Trends in molecular medicine最新文献

Platelet-derived biotherapies are emerging as innovative approaches for complex neurological disorders requiring multimodal interventions. Platelet-derived products, including lysates, platelet concentrate supernatants, secretome, extracellular vesicles, and fractionated components, represent a scalable and clinically accessible biotechnology platform for precision neuromedicine. Platelets provide a reservoir of trophic factors, cytokines, chemokines, lipids, antioxidants, and noncoding RNAs with demonstrated neuroprotective, anti-inflammatory, and antiferroptotic effects in models of neurodegeneration, trauma, and aging. Preclinical and patient-derived omics and neuroimaging data can help characterize mechanisms of action, identify biomarkers, and refine platelet secretome preparations toward indication-specific formulations. Combined with virus inactivation and purification technologies adapted from plasma protein manufacturing, these advances position platelet-derived biotherapies as a rational and versatile path toward future acellular therapeutics for brain disorders.

Mechanical forces regulate development, homeostasis, and repair in the skin, lung, and cornea-external barrier organs that are exposed to stretch, shear, and stiffness. Dysregulated mechanotransduction drives fibrosis, inflammation, and impaired repair via conserved pathways [Piezo1 (Piezo-type mechanosensitive ion channel 1), TRPV4 (transient receptor potential vanilloid 4), and integrin-YAP (Yes-associated protein)]. Targeting these circuits with small molecules, biologics, or stiffness-tuned biomaterials offers a novel category of cross-organ therapies. As mechanosensitive pathways and mechanically informed biomaterials advance toward clinical testing, an integrated cross-organ perspective is urgently needed to address unmet therapeutic needs in chronic barrier diseases. This review unifies disparate insights into biophysics, molecular biology, and clinical practice to reveal how shared mechanisms underpin barrier pathologies and enable breakthrough mechanomedicine treatments.

Mitochondria, once viewed mainly as cellular powerhouses, are now recognised as key regulators of cancer metabolism, redox balance, and immune interactions. While early models emphasised a switch to aerobic glycolysis, many tumours exhibit metabolic plasticity and retain oxidative phosphorylation capacity. Mitochondrial DNA (mtDNA) mutations are common across cancers, yet their roles in carcinogenesis and therapy response remain unclear. Emerging base-editing technologies now enable modelling of these mutations, allowing the exploration of their impact on tumourigenesis, which may differ depending on mutation type, heteroplasmy, and tissue origin. mtDNA alterations also shape immune responses within the tumour microenvironment and therefore may influence treatment sensitivity. This review integrates recent advances on mtDNA's role in cancer biology and explores therapeutic opportunities for targeting mitochondrial metabolism.

An intact gut barrier is crucial to human health. Functional assessment of gut barrier function and permeability in humans is laborious and demanding. Blood-based biomarkers that reflect gut barrier integrity have gained increasing attention for their potential role in monitoring gut barrier impairments across various conditions. Several candidate biomarkers-including intestinal fatty acid-binding protein, citrulline, zonulin, lipopolysaccharide-binding protein, and soluble CD14-reflect epithelial damage, microbial translocation, or tight junction dysfunction. This review highlights novel technologies for quantifying blood-based biomarkers to assess gut barrier function across diseases. Furthermore, it emphasizes the value of integrating complementary blood-based biomarkers across different populations to improve disease monitoring and the development of targeted therapies.

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.