo (3DT1FE) and explore its performance as a SWI surrogate to define PRLs. METHODS: This observational cross-sectional study analyzed MS patients who underwent …

Objectively assessed sleep quality parameters in Multiple Sclerosis at home: Association to disease, disease severity and physical activity.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory autoimmune, neurodegenerative disease that affects regular mobility and leads predominantly to physical disability. Poor sleep quality, commonly reported in MS patients, impacts their physical activity (PA). Accelerometers monitor 24-h activity patterns, offering insights into disease progression in daily life. OBJECTIVE: To test if the sleep quality variables of MS patients, as assessed with wrist-worn accelerometers, differ from those of controls and are associated with PA and disease severity variables. METHODS: Seven-day raw a…

The Role of Chimeric Antigen Receptor T-Cell Therapy in Immune-Mediated Neurological Diseases.

Despite the use of 'high efficacy' disease-modifying therapies, disease activity and clinical progression of different immune-mediated neuro … the common physiopathology, CAR-T therapy in other immune-mediated neurological disease, including multiple sclerosis, chronic inflammatory polyradiculopathy, autoimmune encephalitis, and stiff person syndrome, might be an effective option for patients, avoiding the need for long-term immunosuppressant medications. It may prove to be a more selective immunoablative …

CD70-induced differentiation of proinflammatory Th1/17/22/GM lymphocytes associated with disease progression and immune reconstitution during HIV infection.

Immune overactivation is a hallmark of chronic HIV infection, which is critical to HIV pathogenesis and disease progression. The imbalance o … was recently reported to associate with highly pathogenic proinflammatory Th1/Th17 polarization in multiple sclerosis. Thus, the role of CD70 in the imbalance of Th polarization and immune overactivation during HIV infection needs to be investigated. Here, we found that the elevated frequency of CD70 + CD4+ T cells was negatively correlated with CD4 count and posit …

CD52 mRNA expression predicts prognosis and response to immune checkpoint blockade in melanoma.

The immune-modulating protein CD52 attenuates lymphocyte function and is associated with autoimmune disorders, for example, multiple sclerosis (MS). CD52 represents a therapeutic target in MS and chronic lymphocytic leukemia (CLL). Its expression has prognostic and predictive value in CLL and is prognostic in breast cancer. Its significance in melanoma is unclear. We analyzed CD52 mRNA expression data from tumor bulk tissues of N = 445 untreated melanoma patients from The Cancer Genome Atlas (TCGA) Research Network and of N = 121 melanoma patients undergoing anti-PD-1 immune checkpoint blockad…

Chronic mild hypoxia accelerates recovery from preexisting EAE by enhancing vascular integrity and apoptosis of infiltrated monocytes.

While several studies have shown that hypoxic preconditioning suppresses development of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), no one has yet examined the important clinically relevant question of whether mild hypoxia can impact the progression of preexisting disease. Using a relapsing-remitting model of EAE, here we demonstrate that when applied to preexisting disease, chronic mild hypoxia (CMH, 10% O2) markedly accelerates clinical recovery, leading to long-term stable reductions in clinical score. At the histological level, CMH led to significa…

Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis.

Sporadic amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/antioxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our revie

Inflammation induced neurological handicap processes in multiple sclerosis: new insights from preclinical studies.

Multiple sclerosis (MS) is described as originating from incompletely explained neuroinflammatory processes, dysfunction of neuronal repair mechanisms and chronicity of inflammation events. Blood-borne immune cell infiltration and microglia activation are causing both neuronal destruction and myelin loss, which are responsible for progressive motor deficiencies, organic and cognitive dysfunctions. MRI as a non-invasive imaging method offers various ways to visualise de- and remyelination, neuronal loss, leukocyte infiltration, blood-brain barrier modification and new sensors are emerging to de…

Biomimetic Nanoparticles: Novel Therapeutic Strategies for Autoimmune Diseases.

Autoimmune Diseases (ADs) encompass a multifaceted spectrum of chronic disorders characterized by an aberrant immune response against host t … utoimmune disorders, including rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and celiac disease. By emulating cellular membranes, such as those of erythrocytes, platelets, and leukocytes, BMNPs acquire the ability to evade immune detection, prolong systemic circulation time, and deliver therapeutic payloads directly to infl …

An intricate relationship between fibrosis and autoimmune diseases: a specific focus on unraveling its molecular, immunological, and epigenetic drivers.

Fibrosis is a pathological process of wound healing, characterized by excessive deposition of extracellular matrix (ECM) and chronic activat … mechanisms contribute to fibrosis in several autoimmune disorders, including rheumatoid arthritis, multiple sclerosis, Sjögren's disease, and Crohn's disease. In these conditions, persistent immune activation drives continuous crosstalk between immune cells and stromal fibroblasts, sustaining cytokine signaling and ECM remodeling. Current therapeutic approaches pri …

CA1 parvalbumin interneurons display alterations of myelin patterning driven by microgliosis in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy, characterized by significant reorganization of hippocampal neurona … rkable similarities with those observed in dysmyelinating and neurodegenerative diseases, including multiple sclerosis, suggesting potential common therapeutic targets.