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The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis.

Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates tha

Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.

A prodrug is a molecule that lacks pharmacological activity, but upon enzymatic bioactivation, it can generate a therapeutically active molecule. The primary reason behind the design of a prodrug is to help circumvent challenges associated with the physicochemical properties of a drug molecule, such as solubility, absorption, distribution, and instability. Chemotherapy has been at the forefront of cancer treatment for over 70 years due to its ability to target rapidly proliferating tumor cells. However, a major concern with conventional chemotherapy is the lack of selectivity and its associate

Antioxidant effects of Spirulina platensis (Arthrospira platensis) on cyclophosphamide-induced testicular injury in rats.

Cyclophosphamide (CP) is known to reduce fertility. The protective effects of Spirulina plantesis (SP) against CP-induced testicular toxicity were investigated. Male Wistar rats were categorized into eight groups (n = 7). Four groups of rats were administered CP at a dose of 5 mg in 5 mL distilled water kg-1 per day orally. Two of these groups were received SP (500 and 1000 mg kg-1 per day) orally after CP administration. One of these groups was also received vitamin E (100 mg kg-1 per day) intraperitoneally. A vehicle treated control group, two SP control groups (500 and 1000 mg kg-1 per day)

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs' augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhib

CAR-Based Cell and Gene Therapies: Global Clinical Landscape and Emerging Therapeutic Strategies from ClinicalTrials.gov.

Chimeric Antigen Receptor (CAR)-based cell and gene therapies have become transformative treatments, offering targeted and durable responses, especially in hematologic malignancies. This review analyzes 1,744 CAR clinical trials registered on Clinical-Trials.gov as of 2024, focusing on platform types, indications, target antigens, therapeutic strategies, and late-phase development. CAR-T therapies predominate, followed by CAR-NK, CAR-NKT, CAR-M and CAR-DC platforms. Approximately 92% of trials target tumors, with hematologic malignancies accounting for 65% of indications; CD19 and BCMA are pri

Роль и функции " Ирисина " : перспективы последних изменений и неевродегенеративных заболеваний.

Irisin — пептид, полученный из фибронектина типа III, содержащего домен белка 5 (FNDC5) и производимый главным образом мышечными волокнами в соответствии с регулированием пероксисомных прорациатрированных рецепторов гамма-коативатора 1-альфа (PGC1α) во время упражнения. Ирисин стал объектом обширных исследований в силу его потенциала как метаболического регулятора и его антиоксидантных свойств. В частности, она связана с защитными действиями в мозгу. Несмотря на растущий интерес, остается много вопросов относительно молекулярных механизмов, лежащих в основе их воздействия. В настоящем обзоре р

Targeted approaches in the treatment of osteoporosis: differential mechanism of action of denosumab and clinical utility.

Denosumab is a breakthrough biological drug approved by the Food and Drug Administration and European Medicines Agency for the treatment of osteoporosis in 2010. It is a fully human monoclonal antireceptor activator of nuclear factor kappa-B ligand antibody, which inhibits the activity of osteoclasts, resulting in an antiresorptive effect with a significant increase in bone mineral density. The FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial, comparing denosumab with no treatment in 7868 women with postmenopausal osteoporosis, showed an important reduc

FDA-Approved Drugs for Hematological Malignancies-The Last Decade Review.

Hematological malignancies, also referred to as blood cancers, are a group of diseases involving abnormal cell growth and persisting in the blood, lymph nodes, or bone marrow. The development of new targeted therapies including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and, finally, Chimeric Antigen Receptor T (CAR-T) cells has improved the clinical outcomes for blood cancers. In this review, we summarized 52 drugs that were divided into small molecule and macromolecule agents, approved by the Food and Drug

Gene editing and CRISPR in the clinic: current and future perspectives.

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases whic

Research Hotspots and Trends in Global Cancer immunometabolism:A Bibliometric Analysis from 2000 to 2023.

BackgroundCancer poses a major global health challenge, and immunotherapy, known as the third revolution in cancer treatment, has brought new hope to patients. The emerging field of immunometabolism has further enhanced the safety and efficacy of immunotherapy. Over the past two decades, this field has rapidly evolved in oncology, leading to numerous significant findings. This review systematically examines the literature on immunometabolism in cancer, visualizing research trends and identifying future directions.MethodsA comprehensive literature search was conducted in the Web of Science, Pub

IL-34 в неврологическом гомеостазисе и его многогранная роль в заболеваниях центральной нервной системы.

Interleukin-34 (IL-34), лиганд для рецептора макрофажных колоний (CSF1R), играет незаменимую роль в развитии и поддержании гомеостазиса центральной нервной системы (CNS). В настоящем обзоре систематически излагаются основные механизмы, с помощью которых ось сигнала IL-34/CSF1R регулирует развитие, колонизацию и функциональную дифференциацию иммунных клеток-резидентов, включая микроглию и макрофаги, связанные с границами (BAM). Она подчеркивает свою роль в критических физиологических процессах, таких, как синаптическое обрезка, созревание нервной цепи и поддержание целостности мозгового барьера

Corticosteroid-associated osteonecrosis in paediatric compared with adult patients: are they the same disease?

Osteonecrosis of the femoral head (ONFH) is a debilitating condition with a poorly characterized pathogenesis. Among the reported aetiologies, excessive alcohol consumption and corticosteroid administration are leading causes. Corticosteroids are often administered as a life-saving treatment for primary oncological or autoimmune conditions, but the subsequent development of ONFH can significantly impair the quality of life of both paediatric and adult patients. This review provides a comprehensive summary and critical analysis of recent advances in the understanding of corticosteroid-associate

A novel application perspective of the clinical-used drug verapamil on osteoporosis via targeting Txnip.

BACKGROUND: RANKL and SCLEROSTIN antibodies have provided a strong effective choice for treating osteoporosis in the past years, which suggested novel molecular target identification and therapeutic strategies development are important for the treatment of osteoporosis. The therapeutic effect of verapamil, a drug previously used for cardiovascular diseases, on diabetes was due to the inhibition of TXNIP expression, which has also been reported as a target in mice osteoporosis. Whether verapamil-inhibited TXNIP expression is related to osteoporosis and how it works on the molecular level is wor

Pathogenesis and kidney prognosis of renal amyloidosis.

Light chain (AL), serum amyloid A (AA), transthyretin (ATTR), leukocyte cell derived chemotaxin 2 (ALECT2), and fibrinogen Aa (AFib) amyloidosis are some of the most common types of protein-deposition disorders involving the kidney. Each amyloidogenic protein differs in its origin and little is known about the exact mechanisms that govern renal tropism and tissue injury for each amyloid subtype. While amyloidogenic precursor protein is different in each subtype of amyloidosis, its aggregation into fibrils depositing in target organs and leading to disruption of tissue architecture and progress

Отчет о случае: несекретирующий множественный миелома с эозинофильной реакцией: диагностические вызовы и фокусированный обзор литературы.

Мы сообщаем редкий случай непродуктивного множественного миеломы (НММ) с выраженной эозинофильной апоптозом и значительными трудностями в диагностике. 56-летний мужчина был госпитализирован с повторяющейся болью в поясничной области более чем 10 лет, которая в последние 10 дней быстро усугубилась, сопровождаясь общей болью и потерей веса. Лабораторная оценка показала постоянную эозинофилию, тромбоцитопению, повышение лактата деhidрогеназы и увеличение воспалительных маркеров. Медицинские исследования выявили мультифокальные остеолитические поражения, затрагивающие череп, позвонки, ребра и таз.

CD47-Targeted Therapy in Cancer Immunotherapy: At a Crossroads of Promise and Challenge.

Cluster of differentiation 47 (CD47), an immune checkpoint commonly referred to as the "don't eat me" signal, plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha (SIRPα) on macrophages and dendritic cells (DCs). Although early enthusiasm drove broad clinical development, recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential. The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategie

Кислотный профиль эритроцитов по множеству склерозов связан с курсами болезней, липидной пероксидацией и диетическим влиянием.

Предыстория/цели: Диетический образ жизни, в частности потребление жирных кислот (FA), может быть полезным для смягчения основных патогенных процессов при множественном склерозе (MS); однако данные по-прежнему являются недостаточными, особенно в том, что касается передачи болезни. Таким образом, цели этого исследования заключались в изучении эритроцитного профиля АУ у пациентов с релапсирующими (RR)MS и прогрессивными (P)MS, а также в изучении вопроса о том, является ли пищевая добавка пищевой добавкой n-3 PUFA может повлиять на профиль FA, в зависимости от хода болезни. Методы: профиль FA был

Совпадение в полном тексте источника
… On the other hand, the stabilization of 4-HNE in a 1-palmitoyl-2-oleoyl-s n -glycero-3-phosphocholine (synthetic phosphatidylcholine containing 16:0 (PA)) bilayer was experimentally demonstrated, whereby 4-HNE had the ability to rapidly transfer to the extra- or intracellular space and was able to react …

RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.

Background: RNA therapeutics represent a rapidly advancing field with significant potential for treating viral infections and cancer. This review examines the current landscape of RNA-based strategies, including siRNA, miRNA mimics, and antisense oligonucleotides. For viral infections, the focus is on hepatitis B (HBV) and C (HCV), HIV, and SARS-CoV-2. Approaches include targeting viral transcripts directly (e.g., siRNAs against HBV surface antigen) or host factors critical for viral replication (e.g., anti-miR-122 miravirsen for HCV). The successful development of mRNA vaccines for COVID-19 i

Novel agents in the treatment of multiple myeloma: a review about the future.

Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib,

Совпадение в полном тексте источника
… Proteasome inhibitors Carfilzomib The proteasome is the ultimate destination for ubiquitinated proteins marked for degradation and clearance from the intracellular space. In this way the proteasome acts as a regulator of cytoplasmic protein expression. …

Bridging the Gap in AL and ATTR Cardiac Amyloidosis: Integrating Histopathology, Biomarkers, and Multimodal Imaging for Subtype-Specific Diagnosis.

Cardiac amyloidosis (CA) represents an increasingly recognized but historically underdiagnosed cause of restrictive cardiomyopathy and heart failure. CA is now understood to be more prevalent, particularly in older adults, as advancements in imaging and biomarker technologies have improved detection. The disease results from the misfolding of precursor proteins, primarily immunoglobulin light chains (in light chain (AL) amyloidosis) or transthyretin (in transthyretin (ATTR) amyloidosis), into insoluble fibrils that deposit in myocardial tissue. These deposits cause structural and functional ca