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Adenosine A2A receptor-mediated interactions between Th1+ T cells and the choroid plexus epithelium via IFN-γ signalling control T-Cell infiltration in experimental autoimmune encephalomyelitis.

BACKGROUND: Adenosine A2A receptor (A2AR) antagonists have been consistently demonstrated to protect against multiple sclerosis (MS) pathology, but A2AR knockout (A2AR-/-) mice exhibit exacerbated immune injury, raising concerns regarding the use of A2AR antagonists for MS treatment. Here, we revealed the critical involvement of A2AR-mediated interactions between Th1+ T cells and the choroid plexus (ChP) epithelium in the pathology of experimental autoimmune encephalomyelitis (EAE). METHODS: We assessed the effects of A2AR knockout on ChP gateway activity and the interferon gamma (IFN-γ)-secr

The role of MSCs and CAR-MSCs in cellular immunotherapy.

Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer cells dendritic cells and macrophages, and they are of great importance in cellular immunotherapy. However, the use of CAR-related products faces several challenges, including the poor persistence of cells carrying CARs, cell dysfunction or exhaustion, relapse of disease, immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, low efficacy against solid tumors and immunosuppression by the tumor microenvironment. Another important cell therapy regimen involves mesenchymal stem c

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… MSCs are able to express intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 to increase the adhesion of MSCs and T cells and exert immunosuppressive effects on T cells [ 34 ]. The apoptosis of inflammatory T cells can be induced by the Fas/FasL signaling pathway [ 35 ]. …

Медицинский каннабис и признаки рака: критический обзор.

Онкология остаётся сложным и гетерогенным заболеванием, вызывающим значительную morbidity и mortality по всему миру, несмотря на продвижение в диагностике и лечении. Характерные черты онкологии раскрывают биологические механизмы, поддерживающие развитие опухолей и злокачественное эволюцию, а также помогают выявить потенциальные мишени для терапии. Медикаментозный кресс-масло в основном используется в онкологии для поддерживающей терапии, но растущее предклиническое доказательство указывает на взаимодействие с сигнальными путями, связанными с онкологией. Этот обзорный материал обобщает текущие

Понимание и решение проблемы сопротивления иммуномодуляционным соединениям IMID в множестве миеломы.

Лекарственные средства иммуномодулирования (ИМИД), включая линалидомид и помалидомид в сочетании с протеаозными ингибиторами, дексаметазоном и антиCD38 моноклональными антителами, играют центральную роль в лечении множественной миеломы (ММ) на новых диагностированных и рецидивированных этапах. Эти методы лечения значительно улучшили результаты лечения пациентов во всем мире, в результате чего IMID стали одной из опор MM-терапии. В настоящее время разрабатывается новое поколение более мощных соединений, называемых лигами-модуляторами цереблиона Е3 (CELMODs), которые могут заменить старые IMID.

TNFα inhibitors as targets for protective therapies in MSA: a viewpoint.

Multiple system atrophy (MSA) is a unique and fatal α-synucleinopathy associated with oligodendroglial inclusions and secondary neurodegeneration affecting striatum, substantia nigra, pons, and cerebellum. The pathogenesis remains elusive; however, there is emerging evidence suggesting a prominent role of neuroinflammation. Here, we critically review the relationship between αS and microglial activation depending on its aggregation state and its role in neuroinflammation to explore the potential of TNFα inhibitors as a treatment strategy for MSA and other neurodegenerative diseases.

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… Interleukin-8, intercellular adhesion molecule-1, and TNFα polymorphisms significantly increased the risk of MSA [ 68 ]. … Infante J Llorca J Berciano J Combarros O Interleukin-8, intercellular adhesion molecule-1 and tumour necrosis factor-alpha gene polymorphisms and the risk for multiple system atrophy J Neurol Sci 2005 228 11 13 10.1016/j.jns.2004.09.023 15607204 69. …

Взаимодействие между нейтрофилами и элементами барьера крови и мозга в контексте множественного склероза и ишемического разрушения.

Барьер мозга крови (BBB) представляет собой полупроницаемую мембрану в физиологических условиях, но в патологии, такой, как множественный склероз (MS) и ишемический инсульт (IS), его проницаемость возрастает. В этом обзоре основное внимание уделяется нейтрофильам и их взаимодействию с клеточными компонентами ББД: эндотелиальными клетками (ЭК), перицитами (ПХ) и астроцитами (АК). В настоящее время нейтрофилы получают больше внимания, главным образом благодаря передовым методам исследований, которые показывают сложность их населения. Кроме того, нейтрофилы способны засекать внеклеточные везикли

Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in hematologic diseases by modulating immune responses, supporting hematopoiesis, and remodeling the bone marrow microenvironment. Clinically, MSCs have been explored for graft-versus-host disease and hematopoietic stem cell transplantation support, while their applications in hematologic malignancies, including acute myeloid leukemia, multiple myeloma, and myelodysplastic syndromes, remain under investigation. However, therapeutic heterogeneity, safety concerns, and standardization challenges limit their clinical transla

Cataract Induced by Glucocorticoids.

Glucocorticoids (GCs) remain a cornerstone therapy for noninfectious uveitis and autoimmune disorders; however, chronic administration is strongly associated with sight-threatening complications, particularly glucocorticoid-induced cataracts (GIC). This comprehensive review synthesizes current evidence on the molecular pathogenesis, epidemiological patterns, and clinical management of GIC. Epidemiological analyses indicate that over 50% of patients receiving systemic corticosteroids for >60 days develop ocular complications, with cataract formation (36%) and glaucoma (16%) representing the pre

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-in

Hijacking the helpers: platelet and neutrophil trafficking in AML and therapeutic exploitation.

Acute myeloid leukemia (AML) remains one of the most aggressive and treatment-resistant hematologic malignancies, driven by clonal expansion of immature myeloid blasts in the bone marrow and peripheral blood. Current therapies-chemotherapy and targeted agents-are limited by poor marrow penetration, systemic toxicity, and rapid development of resistant clones, leaving long-term survival rates low. Clinicians face the persistent challenge of delivering effective therapy while minimizing harm. Platelets and neutrophils-beyond their classical roles in hemostasis and innate immunity-actively suppor

The role and mechanisms of mesenchymal stem cells in postoperative cognitive dysfunction via immune network regulation.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery. Its pathophysiology is complex. Neuroinflammation, oxidative stress, and immune imbalance are all involved in this process. These changes can affect postoperative recovery and reduce patients' quality of life. As population aging continues to increase, the prevention and treatment of POCD have become important clinical issues. In recent years, mesenchymal stem cells (MSCs) have attracted attention in neurological diseases because of their immunomodulatory and tissue healing abili

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… Intercellular adhesion molecule-1 (ICAM-1) serves as a co-receptor and also participates in the interaction between MSCs and immune cells [ 39 ]. These contact-dependent signals work together to promote immune tolerance and reduce inflammatory responses. … adhesion molecule-1 Regulatory T cells Transforming Growth Factor-β Interleukin-10 Indoleamine 2,3-Dioxygenase Prostaglandin E2 Hepatocyte Growth Factor Alzheimer’s disease Damage-associated molecular patterns High mobility group box 1 Toll-like receptor 4 The receptor for advanced glycation …

Modulating Post-Stroke Inflammation with FDA-Approved Immunotherapies: A Literature Review.

Stroke has been a topic of extensive research due to its debilitating consequences and high mortality. New findings offer a deeper understanding of specific factors that affect post-stroke recovery and identify therapies that may facilitate this process. One such factor is post-stroke neuroinflammation, a complex and time-dependent process in which acute immune responses can cause significant secondary inflammatory damage if the process is prolonged. Microglia are neuronal immune cells that are highly reactive to cytokines in the neuroenvironment and can, in turn, affect the inflammatory casca

Recent advances in biomimetic nanodelivery systems for cancer Immunotherapy.

Tumor immunotherapy is a developing and promising therapeutic method. However, the mechanism of tumor immune microenvironment and individual differences of patients make the clinical application of immunotherapy still very limited. The resulting targeting of the tumor environment and immune system is a suitable strategy for tumor therapy. Biomimetic nanodelivery systems (BNDS) coated with nanoparticles has brought new hope for tumor immunotherapy. Due to its high targeting, maximum drug delivery efficiency and immune escape, BNDS has become one of the options for tumor immunotherapy in the fut

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… At the cellular level, inflamed endothelial cells lead to upregulations such as vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1). …

Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.

Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its

NF-κB in biology and targeted therapy: new insights and translational implications.

NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other importa

Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

Тригеминальный контакт с артерией у людей, не имеющих тригеминиальной нейронгии - исследование MR.

Основная цель этого исследования состоит в том, чтобы предложить новую нервную сеть, названную BrainNeXt, для автоматизированного обнаружения расстройств мозга с использованием изображений магнитного резонанса (MRI). Кроме того, мы намерены изучить функционирование нашей предлагаемой сети по различным видам медицинского применения. Для обеспечения эффективности классификации изображений с высоким/громким изображением мы собрали новый набор данных МРТ, принадлежащих four Классы:1Болезнь Альцгеймера,2) хроническая ишемия,3) множественный склероз и ()4) контроль. Вдохновленные ConvNeXt, мы спроек

Intestinal barrier functions in hematologic and oncologic diseases.

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complica

The Role of the CREB Protein Family Members and the Related Transcription Factors in Radioresistance Mechanisms.

In the framework of space flight, the risk of radiation carcinogenesis is considered a "red" risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a

Molecular Impact of the Tumor Microenvironment on Multiple Myeloma Dissemination and Extramedullary Disease.

Multiple myeloma (MM) is the most common malignant monoclonal disease of plasma cells. Aside from classical chemotherapy and glucocorticoids, proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are used in the current treatment scheme of MM. The tumor microenvironment (TME) plays a fundamental role in the development and progression of numerous solid and non-solid cancer entities. In MM, the survival and expansion of malignant plasma cell clones heavily depends on various direct and indirect signaling pathways provided by the surrounding bone marrow (BM) niche. In a number

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… BET, Bromodomain and Extra-Terminal motif; CCL2, C-C Motif Chemokine Ligand 2; CXCR4, C-X-C Motif Chemokine Receptor 4, DKK1, Dickkopf-1; FGFR, fibroblast growth factor receptor; ICAM-1, intercellular adhesion molecule-1; IGF1R, insulin-like growth factor 1 receptor; IL6, Interleukin 6; MM, multiple …