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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

Pharmacotherapy of Generalized Myasthenia Gravis with Special Emphasis on Newer Biologicals.

Myasthenia gravis (MG) is a chronic, fluctuating, antibody-mediated autoimmune disorder directed against the post-synaptic neuromuscular junctions of skeletal muscles, resulting in a wide spectrum of manifestations ranging from mild to potentially fatal. Given its unique natural course, designing an ideal trial design for MG has been wrought with difficulties and evidence in favour of several of the conventional agents is weak as per current standards. Despite this, acetylcholinesterases and corticosteroids have remained the cornerstones of treatment for several decades with intravenous immuno

Guarding the heart in the era of immunotherapies: insights for cardio-oncology practice.

The advent of cancer immunotherapies, including immune checkpoint inhibitors (ICI), Chimeric antigen receptor (CAR-T) cell therapies, and bispecific antibodies and other immune-activating platforms such as therapeutic vaccines and oncolytic viruses (often used in combination regimens) has revolutionized oncology by improving patient outcomes across diverse malignancies. However, these therapies are increasingly linked to cardiovascular toxicities such as myocarditis, arrhythmias, and heart failure, posing significant clinical challenges. Here we review current evidence on the mechanisms, clini

Unlocking the potential: advancements and applications of gene therapy in severe disorders.

INTRODUCTION: Several severe disorders, such as inherited diseases (e.g. cystic fibrosis and beta thalassemia), genetic diseases (e.g. malignant tumors and diabetes), and infectious diseases (e.g. HIV) are pose significant challenges to human health. BACKGROUND: Over the past few decades, researchers have been working on gene therapies, and currently, terrible dreams have come true. To date, the Food and Drug Administration (FDA) has approved multiple gene therapies such as Kynamro for familial hypercholesterolaemia, Exondys51 for duchenne muscular dystrophy, Spinraza for spinal muscular atro

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

Efficacy of bortezomib as first-line treatment for patients with multiple myeloma.

Recent years have seen a dramatic change in the approach towards diagnosing and treating Multiple Myeloma. Newer and more target specific approach to treatment has prolonged the survival for patients with multiple myeloma. The proteasome inhibitors make an important class of anti-myeloma drugs that disrupts the proteolytic machinery of the tumor cells preferentially, enhancing their susceptibility to apoptosis. Bortezomib, in particular has shown significant clinical efficacy in myeloma treatment. It is the most commonly used proteasome inhibitor and has been tested to be effective in prolongi

Calcium Signalling in Breast Cancer Associated Bone Pain.

Calcium (Ca2+) is involved as a signalling mediator in a broad variety of physiological processes. Some of the fastest responses in human body like neuronal action potential firing, to the slowest gene transcriptional regulation processes are controlled by pathways involving calcium signalling. Under pathological conditions these mechanisms are also involved in tumoral cells reprogramming, resulting in the altered expression of genes associated with cell proliferation, metastatisation and homing to the secondary metastatic site. On the other hand, calcium exerts a central function in nocicepti

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… For this reason, they are also referred to as “breakthrough pain” due to the ability to overcome the analgesic therapeutic regimen, and their alleviation by mean of currently available drugs is unsatisfactory, and occasionally associated with dose limiting adverse effects. …

Case Report: Endothelial-targeted bridging therapy for a TTP-like phenotype in fulminant iMCD-TAFRO.

BACKGROUND: iMCD-TAFRO (the TAFRO clinical subtype of idiopathic multicentric Castleman disease (iMCD)) is characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Diagnosis is challenging due to its rarity, non-specific early presentation, and overlap with sepsis, lymphoma, and thrombotic microangiopathy (TMA). Endothelial injury is increasingly recognized as a central driver of its severe complications. CASE PRESENTATION: A previously healthy 20-year-old woman presented with rapid progression of fever, anasarca, jaundice, and respiratory failure. Laboratory

Глобальное, региональное и национальное экономическое бремя гематологовых магнестов1990-2021) с прогнозами 2050.

Гематологические колебания (ГМ) обусловливают значительные затраты на здравоохранение и производительность труда во всем мире. Однако различия в экономическом воздействии между регионами и странами по-прежнему недостаточно изучены. Цель этого исследования заключалась в оценке глобального, регионального и национального экономического бремени ТМ и его подтипов (лейкемии, лимфомы без ходжкина, множественной миэломы и Ходжкинской лимфомы) 1990 в адрес 2021, с прогнозами 2050. Методические данные о глобальном бремени болезней 2021 Исследование использовалось для оценки экономического бремени ТМ с и

Эффективность интенсивной антиэпидемиологической терапии, включая оланзапин у нескольких пациентов миэломы, лечившихся высокодозированными мелфаланами с аутологической трансплантацией стволовых клеток.

ЦЕЛЬ: Кондиционирование с использованием высокодозированного мелфалана (MEL), за которым следует аутологическая трансплантация стволовых клеток (ASCT), является стандартным методом лечения множественной миеломы (MM). Оптимальный режим предотвращения тошноты и рвоты, вызванных химиотерапией, не ясен. Мы стремились ретроспективно оценить антиеметический эффект и безопасность four- интенсивный наркологический режим, включая оланзапин (ОЛА) на CINV у пациентов MM, получающих MEL/ASCT. МЕТОДЫ: МЕЛ200 мг/м2) в дневное время 1, за которым следует ASCT в день 3. Пациенты были отнесены к стандартной гр

Реальная эффективность, стойкость, терпимость и безопасность атумумаба в клинической практике.

АИСЮ: Описание 12-month :: эффективность, стойкость, терпимость и безопасность атумумаба (ОМБ) -- высокоэффективной терапии для борьбы с заболеваниями (ДМТ) для повторного склероза (МС) в реальном мире. & МЕТОДЫ: Электронные медицинские записи пациентов, начинающих OMB с октября 2020 по август 2022 на two Был проведен обзор комплексных центров НР. Демографические показатели и характеристики болезней и 6- и 12-month Были проанализированы клинические, описанные пациентами и радиоологические показатели. РЕЗУЛЬТАТЫ: Всего 175 пациенты начали ОМБ со средним возрастом 44.9 (СД) 10.4) и продолжительн

Management of mantle cell lymphoma in the elderly patient.

Mantle cell lymphoma is a relatively rare B-cell lymphoma with a specific genetic lesion and a typical immunophenotypic profile. The median age is 65 years. There is no curative treatment, except allogeneic stem cell transplantation for a selected group of patients. For the majority of patients, especially the elderly, the aim of therapy should therefore be a long progression-free survival. Age and comorbidity may hamper the use of the most active treatment regimen, such as high dose cytarabine and autologous stem cell transplantation. Therefore, it is a challenge to select the most appropriat

Progress and research trends in neurogenic bladder after spinal cord injury bibliometric analysis based on web of science database: An observational study.

Neurogenic bladder (NB) is a significant complication that often occurs after spinal cord injury. It results from urinary dysfunction caused by the injury, disrupting the normal neural control of the bladder and urethra. Symptoms of NB can include urinary frequency, urgency, incontinence, and retention, all of which can greatly impact the quality of life of affected individuals. While there are articles and reviews on NB, fewer specifically address NB following spinal cord injury. This study examined 1095 publications from January 1, 2000, to March 27, 2024, in the Web of Science core database

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, sensitizes lung cancer cells to treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major challenge to targeted therapy for non-small cell lung cancer (NSCLC). We investigated whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse EGFR-TKI resistance in human lung cancer cells and explored the underlying mechanisms. We found that PD 0332991 potentiated gefitinib-induced growth inhibition in both EGFR-TKI-sensitive (PC-9) and EGFR-TKI-resistant (PC-9/AB2) cells by down-regulating proliferation and inducing apoptosis and G0/G1 cell cycle arrest. Tumor xenogra

Bridging the Gap in Secondary Antibody Deficiencies: Current Evidence and Unmet Needs in Diagnosis and Management with Immunoglobulin Replacement.

Secondary antibody deficiency (SAD) represents a substantial yet under-recognised global healthcare burden. It is more prevalent than primary antibody deficiency, but frequently under-diagnosed and variably managed worldwide. Prompt diagnosis is often hindered by insufficient awareness among clinicians, lack of global consensus on screening/monitoring for SAD among at-risk patients, inadequate clinical immunology services and lack of standardised referral pathways/protocols. Management practices vary widely, with little international agreement, particularly regarding threshold to initiate immu

Guselkumab, an inhibitor of the IL-23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naïve or TNFα inhibitor-experienced.

OBJECTIVE: Evaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year. METHODS: Adults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compar

Engineering with Biomedical Sciences Changing the Horizon of Healthcare-A Review.

In the dynamic realm of healthcare, the convergence of engineering and biomedical sciences has emerged as a pivotal frontier. In this review we go into specific areas of innovation, including medical imaging and diagnosis, developments in biomedical sensors, and drug delivery systems. Wearable biosensors, non-wearable biosensors, and biochips, which include gene chips, protein chips, and cell chips, are all included in the scope of the topic that pertains to biomedical sensors. Extensive research is conducted on drug delivery systems, spanning topics such as the integration of computer modelin

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential t

Nanotherapeutics in the EU: an overview on current state and future directions.

The application of nanotechnology in areas of drug delivery and therapy (ie, nanotherapeutics) is envisioned to have a great impact on public health. The ability of nanotherapeutics to provide targeted drug delivery, improve drug solubility, extend drug half-life, improve a drug's therapeutic index, and reduce a drug's immunogenicity has resulted in the potential to revolutionize the treatment of many diseases. In this paper, we review the liposome-, nanocrystal-, virosome-, polymer therapeutic-, nanoemulsion-, and nanoparticle-based approaches to nanotherapeutics, which represent the most suc