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P2X7 Рецептор рентгеновских заболеваний: общие молекулярные механизмы и терапевтические последствия.

Редкие заболевания (РЛ) в индивидуальном порядке редко встречаются, но в совокупности они затрагивают большое число людей во всем мире, и подавляющее большинство из них по-прежнему не имеют эффективных методов лечения, позволяющих вести борьбу с заболеваниями. Благодаря достижениям в области геномики и платформ для обмена данными исследования все чаще переходят от одного заболевания к поиску конвергентных молекулярных путей, которые можно было бы использовать в различных клинически отличных друг от друга структурах. В этом контексте purinergic P2X7 рецептор (P2X7R) превратился в предполагаемую

Четвертое Международное совещание ИСЕВ, ISEV2015.

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Neutrophils unveiled in chronic lymphocytic leukemia.

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strat

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… These receptors activate a series of cellular processes leading to the release of the chromatin-protein mixture into the extracellular space. …

Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.

Acylation modification plays a crucial role in tumor progression through altering protein homeostasis and localization. However, a comprehensive summary of these processes is lacking. Protein acylation modifications are comprehensively summarized and categorized based on the amino acids that are modified. This review focuses on modifications of the lysine (acetylation, succinylation, crotonylation, malonylation, and glutarylation) and cysteine (myristoylation and palmitoylation) groups. The key enzymes involved in the occurrence and erasure of different modifications, as well as their effects

Emerging therapeutic strategies in glioblastsoma: drug repurposing, mechanisms of resistance, precision medicine, and technological innovations.

Glioblastoma (GBM) is an aggressive Grade IV brain tumor with a poor prognosis. It results from genetic mutations, epigenetic changes, and factors within the tumor microenvironment (TME). Traditional treatments like surgery, radiotherapy, and chemotherapy provide limited survival benefits due to the tumor's heterogeneity and resistance mechanisms. This review examines novel approaches for treating GBM, focusing on repurposing existing medications such as antipsychotics, antidepressants, and statins for their potential anti-GBM effects. Advances in molecular profiling, including next-generation

Exploiting Nanomedicine for Cancer Polychemotherapy: Recent Advances and Clinical Applications.

The most important limitations of chemotherapeutic agents are severe side effects and the development of multi-drug resistance. Recently, the clinical successes achieved with immunotherapy have revolutionized the treatment of several advanced-stage malignancies, but most patients do not respond and many of them develop immune-related adverse events. Loading synergistic combinations of different anti-tumor drugs in nanocarriers may enhance their efficacy and reduce life-threatening toxicities. Thereafter, nanomedicines may synergize with pharmacological, immunological, and physical combined tre

Advances in Drug Delivery and Biomaterials: Facts and Vision.

Drug delivery and biomaterials are different fields of science but, at the same time, are tightly related and intertwined. The 2018 CRS Italy Chapter Annual Workshop aims to explore recent advances in design and development in these areas. Many colleagues from Europe participated to the Workshop, stimulating the discussion. To foster the discussion on recent research and networking opportunities, especially among younger attendees, all poster-presenting authors were asked to provide a short talk. The very friendly and stimulating atmosphere allowed the attendees to explore new frontiers and ta

Genetic factors and management strategies in aortic health: a literature review of inherited aortopathy.

Inherited aortopathies, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, are genetic disorders characterized by structural abnormalities of the aorta that predispose individuals to life-threatening complications like aneurysms and dissections. These conditions result from mutations in genes essential for maintaining aortic wall integrity, such as FBN1, TGFBR1, and COL3A1, affecting extracellular matrix components and the transforming growth factor-beta (TGF-β) pathway. Marfan syndrome has a prevalence of approximately 1 in 5000, while Loeys-Dietz syndrome and vascul

Всемирный конгресс молекулярного воображения 2022.

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… Deoxyribonucleoside salvage is a pathway in which cells consume deoxyribonucleosides from extracellular space for intracellular metabolism 2 . …

Current progress in CAR-based therapy for kidney disease.

Despite significant breakthroughs in the understanding of immunological and pathophysiological features for immune-mediated kidney diseases, a proportion of patients exhibit poor responses to current therapies or have been categorized as refractory renal disease. Engineered T cells have emerged as a focal point of interest as a potential treatment strategy for kidney diseases. By genetically modifying T cells and arming them with chimeric antigen receptors (CARs), effectively targeting autoreactive immune cells, such as B cells or antibody-secreting plasma cells, has become feasible. The emerg

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… Once released into the extracellular space, components of NETs can act as autoantigens, causing a break in self-tolerance. This cascade can ultimately precipitate the emergence of autoimmune reactions in susceptible individuals. …

Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?

Neuroblastoma (NB) is the most frequent extracranial pediatric tumor. Despite the current available multiple therapeutic options, the prognosis for high-risk NB patients remains unsatisfactory and makes the disease a clear unmet medical need. Thus, more tailored therapeutic approaches are warranted to improve both the quality of life and the survival of the patients. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that plays a key role in several diseases, including cancer. Preclinical and clinical studies in NB patients convergently indicate that MIF exerts pro-tumorige

Chronic stress and myeloid immunosuppression in cancer: A neuroimmune link to behavioral dysfunction.

Cancer progression is profoundly influenced by the complex interplay between the tumor microenvironment (TME), the immune system, and the patient's psychological state. This review delineates a critical pathway linking chronic stress to worsened cancer outcomes through inflammatory factors, anti-tumor immune suppression, and the induction of behavioral comorbidities. We postulate that sustained stress hormone signaling via the sympathetic nervous system and hypothalamic-pituitary-adrenal axis activation orchestrates a systemic immunosuppressive cascade. A central mechanism is the stress-induce

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… Nucleus Accumbens (NAc) Preservation of blood-brain barrier integrity prevents infiltration of peripheral inflammatory proteinases; stable extracellular space volume; normal neuronal physiology in MSNs. Maintenance of social interaction levels and typical reward processing. … space volume; normal neuronal physiology in MSNs. | Maintenance of social interaction levels and typical reward processing. | Cattaneo et al., 2020 This psychoneuroimmune framework is strongly supported by extensive clinical and translational data ( Table 1 ). …

Nucleotide Metabolism in Health and Disease.

Nucleotide metabolism is a fundamental biochemical process, providing the building blocks for DNA and RNA synthesis while driving critical cellular functions like energy transfer, signal transduction, and coenzyme synthesis. The precise regulation of nucleotide de novo synthesis, salvage, and degradation pathways is imperative for maintaining genomic stability and tissue homeostasis. Aberrations in these networks are increasingly recognized as primary drivers in various pathologies; notably, cancer cells exploit metabolic-functional reprogramming to enable rapid proliferation and therapeutic r

Hemostasis at the edge between physiology and cancer.

Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade-initiated by tissue factor, thrombin generation, and fibrin deposition-shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and

Роль антиоксидантов в множестве миеломы: диагностика, прогнозирование и терапевтическое применение: обзор сюжета.

Множественная миэлома (ММ) — злокачественная клетка B-клеток с моноклональными плазменными клетками, производящими нефункциональные иммуноглобулины. Она по-прежнему неизлечима из-за de novo или приобретенного сопротивления злокачественных клеток стандартным химиотерапиям. Таким образом, понимание механизма терапевтического сопротивления имеет важнейшее значение для разработки более эффективных мер вмешательства и определения новых целей лечения. MM - это разнородная болезнь, характеризующаяся сложными генетическими изменениями, которые имеют решающее значение для прогнозирования стратификации.

Cytokines in CAR T Cell-Associated Neurotoxicity.

Chimeric antigen receptor (CAR) T cells provide new therapeutic options for patients with relapsed/refractory hematologic malignancies. However, neurotoxicity is a frequent, and potentially fatal, complication. The spectrum of manifestations ranges from delirium and language dysfunction to seizures, coma, and fatal cerebral edema. This novel syndrome has been designated immune effector cell-associated neurotoxicity syndrome (ICANS). In this review, we draw an arc from our current understanding of how systemic and potentially local cytokine release act on the CNS, toward possible preventive and

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brai

Skeletal stem cells, a new direction for the treatment of bone and joint diseases.

Skeletal stem cells (SSCs) are tissue-specific stem cells characterized by their capacity for self-renewal and their position at the apex of the differentiation hierarchy. They can generate mature bone cell types essential for bone development, maintenance, and repair. Lineage tracing experiments have demonstrated that SSCs reside in the bone marrow, periosteum, and the resting zone of the growth plate. These findings not only enhance our understanding of bone growth and development mechanisms but also offer novel therapeutic strategies for conditions such as epiphyseal injuries, fractures, os

CAR T cells for pediatric CNS tumors: Clinical experience and reverse translational opportunities.

Central nervous system (CNS) tumors are one of the leading causes of cancer-related mortality in children and young adults. Despite decades of research, effective treatments for these tumors are still lacking and new therapeutic options are urgently needed. While chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of hematologic malignancies, these cellular therapies are only beginning to show evidence of activity in CNS tumors. In this review, we will discuss current CAR T cell clinical trials with a focus on trials in the pediatric CNS tumor space. In addition,

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progress

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… Oxidation of ascorbate in the extracellular space produces H 2 O 2 that enters the cell. In normal cells, ascorbate enters using SVCT2 and exhibits a high ability to metabolize H 2 O 2 , therefore iron metabolism is well maintained resulting in low cellular levels of labile iron (Fe 2+ ). … Oxidation of ascorbate in the extracellular space produces H 2 O 2 that enters the cell. In normal cells, ascorbate enters using SVCT2 and exhibits a high ability to metabolize H 2 O 2 , therefore iron metabolism is well maintained resulting in low cellular levels of labile iron (Fe 2+ ). …