Результаты поиска

Lactylation in health and disease: physiological or pathological?

Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles in different aspects of energy metabolism and signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as a novel posttranslational modification (PTM). Research indicates that Kla is an essential balancing mechanism in a variety of organisms and is involved in many key cellular biological processes through different pathways. Kla is closely related to disease development and represents a potential and important new drug target

Rare Causes of Musculoskeletal Pain: Thinking beyond Common Rheumatologic Diseases.

OBJECTIVES: Rare metabolic bone diseases can present with symptoms mimicking more common rheumatological conditions including spondyloarthritis, osteoarthritis, and fibromyalgia. Increasing awareness of these rare diseases within the rheumatology community is vital to ensure that affected patients are diagnosed and appropriately treated. The literature includes several reports of tumour-induced osteomalacia initially diagnosed as rheumatic disease, but other rare diseases such as X-linked hypophosphatemia (XLH) and hypophosphatasia (HPP) also deserve attention. Here, we describe two cases of a

Совпадение в полном тексте источника
… Following her HPP diagnosis, enzyme replacement therapy (asfotase alfa 80 mg subcutaneously 6 days/week) led to improvements in repeat chair stand assessment (28 seconds at baseline, 16 seconds approximately 1 month after starting treatment, stabilizing at 13 seconds after 6 months) and subjective improvement …

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca

Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.

Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies. Non-viral alternatives including electroporation and multifunctional nanoparticles are interrogated with respect to CAR

Biologics in Kidney Transplantation: Why and How Should We Personalize Their Dosage?

The therapeutic arsenal of immunosuppressive drugs in kidney transplantation has recently expanded with the introduction of biologics, approved or used off-label, that specifically target the immune system. Although therapeutic drug monitoring is well established for calcineurin inhibitors, its utility for biological immunosuppressants remains unclear. The objective of this narrative review was to evaluate whether biologics used to prevent or treat renal allograft rejection could be suitable candidates for therapeutic drug monitoring. This review provides (1) a comprehensive and up-to-date syn

Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familia

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

Myelin Displacement and Revention in the Central Nervous System: Молекулярные механизмы, болезни и перспективные терапевтические цели.

Майлин пластичность имеет основополагающее значение для формирования нейронных сетей и оптимизации нейронных функций, формирования схем, регулирующих эмоции, сознание, сенсацию и управление двигателем. Подкомбинированный олигодендроцитами, миелин подвергается пожизненной реконструкции, которая требует высокой метаболической активности; это делает миелин-олигодендроцитную единицу весьма восприимчивой к метаболическому стрессу, старению и патологическим оскорблениям. Хотя обезвоживание является основной характеристикой различных хронических неврологических расстройств, в настоящем обзоре особо п

Fludarabine in the treatment of chronic lymphocytic leukemia: a review.

Fludarabine (FAMP) is the most effective and most extensively studied purine analog in indolent B-cell malignancies. Its use is indicated for first-and second-line treatment of B-cell chronic lymphocytic leukemia (B-CLL). FAMP as a single agent has produced superior response rates and progression-free survival than standard therapy with chlorambucil and alkylator-based regimen. Efficacy of FAMP may be increased by combining this purine analog with other chemotherapeutic and non-chemotherapeutic agents. FAMP and cyclophosphamide combination (FC) has shown promising results with higher overall r

Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.

This comprehensive review explores the critical intersection of Synthetic Lethality (SL) and DNA Damage Response (DDR) targeting within Cancer Stem Cells (CSCs), a subpopulation central to tumor initiation, metastasis, and therapeutic resistance. CSCs exhibit unique biological properties, including enhanced DNA repair mechanisms and metabolic plasticity, rendering them intrinsically resistant to conventional therapies. The fundamental mechanisms of DDR pathways and their dysregulation in cancer are delineated, highlighting how these vulnerabilities can be exploited through SL. The review synth

Convergence of mRNA technology and chimeric antigen receptor therapy: targeted technology optimizing targeted therapy.

Engineering cells to express chimeric antigen receptors (CARs) represents a novel approach in cancer immunotherapy, demonstrating remarkable efficacy in the treatment of hematologic malignancies while also encountering numerous challenges. Against the backdrop of the widespread application of COVID-19 mRNA vaccines, the integration of mRNA technology to produce CAR cells and enhance CAR therapies marks the cutting edge of cancer treatment innovation, offering potential solutions to the challenges faced by traditional CAR therapies. This convergence offers distinct advantages. It enables the ge

Использование нефротоксичных препаратов у взрослых, страдающих хроническим заболеванием почек, в рамках обычного лечения в Швеции и США.

Характеристика применения нефротоксичных препаратов у пациентов с хроническим заболеванием почек (CKD) G3-5 в обычном уходе. Мы изучали когорты взрослых с подтвержденным ККД G3-5 :: рутинная медицинская помощь 1 Январь 2016 до конца 31 декабрь 2018 В two [Stockholm CREAM, Стокгольм, Швеция (N = 57 880) и Geininger, PA, USA (N = 16 255] Мы оценили долю пациентов, получающих нефротоксичные препараты внутри 1 Год в целом и по базовой функции почек, ранжировали основных плательщиков и изучили связь между получением нефротоксичных лекарств и возрастом, сексом, СКД G-стадиями коморбиды и осведомленн

Carfilzomib-Induced Thrombotic Microangiopathy: Focus on Pathogenesis.

Drug-induced thrombotic microangiopathies present in similar fashion but have varied pathogenic mechanisms. Carfilzomib is an irreversible proteasome inhibitor. Since its initial approval as a single agent for the treatment of relapsed or refractory multiple myeloma in 2012, there have been increasing reports of carfilzomib-induced thrombotic microangiopathy. However, the mechanism of this disease process is not fully understood. Without treatment, there is a high likelihood of end-organ damage, especially in the kidneys, and death. In recent reports, the lifesaving role of eculizumab, a termi

Proceedings of the CIMAGO Meeting - Challenges in Oncobiology Coimbra, 31st january 2020.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

The Crystalline Nephropathies.

Crystalline nephropathies are a unique form of kidney disease characterized by the histologic finding of intrarenal crystal deposition. The intrinsic nature of some molecules and ions combined with a favorable tubular fluid physiology leads to crystal precipitation and deposition within the tubular lumens. Crystal deposition promotes kidney injury through tubular obstruction and both direct and indirect cytotoxicities. Further kidney injury develops from inflammation triggered by these crystals. From a clinical standpoint, the crystalline nephropathies are associated with abnormal urinalysis a

Risk of malignancy in adult patients with congenital heart disease: a clinical practice review.

This paper presents case studies of adult patients with congenital heart disease (CHD) who developed cancer and also discusses relevant epidemiological studies, risk factors, and reports on early detection. Herein, we describe three cases: a 63-year-old man with an atrial septal defect and multiple myeloma; a 48-year-old man with tetralogy of Fallot and colorectal cancer; and a 25-year-old man with Fontan circulation and hepatocellular carcinoma (HCC). Previous studies have found that the incidence of cancer in adult patients with CHD is higher than that in the general population. The manageme

Целенаправленная деградация белка разрушает ненаркомные цели, чтобы обратить вспять иммунное уклонение и терапию устойчивости к раку.

Таргетированная деградация белков (ТД) использует эндогенные протеолитические системы — систему убиквина и протеасомы и лизосомальные пути — для селективного удаления белков, вызывающих болезни, которые не реагируют на традиционное ингибирование. В онкологической иммунотерапии ТД разрушает критические иммунодепрессивные узлы в экзоцитоплазматическом, мембранном и цитоплазматическом компартментах, перепрограммируя микросреду опухоли от иммунологически «холодной» к «горячей» состоянию. Эта статья рассматривает молекулярные принципы инженерии бифункциональных деградаторов и обобщает клинические д

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN

The journey of boswellic acids from synthesis to pharmacological activities.

There has been a lot of interest in using naturally occurring substances to treat a wide variety of chronic disorders in recent years. From the gum resin of Boswellia serrata and Boswellia carteri, the pentacyclic triterpene molecules known as boswellic acid (BA) are extracted. We aimed to provide a detailed overview of the origins, chemistry, synthetic derivatives, pharmacokinetic, and biological activity of numerous Boswellia species and their derivatives. The literature searched for reports of B. serrata and isolated BAs having anti-cancer, anti-microbial, anti-inflammatory, anti-arthritic,

Using Dose-Escalation and -Expansion Cohort Study as Pivotal Trial for Targeted Anticancer Drug Approval.

Early-phase clinical trials (EPCTs) have been increasingly adopted as the pivotal trial to support US Food and Drug Administration (FDA) approval of novel anticancer drugs. Among EPCT designs, dose-escalation and -expansion cohort (DEEC) substantially reduces the time and resources that are required in the traditional three-phase paradigm. DEEC facilitates expedited approvals of investigational drugs, particularly those targeting novel mechanisms, helping to address the pressing needs of patients with cancer. From 2012 to 2023, DEECs provided pivotal trial evidence that supported the FDA appro