摘要: In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians. This consensus provides a comprehensive assessment of biomarkers associated with liver aging and presents a systematic framework to characterize these into three dimensions: functional, imaging, and humoral. For the functional domain, we highlight biomarkers associated with cholesterol metabolism and liver-related coagulation function. For the imaging domain, we note that hepatic steatosis and liver blood flow can serve as measurable biomarkers for liver aging. Finally, in the humoral domain, we pinpoint hepatokines and enzymatic alterations worthy of attention. The aim of this expert consensus is to establish a foundation for assessing the extent of liver aging and identify early signs of liver aging-related diseases, thereby improving liver health and the healthy life expectancy of the elderly population.

摘要: Transmembrane protein 106B (TMEM106B), previously identified as a risk factor in frontotemporal lobar degeneration, has recently been detected to form fibrillar aggregates in the brains of patients with various neurodegenerative diseases (NDs) and normal elders. While the specifics of when and where TMEM106B fibrils accumulate in human brains, as well as their connection to aging and disease progression, remain poorly understood. Here, we identified an antibody (NBP1-91311) that directly binds to TMEM106B fibrils extracted from the brain in vitro and to Thioflavin S-positive TMEM106B fibrillar aggregates in brain sections. We discovered that TMEM106B fibrils deposit in the human brain in an age-dependent manner. Notably, the TMEM106B fibril load in the brains of Parkinson's disease with dementia patients was significantly higher than in age-matched elders. Additionally, we found that TMEM106B fibrils predominantly accumulate in astrocytes and neurons and do not co-localize with the pathological deposition formed by other amyloid proteins such as α-synuclein, Aβ, and Tau. Our work provides a comprehensive analysis of the burden and cellular distribution of TMEM106B fibrils in human brains, underscoring the impact of both aging and disease conditions on TMEM106B fibril deposition. This highlights the potential significance of TMEM106B fibrils in various age-related NDs.

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摘要: In recent years, the world has faced significant challenges with the coronavirus disease 2019 (COVID-19) pandemic, as well as other infectious diseases such as Zika and Ebola. Furthermore, the rapid rise of non-communicable diseases such as diabetes, heart disease, and cancer has placed tremendous strain on healthcare resources and systems. Unfortunately, advancements in drug development, diagnostics, and therapeutics have struggled to keep pace with the emergence and progression of diseases, necessitating the exploration of new technologies for the discovery and development of biomedicines and biotherapies. Synthetic biology, a revolutionary field in modern science, holds great promise in advancing drug development and disease treatment. This review provides a comprehensive overview of recent developments in the application of synthetic biology to medicine, with a specific focus on its role in drug discovery, drug production, and the diagnosis and treatment of various diseases.

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摘要: Astrocytes are crucial for central nervous system (CNS) development and function, with their differentiation being stringently controlled by epigenetic mechanisms, such as histone modifications. Enhancer of Zeste Homologue 2 (EZH2), a histone methyltransferase, is essential for the suppression of gene expression. However, the role of EZH2 in astrocyte early morphogenesis has remained unclear. Using an astrocyte-specific Ezh2 knockout (cKO) mouse model, we examined the effects of EZH2 deletion on astrocyte morphogenesis, blood-brain barrier (BBB) integrity and neurodevelopment. Loss of EZH2 led to increased glial fibrillary acidic protein (GFAP) expression, altered astrocyte morphology and reduced coverage of astrocytic endfeet on blood vessels, compromising BBB integrity. Vascular abnormalities, characterised by increased vascular density and smaller vessel diameter, mirrored compensatory changes seen in moyamoya disease. RNA-sequencing and ChIP-seq identified Ddn as a key upregulated gene in Ezh2cKO astrocytes, influencing cytoskeletal changes via the MAPK/ERK pathway. Behavioural analysis revealed autism-like traits, such as reduced vocalisations, without significant anxiety-like behaviour. These findings highlight EZH2 as a critical regulator of astrocyte function, with its disruption contributing to neurodevelopmental disorders. This study provides novel insights into the molecular pathways governing astrocyte differentiation and suggests EZH2 as a promising therapeutic target for gliomas and other CNS disorders.

摘要: Genetic diseases have long posed significant challenges, with limited breakthroughs in treatment. Recent advances in gene editing technologies offer new possibilities in gene therapy for the treatment of inherited disorders. However, traditional gene editing methods have limitations that hinder their potential for clinical use, such as limited editing capabilities and the production of unintended byproducts. To overcome these limitations, prime editing (PE) has been developed as a powerful tool for precise and efficient genome modification. In this review, we provide an overview of the latest advancements in PE and its potential applications in the treatment of inherited disorders. Furthermore, we examine the current delivery vehicles employed for delivering PE systems in vitro and in vivo, and analyze their respective benefits and limitations. Ultimately, we discuss the challenges that need to be addressed to fully unlock the potential of PE for the remission or cure of genetic diseases.