Trends in molecular medicine最新文献

Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) - a protease released by skeletal muscle during PA - acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.g., hippocampus and prefrontal cortex) that support performance in specific cognitive domains including memory, learning, and executive function. However, the evidence regarding the role of PA-induced changes in CTSB as a mediator of PA-induced cognitive health in humans is mixed. To guide future research, this article identifies key factors that may explain the observed heterogeneity in the findings from human studies and proposes a PA-CTSB-cognition model.

Biological sex strongly impacts tuberous sclerosis complex (TSC) symptoms like epilepsy and autism. However, the mechanisms driving this influence remain largely unknown. Here, we discuss how sex-specific changes in brain synapses and neural networks may drive these differences, offering insights that could be crucial for developing targeted therapies for TSC.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that represents a significant public health challenge worldwide. This multifactorial condition results from complex interactions among genetic, environmental, immune, and microbial factors. Some beneficial microbes, known as probiotics, have been identified as promising therapeutic agents for inflammatory conditions, such as IBD. In this review, we explore the potential of probiotics as a therapeutic strategy for managing IBD. Probiotics have shown promise due to their ability to modulate the gut microbiota, regulate histamine levels, and enhance vitamin D metabolism, thereby promoting a tolerant immune profile and reducing inflammation. While the exact mechanisms underlying these benefits remain incompletely understood, probiotics represent a novel and emerging approach for alleviating the exacerbated inflammation characteristic of this disorder.

Beta-thalassemia is a severe, hereditary blood disorder characterized by anemia, transfusion dependence, reduced life expectancy, and poor quality of life. Allogeneic transplantation of hematopoietic stem cells (HSCs) is the only curative treatment for transfusion-dependent β-thalassemia, but a lack of compatible donors prevents the use of this approach for most patients. Over the past 20 years, the rise of gene therapy and the development of lentiviral vectors and genome-editing tools has extended curative options to a broader range of patients. Here, we review breakthroughs in gene addition- and genome-editing-based therapies for β-thalassemia, the clinical outcomes enabling approval by regulatory agencies, and perspectives for further development.

Spinal muscular atrophy (SMA) is a devastating, degenerative, paediatric neuromuscular disease which until recently was untreatable. Discovery of the responsible gene 30 years ago heralded a new age of pioneering therapeutic developments. Three disease-modifying therapies (DMTs) have received regulatory approval and have transformed the disease, reducing disability and prolonging patient survival. These therapies - with distinct mechanisms, routes of administration, dosing schedules, side effect profiles, and financial costs - have dramatically altered the clinical phenotypes of this condition and have presented fresh challenges for patient care. In this review article we discuss potential strategies to maximise clinical outcomes through early diagnosis and treatment, optimised dosing, use of therapeutic combinations and state-of-the-art physiotherapy techniques, and the development of innovative therapies targeting alternative mechanisms.

Bilirubin reductase (BilR), a gut microbiota-derived enzyme that reduces bilirubin to urobilinogen, was recently identified. Given the role of bilirubin in preventing modern diseases, understanding the link between the gut microbiota and health via modulation of bilirubin metabolism marks a major advance in medical research and potential treatments.

Disturbances in kidney tubular cell metabolism are increasingly recognized as a feature of acute kidney injury (AKI). In AKI, tubular epithelial cells undergo abnormal metabolic shifts that notably disrupt NAD⁺ metabolism. Recent advancements have highlighted the critical role of NAD⁺ metabolism in AKI, revealing that acute disruptions may lead to lasting cellular changes, thereby promoting the transition to chronic kidney disease (CKD). This review explores the molecular mechanisms underlying metabolic dysfunction in AKI, with a focus on NAD⁺ metabolism, and proposes several cellular processes through which acute aberrations in NAD⁺ may contribute to long-term changes in the kidney.

Seven primary familial brain calcification genes have been identified but their role in disease mechanisms has been less explored. Cheng et al. recently demonstrated that astrocyte-mediated regulation of brain phosphate (P_i) involves direct and functional interactions among three of these proteins, paving the way for new strategies to combat brain calcification.