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CAR-T cells targeting CD19 for the treatment of ANCA vasculitis.

Autoimmune anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) and glomerulonephritis is characterized by the presence of autoantibodies (so-called ANCA), which, by binding to the body's own antigens, lead to damaged blood vessels (vasculitis) and subsequently to organ damage, particularly of the kidneys. The primary endogenous antigens are the enzymes proteinase 3 (PR3) and myeloperoxidase (MPO) expressed by neutrophil granulocytes and monocytes. In addition to the autoantibodies, both T-cellular response to those autoantigens and monocyte/macrophage-mediated process

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… This neutrophil and monocyte activation leads to degranulation of toxic granula-proteins, generation of reactive oxygen species and formation of neutrophil extracellular traps (NETs) [ 15–18 ]. …

Прогресс в оказании поддержки в проведении обзора по множественным болезням, связанным с миеломой.

Множественная миелома (ММ) — неизлечимая порча плазменных клеток, характеризующаяся увеличением производства моноклонального иммуноглобулина. Пациенты с ММ подвержены высокому риску возникновения осложнений, связанных с заболеваниями. Остеолитическая болезнь костей one - из наиболее распространенных осложнений, связанных с заболеваниями, которые приводят к хронической боли и патологии скелета, что в значительной степени способствует высоким уровням заболеваемости и смертности среди пациентов с ОМ. Помимо стандартной антиММ-терапии, для улучшения качества жизни пациентов, страдающих ММ, необход

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future. Here, we introduce the various bone and joint diseases and their biology, and the conditions of organoid culture, comparing the in vitro models among 2D, 3D, and organoids. We summarize the differin

Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

Advanced multifunctional thermo- and electro-stimulative hydrogels for bone regeneration.

Bone defects caused by trauma, infection, tumors, osteoporosis, and diabetes disrupt skeletal integrity and impair regeneration. The healing process involves inflammatory hematoma formation, callus development, and remodeling, coordinated by diverse cells and signaling pathways. Conventional grafts and inorganic implants are limited by donor scarcity, immune rejection, and low bioactivity, necessitating more effective repair strategies. Recently, multifunctional smart hydrogels have emerged as a frontier in bone regeneration due to their biocompatibility, tunable structure, and ability to inte

Navigating through novelties concerning mCRC treatment-the role of immunotherapy, chemotherapy, and targeted therapy in mCRC.

Over the course of nearly six decades since the inception of initial trials involving 5-FU in the treatment of mCRC (metastatic colorectal cancer), our progressive comprehension of the pathophysiology, genetics, and surgical techniques related to mCRC has paved the way for the introduction of novel therapeutic modalities. These advancements not only have augmented the overall survival but have also positively impacted the quality of life (QoL) for affected individuals. Despite the remarkable progress made in the last two decades in the development of chemotherapy, immunotherapy, and target the

Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-β, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and o

Learn from antibody-drug conjugates: consideration in the future construction of peptide-drug conjugates for cancer therapy.

Cancer is one of the leading causes of death worldwide due to high heterogeneity. Although chemotherapy remains the mainstay of cancer therapy, non-selective toxicity and drug resistance of mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed to improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" is just passable, due to the potential toxicities to normal tissues and unsatisfactory synergistic effects, especially for the combined drugs with different pharmacokinetic properties. The drug

Bench-to-bedside review: Angiopoietin signalling in critical illness - a future target?

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and - despite many unanswered questions - therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting mu

The therapeutic potential of colchicine in oncology studies: from structural modification and targeted delivery to clinical management.

Colchicine, a classical microtubule-targeting agent (MTA), exhibits remarkable anti-tumor potential, but its clinical translation is severely restricted by a narrow therapeutic window, systemic off-target toxicity, and complex pharmacokinetic vulnerabilities. Driven by the objective of "toxicity reduction and efficacy enhancement," this review comprehensively summarizes colchicine's multidimensional translational research. First, precise chemical modifications of its tricyclic scaffold and multi-site synergistic strategies are analyzed, exploring structure-activity relationship (SAR) mechanism

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogeno

The role of biomarkers in the management of bone-homing malignancies.

Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer. Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for th

Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.

Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies-autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients' quality of life. To date, there is still no drug target that can act in rheumatoid arthritis. Therefore, the search for novel drug targets has become urgent. Due to their unique physicochemical properties, calcium ions play an important role in all cellula

S1PR4-dependent Воздействие этрасимод на первичную активацию миэлоидных иммунных клеток человека.

ИСТОРИЯ ВОПРОСА: Sphingosine-1-phosphate (S1P) и его five Рецепторы S1PR1-5 играть важную роль в миграции, дифференциации и активации различных иммунных клеток. Недавно было утверждено несколько модуляторов S1PR с особой избирательностью для лечения различных подстрекательских заболеваний. Среди них Озанимод, S1PR1/5 Модулятор, утвержденный для лечения язвительного колита и множественных склерозов, и Etrasimod, S1PR1/4/5 Модулятор, утвержденный для лечения язвительного колита. Хронические самовоспалительные заболевания, такие, как вспыльчивые болезни кишечника (ББК) и язвительный колит, характ

The Role of Thalidomide and Its Analogs in the Treatment of Hereditary Hemorrhagic Telangiectasia: A Systematic Review.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations and telangiectases, in which the endothelium and immune system play a role in the pathophysiology. Therefore, treatments with antiangiogenic properties which are also regarded as immunomodulators were demonstrated to play an important role in treatment. This systematic review aimed to gather the accumulated information of the use of thalidomide and its analogs in the treatment of HHT. Methods: In this systematic review, publications that were published up to March 2024 and met the

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… Impaired Release of Neutrophil Extracellular Traps and Anemia-Associated T Cell Deficiency in Hereditary Hemorrhagic Telangiectasia. J. Clin. Med. 2020;9:767. doi: 10.3390/jcm9030767. 40. Al-Samkari H. …

Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment.

OBJECTIVE: Interleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potenti

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… Neutrophil extracellular traps and interleukin 17 in ankylosing spondylitis. Mediterr J Rheumatol. (2021) 32:182–5. 10.31138/mjr.32.2.182 41. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, et al. …

Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer.

BackgroundThere is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes.MethodsThe heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was vali

Регулирование глюкозы как движущая сила аутоиммунной мимикрии, воспаления и психиатрических Симптомов: обзор наизусть.

Происхождение глицемии влияет на широкий спектр психических и физиологических симптомов. Многие психические заболевания связаны с плохим регулированием глюкозы. Антиядерные антитела (АНА), широко используемые для выявления аутоиммунных заболеваний, могут иногда отражать переходную метаболическую активацию иммунной системы, а не хроническую патологию. Имеющиеся данные свидетельствуют о том, что регулирование глюкозы, включая глицемическую изменчивость, реактивную гипогликемию и постприндиальные шипы, может вызвать системное воспаление, нейропсихиатрические симптомы и временное производство авто

Протеомический анализ показывает, что потенциальные молекулы могут выступать посредником в кортикальной патологии и выявлять возможные биомаркеры в животной модели множественного склероза.

ВВЕДЕНИЕ: Множественный склероз (MS) представляет собой сложное нейродегенеративное заболевание, характеризующееся повторяющимися вспышками, обезвоживанием, повреждением аксона и последующей потерей функции. MS представляет широкий спектр клинических курсов, прогрессивные формы которых приводят к необратимой неврологической инвалидности. Кортикальные демиелионирующие повреждения имеют ключевое значение для патологии этих прогрессивных форм, и в последние десятилетия они приобретают решающее значение в силу их тесной связи с физической инвалидностью и когнитивным упадком. Несмотря на это, механ