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Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by ¹H HR-MAS NMR Metabolomics.

Multiple myeloma (MM) is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased ¹H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusteriza

Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks.

Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host's immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional,

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… Non-targeted liposomes localized to the tumor stroma, extracellular space and even to tumor-associated macrophages, while targeted immunoliposomes localized to the cytoplasm of cells bearing the corresponding antigen after being internalized. …

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme β-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB). Other treatment approaches, such as gene or chaperone therapies are still in expe

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… This facilitates receptor-mediated transcytosis of LNP through the BBB and into the brain extracellular space 187 . Notably, multifunctional nanopolymers (MNPs) have been also used for the therapy of CNS owing to the capacity to cross the BBB 188 . …

The Role of Irisin and Physical Activity in Breast Cancer.

BACKGROUND/AIM: Irisin, a myokine released during physical activity, has been proposed as a mediator of exercise's protective effects against breast cancer (BC). This review underscores the critical role of irisin in mediating the anticancer effects of exercise and its potential application in BC prevention and prognosis. MATERIALS AND METHODS: Studies published up to 2025 were identified in PubMed, Scopus, and Web of Science databases. Data from experimental models, clinical trials, and observational studies were analyzed with emphasis on exercise-induced irisin secretion and its effects on

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.

Glioblastoma (GBM) tumors are the most aggressive primary brain tumors in adults that, despite maximum treatment, carry a dismal prognosis. GBM tumors exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells and creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring the proliferation of immunosuppressive cells and inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, and CAR-T cell therapy, represent promising avenues f

Цереброспинный грипп и биомаркеры крови для нейроаксональных повреждений при многоразовом склерозе

После появления новых данных о том, что нейродегенеративные процессы в множестве склероза (MS) присутствуют на ранних стадиях, был проявлен активный научный интерес к биомаркерам нейро-аксональных повреждений в жидкостях организма пациентов, страдающих с склерозом. Недавно проведенные исследования позволили ввести новые потенциальные биомаркеры, но в то же время прояснили патогенетическое и клиническое значение хорошо известных. В настоящем документе рассматриваются имеющиеся данные о биомаркерах нейроаксональных повреждений в крови и цереброспинных жидкостях и освещается их связь с клинически

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… Figure 2 Membrane, cytoplasmic, and nuclear markers of neuroaxonal damage in the central nervous system (CNS) and their dynamics within three compartments (extracellular space, cerebrospinal fluid, and blood). …

Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.

Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway - has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequ

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

Patterns of Glomerular Injury: Histopathological Classification and Clinical Correlation.

Glomerular diseases represent a diverse group of conditions that significantly contribute to chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Understanding the histopathological patterns of glomerular injury is essential for accurate diagnosis, prognosis, and targeted therapy. This comprehensive review explores the morphologic, immunopathologic, and clinical characteristics of major glomerular disorders, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, immunoglobulin A nephropathy, lupus nephritis, and others. Histological

Acute Kidney Injury in Monoclonal Gammopathies.

Monoclonal gammopathies (MG) encompass a variety of disorders related to clonal expansion and/or malignant transformation of B lymphocytes. Deposition of free immunoglobulin (Ig) components (light or heavy chains, LC/HC) within the kidney during MG may result over time in multiple types and degrees of injury, including acute kidney injury (AKI). AKI is generally a consequence of tubular obstruction by luminal aggregates of LC, a pattern known as "cast nephropathy". Monoclonal Ig LC can also be found as intracellular crystals in glomerular podocytes or proximal tubular cells. Proliferative glom

No patient left behind: The promise of immune priming with epigenetic agents.

Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as

Preclinical efficacy of tasquinimod in myelodysplastic neoplasms: Restoring erythropoiesis and mitigating bone loss.

Myelodysplastic neoplasms (MDSs) are clonal disorders characterized by ineffective hematopoiesis, dysplasia, and a risk of transformation into acute myeloid leukemia. MDS is also associated with a higher incidence of osteoporosis, suggesting a complex interplay between hematopoiesis, the bone marrow (BM) microenvironment, and bone homeostasis. Targeting inflammation has emerged as a promising therapeutic strategy, particularly in lower risk MDS. Tasquinimod (TASQ) is a small-molecule inhibitor of the inflammatory alarmin S100A9, blocking its interaction with TLR4 and RAGE receptors. We investi

Nanoparticle-Based Drug Delivery System: A Patient-Friendly Chemotherapy for Oncology.

Chemotherapy is widely used to treat cancer. The toxic effect of conventional chemotherapeutic drugs on healthy cells leads to serious toxic and side effects of conventional chemotherapy. The application of nanotechnology in tumor chemotherapy can increase the specificity of anticancer agents, increase the killing effect of tumors, and reduce toxic and side effects. Currently, a variety of formulations based on nanoparticles (NPs) for delivering chemotherapeutic drugs have been put into clinical use, and several others are in the stage of development or clinical trials. In this review, after b

Liposomal Drug Delivery Systems and Anticancer Drugs.

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredien

Hematopoietic Niche Hijacking in Bone Metastases: Roles of Megakaryocytes, Erythroid Lineage Cells, and Perivascular Stromal Subsets.

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage "vicious cycle" of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of undera

Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among cancers worldwide. This review addresses the complex landscape of CRC, focusing on incidence, mortality trends, preventive strategies, and the evolving therapeutic approaches, particularly highlighting the role of platinum-based drugs like oxaliplatin (OXP). It also underscores the increasing burden of CRC, with factors such as westernized diets, aging populations, and genetic predispositions contributing to its prevalence. Therapeutically, early detection greatly enh

Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.

As an effective treatment for diabetes, islet transplantation has garnered significant attention and research in recent years. However, immune rejection and the toxicity of immunosuppressive drugs remain critical factors influencing the success of islet transplantation. While immunosuppressants are essential in reducing immune rejection reactions and can significantly improve the survival rate of islet transplants, improper use of these drugs can markedly increase mortality rates following transplantation. Additionally, the current availability of islet organ donations fails to meet the demand

Between Charybdis and Scylla-an Odyssey in AL amyloidosis: insights and learnings from a narrative review and case report series.

Being "between Scylla and Charybdis" is an idiom derived from Greek mythology to mean "between a rock and a hard place" and clinicians managing amyloid light-chain (AL) amyloidosis often find themselves in this predicament. AL amyloidosis is caused by monoclonal light chains, most commonly produced by CD-38 positive plasma cells in target organs. The disease usually involves significant cardiac and/or renal involvement, but the systemic nature of the disease often leads to variable and non-specific manifestations that can critically delay early diagnosis and treatment. Here, we present a case

Atlas (Human Microglia Atlas) раскрывает изменения в связанных с болезнями микроглиях в нейродегенеративных условиях.

Регулируемая микроглией активация, приводящая к нейроинфламмации, имеет решающее значение для развития и развития нейродегенеративных заболеваний. Мы построили атлас человеческих иммунных клеток мозга за счет интеграции nineteen Однонуклеусный RNA-seq и одноклеточные наборы данных RNA-seq из многочисленных нейродегенеративных условий, включая 241 образцы от пациентов с болезнью Альцгеймера, расстройством аутистического спектра, эпилепсией, множественным склерозом, заболеваниями тела Льюи, COVID-19, и здоровый контроль. Комплексный Human Microglia Atlas (HuMicA) включает в себя: 90,716 Ядра/кле

Cancer stem cell impact on clinical oncology.

Cancer is a widespread worldwide chronic disease. In most cases, the high mortality rate from cancer correlates with a lack of clear symptoms, which results in late diagnosis for patients, and consequently, advanced tumor disease with poor probabilities for cure, since many patients will show chemo- and radio-resistance. Several mechanisms have been studied to explain chemo- and radio-resistance to anti-tumor therapies, including cell signaling pathways, anti-apoptotic mechanisms, stemness, metabolism, and cellular phenotypes. Interestingly, the presence of cancer stem cells (CSCs), which are

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… These proteins use ATP-dependent drug efflux pumps for drug elimination, mostly into the extracellular space, and they have been found to be overexpressed in CSCs using side population assays[ 41 , 98 - 100 ]. …