Trends in molecular medicine最新文献

Clonal hematopoiesis is emerging as a surprising modifier of Alzheimer's disease. Recent findings suggest that mutant myeloid cells may enter or expand within the brain, adopting either inflammatory or reparative states. We propose that their effects depend on the mutation, timing, clone size, brain niche, and disease stage.

In a recent study in Cell, Liu et al. identify β-hydroxybutyrate as a practical metabolic adjuvant for CAR-T cells. By fueling the TCA cycle and reshaping transcriptional and epigenetic programs, this ketone body enhances proliferation, persistence, and tumor control, suggesting that metabolic supplementation may offer a simple route to more effective adoptive immunotherapy.

Glucagon-like peptide-1 receptor agonists (GLP1-RAs), widely used for type 2 diabetes mellitus, are emerging as promising neuroprotective therapies in Alzheimer's disease (AD) and Parkinson's disease (PD). Agents such as exenatide, lixisenatide, and liraglutide have demonstrated disease-modifying potential in preclinical and clinical studies. However, translation remains hindered by the absence of validated biomarkers to guide patient selection, track target engagement, and monitor progression. Here, we review the mechanistic links between GLP1-RA signaling and neurodegeneration, summarize the evolving clinical evidence, and highlight emerging blood-based and molecular biomarkers, including those tied to insulin signaling, neurodegeneration, and metabolic and cardiovascular dysfunction, that may accelerate therapeutic development. Integrating these biomarkers with digital phenotyping and artificial intelligence could enable precision approaches to advance GLP1-RA research and clinical use in neurodegeneration.

Despite revolutionary molecular targeting therapies introduced over the past two decades for the management of inflammatory bowel disease (IBD), there remains significant variability in drug efficacy, which likely reflects the multifactorial basis and the complex and dynamic nature of the disorder. The presence of different molecular mechanisms and the diversity of cytokine expression profiles that drive distinct subtypes or different phases of IBD could affect the response to current pharmacological treatments. In this review we discuss the distinct roles of cytokines across different disease phases, and emphasize the importance of tailored drug use based on available biomarkers to deliver molecular targeted agents suited to the condition of each patient.

Previous epidemiological studies have associated viral pneumonia with an increased risk of lung cancer. Recently, Qian et al. revealed that epigenetic reprogramming following respiratory viral infections accelerates tumorigenesis by orchestrating a protumor microenvironment, providing mechanistic insights and potential therapeutic strategies for intercepting lung cancer progression after viral pneumonia.

Peripheral nerve regeneration declines with aging and prolonged denervation, yet the underlying mechanisms have remained elusive. Recent studies identify senescent Schwann cells (senSCs) as a key contributor. Following injury, repair Schwann cells (SCs) enter a senescent state marked by p16^INK4a/p21^CIP1 upregulation and secretion of a senescence-associated secretory phenotype (SASP) that impairs axonal regrowth. Clearing senSCs in preclinical models restores regeneration, suggesting that failed repair results from active inhibition rather than diminished capacity. Moreover, SASP-like signatures emerge across neuropathies of diverse etiology, suggesting broader relevance. In this review, we synthesize emerging evidence linking SC senescence to impaired regeneration and chronic neuropathies and outline therapeutic strategies targeting senescence. We also examine translational challenges and explore how these approaches could advance nerve repair and neuropathy treatment.

Long COVID may reflect a failure of coordinated physiological recovery rather than persistent infection. Emerging evidence identifies inflammation-driven disruption of erythropoiesis and hormonal balance as central mechanisms linking immune dysregulation, metabolic stress, and persistent symptoms. This framework positions erythroid-endocrine pathways as key determinants of recovery and promising therapeutic targets.

Single cell RNA sequencing (scRNA-seq) has revolutionized the field of biology and become the most powerful tool for evaluating transcriptional profiles of a biological sample. Given its power, it is widely utilized across multiple disciplines, including chimeric antigen receptor (CAR)-T cell therapy. In this review, we provide a comprehensive summary of published studies that have used scRNA-seq to analyze clinical CAR-T cells, focusing on T cell exhaustion, cytotoxicity, memory, expansion, clonal diversity, and cytokines. We also highlight findings on activation, CD4+/CD8+ ratios, proliferation, regulatory T cells (Tregs) and metabolism, and their relevance to patient response across diseases. Finally, we discuss the limitations and future directions of scRNA-seq in CAR-T cell research, providing key insights for clinicians and researchers.

By identifying graft ferroptosis as a druggable vulnerability, Veeckmans et al. show that FXT-001 intercepts lipid-radical injury during machine perfusion and improves liver and lung graft function. This work supports rather than proves machine perfusion as a therapeutic window for preimplantation graft repair, a concept that now requires postimplantation validation.

Tuberculosis (TB) remains a major global health burden, prompting heightened efforts towards host-directed therapies (HDT). Autophagy, a key antimicrobial and immunomodulatory process, is a promising candidate for HDT. However, despite encouraging preclinical results, autophagy-targeting strategies have shown limited clinical success, in part due to the lack of accurate profiling of patient-derived autophagy flux across the TB spectrum. This gap limits our understanding of baseline autophagy dynamics and hinders the rational design of HDT. This review highlights patient-derived autophagic flux as a dynamic, quantitative readout of autophagy activity and an underutilized element in TB biomarker and therapeutic research. We examine autophagy flux assessment methodologies and propose its role as a biomarker for TB diagnosis, prognosis, and patient stratification in personalized HDT strategies.