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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

IL-34 в неврологическом гомеостазисе и его многогранная роль в заболеваниях центральной нервной системы.

Interleukin-34 (IL-34), лиганд для рецептора макрофажных колоний (CSF1R), играет незаменимую роль в развитии и поддержании гомеостазиса центральной нервной системы (CNS). В настоящем обзоре систематически излагаются основные механизмы, с помощью которых ось сигнала IL-34/CSF1R регулирует развитие, колонизацию и функциональную дифференциацию иммунных клеток-резидентов, включая микроглию и макрофаги, связанные с границами (BAM). Она подчеркивает свою роль в критических физиологических процессах, таких, как синаптическое обрезка, созревание нервной цепи и поддержание целостности мозгового барьера

CAR-T cell therapy in Multiple Myeloma: current status and future challenges.

The treatment of multiple myeloma has changed dramatically in recent years, with huge strides forward made in the field. Chimeric antigen receptor T-cell therapy targeting the B cell maturation antigen (BCMA) is now widely approved in relapsed refractory patients and is moving into earlier treatment lines. In this review, we discuss the evidence underpinning current regulatory approvals and consider mechanisms through which CAR-T cell efficacy could be improved. These include tackling BCMA-loss, harnessing the immunosuppressive tumour microenvironment, manufacturing concerns including the pote

Health and economic impact of caregiving on informal caregivers of people with chronic diseases in sub-Saharan Africa: A systematic review.

With a disproportionate burden of chronic diseases and severe shortage of health workers in sub-Saharan Africa, the region implicitly relies on informal caregivers (ICGs) to support the patients both within and outside the health facilities. The aim of this review is to systematically summarise evidence on the health and economic impact of caregiving on informal caregivers of patients with chronic diseases in sub-Saharan Africa. Medline (Ovid), CINAHL (EBSCOhost), PsycINFO (Ovid), Embase (Ovid), Global Health, and Web of Science databases were systematically searched to identify original artic

Evaluation and Treatment of Obesity and Its Comorbidities: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent mult

Cancer Immunotherapy with Immune Checkpoint Inhibitors-Biomarkers of Response and Toxicity; Current Limitations and Future Promise.

Immune checkpoint inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and tumour mutational burden, none of which are particularly sensitive or specific. Emerging tumour

Muscle and Bone Defects in Metastatic Disease.

PURPOSE OF REVIEW: The present review addresses most recently identified mechanisms implicated in metastasis-induced bone resorption and muscle-wasting syndrome, known as cachexia. RECENT FINDINGS: Metastatic disease in bone and soft tissues is often associated with skeletal muscle defects. Recent studies have identified a number of secreted molecules and extracellular vesicles that contribute to cancer cell growth and metastasis leading to bone destruction and muscle atrophy. In addition, alterations in muscle microenvironment including dysfunctions in hepatic and mitochondrial metabolism ha

Hiv and Lymphoma: from Epidemiology to Clinical Management.

Patients infected with human immunodeficiency virus (HIV) are at increased risk for developing both non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Even if this risk has decreased for NHL after the introduction of combination antiretroviral therapy (cART), they remain the most common acquired immune deficiency syndrome (AIDS)-related cancer in the developed world. They are almost always of B-cell origin, and some specific lymphoma types are more common than others. Some of these lymphoma types can occur in both HIV-uninfected and infected patients, while others preferentially develop

Proceedings of Reanimation 2022, the French Intensive Care Society International Congress.

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Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

От генов к окружающей среде: жизненный подход к профилактике педиатрических аутоиммунных заболеваний.

Аутоиммунные заболевания у детей, включая тип 1 Все более серьезной проблемой для здоровья людей во всем мире являются диабет, болезни селиака и детский артрит. Этот всплеск, слишком быстрый для того, чтобы его можно было объяснить только генетическими изменениями, подчеркивает важнейшую роль экологических факторов и подчеркивает настоятельную необходимость принятия активных превентивных мер. Этот обзор представляет собой комплексную, основанную на фактических данных основу для профилактики педиатрических аутоиммунных заболеваний по всему спектру услуг, начиная с первичной и заканчивая третичн

The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.

Neuropathic pain, a chronic condition arising from injury or dysfunction of the somatosensory nervous system, is characterized by persistent hypersensitivity and spontaneous pain. The chemokine receptor CCR5 (C-C motif chemokine receptor 5) has recently been identified as a critical mediator in neuroinflammation and neuropathic pain signaling pathways. Expressed on immune cells and neurons, CCR5 regulates immune cell recruitment and activation, thereby contributing to neuronal sensitization and maintenance of pain states. This review examines the currently characterized molecular mechanisms th

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… Stromal down-regulation of macrophage CD4/CCR5 expression and NF-κB activation mediates HIV-1 non-permissiveness in intestinal macrophages. PLoS Pathog. 2011;7:e1002060. doi: 10.1371/journal.ppat.1002060. 102. …

Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

The investigation of oncolytic viruses in the field of cancer therapy.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in

Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse.

Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patie

Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.

Hyaluronic acid (HA) is a linear polysaccharide and crucial component of the extracellular matrix (ECM), maintaining tissue hydration and tension. Moreover, HA contributes to embryonic development, healing, inflammation, and cancerogenesis. This review summarizes new research on the metabolism and interactions of HA with its binding proteins, known as hyaladherins (CD44, RHAMM), revealing the molecular basis for its distinct biological function in the development of cancer. The presence of HA on the surface of tumor cells is a sign of an adverse prognosis. The involvement of HA in malignancy h

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

Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.

Acute myeloid leukemia (AML) is a high-risk hematologic malignancy with poor long-term survival and frequent relapse, sustained by leukemic stem cells, antigenic heterogeneity, and an immunosuppressive bone marrow niche. Although chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in B-cell malignancies, its application in AML is restricted by on-target myelotoxicity from antigen overlap with normal progenitors, heterogeneous and dynamic antigen expression, rapid T-cell exhaustion in suppressive microenvironments, limited manufacturing windows with compromised T-cell qual

Lysosomal storage diseases.

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage ca

Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.

In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review su