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CAR T клеточная терапия в неврологических расстройствах, вызванных автоантибиозами: многообещающая стратегия.

Клеточная терапия химерного антигенного рецептора (CAR) Т становится перспективным подходом к неврологическим аутоиммунным расстройствам на базе клеток B, особенно тем, которые характеризуются патогенными автоантиорганизмами, направленными на ключевые нейронные структуры. Эти заболевания, включая расстройство спектрального спектра нейромиелита, миастения гравис, синдром Ламберта-Итона миастеника, болезнь, связанная с антителами MOG, энцефалит рецептора против NMDA, диацилглицирол губазы альфа антитела, ассоциируемый с энцефалитом, синдромом жесткого человека и множественным склерозом, могут бы

Воздействие N-ацетилцистистайна на PET-MRI у пациентов с множественным склерозом.

Цель этого исследования заключалась в изучении вопроса о том, привело ли управление N-ацетилцистином (NAC) у пациентов с множественным склерозом (MS) к изменению нейрофизиологической функции, определяемой сочетанием функциональных связей (FC) на основе восстановления зависимости от уровня кислорода крови (BOLD) fMRI и метаболизма церебральной глюкозы с использованием фтородоксиглюкозы позитронной эмиссии (FDG PET) и были ли эти изменения связаны с улучшением симптомов. МЕТОДЫ: Thirty-six Пациенты с мягким или умеренным склерозом были случайно выбраны либо в NAC плюс стандарт ухода, либо только

Guideline "diagnosis and non interventional therapy of neuropathic pain" of the German Society of Neurology (deutsche Gesellschaft für Neurologie).

2019 the DGN (Deutsche Gesellschaft für Neurology) published a new guideline on the diagnosis and non-interventional therapy of neuropathic pain of any etiology excluding trigeminal neuralgia and CRPS (complex regional pain syndrome). Neuropathic pain occurs after lesion or damage of the somatosensory system. Besides clinical examination several diagnostic procedures are recommended to assess the function of nociceptive A-delta and C-Fibers (skin biopsy, quantitative sensory testing, Laser-evoked potentials, Pain-evoked potentials, corneal confocal microscopy, axon reflex testing). First line

A comprehensive review on pain: Model, target, therapy, and prospect (Review).

Pain serves as both a protective physiological response essential for species survival and a global health issue affecting human well‑being and societal development. The present review systematically summarized and analyzed the research progresses on pain through a multidimensional analytical framework encompassing animal models, molecular targets, therapeutic approaches and future prospects. In animal modeling, neuropathic pain paradigms have evolved from traditional mechanical compression to composite models that combine dynamic displacement and chemical stimulation. Cancer‑induced pain mode

LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.

Dysregulation of target genes of nonsense-mediated decay (NMD) in the brain remains sparsely known in tauopathies. PS19 transgenic mice expressing human mutant P301S tau were evaluated for levels of lncRNA Gas5, a target of NMD. The results show Gas5 decreased in the brains of PS19 mice as they aged. We evaluated the consequences of blocking the NMD-mediated turnover of Gas5 using a small molecule administered intranasally to PS19 mice. The results show NPC86 disassociated Upf1 and Gas5, thereby hindering NMD. NPC86 treatment increased Gas5 levels in the cortex of male PS19 mice concurrent wit

Роль микроглии в синаптогенезе, синаптической и синаптической пластичности в физиологических условиях и в нарушениях центральной нервной системы.

Микроглии являются постоянными иммунными клетками мозга, которые были широко изучены для их иммунного наблюдения и фагоцитоза. В последние годы постепенно признается важная роль микроглии в синапсовом образовании, ликвидации и пластичности. Синапсы являются основным режимом связи между нейронами. Они постоянно меняются в количестве и пластичности на протяжении всего жизненного цикла, который является основой обучения и памяти. Микроглии являются сильно мотилированными, ветковыми формами, которые осуществляют мониторинг микроокружающей среды центральной нервной системы (КНС) и поощряют синапсов

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating t

Surgical techniques for patients with cancer-related neuropathic pain.

In this manuscript, we discuss the use of neuromodulatory techniques such as intrathecal therapy (IT) and spinal cord stimulation (SCS) for cancer pain in neuro-oncology patients. Currently, cancer pain management relies on oral opioids, which have a number of systemic side effects particularly in a chronic setting. An escalation of pain therapy for pain relief, such as neuromodulation, is necessary to improve neuro-oncology patients' quality of life. The paper highlights the need for more comprehensive pain management for patients during and after receiving cancer therapies. IT allows analges

The Power of Movement: How Exercise Influences Chemotherapy-Induced Peripheral Neuropathy.

As the number of cancer patients and survivors increases, we face a rising challenge: the long-term impact of the adverse effects of cancer treatment. One of the known adverse effects is chemotherapy-induced peripheral neuropathy (CIPN), which courses with pain complaints. The treatments of CIPN have reduced efficacy. The neurobiological causes of CIPN have been mainly ascribed to peripheral nerve damage, but recent studies show effects in the brain, namely in the descending pain modulatory systems. Physical exercise seems to be associated with better outcomes in CIPN patients, but the mechani

Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familia

TAFRO syndrome: current perspectives.

Multicentric Castleman's disease (MCD), a distinct subtype of Castleman's disease, is a rare, nonneoplastic, lymphoproliferative disorder. Patients with MCD present with systemic symptoms and multiple lymphadenopathy. Lymph node biopsy is necessary for the diagnosis of various histological MCD patterns including hyaline vascular, plasma cell, and mixed types. Human herpesvirus 8 (HHV8) infection was identified as an important etiology of MCD among immunocompromised patients such as those positive for human immunodeficiency virus. Although HHV8-negative MCD was reported in immunocompetent patie

Influence and Role of Regulatory B Cells in Organ Transplantation: The State of the Art, Prospects, and Emerging Insights.

B cells have attracted increasing interest in the field of organ transplantation due to their newly discovered immunoregulatory properties in alloimmune responses. Traditionally, B cells have been primarily associated with adaptive immunity to foreign substances and alloreactive immune response to allografts, differentiating into antibody-producing plasma cells or memory cells upon antigen recognition and T cell collaboration. However, the existence of B cells with regulatory functions (Bregs) in humans has been widely confirmed, highlighting the presence of this subset, which has immunosuppre

Роль оси CXCL12/CXCR4/CXCR7 в когнитивном повреждении, связанном с нейродегенеративными заболеваниями.

Нейродегенеративные заболевания, включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS) и амиотропический боковой склероз (ALS), характеризуются постепенной нейронной потерей и когнитивным расстройством (CI). Ось Cystine-X-cystine chemokine ligand 12 (CXCL12)/CXC chemokine рецептор типа 4 (CXCR4)/CXC chemokine рецептор типа 7 (CXCR7) стала критическим молекулярным путем развития CI в этих расстройствах. В настоящем обзоре изучается роль этой оси в патогенезе интеллигенции в связи с этими нейродегенеративными заболеваниями, синтезируются имеющиеся данные и ее посл

Targeted drug approvals in 2023: breakthroughs by the FDA and NMPA.

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Роль окситоцина и Васопрессина в нейропсихиатрических расстройствах: терапевтический потенциал агонистов и антагонистов.

Окситоцин (OT) и вазопрессин (AVP) являются гипоталамическими нейропептидами, которые традиционно ассоциируются с их регулирующей ролью в размножении, гомеостазисе воды и социальном поведении. Интересно, что в последние годы эта роль расширилась и эти нейропептиды стали лечебными мишенями для различных нейропсихиатрических заболеваний, таких, как аутизм, зависимость, шизофрения, депрессия и тревожное расстройство. В связи с химическими и физическими характеристиками этих нейропептидов, включая короткий период полураспада, плохое проникновение через мозговые барьеры, беспорядочность для AVP и O

Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.

The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic

Autonomic control of ventricular function in health and disease: current state of the art.

PurposeCardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure.MethodsData from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clini

Fc Epsilon RI-Neuroimmune Interplay in Pruritus Triggered by Particulate Matter in Atopic Dermatitis Patients.

Atopic dermatitis (AD) is the most common chronic relapsing neuroinflammatory skin disease that is characterized by a complex and multifactorial pathophysiology. It reflects a profound interplay between genetic and environmental factors, and a recently disclosed neuroimmune dysregulation that drives skin barrier disruption, pruritus, and microbial imbalance. In terms of the key external environmental players that impact AD, air quality and itch severity linkage have been thoroughly researched. The impact of ambient air pollutants including particulate matter (PM) and AD pruritic exacerbation h

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023.

With 54 new drugs and seven cellular and gene therapy products, the approvals by the US Food and Drug Administration (FDA) recovered 2023 from the 2022 dent back to the levels of 2020-2021. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition ("first-in-indication"), first drug using a novel molecular mechanism ("first-in-class"), and "next-in-class," i.e., a drug using an already exploited molecular mechanism. We identify four (7%) "first-in-indication," 22 (36%) "first-in-class," and 35 (57%) "next-in-class

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… Therefore, GABA modulators have been investigated in the treatment of postpartum depression. Zuranolone is an oral, synthetic neuroactive steroid and a positive allosteric modulator of the GABA A receptor (Heo 2023b ). …

When to investigate for secondary hyperhidrosis: data from a retrospective cohort of all causes of recurrent sweating.

Background: Identification of underlying diseases is crucial for secondary hyperhidrosis management, but data are lacking to guide appropriate investigation.Objective: To describe aetiologies of recurrent sweating in a hospital setting and the diagnostic performance parameters of their respective clinical/biological features.Patients and Methods: We performed a monocentric evaluative study in a tertiary care centre. Patients with recurrent generalised sweating were selected via the Clinical Data Warehouse (CDW) by screening all electronic hospital documents from the year 2018 using a keyword-b