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The Treatment Gap in Osteoporosis.

Worldwide, there are millions of people who have been diagnosed with osteoporosis, a bone disease that increases the risk of fracture due to low bone mineral density and deterioration of bone architecture. In the US alone, there are approximately ten million men and women diagnosed with osteoporosis and this number is still growing. Diagnosis is made by measuring bone mineral density. Medications used for the treatment of osteoporosis are bisphosphonates, denosumab, raloxifene, and teriparatide. Recently, romosozumab has been added as well. In recent years, a number of advances have been made

Pharmacovigilance in Cell and Gene Therapy: Evolving Challenges in Risk Management and Long-Term Follow-Up.

Cell and gene therapies, including CAR T-cells, CRISPR-based genome editing, and next-generation viral and non-viral delivery platforms, are transforming treatment paradigms across cancer, rare genetic disorders, immune dysregulation, and neurodegenerative disease. These therapies offer curative potential but also present safety challenges owing to prolonged biological activity, systemic immune engagement, and lasting genomic alterations. This review examines the range of related toxicities, including immune complications, genotoxicity, and organ-specific effects, with attention to atypical pr

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS.

CONTEXT: Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ). OBJECTIVE: We aimed to identify the differences various aspects of MRONJ among distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in eac

Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.

The nervous system plays a critical role in developmental biology and oncology, influencing processes from ontogeny to the complex dynamics of cancer progression. Interactions between the nervous system and cancer significantly affect oncogenesis, tumor growth, invasion, metastasis, treatment resistance, inflammation that promotes tumors, and the immune response. A comprehensive understanding of the signal transduction pathways involved in cancer biology is essential for devising effective anti-cancer strategies and overcoming resistance to existing therapies. Recent advances in cancer neurosc

Revolutionary drug repositioning: the preventive and therapeutic potential of metformin and other antidiabetic drugs in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Anti-vascular endothelial growth factor (anti-VEGF) injections remain the first-line therapy for AMD. However, their high cost and the need for frequent administration pose challenges to long-term adherence, highlighting the need for accessible and cost-effective preventive strategies. Emerging evidence suggests that traditional antidiabetic drugs, such as metformin, sulfonylureas, and thiazolidinediones, may offer neuroprotective benefits, opening new avenues for AMD prevention. Among these, me

Adjuvant breast cancer treatments cardiotoxicity and modern methods of detection and prevention of cardiac complications.

The most common cancer diagnosis in female population is breast cancer, which affects every year about 2.0 million women worldwide. In recent years, significant progress has been made in oncological therapy, in systemic treatment, and in radiotherapy of breast cancer. Unfortunately, the improvement in the effectiveness of oncological treatment and prolonging patients' life span is associated with more frequent occurrence of organ complications, which are side effects of this treatment. Current recommendations suggest a periodic monitoring of the cardiovascular system in course of oncological t

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia.

Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional land

Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases.

Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significan

Explainable artificial intelligence for precision medicine in acute myeloid leukemia.

Artificial intelligence (AI) can unveil novel personalized treatments based on drug screening and whole-exome sequencing experiments (WES). However, the concept of "black box" in AI limits the potential of this approach to be translated into the clinical practice. In contrast, explainable AI (XAI) focuses on making AI results understandable to humans. Here, we present a novel XAI method -called multi-dimensional module optimization (MOM)- that associates drug screening with genetic events, while guaranteeing that predictions are interpretable and robust. We applied MOM to an acute myeloid leuk

Rare diseases and orphan drugs: Latvian story.

BackgroundTen years have passed since Latvia became a Member State of the EU in 2004. As a result European regulations, including those related to rare diseases and orphan drugs, have been applied to Latvian legislative system. Orphan diseases have been recognized as a priority area for action in the public health system, though there are significant differences in the national healthcare services for rare diseases among the EU States. This study aims to determine situation in the field of rare diseases in Latvia and compare it with other European countries.MethodsWe used the national plan for

Нейрофизиологические, радиологические и молекулярные биомаркеры условий, связанных с болью: обзор " Umbrella " .

Справочная информация/цели: Боль и условия, связанные с болью, считаются глобальным медико-санитарным и финансовым бременем. В целях совершенствования методов обезболивания, оценки болеутоляющей силы и диагностики боли были предложены различные биомаркеры. Поскольку их клиническая полезность еще не доказана, цель этого зонтичного обзора заключается в обобщении имеющихся данных о всех видах обезболивающих биомаркеров. Методы: Систематические обыски проводились в Пуббмеде, Скопусе и Кокрейнской библиотеке с момента их создания 2 Июнь 2025. Приемлемыми исследованиями были систематические обзоры и

Cardiotoxicity Induced by Anticancer Therapies: A Call for Integrated Cardio-Oncology Practice.

The introduction of novel oncologic therapies, including targeted agents, immunotherapies, and antibody-drug conjugates, has transformed the therapeutic landscape of cancer care. This evolution has resulted in a dual clinical scenario; while survival outcomes have markedly improved, leading to a growing population of long-term cancer survivors, an increasing incidence of previously unrecognized treatment-related toxicities has emerged. Among these, cardiovascular adverse events represent some of the most prevalent and clinically significant complications observed in both conventional chemother

Совпадение в полном тексте источника
… Based on these findings, pharmacogenomic testing for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 variants is currently recommended for pediatric patients receiving doxorubicin or daunorubicin, whereas no recommendation exists for adults [ 20 ]. …

Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicin

Совпадение в полном тексте источника
… These molecular signatures guide pharmacogenomic testing to predict therapeutic response profiles including differential drug efficacy, dose sensitivity, and resistance patterns. …

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G

Усиленная диагностика заболевания множественным склерозом на основе подхода, основанного на ансамблях

Множественный склероз (MS) — болезнь, наносящая удар по центральной нервной системе. Согласно самым последним статистическим данным MS Atlas 2.8 million люди во всем мире диагностировали MS. Недавно в рамках исследований стали изучаться методы машинного обучения для прогнозирования НР с использованием различных данных. Целью настоящего документа является разработка комплексного подхода к диагностике MS с использованием профилей выражения генов при одновременном решении проблемы классового дисбаланса, связанной с данными. Предлагается иерархический комплексный подход с использованием методов го

Варианты фармакологического лечения когнитивной дисфункции, вызванной множественным склерозом: сетевой метаанализ.

ЦЕЛИ: Сопоставление воздействия различных видов фармакологического лечения на результаты частичных тестов и неблагоприятное воздействие на пациентов с когнитивной дисфункцией (КД), вызванной множественным склерозом (МС), посредством сетевого метаанализа. МЕТОДЫ: База данных PubMed, Embase, Cochrane Bibrary и Web of Science были систематически извлечены для случайных контролируемых испытаний (RCTs), в ходе которых оценивалось влияние различных видов фармакологического лечения на компакт-диски у пациентов с MS. Поиск был обновлен до октября 8, 2024. Для оценки качества приемлемых исследований ис

Old Drugs, New Battles: Unleashing Repurposed Drug Classes in Triple-Negative Breast Cancer Treatment.

Cancer remains a major global health challenge, with triple-negative breast cancer (TNBC) representing one of the most aggressive and difficult-to-treat subtypes, characterized by poor prognosis and limited therapeutic options. Current treatments, including chemotherapy, are hindered by high recurrence rates, drug resistance, and severe side effects, highlighting the urgent need for novel therapeutic strategies to address these challenges. Drug repurposing, which involves the application of existing FDA-approved (Food and administration) drugs for new oncological uses, offers a cost-effective

Okay, so I need to translate this medical text into Russian. Let me first read through the original sentence carefully. The sentence is: "N-Azacytidine Inhibits Myeloma Cell Growth While Preserving Multiple Myeloma Patient Derived-Bone Marrow Mesenchymal Stromal Cells Differentiation." Hmm, the key here is to translate it accurately using proper clinical and anatomical terms. Let me break it down. First, "N-Azacytidine" is a drug name. In Russian, drug names are often transliterated or use the original name with some adaptation. I think in Russian medical literature, they might use the international nonproprietary name, which is "N-азацидидин" or maybe "N-азацидид"? Wait, no, let me check. Wait, the international nonproprietary name for N-Azacytidine is "азацидидин" (azacitidine) in Russian. Wait, but the chemical name is N-Azacytidine, which is a nucleoside analog. In Russian, the term for azacitidine is "азацидидин" (azacitidine). Wait, but the original says "N-Azacytidine", so maybe it's "N-азацидидин" but I think in Russian medical terms, they might just use "азацидидин" without the

Множественная миелома (ММ) — неизлечимая гематологическая порча, вызванная аномальным распространением неизлечимо дифференцированных плазменных клеток в костном мозге. Текущие исследования показывают, что N-azacytidine как эпигенетическое лекарство и нуклеозный метаболический ингибитор могут быть эффективными при лечении MM. Вместе с тем данные о мезенхимальных стромальных клетках костного мозга (МСЦВ) в качестве критической клеточной популяции в процессах гематопоизи и реконструирования костей ограничены.МЕТОДЫ: Воздействие N-azacytidine на клеточную линию миэломы AMO-1, мезенхимальные строма

Primary mesenchymal stromal cells in co-culture with leukaemic HL-60 cells are sensitised to cytarabine-induced genotoxicity, while leukaemic cells are protected.

Tumour microenvironments are hallmarked in many cancer types. In haematological malignancies, bone marrow (BM) mesenchymal stromal cells (MSC) protect malignant cells from drug-induced cytotoxicity. However, less is known about malignant impact on supportive stroma. Notably, it is unknown whether these interactions alter long-term genotoxic damage in either direction. The nucleoside analogue cytarabine (ara-C), common in haematological therapies, remains the most effective agent for acute myeloid leukaemia, yet one-third of patients develop resistance. This study aimed to evaluate the bidirect