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Высокий уровень распространенности GALC Gene Options на взрослых с нейродегенеративными условиями.

ОКРУЖАЮЩАЯ СРЕДА И ЦЕЛЬ: Дефицит галактоцереброзидаза (ГАЛК) вызывает болезнь Краббе, тяжёлое лизосомальное нейродегенеративное состояние. Появляющиеся данные указывают на то, что гетерозиговые варианты GALC могут способствовать множеству склерозов, расстройству гиперактивности, отсутствию внимания, и синуклейнопатии. Мы намерены изучить потенциальную связь между гетероциговидными вариантами GALC и нейродегенеративными расстройствами, расширяя существующую литературу. МЕТОДЫ: Мы провели обследование 110 взрослых с симптомами, которые разделяются лизосомными расстройствами хранения (ЛСД) и расп

Hypertrophic Cardiomyopathy Phenocopies: Classification, Key Features, and Differential Diagnosis.

Among cardiomyopathies, the hypertrophic phenotype is the most common, and hypertrophic cardiomyopathy (HCM) phenocopies represent a heterogeneous group of conditions. They are defined by a left ventricular wall thickness ≥15 mm in the absence of other causes such as loading conditions, ischemia, or valvular disease. Although they mimic similar clinical and morphological features, their etiologies are distinct and include genetic, metabolic, and infiltrative mechanisms. Therefore, accurate classification and differential diagnosis are crucial for effective management and treatment. Sarcomeric

The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.

Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, characterized by rapid progression, treatment resistance, and poor prognosis, with a survival rate of less than five years despite advances in medical interventions. A hallmark of GBM is metabolic reprogramming, which supports tumor growth and progression. Mitochondrial dysfunction plays a critical role in this metabolic shift by altering energy production and disrupting key cellular pathways. However, the precise molecular mecha-nisms underlying these alterations remain inadequately understood. This review highlights th

The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles publ

Dysregulation of sphingolipid metabolism in pain.

Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transducti

Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.

Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrop

Toxicity studies of WY-14,643 (CAS No. 50892-23-4) administered in feed to male Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.

Wy-14,643 was selected for inclusion in a series of studies on peroxisome proliferators because it is known to produce considerable peroxisome proliferation and hepatocarcinogenicity in rats. Male Sprague-Dawley rats were exposed to Wy-14,643 (greater than 98% pure) in feed for up to 3 months; male B6C3F1 mice and male Syrian hamsters were exposed to Wy-14,643 in feed for 2 weeks or up to 3 months. Animals were evaluated for clinical pathology, plasma concentrations of Wy-14,643, reproductive system effects, cell proliferation and peroxisomal enzyme analyses, and histopathology. Single and mul

Синергическое регенеративное, иммунодуляционное и антивоспалительное воздействие ваниллина и адипозы производных стволовых клеток в животной модели купризонного склероза.

ЦЕЛИ: Ваниллин как потенциальный терапевтический агент наряду с трансплантацией нейротрофических факторов, отделяющих клетки, считается перспективным средством лечения неврологических расстройств. В этом исследовании последствия ваниллина в сочетании с трансплантацией стволовых клеток, полученных человеком, были оценены с точки зрения дифференциации олигодендроцитов, повторного сглаживания и улучшения моторных функций. МАТЕРИАЛЫ И МЕТОДЫ: Женский C57BL/6 Мышей кормили кухонной зоной.400 мг/кг/сут.) 5 неделями, чтобы вызвать MS. Демилинированные мыши были разделены на группы MS, MS/vanillin, MS

Exploring Human Brain Metabolism via Genome-Scale Metabolic Modeling with Highlights on Multiple Sclerosis.

Cerebral dysfunctions give rise to a wide range of neurological diseases due to the structural and functional complexity of the human brain stemming from the interactive cellular metabolism of its specific cells, including neurons and glial cells. In parallel with advances in isolation and measurement technologies, genome-scale metabolic models (GEMs) have become a powerful tool in the studies of systems biology to provide critical insights into the understanding of sophisticated eukaryotic systems. In this study, brain cell-specific GEMs were reconstructed for neurons, astrocytes, microglia,

Pharmacokinetic study of omacetaxine mepesuccinate administered subcutaneously to patients with advanced solid and hematologic tumors.

PurposeOmacetaxine mepesuccinate is a first-in-class cephalotaxine demonstrating clinical activity in chronic myeloid leukemia. A subcutaneous (SC) formulation demonstrated efficacy and safety in phase 1/2 trials in patients previously treated with ≥1 tyrosine kinase inhibitor. This study assessed pharmacokinetics and safety of SC omacetaxine in patients with advanced cancers.MethodsOmacetaxine 1.25 mg/m(2) SC was administered BID, days 1-14 every 28 days for 2 cycles, until disease progression or unacceptable toxicity. Blood and urine were collected to measure omacetaxine concentrations and i

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.

The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor progn

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… inhibition, but the addition of exogenous recombinant Shh protein did not. 384 The lack of Hhat inhibitor studies may be due to the need to use radiolabeled fatty acid substrates to measure activity, which has limitations in terms of throughput, cost and safety. 385 Recently, Andrei et al. proposed an acylation-coupled …

Высоко избирательная и верзольная платформа для визуализации липаса Моноацилглицерол.

Monoacylglycerol Lipase (MAGL) — ключевой фермент для прекращения сигнала в эндоканнабиноидной системе (ECS). Ингибиция MAGL приводит к косвенной активации каннабиноидных рецепторов, что дает уникальные преимущества для лечения, например, множественных склерозов, эпилепсии и других неврологических расстройств. Технологии молекулярной съемки являются ценными инструментами, позволяющими преодолеть нынешнее плохое понимание распределения и роли MAGL в пато- и физиологических процессах в рамках сигнала ECS. В этой связи мы представляем информацию о проектировании, синтезе и подтверждении высокосел

Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- a

Statins: a repurposed drug to fight cancer.

As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subt

The Gut-Bone Marrow Axis: Deciphering the Mechanistic Impact of Microbial Metabolites on Hematopoietic Homeostasis and Disorders.

The gut microbiota is increasingly recognized as a dynamic endocrine-like microbial network that exerts systemic effects far beyond the gastrointestinal tract. Emerging evidence supports the existence of a "gut-bone marrow axis" through which gut-derived signals orchestrate hematopoietic homeostasis. However, shifting from correlative observations to causal mechanisms remains a major challenge in defining precise microbial impacts on hematopoietic outcomes. In this review, we systematically synthesize current knowledge on the molecular mechanisms by which microbial products-specifically short-

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

Targeting the proteasome in cancer therapy: development and future opportunities in natural products.

BACKGROUND: The ubiquitin-proteasome pathway is a critical therapeutic target in malignancies, particularly multiple myeloma. The development of proteasome inhibitors (PIs) has marked a milestone in multiple myeloma therapy and now constitutes the backbone of frontline treatment regimens. However, primary and acquired resistance remain a major challenge, underscoring the need to identify new PIs as well as agents that can resensitize resistant cells. METHOD: This review provides an overview of the current clinical applications of PIs and offers a comprehensive summary of natural products that

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to O

Characteristics of Traditional Chinese Medicine Use in Pediatric Cancer Patients: A Nationwide, Retrospective, Taiwanese-Registry, Population-Based Study.

BackgroundLarge-scale surveys of complementary traditional Chinese medicine (TCM) use in pediatric cancer patients are lacking. The aim of our study was to investigate the use of TCM in pediatric cancer patients.MethodsWe analyzed cancer patients younger than 18 years (n = 12 965) who were registered in the National Health Insurance Research Database in Taiwan between 2001 and 2011. Patients were categorized into TCM or non-TCM users based on their use of TCM.ResultsIn Taiwan, 8086 (62.4%) children with cancer sought TCM treatment at some point. Children in older age groups, including school-a

The Liver in Systemic Illness

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