Trends in molecular medicine最新文献

Aging, once viewed as an irreversible process, is now considered a modifiable process. Recent advances in cellular reprogramming reveal that transient expression of reprogramming factors can reverse molecular hallmarks of aging while preserving somatic cell identity. This 'partial reprogramming' rejuvenates tissues, restores regenerative capacity, and, in some models, extends lifespan without the tumorigenic risks of full dedifferentiation. In this review, we summarize genetic and chemical strategies for partial reprogramming, discuss their tissue-specific effects in vivo, and evaluate their implications for tissue regeneration and age-related disease. We further examine key challenges for clinical translation, including safety, delivery strategies, and temporal control of reprogramming.

Whether endometriosis is a progressive disease remains debated. Central to this debate is understanding the natural history of endometriotic lesions, which are essentially wounds undergoing repeated tissue injury and repair. Viewing the disease through this lens, we reassess the literature on the progression, or absence thereof, of endometriosis and offer our perspective on this debate by delineating the aggravating and mitigating factors that influence lesional progression. We propose that the degree of lesional fibrosis, measurable via elastography as lesional stiffness, represents a promising marker for progression, as it correlates with aberrant histology, molecular alterations, symptom severity, clinical prognosis, and lesional mechanobiology. Lesional stiffness could aid in diagnosis, guide treatment choice, and predict outcomes, providing a valuable tool for managing endometriosis.

Bacteriophages (phages) are emerging as programmable biological therapeutics in oncology, extending beyond their traditional antimicrobial applications. This review proposes a phage-microbiome-immune-oncology axis that links microbial dynamics, immune modulation, and engineered phages to guide precision cancer prevention and therapy. Phages can eliminate cancer-associated bacteria, remodel the tumor microenvironment, enhance antitumor immunity, and deliver targeted therapeutic payloads. However, several critical challenges must be addressed to realize this therapeutic potential, particularly host immune responses that limit repeat dosing, inefficient tumor penetration, and the need for rigorous clinical validation. By examining phage-host-tumor interactions through robust model systems and highlighting translational opportunities, this review establishes phage therapy as a promising frontier in precision oncology that warrants accelerated clinical development.

Therapy-resistant cancers exploit cellular stress programs to survive. Evidence from neuroendocrine prostate cancer reveals that the loss of nitric oxide-dependent redox signaling amplifies endoplasmic reticulum stress and lineage plasticity. Restoring physiological nitroso-redox balance may reprogram stress adaptation and expose new vulnerabilities in aggressive cancers.

The placenta is an essential organ that supports fetal development during pregnancy. The establishment of human trophoblast stem cells has enhanced our understanding of placental development; however, their limited diversity constrains our ability to capture interindividual variation. Patient-specific trophoblast stem cells (pTSCs), derived from induced pluripotent stem cells, fibroblasts, cytotrophoblasts, or chorionic villus tissue, retain the unique genetic and epigenetic backgrounds of individual patients. Notably, chorionic villus-derived trophoblast stem cells can be obtained without terminating a pregnancy, allowing for integration with prospective clinical data. pTSCs, therefore, provide powerful platforms to investigate the pathogenesis of placental disorders, assess individual risk, and advance personalized therapeutic strategies. This review highlights recent advances in pTSC derivation and discusses their potential applications.

Intercepting cancer development with immune-modulating approaches before cancer has established is an emerging and promising strategy to reduce the global cancer burden. By safely harnessing the immune system, cancer vaccines can enhance immune surveillance and lead to the elimination of transforming cells at the earliest stages of carcinogenesis, particularly when the immune microenvironment is least hostile and the potential for cure is greatest. In this review, we discuss the fundamental rationale behind immuno-interception strategies, provide an overview of advances in cancer interception clinical trials, and highlight key considerations and future directions for achieving effective cancer interception.

A recent study by Angelino et al. uncovered an intracellular signaling pathway involved in musculoskeletal mitochondrial dysfunction in cancer cachexia. Both humans and mice with cancer cachexia display impaired 3',5'-cyclic adenosine monophosphate (cAMP)-protein kinase A-cAMP response element-binding protein 1 signaling, which leads to mitochondrial dysfunction. By rescuing this pathway with a phosphodiesterase-4 inhibitor, the authors highlight a potential therapeutic strategy for cancer cachexia.

Ferroptosis, a regulated form of cell death, is determined by iron-dependent lipid peroxidation. A selenoenzyme called glutathione peroxidase 4 (GPX4) detoxifies phospholipid hydroperoxides at the heart of this process. As the pivotal gatekeeper of ferroptosis, GPX4 is implicated in a wide range of pathologies, including cancer, neurodegeneration, acute renal failure, and infection. In this review, we discuss how GPX4 transcription and mRNA stability are controlled by transcription factors, epigenetic modifications, and noncoding RNAs and how GPX4 degradation and activity are modulated by post-translational modifications, including ubiquitination, phosphorylation, palmitoylation, methylation, hydroxylation, and lactylation. We also summarize new therapeutic methods targeting GPX4, namely the ferroptosis inducers for cancer therapy and ferroptosis inhibitors that prevent ferroptosis-related damage.