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ENPP1/CD203a-targeting heavy-chain antibody reveals cell-specific expression on human immune cells.

ENPP1/CD203a is a membrane-bound ectonucleotidase capable of hydrolyzing ATP, cGAMP and other substrates. Its enzymatic activity plays an important role in the balance of extracellular adenine nucleotides and the modulation of purinergic signaling, in soft tissue calcification, and in the regulation of the cGAS/STING pathway. However, a detailed analysis of ENPP1 surface expression on human immune cells has not been performed. Here, we selected VHH domains from human ENPP1-immunized alpacas to generate heavy-chain antibodies targeting ENPP1, and analyzed cell surface expression on all circulat

Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.

Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulato

Exploratory Analysis of Circulating miRNA Signatures in Atrial Fibrillation Patients Determining Potential Biomarkers to Support Decision-Making in Anticoagulation and Catheter Ablation.

Novel biomarkers are desired to improve risk management for patients with atrial fibrillation (AF). We measured 179 plasma miRNAs in 83 AF patients using multiplex qRT-PCR. Plasma levels of eight (i.e., hsa-miR-22-3p, hsa-miR-128-3p, hsa-miR-130a-3p, hsa-miR-140-5p, hsa-miR-143-3p, hsa-miR-148b-3p, hsa-miR-497-5p, hsa-miR-652-3p) and three (i.e., hsa-miR-144-5p, hsa-miR-192-5p, hsa-miR-194-5p) miRNAs showed positive and negative correlations with CHA2DS2-VASc scores, respectively, which also showed negative and positive correlations with catheter ablation (CA) procedure, respectively, within t

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

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… The automation of Sanger sequencing with fluorescently labeled primers or ddNTPs facilitated major milestones, including the completion of the Human Genome Project. …

Oxidative Stress in Multiple Myeloma: Pathogenic Mechanisms, Biomarkers, and Redox-Targeted Therapeutic Strategies.

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by high metabolic activity, chronic endoplasmic reticulum stress, and persistent redox imbalance. Excessive immunoglobulin synthesis and adaptation to the hypoxic bone marrow microenvironment lead to sustained production of reactive oxygen species (ROS). Their excessive accumulation promotes genomic instability, disease progression, osteolytic bone disease, and resistance to therapy. Paradoxically, MM cells adapt to oxidative stress by activating antioxidant and metabolic defense mechanisms, including Nuclear factor ery

The Roles of EDA2R in Ageing and Disease.

Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clo

Artificial intelligence in immunotherapy: revolutionizing diagnostic and therapeutic applications in cancer and autoimmune diseases.

Artificial intelligence (AI) is increasingly advancing precision immunotherapy by integrating high-dimensional biomedical data to support diagnosis, treatment selection, and longitudinal monitoring in both cancer and autoimmune diseases. This review summarizes AI applications in biomarker discovery, prediction of immune checkpoint inhibitor (ICI) response and toxicity, neoantigen prioritization, CAR-T cell optimization, and therapeutic antibody engineering. In oncology, multimodal models combining multi-omics, medical imaging, and clinical variables improve patient stratification and non-invas

Ферроптоз в множестве миеломы: молекулярные механизмы и терапевтические возможности.

Множественная миелома (ММ) — гематологическая порча, вызванная распространением клональных плазменных клеток, и остается в значительной степени неизлечимой из-за рецидива заболеваний и приобретенной лекарственной устойчивости. Ферроптоз, основанная на железной зависимости форма регулируемой клеточной смертности, характеризующейся чрезмерным липидным пероксидацией, стала потенциальной терапевтической целью в раке и все чаще причастна к биологии MM. В отличие от апоптоза и других классических путей смерти клеток, ферроптоз тесно связан с дисрегулируемым метаболизмом железа, окислительным стрессо

Использование микробиомных средств для совершенствования методов лечения нейродегенеративных заболеваний: данные о воздействии вдоль оси микробиота-гут-мозгов.

Недавно в качестве полезной модели для понимания возникновения и развития нейродегенеративных заболеваний (НДД) появилась ось микробиота-гут-мозгов (МГБА). Меры воздействия на основе микробиома с использованием биотических добавок (пробиотики, предбиотики, синдиотики, постбиотики) могут модифицировать MGBA и служить подходящими решениями для снижения риска неврологических изменений, связанных с НИЗ, и регулирования симптомов. В настоящем описательном обзоре содержится резюме функционирования МГБС и его взаимодействия с заболеваниями, связанными с началом и развитием НИЗ. Проводится обзор мероп

New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes.

Classical hairy cell leukemia (HCL-c) is a rare lymphoid neoplasm. BRAFV600E mutation, detected in more than 80% of the cases, is described as a driver mutation, but additional genetic abnormalities appear to be necessary for the disease progression. For cases of HCL-c harboring a wild-type BRAF gene, the differential diagnosis of the variant form of HCL (HCL-v) or splenic diffuse red pulp lymphoma (SDRPL) is complex. We selected a panel of 21 relevant genes based on a literature review of whole exome sequencing studies (BRAF, MAP2K1, DUSP2, MAPK15, ARID1A, ARID1B, EZH2, KDM6A, CREBBP, TP53, C

The future of NMR metabolomics in cancer therapy: towards personalizing treatment and developing targeted drugs?

There has been a recent shift in how cancers are defined, where tumors are no longer simply classified by their tissue origin, but also by their molecular characteristics. Furthermore, personalized medicine has become a popular term and it could start to play an important role in future medical care. However, today, a "one size fits all" approach is still the most common form of cancer treatment. In this mini-review paper, we report on the role of nuclear magnetic resonance (NMR) metabolomics in drug development and in personalized medicine. NMR spectroscopy has successfully been used to evalu

Chronic stress in solid tumor development: from mechanisms to interventions.

Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells.

Circulating Exosomes Derived-miR-146a from Systemic Lupus Erythematosus Patients Regulates Senescence of Mesenchymal Stem Cells.

The senescence of mesenchymal stem cells (MSCs) plays a crucial role in the development and progression of systemic lupus erythematosus (SLE). Exosomes, small spherical bilayer proteolipid vesicles, contribute to the communication between various cells and their microenvironment by transferring information via their cargo, including the proteins, lipids, and RNAs. While exosomal miRNAs participate in various biological activities, correlations of circulating exosomes with senescent signs of BM-MSCs remain unclear. In our study, we aimed at exploring the roles of circulating exosomal miRNAs in

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

Циркуляция уровней инсулиновоподобных факторов роста I (IGF-I) и риска множественной миэломы: исследование наблюдений и менделии случайности.

Доказательства взаимосвязи между инсулиновыми факторами роста (ИПФ) и множеством миэломы (ММ) являются непоследовательными. Мы изучили общие концентрации ФУИ-I и риск ММ путем объединения исходных серологических данных среди участников Биобанка Соединенного Королевства (n = 444 187; 732 ДТП MM) с two- выборка менделианского анализа случайности (MR) с использованием выявленных генетических вариантов, связанных с циркуляцией общего ФУИ-I и связывающего белка ФУИ; 3 (В тыс.IGFBP-3) в консорциуме " ИнтерЛимф " ( " Интерлимф " )2434 ММ и их 2567 - контроль). Наконец, для сравнен

A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors.

The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challenging to treat because of their fast development and early metastases. The treatment of these patients must not be jeopardized, and they must be protected as much as possible from the continuous spread of the COVID-19 infection. Initially identified in December 2019 in Wuhan, China, the contagious coronavirus illness 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (S

Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells.

Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM)

The Emerging Role of Oncolytic Virotherapy in Glioblastoma Management.

Glioblastoma (GBM) is an aggressive and common form of central nervous system primary malignant tumor in adults. GBM accounts for about half of all gliomas. Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12-15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance. Recurrence is nearly universal, underscoring the need for novel therapies. Oncolytic virotherapy demonstrates a promising strategy that combines direct tumor cell lysis with immune activation. Tumor-selective viruses replicate within malignant cells, induce cell d

Роль микробиомы в множестве миелом: новые знания и терапевтические возможности.

Множественная миелома — гематологический рак, описываемый распространением плазменных клеток в костном мозге, что вызывает иммунную дисфункцию и другие аномалии. Микробиом кишечника, микробное сообщество в желудочно-кишечном тракте, было обнаружено, что он модифицирует системный иммунитет, воспаление и метаболизм. Хотя взаимосвязь между кишечным микробиомом и множеством миелома была обнаружена в недавних исследованиях, существует пробел в знаниях, связывающий воздействие микробиома на патогенез и лечение множественной миеломы. Несбалансированность в кишечном микробиоме, дисбиозе, может влиять

Monoclonal Antibodies Against Myeloid Leukemia Cells: Current Knowledge and Future Directions.

Monoclonal antibodies targeting specific cell surface antigens have emerged as a promising therapeutic approach for acute myeloid leukemia (AML), thus widening the treatment landscape of this heinous disease. These antibodies have been designed to selectively target and eliminate leukemic cells while limiting damage to the normal hematopoietic counterpart. Among the potential targets on AML cells, CD33, CD123, and CD47 have shown the major potential in preclinical and clinical trials. Additionally, conjugation of monoclonal antibodies with cytotoxic agents has further enhanced their therapeuti