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Neovascular Age-Related Macular Degeneration: Therapeutic Management and New-Upcoming Approaches.

Age-related macular degeneration (AMD) constitutes a prevalent, chronic, and progressive retinal degenerative disease of the macula that affects elderly people and cause central vision impairment. Despite therapeutic advances in the management of neovascular AMD, none of the currently used treatments cures the disease or reverses its course. Medical treatment of neovascular AMD experienced a significant advance due to the introduction of vascular endothelial growth factor inhibitors (anti-VEGF), which dramatically changed the prognosis of the disease. However, although anti-VEGF therapy has be

Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigene

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… In metabolic dysfunction‐associated steatohepatitis (MASH), neutrophil extracellular traps (NETs) induce hepatocyte senescence that in turn propagates steatosis and fibrosis [ 168 ], and in metabolic dysfunction‐associated steatotic liver disease (MASLD), senescent hepatocyte burden correlates directly …

A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.

BACKGROUND: CAR-T cell gene therapy has advanced from an experimental concept to a standard curative treatment for selected hematologic malignancies. Substantial clinical evidence has established CAR-T therapy as a cornerstone for relapsed/refractory B-cell malignancies and multiple myeloma, demonstrating durable, long-term remissions. In 2025, the U.S. Food and Drug Administration (FDA) eliminated the Risk Evaluation and Mitigation Strategy (REMS) requirement, reflecting improved clinical management of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome

CAR T cell therapy for refractory pediatric systemic lupus erythematosus: a new era of hope?

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE invol

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… Autoantibodies are thought to contribute to SLE pathogenesis in many ways, including from deposition as well as direct damage to tissues, stimulation of interferon production and signaling, and binding to and increasing the immunogenicity of neutrophil extracellular traps [ 32 , 33 ]. …

Extracellular vesicles in multiple myeloma-bone marrow niche crosstalk: from cellular dialogue to clinical perspectives.

Multiple myeloma (MM) is a haematological neoplasia defined by the clonal expansion of malignant plasma cells within the intricate and dynamic ecosystem of the bone marrow (BM). Although genetic aberrations intrinsic to tumour cells play a critical role in MM initiation, the advancement and aggressiveness of the disease are heavily influenced by ongoing signalling exchanges and persistent interactions with the surrounding microenvironment. Extracellular vesicles (EVs) are increasingly recognized as essential messengers in this reciprocal communication, acting as membrane-encapsulated vehicles

The effect of pamidronate delivery in bisphosphonate-naïve patients on neutrophil chemotaxis and oxidative burst.

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ), a morbid condition associated with bisphosphonate administration, has not been fully elucidated. Recent research utilizing a murine model has revealed that the neutrophil becomes dysfunctional following exposure to bisphosphonates. Accordingly, the impairment of neutrophil function could play an important role in the pathogenesis of MRONJ via an infectious mechanism mediated by the suppression of the innate immune system. Currently, the existing human data are insufficient to substantiate this theory. To investigate, we i

Passive Monoclonal and Polyclonal Antibody Therapies

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The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer "Omics".

Mass spectrometry (MS) is an essential analytical technology on which the emerging omics domains; such as genomics; transcriptomics; proteomics and metabolomics; are based. This quantifiable technique allows for the identification of thousands of proteins from cell culture; bodily fluids or tissue using either global or targeted strategies; or detection of biologically active metabolites in ultra amounts. The routine performance of MS technology in the oncological field provides a better understanding of human diseases in terms of pathophysiology; prevention; diagnosis and treatment; as well a

The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis.

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the t

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… Furthermore, leukocyte activation induced by their direct interaction with the tumor mass causes an increase in pro-thrombotic activity through the expression of specific adhesion molecules on the lymphocyte surface and through the formation of neutrophil extracellular traps (NETs), an intricate network … Neutrophil Extracellular Traps in Cancer Therapy Resistance. Cancers. 2022;14:1359. doi: 10.3390/cancers14051359. 27. Tafur A.J., Wysokinski W.E., McBane R.D., Wolny E., Sutkowska E., Litin S.C., Daniels P.R., Slusser J.P., Hodge D.O., Heit J.A. …

Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.

Osteoblasts are mainly derived from mesenchymal stem cells in the bone marrow. These stem cells can differentiate into osteoblasts, which have the functions of secreting bone matrix, promoting bone formation, and participating in bone remodeling. The abnormality of osteoblasts can cause a variety of bone-related diseases, including osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, with the side effects caused by the application of PTH drugs, biphosphonate drugs, and calmodulin drugs, people have carried out more in-depth research on the mechanism of osteoblast

Advances in materials used for minimally invasive treatment of vertebral compression fractures.

Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and

Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review.

The prevalence of cancers has actually increased during the last few decades, affecting almost all human societies. Despite progress in therapeutic protocols, cancer is still the main cause of global human mortality. Although the advancement of modern immunotherapeutic approaches can increase the survival rate of cancer patients, new modalities are essential for improved therapeutic outcomes. Extracellular vesicles (EVs) are nanosized particles and are used for cell-free approaches instead of direct whole cell-based administration. It has been thought that EVs can reduce the risks and side eff

Targeting the NLRP3 inflammasome in kidney disease: molecular mechanisms, pathogenic roles, and emerging small-molecule therapeutics.

Inflammatory responses represent a core pathological process driving the progression of both acute and chronic kidney diseases. As a key effector of the innate immune system, the NLRP3 inflammasome is widely activated in renal resident cellsand infiltrating immune cells, positioning it as a critical nexus linking metabolic dysregulation, cellular stress, and tissue injury. Accumulating preclinical and clinical evidence in recent years demonstrates that aberrant activation of the NLRP3 inflammasome directly promotes glomerular damage, tubulointerstitial inflammation, fibrosis, and vascular dysf

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… In SLE, abundant neutrophil extracellular traps (NETs) are released into the circulation. These NETs directly activate the NLRP3 inflammasome in both human and murine macrophages, triggering robust IL-1β and IL-18 secretion. …

C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions.

Physiologically, the C-X-C chemokine receptor type 4 (CXCR4) signalling pathway regulates key aspects of tumor behavior (growth, metastasis, and immune evasion) and modulates immune system function. Anticancer researchers have identified peptide-based CXCR4 antagonists as promising candidates due to their high targeting specificity and favorable safety profiles. This review provides an analytical examination of CXCR4 antagonistic peptides,the selective Mavorixafor (X4P-001), an advanced, selective CXCR4 inhibitor. When Mavorixafor binds to the same location as C-X-C motif chemokine ligand 12 (

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… The role of neutrophil extracellular traps in cancer metastasis Clin Transl Med 10 2020 e126 10.1002/ctm2.126 PMC7580875 32961033 79 Warren J.T. Walkovich K.J. Bolyard A.A. …

The Metabolic Features of Osteoblasts: Implications for Multiple Myeloma (MM) Bone Disease.

The study of osteoblast (OB) metabolism has recently received increased attention due to the considerable amount of energy used during the bone remodeling process. In addition to glucose, the main nutrient for the osteoblast lineages, recent data highlight the importance of amino acid and fatty acid metabolism in providing the fuel necessary for the proper functioning of OBs. Among the amino acids, it has been reported that OBs are largely dependent on glutamine (Gln) for their differentiation and activity. In this review, we describe the main metabolic pathways governing OBs' fate and functio

The anti-inflammatory effects of mesenchymal stem cells and their research progress in hematopoietic stem cell transplantation: A comprehensive review.

Hematopoietic stem cell transplantation (HSCT) is frequently accompanied by severe inflammation-related complications, among which graft-versus-host disease (GVHD) stands out as one of the most common and life-threatening. As a systemic inflammatory disorder, GVHD arises when donor T cells recognize the recipient's alloantigens and initiate an immune attack. Currently, effective second-line treatment options remain scarce for patients with antibiotic-resistant or steroid-refractory GVHD. Mesenchymal stem cells (MSCs) are non-hematopoietic cells widely distributed in fetal and adult tissues and

The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.

The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintain

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… Ultimately, the platelet TLR4-NF-κB pathway and the neutrophil NLRP3 inflammasome form a transcellular interaction loop: CXCL4 induces formation of neutrophil extracellular traps (NETs), and mtDNA released from NETs in turn reactivates platelets to secrete IL-1β and IL-8 [ 85 – 87 ]. …

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

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… Neutrophil Extracellular Traps (NETs) secreted by activated neutrophils are extracellular fibrous networks consisting of DNA and proteins ( 58 ). …

Calcium Signalling in Breast Cancer Associated Bone Pain.

Calcium (Ca2+) is involved as a signalling mediator in a broad variety of physiological processes. Some of the fastest responses in human body like neuronal action potential firing, to the slowest gene transcriptional regulation processes are controlled by pathways involving calcium signalling. Under pathological conditions these mechanisms are also involved in tumoral cells reprogramming, resulting in the altered expression of genes associated with cell proliferation, metastatisation and homing to the secondary metastatic site. On the other hand, calcium exerts a central function in nocicepti

Парадокс ХЛА среди различных групп населения в процессе склероза: систематический обзор.

Множественный склероз (МС) свидетельствует о неоднородности курсов по болезням. Несмотря на то, что ХЛА ДРБ1*15::01 представляет собой самый сильный фактор генетического риска для MS-чувствительности, принося примерно в три раза больший риск, не влияет ли эта аллея на прогрессию заболеваний по-прежнему спорным образом. МЕТОДЫ: Этот систематический обзор был проведен с целью уточнения взаимосвязи между полиморфизмом ВЛА и ходом многочисленных склерозов с момента их создания до ноября 2025. A three- для учета ненезависимости статистических данных использовался метаанализ случайного воздействия н