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Неврологические расстройства и атрофия серой материи мозга в первичном прогрессивном множественном склерозе определяются микроструктурными изменениями, но не нагрузкой на повреждение.

ИСТОРИЯ ВОПРОСА: Обычные МРТ, такие, как количество и объем повреждений MS, являются гистологически неконкретными и не могут в достаточной степени объяснить клиническую инвалидность или атрофию головного мозга в MS. Тем не менее в демиелионирующих досках проявляются различные гистопатологические особенности в подтипах релапсирующих и прогрессивных множественных склерозов (MS). Цель этого исследования заключалась в оценке микроструктурных характеристик MS-повреждений с использованием количественных МРТ и изучении их связей с атрофией серой материи (GM) и клинической инвалидностью.МЕТОДЫ: 56 кон

The Circular Life of Human CD38: From Basic Science to Clinics and Back.

Monoclonal antibodies (mAbs) were initially considered as a possible "magic bullet" for in vivo elimination of tumor cells. mAbs represented the first step: however, as they were murine in nature (the earliest experience on the field), they were considered unfit for human applications. This prompted the development of techniques for cloning the variable regions of conventional murine antibodies, genetically mounted on human IgG. The last step in this years-long process was the design for the preparation of fully human reagents. The choice of the target molecule was also problematic, since canc

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… Indeed, NAD + , as is also the case for adenosine triphosphate (ATP), is increased in the extracellular space during inflammatory or neoplastic conditions, where these adenine nucleotides are believed to act as danger signals, alerting the immune system to avoid possible tissue damages through binding …

Механистические знания о перекрестке нейроглии в нейродегенеративных заболеваниях.

Нейродегенеративные заболевания, такие, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), Множественный Склероз (MS) и болезнь Хантингтона (HD), хотя и отличаются по своим клиническим проявлениям, имеют общую отличительную черту: нарушенная нейро-воспалительная среда, вызванная дисрегулированием нейроглиальной межклеточной связи. Нейроглиальный перекресток физиологически обеспечивается внеклеточными посредниками и деятельностью коннексинов (Cxs), формирующими белки пятен соединений пятен (Gjs) и гемиханнелей (HC), которые поддерживают внутриклеточный и внеклеточный гомеостаз. Однако накоп

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… HCs are also involved in the interaction between intracellular and extracellular spaces and can be classified as homomeric or heteromeric, based on their Cxs composition ( Vicario and Parenti, 2022 ; Figure 1 ). …

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

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… Mechanistically, ATTR-wt leads to the deposition of non-mutated TTR protein in the myocardial extracellular space, leading to restrictive cardiomyopathy, arrhythmias, and heart failure. …

Cardiac amyloidosis and aortic stenosis: a state-of-the-art review.

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aort

Microgel-Based 3D Bioprinting: A Convergent Strategy Integrating Material Design, Jamming Dynamics, and Biological Function.

Driven by rapid technological innovation and an increasing demand for personalized medicine, microgel-based bioprinting emerges as a versatile strategy for generating physiologically relevant tissue models and patient-specific constructs. By integrating microgel systems with 3D bioprinting, this approach enables the creation of complex, cell-laden architectures that closely recapitulate native tissue architecture and function. Pivotal to this potential are microgels that offer significant advantages over conventional hydrogel-based bioinks, including tunable rheological behavior, enhanced prin

The Role of Extracellular Vesicles in Bone Regeneration and Associated Bone Diseases.

Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, non-coding RNAs (ncRNAs), proteins, cytokines, and lipids, and mediate intercellular signal transduction. Bone is a connective tissue with a nerve supply and high vascularization. The repair process after injury is highly complex, involving interactions among multiple cell types and bi

Recent advances in understanding and treating immunoglobulin light chain amyloidosis.

Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by misfolded Ig light chain deposition in vital organs of the body, resulting in proteotoxicity and organ dysfunction. Owing to its diverse clinical presentations and a tendency to mimic common medical conditions, AL amyloidosis is often diagnosed late and results in dismal outcomes. Early referral to a specialized center with expertise in management of AL amyloidosis is always recommended. The availability of sensitive biomarkers and novel therapies is reforming our approach to how we manage AL amy

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… Proc Natl Acad Sci U S A. 2010 ; 107 ( 9 ): 4188 – 93 . 10.1073/pnas.0912263107 20150510 PMC2840082 12 Teng J Turbat-Herrera EA Herrera GA : Extrusion of amyloid fibrils to the extracellular space in experimental mesangial AL-amyloidosis: transmission and scanning electron microscopy studies and correlation …

Myelin Displacement and Revention in the Central Nervous System: Молекулярные механизмы, болезни и перспективные терапевтические цели.

Майлин пластичность имеет основополагающее значение для формирования нейронных сетей и оптимизации нейронных функций, формирования схем, регулирующих эмоции, сознание, сенсацию и управление двигателем. Подкомбинированный олигодендроцитами, миелин подвергается пожизненной реконструкции, которая требует высокой метаболической активности; это делает миелин-олигодендроцитную единицу весьма восприимчивой к метаболическому стрессу, старению и патологическим оскорблениям. Хотя обезвоживание является основной характеристикой различных хронических неврологических расстройств, в настоящем обзоре особо п

Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives.

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of "onco-channelopathy". Here, we review the contribution of ion channels and transporters in multiple myeloma (

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… Yanamandra et al. [ 50 ] demonstrated that the farnesyltransferase inhibitor, tipifarnib, induces Ca 2+ influx from the extracellular space via Orai3, resulting in an increase of cytosolic calcium that leads to ER stress, cell membrane damage and, ultimately, to MM cell death [ 50 ]. …

Host impairments in patients with neoplastic diseases.

Healthy individuals possess an immune system comprising physical barriers, innate and acquired immunity as well as the indigenous microflora that populate the body surfaces. The immune system maintains constant vigilance over the body at the cellular level as well as at the interface between the host integument and the resident microflora. However, neoplastic diseases and their treatment often lead to impaired immunity resulting in an increased risk of infections due to viruses, bacteria, fungi, and protozoa. This chapter explores the various aspects of host impairment focusing on the componen

Targeting the NLRP3 inflammasome in kidney disease: molecular mechanisms, pathogenic roles, and emerging small-molecule therapeutics.

Inflammatory responses represent a core pathological process driving the progression of both acute and chronic kidney diseases. As a key effector of the innate immune system, the NLRP3 inflammasome is widely activated in renal resident cellsand infiltrating immune cells, positioning it as a critical nexus linking metabolic dysregulation, cellular stress, and tissue injury. Accumulating preclinical and clinical evidence in recent years demonstrates that aberrant activation of the NLRP3 inflammasome directly promotes glomerular damage, tubulointerstitial inflammation, fibrosis, and vascular dysf

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… The effect and inhibition of inflammatory cytokines on NLRP3 Inflammatory cytokines are endogenous substances secreted into the extracellular space by immune cells upon activation, which can exert activating or inhibitory effects on surrounding other immune cells. …

Взаимодействие с Мозгом: Как нанотехнология может способствовать.

Соединение искусственных устройств с человеческим мозгом является главной целью нейротехнологий. Однако наше воображение часто ограничивается существующими парадигмами и технологиями. Со временем, наряду с имеющейся технологией, изменились предложения в отношении интерфейсов мозга и автомата. Механические рычаги и кабельные лебедки использовались для перемещения частей мозга в механическую эпоху. Сложное электронное проводка и дистанционное управление возникли в эпоху электронной связи, что в конечном счете привело к созданию компьютерных интерфейсов. Тем не менее, наши мозги настолько сложны,

Neutrophil extracellular traps in homeostasis and disease.

Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the

Diffuse alveolar hemorrhage in rheumatic diseases: Clinical features, diagnosis, and management.

Diffuse alveolar hemorrhage (DAH) is a catastrophic pulmonary manifestation of systemic autoimmune and rheumatic diseases, particularly systemic lupus erythematosus (SLE), ANCA-associated vasculitis (AAV), and antiphospholipid syndrome (APS). It arises from immune-mediated injury to the pulmonary microcirculation, leading to intra-alveolar bleeding, respiratory failure, and high mortality. Despite advances in immunosuppression, DAH continues to pose major diagnostic and therapeutic challenges, with limited consensus on optimal management. We conducted an updated and comprehensive review of the

The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.

Heat shock protein 90 (HSP 90) and its isoforms are a group of homodimeric proteins that regulate several cellular processes, such as the elimination of misfolded proteins, cell development and post-translational modifications of kinase proteins and receptors. Due to its involvement in extracellular matrix (ECM) remodelling, myofibroblast differentiation and apoptosis, HSP 90 has been investigated as a key player in the pathogenesis of lung fibrosis. Idiopathic pulmonary fibrosis (IPF) is the most common and deadly interstitial lung disease, due to the progressive distortion of lung parenchyma

Evolution of Chronic Lesion Tissue in Relapsing-Remitting Patients With Multiple Sclerosis: An Association With Disease Progression.

BACKGROUND AND OBJECTIVES: In this study, we examine the long-term changes in chronic lesion tissue (CLT) among patients with relapsing-remitting MS (RRMS), focusing on its impact on clinical and radiologic disease progression indicators. METHODS: The study involved 72 patients with multiple sclerosis with at least a 5-year follow-up. Annual assessments used 3D fluid-attenuated inversion recovery (FLAIR), precontrast and postcontrast 3D T1, and diffusion-weighted MRI. Lesion segmentation was conducted using iQ-MS software, while brain structures were segmented using AssemblyNet. Volumetric ch

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… Elevated MD in chronic white matter MS lesions reflects enlargement of the extracellular space, 30-33 which is caused by a combination of ongoing tissue loss and the relatively rigid structure of chronic lesion. 34 Therefore, the significantly higher MD at baseline and the larger increase in MD during …

Воздействие метаболического синдрома на нейроинфламму и мозговой барьер.

Метаболический синдром, который включает диабет и ожирение. one из самых распространенных медицинских заболеваний. Она вызывает системное воспаление, приводящее к далеко идущим последствиям для тела, которое все еще обнаруживается. Neuropathology, вызванная метаболическим синдромом, часто является результатом повышения проницаемости кровеносного мозга (ББД). ББД, система, предназначенная для ограничения проникновения токсинов, иммунных клеток и патогенов в мозг, имеет жизненно важное значение для надлежащей нейронной функции. Местное и системное воспаление, вызванное ожирением или типом 2 Мели

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications.

The peripheral nervous system undergoes sufficient stress when affected by diabetic conditions, chemotherapeutic drugs, and personal injury. Consequently, peripheral neuropathy arises as the most common complication, leading to debilitating symptoms that significantly alter the quality and way of life. The resulting chronic pain requires a treatment approach that does not simply mask the accompanying symptoms but provides the necessary external environment and neurotrophic factors that will effectively facilitate nerve regeneration. Under normal conditions, the peripheral nervous system self-r