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Стратегия FACS-Proteomics, направленная на экстраклелектальную эмоциональную характеристику однофенотипов в биологических жидкостях: изучение роли лейкоцитных ЭМ в множественном склерозе.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Изоляция и протеомика внеклеточной везиклетки (ЭМ) от жидкостей организма сопряжены с трудностями из-за их большой неоднородности. Недавно мы продемонстрировали, что срабатывание ячеек (FACS) с флюоресцентной активацией эффективно изолирует весь ЭМ-диапазон непосредственно от нетронутых жидкостей тела, что позволяет провести всеобъемлющий протеомикальный анализ ЭМ. Здесь мы впервые описали однофенотипный ЭВ, сортируя лейкоцитные ЭВ (Leuko EVs) из периферической крови и слез здоровых добровольцев.Используя оптимизированный и запатентованный протокол пятна всего ЭМ-отсека,

Cardiomyopathy: pathogenesis and therapeutic interventions.

Cardiomyopathy is a group of disease characterized by structural and functional damage to the myocardium. The etiologies of cardiomyopathies are diverse, spanning from genetic mutations impacting fundamental myocardial functions to systemic disorders that result in widespread cardiac damage. Many specific gene mutations cause primary cardiomyopathy. Environmental factors and metabolic disorders may also lead to the occurrence of cardiomyopathy. This review provides an in-depth analysis of the current understanding of the pathogenesis of various cardiomyopathies, highlighting the molecular and

CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon.

Although current treatments for autoimmune diseases can effectively control symptoms, they rarely lead to cures and often require lifelong use, accompanied by considerable adverse effects. This emphasizes the urgent need for more targeted therapies that offer long-term efficacy and curative potential. Chimeric antigen receptor (CAR) T-cell therapy presents a promising option by specifically targeting and eliminating autoreactive B cells, with the potential to reset the patient's immune system and promote long-term immune balance. Originally developed for treating hematologic malignancies, wher

Oncolytic Adenovirus: Prospects for Cancer Immunotherapy.

Immunotherapy has moved to the forefront of modern oncologic treatment in the past few decades. Various forms of immunotherapy currently are emerging, including oncolytic viruses. In this therapy, viruses are engineered to selectively propagate in tumor cells and reduce toxicity for non-neoplastic tissues. Adenovirus is one of the most frequently employed oncolytic viruses because of its capacity in tumor cell lysis and immune response stimulation. Upregulation of immunostimulatory signals induced by oncolytic adenoviruses (OAds) might significantly remove local immune suppression and amplify

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… For instance, Ad5 binds predominantly to the coxsackievirus and adenovirus receptor (CAR/CXADR) ( Lopez-Gordo et al., 2017 ), whereas adenovirus type 3 (Ad3) has a high binding affinity for desmoglein-2 ( Wang H. et al., 2011 ), CD46, CD80, or CD86 ( Hall et al., 2009 ). … Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat. Med. 17:2270. 10.1038/nm.2270 Wang P., Li X., Wang J., Gao D., Li Y., Li H., et al. (2017). Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent. Nat. …

Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.

BACKGROUND: Cancer represents a major global public health issue, and recent research has focused on improving the efficacy of existing therapeutic approaches. In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment-resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance. MAIN BODY: Combination-based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have b

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… ‐2 and CD46. … Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat Med. 2011;17(1):96‐104. 10.1038/nm.2270 91. Havunen R, Siurala M, Sorsa S, et al. Oncolytic adenoviruses armed with tumor necrosis factor alpha and interleukin‐2 enable successful adoptive cell therapy. …

CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.

Chimeric Antigen Receptor (CAR)-T cell therapy has rapidly emerged as a groundbreaking approach in cancer treatment, particularly for hematologic malignancies. However, the application of CAR-T cell therapy in solid tumors remains challenging. This review summarized the development of CAR-T technologies, emphasized the challenges and solutions in CAR-T cell therapy for solid tumors. Also, key innovations were discussed including specialized CAR-T, combination therapies and the novel use of CAR-Treg, CAR-NK and CAR-M cells. Besides, CAR-based cell therapy have extended its reach beyond oncology

B-cell targeted therapeutics in clinical development.

B lymphocytes are the source of humoral immunity and are thus a critical component of the adaptive immune system. However, B cells can also be pathogenic and the origin of disease. Deregulated B-cell function has been implicated in several autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B cells contribute to pathological immune responses through the secretion of cytokines, costimulation of T cells, antigen presentation, and the production of autoantibodies. DNA-and RNA-containing immune complexes can also induce the production of type

Повышенное гликозилирование автоантител во время лечения истощения клеток B.

Для ряда хронических аутоиммунных заболеваний характерна повышенная аутоантибодиозная гликозилация Fab. Остается неясным, связаны ли Fab glycans со состоянием заболевания или развитием, но могут ли они служить его показателем. Многие аутоиммунные заболевания лечатся с помощью методов лечения истощения клеток В, что в первую очередь приводит к сокращению числа автоантител. Возникает вопрос, может ли терапия разрушения клеток B оказать воздействие на гликозилацию Fab. Здесь мы изучили продольное воздействие терапии истощения клеток B на гликозилацию Fab для общего ИгГ и IgG автоантифитов в ревма

Клеточная терапия ревматических и мышечных заболеваний.

Значительная часть пациентов, у которых диагностированы ревматологические и мускулоскелетные заболевания (РМ), демонстрируют устойчивость к традиционной терапии или испытывают повторяющиеся симптомы. Эти заболевания, к которым относятся аутоиммунные расстройства, такие, как множественный склероз, ревматоидный артрит и системный волшебный эритематос, характеризуются наличием автоматически реактивных клеток B, играющих решающую роль в их патогенезе. Стойкость этих самореактивных клеток В в лимфатических органах и воспаленных тканях снижает эффективность таких моноклонных антител, как ритуксимаб,

HMGB1: новая биомаркировка и лечебная цель аутоиммунной и аутовоспалительной кожных заболеваний.

Вставка 1 группы высокой подвижности (HMGB1) выражена почти во всех человеческих клетках. Во время активации клеток и клеточной смерти нуклеопротеин HMGB1 может перемещаться в внеклеточное пространство, тем самым посредничая ранним подстрекательским ответом как сигнализация или молекулярный рисунок, связанный с повреждением (DAMP). Внешнеклеточный HMGB1 взаимодействует с иммунными клетками, связываясь с системой распознавания рецепторов Toll-подобных (TLR), включая TLR2 и TLR4, и рецептором для современных продуктов для гликации (RAGE), тем самым содействуя иммунной реакции для защиты хоста от

B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.

B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms un

Включаю T-камеры для очистки.

Те, кто занимается клетками, представляют собой преобразующий подход к иммунотерапии рака, стимулирующий использование двухуровневых и многообразных антителных конструкций для перенаправления китотоксичности Т-клеток на злокачественные клетки. Эти молекулы соединяют клетки Т и клетки опухоли, одновременно связывая CD3 с Т клетками и связанными с опухолью антигенами на раковые клетки, что позволяет точно определить иммунную направленность даже в иммунологических "холодных" опухолях. Последние достижения включают в себя условное использование Т-клеток, активированное микроэкологическими протезам

Review of Paraneoplastic Syndromes in Children with Malignancy.

A paraneoplastic syndrome (PNS) is a set of symptoms and signs that can accompany the formation of a cancer but is not due to its direct infiltration or metastasis. PNS results from the secretion of peptides or hormones by tumor cells or from an immunological cross-reaction between the tumor antigens and host antigens. In the adult population, PNS affects up to 15% of patients with cancer, but data on pediatric patients remain lacking. The remarkable fact is that PNS can precede an oncology diagnosis, even by months or years. PNS can involve virtually any organ of the human body. In children,

Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases.

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionized the treatment landscape of haematological malignancies. The past 2 years has witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis and anti-synthetase syndrome. In comparison with existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promi

Shaping the future of multiple myeloma with artificial intelligence and digital twins: from concept to clinic.

Multiple myeloma (MM) is an incurable hematological malignancy with significant clinical and biological heterogeneity. Despite development and refinement of numerous prognostic models for MM, challenges with accurate and reliable risk stratification remain, highlighted by unexpected, early relapse or progression of disease in patients termed functional high-risk (FHR). To improve decision-making and optimise outcome, there is an unmet need for precise identification of high-risk (HR) patients, to enable tailored therapeutic strategies. With a complex and rapidly evolving treatment landscape, a

Inflammation in Cardiomyopathies: Cellular Mechanisms Across Cardiac Phenotype.

Cardiomyopathies are traditionally classified by structural and genetic phenotypes, but emerging evidence highlights chronic myocardial inflammation as a pivotal driver of disease progression across different etiologies. This review synthesizes the current literature on the cellular and molecular inflammatory mechanisms underlying hypertrophic cardiomyopathy, Anderson-Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy. Across these distinct conditions, endogenous triggers such as metabolic substrates, misfolded amyloid fibrils, mechanical stress, or v

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

Cancer immunotherapies: A hope for the uncurable?

The use of cancer immunotherapies is not novel but has been used over the decades in the clinic. Only recently have we found the true potential of stimulating an anti-tumor response after the breakthrough of checkpoint inhibitors. Cancer immunotherapies have become the first line treatment for many malignancies at various stages. Nevertheless, the clinical results in terms of overall survival and progression free survival were not as anticipated. Majority of cancer patients do not respond to immunotherapies and the reasons differ. Hence, further improvements for cancer immunotherapies are cruc

Integumentary System

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Cellular Therapy for Systemic Autoimmune Diseases: New Opportunities for Future Research and Interdisciplinary Collaboration.

Systemic autoimmune diseases (sAIDs) affect 1 in 10 people and represent a leading cause of death in women under the age of 65 years. Despite the emergence of targeted-biologic therapies, mortality rates for sAIDs have not improved. Emerging cellular therapies represent a promising therapeutic strategy for patients living with sAIDs given their potential to induce sustained remission and limit long-term exposure to glucocorticoids. Encouraging outcomes from a case series of patients with systemic lupus erythematosus, idiopathic inflammatory myopathy, and systemic sclerosis (SSc) have ignited c