Trends in molecular medicine最新文献

Group 2 innate lymphoid cells (ILC2s) are emerging players in tumor immunity. ILC2 heterogeneity confers tissue-specific outcomes, with sometimes opposing effects on the prognosis and progression of various cancers. The role of ILC2s in breast and ovarian cancer is an active area of investigation, with research aimed at leveraging these cells to enhance immunotherapy.

Recent breakthroughs in gene therapy for autosomal recessive deafness 9 (DFNB9) caused by OTOF mutations have transformed treatment paradigms for hereditary hearing loss (HHL). To date, eight clinical trials targeting DFNB9 have been registered in 51 centers across eight countries, demonstrating the rapid progress of gene therapy in auditory medicine. These pioneering studies establish the framework for the clinical translation of gene therapy targeting HHL. This review synthesizes progress in OTOF-related clinical trials, highlighting translational foci such as inner ear drug delivery, trial design, safety assessments, and auditory restoration outcomes. Key challenges in optimizing future therapeutic strategies - including addressing anatomical constraints, refining patient selection criteria, and standardizing outcome measures - are critically examined.

A groundbreaking study by Yue et al. reveals adenosine signaling as the convergent mechanism underlying the rapid antidepressant effects of both ketamine and electroconvulsive therapy. This discovery not only resolves a longstanding mechanistic puzzle but also opens new therapeutic avenues, including novel ketamine derivatives and nonpharmacological interventions that harness adenosine's antidepressant potential.

Cardiac organoids are 3D self-assembling structures that recapitulate some of the functional, structural, and cellular aspects of the developing heart. Cardiac organoid modeling has overcome many of the limitations of current cardiac modeling systems by providing a human-relevant, multicellular, spatially advanced model that can replicate early key developmental stages of human cardiogenesis. Recent advancements in cardiac organoid modeling have enabled further understanding of cardiogenesis, cardiovascular disease, and drug-induced cardiotoxicity. Emerging tools to effectively characterize cardiac organoid models to understand their morphology, function, and cellular phenotype will enable further understanding of cardiac development, cardiovascular disease, and preclinical drug discovery.

With the use of assisted reproductive technology to treat infertility, there has been an increase in the condition known as empty follicle syndrome (EFS). EFS is characterized by the failure to retrieve oocytes from multiple mature follicles despite normal follicle development following ovarian stimulation. Despite its clinical significance, there is a lack of comprehensive and up-to-date reviews on this syndrome. In addition, the borderline form of EFS, that is characterized by low oocyte retrieval rates and is more common in clinical practice, has not been extensively discussed. This review aims to update perspectives on EFS, and covers its classification, etiology, treatment, prediction, prevention, and prognosis with the goal of leading to better clinical management and future research that improves outcomes for infertility patients.

Huntington's disease (HD) is usually described as rare, tragic, and intractable. Yet, HD offers a strategically unique entry point for neuroscience. With its genetic clarity, relatively predictable course, and organized global community, HD provides the clearest path to advancing brain repair.

The muscle regeneration niche comprises various cell types, including muscle stem cells (MuSCs; also termed satellite cells), immune cells, and stromal cells, all of which have crucial roles in the regeneration process. Intracellular metabolic reprogramming during injury responses is closely linked to the functional activities of these cells, thus necessitating a comprehensive understanding for developing targeted metabolic interventions that promote regeneration. Recent studies have suggested the existence of a more intricate network, involving cell-cell metabolic crosstalk and even cross-organ regulation, which underpins muscle regeneration. In addition, aging and diseases that disrupt overall metabolic homeostasis contribute to muscle dysfunction, due, in part, to metabolic disorders in the regeneration niche. In this review, we provide a comprehensive overview of the metabolic profile within the muscle regeneration niche and highlight potential interventions to reprogram metabolism to improve regenerative capacity.

Ferroptosis, a regulated cell death pathway driven by iron-catalyzed lipid peroxidation, has recently been implicated as a major cause of hepatic injury in metabolic dysfunction-associated fatty liver disease (MAFLD). This review highlights how the identification of hyperoxidized peroxiredoxin 3 (PRDX3) as a ferroptosis-specific marker has led to the discovery that ferroptosis contributes to liver injury in MAFLD, and summarizes other emerging evidence connecting ferroptosis to MAFLD pathogenesis. These new findings suggest that dietary fat composition and genetic variants such as PNPLA3(I148M) may affect the progression of MAFLD by regulating cellular sensitivity to ferroptosis. Recognizing MAFLD as a ferroptotic disease provides novel insights into the pathogenesis of the disease, and supports the exploration of ferroptosis as a potential target for therapeutic intervention.

Cachexia and hypercalcemia frequently complicate advanced renal cancer. A recent Nature Medicine study by Abu-Remaileh et al. shows that pharmacologic hypoxia-inducible factor 2 (HIF2) inhibition rapidly suppresses parathyroid hormone-related protein (PTHrP), reverses metabolic wasting, and normalizes calcium levels, redefining these paraneoplastic syndromes as targetable endocrine disorders rather than secondary consequences of tumor burden.