Trends in molecular medicine最新文献

Hyaluronan synthases (HASs) are essential enzymes for hyaluronic acid (HA) production; a key component for joint lubrication and cartilage health. Dysregulated HA synthesis contributes to joint dysfunction. In this Forum, we discuss the role of HAS in matrix assembly, inflammation and the pathogenesis of osteoarthritis (OA).

The central nervous system (CNS) orchestrates homeostatic responses and organismal behaviors by integrating cues from the whole body. Like other peripheral tissues, skeletal muscle can signal to the brain, and this occurs via muscle-secreted signaling factors (myokines/myometabolites). In this review article, we examine exercise-induced myokines and myometabolites that improve cognitive capacity and impede neurodegeneration and, conversely, detrimental myokines secreted by diseased muscles that negatively impact brain function. Cellular processes modulated by myokines in the CNS include proteostasis, angiogenesis, neurogenesis, synaptic plasticity, cell senescence, and neuroinflammation, resulting in the modulation of diverse behaviors, such as motor control, memory, foraging, and sleep. Collectively, muscle-to-brain signaling emerges as an important influencer of CNS function and aging, with the prospect of utilizing myokine-/myometabolite-based therapies for treating neurodegeneration.

Invasive candidiasis is a severe fungal infection with management challenges due to a lack of biomarker-guided patient stratification and limited availability of antifungal drugs. Liu et al. identified the cytokine Meteorin-like as a key regulator and potential theranostic target, offering new hope for better diagnosis and treatment of these life-threatening infections.

Interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), have dismal prognoses, with a median survival of 3-5 years, owing to a lack of early biomarkers or effective treatments. This review highlights the lung microbiome as a key biological factor in IPF pathogenesis and a promising therapeutic target. Elevated burdens of pathogenic bacteria, including Streptococcus and Staphylococcus, in bronchoalveolar lavage fluid correlate with accelerated progression and higher mortality. These bacteria release toxins and activate Th17-driven inflammation, providing mechanistic links to alveolar injury and fibrosis. Host genetics and systemic factors, including oral-gut-lung interactions, further shape disease progression. Although antibiotic trials have been unsuccessful, embracing the microbiome as an active participant in IPF may open unprecedented opportunities for personalized interventions.

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.