Physiological and pathological insights into exosomes in the brain

Exosomes are small vesicles secreted by all cell types in the brain and play a role in cell-cell communication through the transfer of cargo or encapsulation.Exosomes in the brain have considerable impact on neuronal development,activation,and regeneration.In addition,exosomes are reported to be involved in the onset and propagation of various neurodegenerative diseases.In this review,we discuss the content of exosomes derived from major cell types in the brain,and their function under physiological and pathological conditions.

The landscape of aging

Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.

APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation

Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death world-wide.Thus,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinical models are focus areas for researchers and drug developers(Cai et al.,2022a).The polymorphic protein apolipoprotein E(APOE),central to lipid transport and metabolism,is well-recognized for the role of its isoforms as important predictors for human cardiovascular disorders and neurodegenerative diseases(Tudorache et al.,2017).Plasma APOE is generated primarily from liver hepatocytes,accounting for around 75%of the APOE production from the whole body(Getz and Reardon,2009),and plays important functional roles in monocytes/macrophages,adipocytes,and the central nervous system(Kockx et al.,2018).However,despite the fact that APOE is widely expressed in different mammalian cells,studies on the functional roles of APOE mostly focus on its extracellular secreted form,and the specific effects of APOE,particularly intracellular form in cell types closely related to human cardiovascular diseases are therefore still poorly understood.

Inflammatory biomarkers and cerebral small vessel disease:a community-based cohort study

Background and purpose Although inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease(CSVD),previous findings remain largely inconclusive and vary according to disease status and study designs.The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.Methods A group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects.The biomarker panel was grouped as follows:systemic inflammation(high-sensitivity C reactive protein(hsCRP),interleukin 6 and tumour necrosis factorα),endothelial-related inflammation(E-selectin,P-selectin,intercellular adhesion molecule 1,vascular cell adhesion molecule 1(VCAM-1),CD40 ligand,lipoprotein-associated phospholipase A2,chitinase-3-like 1 protein and total homocysteine(tHCY))and media-related inflammation(matrix metalloproteinases 2,3 and 9,and osteopontin).The association(s)between different inflammatory groups and white matter hyperintensity(WMH),lacunes,cerebral microbleeds(CMBs),enlarged perivascular space(PVS)and the number of deep medullary veins(DMVs)were investigated.Results High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume(R^(2)=0.435,p=0.015)and the presence of lacunes(R^(2)=0.254,p=0.027).Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH(β=0.063,p=0.005)and tHCY was significant for lacunes(β=0.069,p<0.001).There was no association between any group of inflammatory biomarkers and CMBs or PVS.Systemic inflammatory biomarkers were associated with fewer DMVs(R^(2)=0.032,p=0.006),and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP(β=−0.162,p=0.007)was significant.Conclusion WMH and lacunes were associated with endothelial-related inflammatory biomarkers,and fewer DMVs were associated with systemic inflammation,thus suggesting different underlying inflammatory processes and mechanisms.

阿尔茨海默病的血液生物标志物:一项基于中国多中心的横断面和纵向研究

阿尔茨海默病(AD)的生物标志物在血液中含量可能因种族、老年性疾病与各种环境风险因素等不同而存在差异,尚缺乏系统性的研究来评估AD生物标志物在中国老年及AD患者人群中的变化以及是否具有准确预测脑内淀粉样蛋白沉积的能力.本工作为一项多中心纵向队列研究,共纳入来自全国各地6个不同临床中心的817个血液样本.研究测量了多个国际上通用的AD生物标志物,包括β-淀粉样蛋白40与42、磷酸化Tau(pTau)蛋白、总Tau蛋白、神经纤维丝轻链(NFL)和胶质纤维酸性蛋白(GFAP),并使用淀粉样斑块PET示踪剂和核磁结构影像对受试者进行综合评估.研究发现,APOE基因型与血浆pTau或血清GFAP组合的预测模型对脑内淀粉样斑块的沉积状态具有较好的区分能力.此外,研究还发现GFAP基线水平越高的患者其神经退行性变的速度越快.本研究结果基于多中心数据,论证了AD血液生物标志物在中国汉族人群中的实用性和应用前景,提示了血液pTau和GFAP是检测AD早期症状的有效指标,为我国AD的早期诊断和治疗提供了参考.

衰老和疾病相关的认知功能下降:表观遗传生物标志物及治疗靶点

Epigenetic mechanisms,including DNA methylation,histone modification,and non-coding RNAs(ncRNAs),have been widely implicated in synaptic plasticity,memory formation,and memory consolidation.Dysregulation in epigenetic mechanisms has been reported in aged brains as well as age-related diseases,such as Alzheimer’s disease(AD).The reversible nature of epigenetic changes and their role in regulating gene expression in response to environmental stimuli make them exciting targets for therapy.Here,we will briefly discuss epigenetic changes in aged and AD brains,epigenetic biomarkers for diagnosis and prognosis,as well as HDAC-based treatment regimes.

探究非编码RNA在学习记忆过程中的作用机制

The mechanisms underlying learning and memory have been a longstanding focus of neuroscience research.In recent decades,there has been a substantial increase in the investigation and understanding of the intricate molecular processes involved in learning and memory.Epigenetic mechanisms,which encompass dynamic and reversible modifications at various levels of cellular regulation.