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Cuproptosis Inducers in Cancer Therapy: State of the Art and Challenges.

Cancer continues to be the primary cause of death despite significant progress in medicine, and finding effective therapies remains a challenge. New treatments are needed to minimize the harmful effects on the body and increase the selectivity of drugs. These therapies must also overcome cancer cell resistance and prevent metastasis. Metal-based drugs are becoming increasingly crucial for treating tumors, and copper ion-based systems and nanoparticles have been identified as having unique properties and anticancer potential. Given the key role exerted by Cu in the etiology, severity, and progr

Естественные и синтетические АМП из Латинской Америки по всему спектру технологий и приложений в области разнообразия.

Биоразнообразие в Латинской Америке примерно 60% в целом по миру, подпитывая научные исследования в области природных продуктов, весьма значимой области открытия наркотиков по сей день. Это сопровождается увеличением числа антимикробных пептидов (АМП), полученных из натуральных продуктов в регионе, которые за последнее десятилетие были переработаны путем модификации, усовершенствования и уточнения их физико-химических свойств и антимикробной эффективности с использованием подходов, которые варьируются от изучения рациональной конструкции и соотношения структуры-активности (САР) до методов иску

Glucocorticoids-based prodrug design: Current strategies and research progress.

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side e

Multiple Myeloma Therapy: Emerging Trends and Challenges.

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergenc

Синергистические механизмы традиционной китайской медицины и протеиновых ингибаторов в многократной терапии миеломы: всеобъемлющий обзор.

Множественная миелома (ММ) — клональная плазменная порча клеток, характеризующаяся инфильтрацией костного мозга, производством моноклонального иммуноглобулина и многосистемным повреждением. Протеозные ингибиторы (ИП), такие, как бортезомиб, карфилзомиб и иксазомиб, значительно улучшили без прогрессии и общее выживание пациентов с ОМ. Однако резистентность к лекарственным препаратам и неблагоприятные последствия, включая периферическую нейропатию и кардиотоксичность, по-прежнему являются основными ограничениями для долгосрочного контроля за заболеваниями. Цель настоящего обзора заключается в вс

Advances and development of prostate cancer, treatment, and strategies: A systemic review.

The most common type of cancer in the present-day world affecting modern-day men after lung cancer is prostate cancer. Prostate cancer remains on the list of top three cancer types claiming the highest number of male lives. An estimated 1.4 million new cases were reported worldwide in 2020. The incidence of prostate cancer is found predominantly in the regions having a high human development index. Despite the fact that considerable success has been achieved in the treatment and management of prostate cancer, it remains a challenge for scientists and clinicians to curve the speedy advancement

Immune mechanism of low bone mineral density caused by ankylosing spondylitis based on bioinformatics and machine learning.

Background and Objective: This study aims to find the key immune genes and mechanisms of low bone mineral density (LBMD) in ankylosing spondylitis (AS) patients. Methods: AS and LBMD datasets were downloaded from the GEO database, and differential expression gene analysis was performed to obtain DEGs. Immune-related genes (IRGs) were obtained from ImmPort. Overlapping DEGs and IRGs got I-DEGs. Pearson coefficients were used to calculate DEGs and IRGs correlations in the AS and LBMD datasets. Louvain community discovery was used to cluster the co-expression network to get gene modules. The modu

Asia-inclusive global development of pevonedistat: Clinical pharmacology and translational research enabling a phase 3 multiregional clinical trial.

The investigational NEDD8-activating enzyme inhibitor pevonedistat is being evaluated in combination with azacitidine versus single-agent azacitidine in patients with higher-risk myelodysplastic syndrome (higher-risk MDS), higher-risk chronic myelomonocytic leukemia (higher-risk CMML), or low-blast acute myeloid leukemia (AML) in a Phase 3 trial PANTHER. To support Asia-inclusive global development, we applied multiregional clinical trial (MRCT) principles of the International Conference on Harmonisation E17 guidelines by evaluating similarity in drug-related and disease-related intrinsic and

Targeted drug combination therapy design based on driver genes.

Targeted therapies against cancer types with more than one driver gene hold bright but elusive promise, since approved drugs are not available for all driver mutations and monotherapies often result in resistance. Targeting multiple driver genes in different pathways at the same time may provide an impact extensive enough to fight resistance. Our goal was to find synergistic drug combinations based on the availability of targeted drugs and their biological activity profiles and created an associated compound library based on driver gene-related protein targets. In this study, we would like to

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

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

Drug Repurposing at the Interface of Melanoma Immunotherapy and Autoimmune Disease.

Cancer cells have a remarkable ability to evade recognition and destruction by the immune system. At the same time, cancer has been associated with chronic inflammation, while certain autoimmune diseases predispose to the development of neoplasia. Although cancer immunotherapy has revolutionized antitumor treatment, immune-related toxicities and adverse events detract from the clinical utility of even the most advanced drugs, especially in patients with both, metastatic cancer and pre-existing autoimmune diseases. Here, the combination of multi-omics, data-driven computational approaches with

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… . | http://dailymed.nlm.nih.gov/dailymed/about.cfm Omics data (Target/Drug) NCBI-GEO | Store the gene expression profiling and RNA methylation profiling managed by the National Center for Biotechnology Information. | http://www.ncbi.nlm.nih.gov/geo/ Sequence Read Archive (SRA) | Repository of high throughput …

The 20th Anniversary of Pegaptanib (MacugenTM), the First Approved Aptamer Medicine: History, Recent Advances and Future Prospects of Aptamers in Therapy.

In addition to classic small-molecule drugs and modern protein-based biologics, an intriguing class of medicines is the therapeutic oligonucleotides. Most approved drugs in this category are antisense oligomers or those acting via RNA interference, both of which use base hybridization. Aptamers, also known as chemical antibodies form a smaller, yet equally interesting group of oligonucleotides that can recognize a wide range of molecular targets. Despite their high potential, only two aptamers have been approved to date, pegaptanib (MacugenTM) and avacincaptad pegol (IzervayTM), both for the t

Immune mediated inflammatory diseases: moving from targeted biologic therapy, stem cell therapy to targeted cell therapy.

Despite the advancements in targeted biologic therapy for immune-mediated inflammatory diseases (IMIDs), significant challenges persist, including challenges in drug maintenance, primary and secondary non-responses, and adverse effects. Recent data have strengthened the evidence supporting stem cell therapy as an experimental salvage therapy into a standard treatment option. Recent preclinical and clinical studies suggested that chimeric antigen receptor T cell (CAR-T) therapy, which depleting tissue and bone marrow B cells, may lead to improvement, even inducing long-lasting remissions for pa

Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response.

Alpha-ketoglutarate (αKG) emerged as a key regulator of energetic and redox metabolism in cells, affecting the immune response in various conditions. However, it remained unclear how the exogenous αKG modulates the functions of dendritic cells (DCs), key cells regulating T-cell response. Here we found that non-toxic doses of αKG display anti-inflammatory properties in human APC-T cell interaction models. In a model of monocyte-derived (mo)DCs, αKG impaired the differentiation, and the maturation of moDCs induced with lipopolysaccharide (LPS)/interferon (IFN)-γ, and decreased their capacity to

NF-κB: master regulator of cellular responses in health and disease.

The NF-κB transcription control proteins play widespread roles in cellular behavior, regulating immune responses, inflammation, cell survival, proliferation, and development. Here, we attempt to comprehensively review these diverse functions and underlying mechanisms, leading readers to relevant references of both historic and topical importance. Because of the huge number of NF-κB control mechanisms and functions, and the vast literature that describes these, being comprehensive is a daunting task but we hope that readers will find clues to lead them to whatever understanding they may seek. A

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The evolving global landscape of first-in-class oncology drug innovation.

First-in-class (FIC) oncology drugs-defined by their novel mechanisms of action or targeting of previously unaddressed molecular targets-have emerged as a leading force in cancer therapeutic innovation. In this Review, we delineate the global landscape of FIC oncology drug approvals between 2009 and 2024 and analyze the evolving characteristics of both approved FIC therapies and potential FIC (PFIC) candidates in clinical development. To clarify the underlying dynamics of this evolution, we construct an analytic framework encompassing four distinct archetypes of FIC development: new targets, n

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs

Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma.

Haematopoiesis is a tightly orchestrated process where a pool of hematopoietic stem and progenitor cells (HSPCs) with high self-renewal potential can give rise to both lymphoid and myeloid lineages. The HSPCs pool is reduced with ageing resulting in few HSPC clones maintaining haematopoiesis thereby reducing blood cell diversity, a phenomenon called clonal haematopoiesis. Clonal expansion of HSPCs carrying specific genetic mutations leads to increased risk for haematological malignancies. Therefore, it comes as no surprise that hematopoietic tumours develop in higher frequency in elderly peopl