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Роль микроглии в множественном склерозе: последствия для лечения ингибиторами тиросина Брютона.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, затрагивающее центральную нервную систему (CNS), характеризующееся воспалением и нейродегенерацией. Патофизиология MS, особенно его прогрессивные формы, включает различные клеточные компоненты, включая микроглию, являющиеся основными постоянными иммунными клетками CNS. В настоящем обзоре рассматривается роль микроглии в нейроинфламмации, ремонте тканей и нейронном гомеостазе, а также их участие в MS и изучаются потенциальные терапевтические стратегии, ориентированные на микроглиальную функцию.МЕТОДЫ: Поиск литературы, проведенн

Profile of pomalidomide and its potential in the treatment of myelofibrosis.

Myelofibrosis, a Philadelphia-negative myeloproliferative neoplasm, is in a new treatment era after the discovery of the JAK2V617F mutation in 2005. JAK inhibitors boast improvements in disease-related symptoms, splenomegaly, and overall survival; however, treatment of myelofibrosis remains a challenge, given the lack of improvement in cytopenias with these agents. Second-generation immunomodulatory agents, such as pomalidomide, have shown efficacy in myelofibrosis-associated anemia within multiple clinical trials. Five major pomalido-mide clinical trials have been completed to date, and demon

Уровни сериального синтоксина IL-6, IL-16, IL-18 и IL-36 у пациентов с множественным склерозом из Западного региона Саудовской Аравии: ассоциации с продолжительностью болезни и инвалидностью.

Справочная информация: Системное воспаление способствует патобиологии множественных склерозов (МС), однако данные о биомаркировке сыворотки, полученные от населения Ближнего Востока, остаются ограниченными. В ходе этого исследования была проведена оценка уровней содержания сыворотки ИЛ-6, ИЛ-16, ИЛ-18 и ИЛ-36 среди взрослых саудовцев и МS в сравнении с соответствующими мерами контроля за состоянием здоровья и были изучены связи с продолжительностью заболеваний, фенотипом, лечением и инвалидностью. Методы: Это одноцентральное, перекрестное, параллельное исследование по вопросам контроля за конк

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… No participants in this cohort were receiving injectable platform therapies (interferon-beta or glatiramer acetate) at the time of sampling, so this category does not appear in the analysis. 2.4. Clinical Assessment 2.4.1. …

Immune mechanism of low bone mineral density caused by ankylosing spondylitis based on bioinformatics and machine learning.

Background and Objective: This study aims to find the key immune genes and mechanisms of low bone mineral density (LBMD) in ankylosing spondylitis (AS) patients. Methods: AS and LBMD datasets were downloaded from the GEO database, and differential expression gene analysis was performed to obtain DEGs. Immune-related genes (IRGs) were obtained from ImmPort. Overlapping DEGs and IRGs got I-DEGs. Pearson coefficients were used to calculate DEGs and IRGs correlations in the AS and LBMD datasets. Louvain community discovery was used to cluster the co-expression network to get gene modules. The modu

The Oncolytic Virotherapy Era in Cancer Management: Prospects of Applying H-1 Parvovirus to Treat Blood and Solid Cancers.

Non-Hodgkin lymphoma (NHL) and leukemia are among the most common cancers worldwide. While the treatment of NHL/leukemia of B-cell origin has much progressed with the introduction of targeted therapies, few treatment standards have been established for T-NHL/leukemia. As presentation in both B- and T-NHL/leukemia patients is often aggressive and as prognosis for relapsed disease is especially dismal, this cancer entity poses major challenges and requires innovative therapeutic approaches. In clinical trials, oncolytic viruses (OVs) have been used against refractory multiple myeloma (MM). In pr

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… Autophagy ( 2013 ) 9 : 413 – 4 . 10.4161/auto.22867 23322106 PMC3590261 61 Naik S Nace R Barber GN Russel SJ Potent systemic therapy of multiple myeloma utilizing oncolytic vesicular stomatitis virus coding for interferon-beta . …

Zoledronic acid enhances lipopolysaccharide-stimulated proinflammatory reactions through controlled expression of SOCS1 in macrophages.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of nitrogen-containing bisphosphonate (NBP) use. Many studies have shown that BRONJ is limited to the jawbone and does not occur in the other bones. We hypothesized that BRONJ is related to local bacterial iections and involves the innate immune system. To examine the relationship between BRONJ and innate immunity, we examined the effects of NBPs on macrophages, one of the important cell types in innate immunity. The expression of toll-like receptor-4 (TLR4) in cells after pretreatment with zoledronic acid (ZOL) d

Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea.

Hematopoietic stem cell transplantation (HSCT) is a treatment for hematologic malignancies, immune deficiencies, or genetic diseases, ect. Recently, the number of HSCTs performed in Korea has increased and the outcomes have improved. However, infectious complications account for most of the morbidity and mortality after HSCT. Post-HSCT infectious complications are usually classified according to the time after HSCT: pre-engraftment, immediate post-engraftment, and late post-engraftment period. In addition, the types and risk factors of infectious complications differ according to the stem cell

Interleukin-6: obstacles to targeting a complex cytokine in critical illness.

Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and anti-inflammatory functions. An adequate understanding of the complex processes by which IL-6 signalling occurs is c

Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.

Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effec

Alternative management of Covid-19 infection.

Cytokine storm is a life-threatening complication of Covid-19 infection. Excessive cytokines are the products of hyperactive immune inflammatory response mounted by the host against the virus. There is no agreed treatment for cytokine storm. Three therapeutic agents with proven immune-modulatory properties in regular use in a wide range of inflammatory disorders (high dose intravenous immunoglobulin, Rituximab and thalidomide) are proposed for the treatment of cytokine storm. Safety and efficacy of the proposed treatment should be assessed by randomised controlled clinical trials. The use of t

Nanotherapeutics in the EU: an overview on current state and future directions.

The application of nanotechnology in areas of drug delivery and therapy (ie, nanotherapeutics) is envisioned to have a great impact on public health. The ability of nanotherapeutics to provide targeted drug delivery, improve drug solubility, extend drug half-life, improve a drug's therapeutic index, and reduce a drug's immunogenicity has resulted in the potential to revolutionize the treatment of many diseases. In this paper, we review the liposome-, nanocrystal-, virosome-, polymer therapeutic-, nanoemulsion-, and nanoparticle-based approaches to nanotherapeutics, which represent the most suc

Выражения и индукции MHC классов I и II в олигодендроцитах варьируются в зависимости от возраста.

Олигодендроглия, выражающая основные молекулы гистокомпьютерного комплекса (MHC), стала представлять большой интерес для многочисленных исследований склероза (MS), однако их роль в старении все еще проясняется. Используя мышей I и II классов MHC, мы сравнили выражение MHC у неонатальных, молодых взрослых (8-16 недель) и стареющих (52 недели) мышей в исходном режиме и после стереотактических родов AAV-GFAP-IFN. Мы обнаружили, что в наивном мозге и спинном мозге присутствовали MHC класса I, выражающие олигодендроглию, в то время как MHC II-выражающий олигодендроглия был виден только в спинном мо

Изучение роли Т клеток в болезни Альцгеймера и других нейродегенеративных заболеваниях: новые терапевтические идеи из Т Клеток на симпозиуме по мозгам.

В этой статье подытоживаются итоги первого симпозиума "Те ячейки в мозгу", проведенного в Колумбийском университете. Эксперты собрались для изучения роли Т клеток в нейродегенеративных заболеваниях. Ключевые темы включали характеристику антигенной иммунной реакции, репертуар T рецептора клеток (TCR), микробную этиологию болезни Альцгеймера (AD) и перекресток клеток микроглиа-Т с уделением особого внимания тому, как Т клетки влияют на нейроинфламмацию и АД биомаркеры, такие как амилоидная бета и тау. На симпозиуме были также рассмотрены иммунотерапии АД, включая исследование валацикловирусного

Dissecting Bone Marrow Fibrosis in Philadelphia-Negative Myeloproliferative Neoplasms: Multiple Roads Lead to Rome.

Philadelphia-negative myeloproliferative neoplasms (MPN), a spectrum of blood malignancies characterized by uncontrolled myeloid proliferation, persist as a key challenge in onco-hematology due to their intricate molecular background, heterogeneous clinical phenotypes, and variable prognoses. Although generally accepted as indolent disorders, a considerable fraction of MPN patients exhibit progressive, and sometimes accelerated, bone marrow fibrosis, reflecting a critical shift toward a more debilitating condition marked by an increased symptom burden. As marrow scarring advances, hematopoieti

Потенциальные цели микроглии в лечении нейродегенеративных заболеваний: механизм и терапевтические последствия.

В случае различных нейродегенеративных расстройств активируются микроглиальные клетки. Кроме того, дисфункциональная и гиперактивированная микроглия инициирует митохондриальную автофагию, окислительный стресс и патологическое накопление белка, заканчивающееся нейроинфламмацией, которая усугубляет повреждения допаминергических нейронов и вносит значительный вклад в патологию нейродегенеративного расстройства. Микроглиальная чрезмерная активация тесно связана с секрецией провоспалительных цитокинов, фагоцитозом травмированных нейронов и модуляцией нейротоксичной среды. В этом обзоре резюмируется

Cardiotoxicity of Non-Anthracycline Cancer Chemotherapy Agents.

Throughout the last decades, newly developed chemotherapeutic agents and immunotherapies that target signaling pathways have provided patients with better prognoses, improved their quality of life and increased survival rates, thus converting cancer to a stable chronic disease. However, non-anthracycline cancer chemotherapy agents and immunotherapies including human epidermal growth factor receptor 2 (HER2) inhibitors, vascular endothelial growth factor (VEGF) inhibitors, Bcr-Abl tyrosine-kinase inhibitors (TKI), proteasome inhibitors, immune checkpoint inhibitors and chimeric antigen receptor

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.

Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serv

Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets.

Cytotoxic CD4+ T lymphocytes are a unique subset of CD4+ T cells characterized by their cytokine secretion and cytolytic activity. Unlike traditional CD4+ helper T cells, cytotoxic CD4+ T lymphocytes exhibit similar cytotoxicity to that of CD8+ T cells, revealing unexpected plasticity in CD4+ T-cell functions. This flexibility suggests that CD4+ T cells can transform and acquire effector functions beyond their conventional functions, emphasizing their importance in various immune responses. Despite the identification of cytotoxic CD4+ T lymphocytes decades ago, recent advancements have broaden

Декодирование потенциального воздействия Plasma hsa-miR-24-3p и hsa-miR-181 d-3p экспрессии, Plasma IFN-__ Уровни и IFNG rs2069727 T/C Генетический вариант на риск множественных склерозов и глатирмерную ацетативную обработку.

Множественный склероз (MS) — аутоиммунное нейродегенеративное расстройство, наиболее распространенным подтипом которого является релапсирующий MS (RRMS). Интерферон (IFN-__) играет двойную роль в патогенезе MS. МикроРНК (миРНК) стали потенциальными диагностическими биомаркерами. В этом исследовании изучалось воздействие относительного выражения уровней Hsa-miR-24-3p и hsa-miR-181d-3p, плазмы IFN-__ и варианта IFNG rs2069727 T/C на риск MS, при этом оценивалась их взаимосвязь и диагностический потенциал. Это тематическое исследование состояло из двух совпадающих групп: группы генетического поли

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… The most used treatments for male patients with RRMS were interferon-beta (24.5%) and teriflunomide (24.5%), while the most frequently used treatment for female patients was teriflunomide (24.5%) (Table  2 ). …

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

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… Histone deacetylase inhibitors enhance cell killing and block interferon-beta synthesis elicited by infection with an oncolytic parainfluenza virus. Viruses. 2019;11:431. doi: 10.3390/v11050431. 67. Jaime-Ramirez A.C., Yu J.G., Caserta E., Yoo J.Y., Zhang J., Lee T.J., et al. …