Sub-cellular biochemistry最新文献

The cholesterol of the host cell plasma membrane and viral M2 protein plays a crucial role in multiple stages of infection and replication of the influenza A virus. Cholesterol is required for the formation of heterogeneous membrane microdomains (or rafts) in the budozone of the host cell that serves as assembly sites for the viral components. The raft microstructures act as scaffolds for several proteins. Cholesterol may further contribute to the mechanical forces necessary for membrane scission in the last stage of budding and help to maintain the stability of the virus envelope. The M2 protein has been shown to cause membrane scission in model systems by promoting the formation of curved lipid bilayer structures that, in turn, can lead to membrane vesicles budding off or scission intermediates. Membrane remodeling by M2 is intimately linked with cholesterol as it affects local lipid composition, fluidity, and stability of the membrane. Thus, both cholesterol and M2 protein contribute to the efficient and proper release of newly formed influenza viruses from the virus-infected cells.

RNA is a central molecule in the life cycle of viruses, acting not only as messenger (m)RNA but also as a genome. Given these critical roles, it is not surprising that viral RNA is a hub for host-virus interactions. However, the interactome of viral RNAs remains largely unknown. This chapter discusses the importance of cellular RNA-binding proteins in virus infection and the emergent approaches developed to uncover and characterise them.

Musculoskeletal ageing is a major health challenge as muscles and bones constitute around 55-60% of body weight. Ageing muscles will result in sarcopenia that is characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes. In recent years, a few consensus panels provide new definitions for sarcopenia. It was officially recognized as a disease in 2016 with an ICD-10-CM disease code, M62.84, in the International Classification of Diseases (ICD). With the new definitions, there are many studies emerging to investigate the pathogenesis of sarcopenia, exploring new interventions to treat sarcopenia and evaluating the efficacy of combination treatments for sarcopenia. The scope of this chapter is to summarize and appraise the evidence in terms of (1) clinical signs, symptoms, screening, and diagnosis, (2) pathogenesis of sarcopenia with emphasis on mitochondrial dysfunction, intramuscular fat infiltration and neuromuscular junction deterioration, and (3) current treatments with regard to physical exercises and nutritional supplement.

Cellular senescence is a permanent state of growth arrest coupled with profound changes in phenotype that can be triggered by multiple extrinsic or intrinsic stimuli. Senescence is a process-level example of the evolution of ageing mechanisms through antagonistic pleiotropy and plays a primary role in tumour suppression, although evidence is mounting for its involvement in other fundamental physiological processes. Evidence from human premature ageing diseases and from transgenic mice in which it is possible to specifically delete senescent cells is consistent with a model in which the accumulation of senescent cells through the life course is responsible for later life chronic disease and impairment. The removal of senescent cells or their reversion to a phenotypically benign state is thus an important emerging goal of translational medicine.Modern bioinformatic approaches based on text mining have compiled co-mentions of cell senescence and age-related diseases allowing an impartial ranking of the impairments most closely associated with this process. Following this schema, the evidence for the involvement of senescence in several highly ranked pathologies is reviewed, alongside potential methods for the ablation of senescent cells or their reversion to their primary phenotype with polyphenolics or inhibitors of p38 MAP kinase. Lastly, the potential for senescence to act as a barrier to the development of bioartificial organs designed to treat some of these conditions is discussed.

Circular RNAs (circRNAs) are closed-loop RNA transcripts formed by a noncanonical back splicing mechanism. circRNAs are expressed in various tissues and cell types in a temporospatially regulated manner and have diverse molecular functions including their ability to act as miRNA sponges, transcriptional and splicing regulators, protein traps, and even templates for polypeptide synthesis. Emerging evidence suggests that circRNAs are themselves dynamically regulated throughout development in various organisms, with a substantial accumulation during ageing. Their regulatory roles in cellular pathways associated with ageing and senescence, as well as their implications in ageing-related diseases, such as neurological disease, cancer, and cardiovascular disease, suggest that circRNAs are key molecular determinants of the ageing process. Their unique structure, expression specificity, and biological functions highlight a potential capacity for use as novel biomarkers for diagnosis, prognosis, and treatment outcomes in a variety of conditions including pathological ageing. CircRNA may also have potential as target for interventions that manipulate ageing and longevity. In this chapter, we discuss the most recent advances in circRNA changes in ageing and ageing-associated disease.

African swine fever virus is a complex double-stranded DNA virus that exhibits tropism for cells of the mononuclear phagocytic system. Virus replication is a multi-step process that involves the nucleus of the host cell as well the formation of large perinuclear sites where progeny virions are assembled prior to transport to, and budding through, the plasma membrane. Like many viruses, African swine fever virus reorganises the cellular architecture to facilitate its replication and has evolved multiple mechanisms to avoid the potential deleterious effects of host cell stress response pathways. However, how viral proteins and virus-induced structures trigger cellular stress pathways and manipulate the subsequent responses is still relatively poorly understood. African swine fever virus alters nuclear substructures, modulates autophagy, apoptosis and the endoplasmic reticulum stress response pathways. The viral genome encodes for at least 150 genes, of which approximately 70 are incorporated into the virion. Many of the non-structural genes have not been fully characterised and likely play a role in host range and modifying immune responses. As the field moves towards approaches that take a broader view of the effect of expression of individual African swine fever genes, we summarise how the different steps in virus replication interact with the host cell and the current state of knowledge on how it modulates the resulting stress responses.

Human endogenous retroviruses (HERVs), which are conserved sequences of ancient retroviruses, are widely distributed in the human genome. Although most HERVs have been rendered inactive by evolution, some have continued to exhibit important cytological functions. HERVs in the human genome perform dual functions: on the one hand, they are involved in important physiological processes such as placental development and immune regulation; on the other hand, their aberrant expression is closely associated with the pathological processes of several diseases, such as cancers, autoimmune diseases, and viral infections. HERVs can also regulate a variety of host cellular functions, including the expression of protein-coding genes and regulatory elements that have evolved from HERVs. Here, we present recent research on the roles of HERVs in viral infections and cancers, including the dysregulation of HERVs in various viral infections, HERV-induced epigenetic modifications of histones (such as methylation and acetylation), and the potential mechanisms of HERV-mediated antiviral immunity. We also describe therapies to improve the efficacy of vaccines and medications either by directly or indirectly targeting HERVs, depending on the HERV.

The gap between improvements in lifespan and age-related health is widening. Globally, the demographic of ageing is increasing and there has emerged a 'diseasome of ageing', typified by a range of non-communicable diseases which share a common underlying component of a dysregulated ageing process. Within this, chronic kidney disease is an emerging global epidemic.The extensive inter-individual variation displayed in how people age and how their diseasome manifests and progresses, has required a renewed focus on their life course exposures and the interplay between the environment and the (epi)genome. Termed the exposome, life course abiotic and biotic factors have a significant impact on renal health.We explore how the exposome of renal ageing can predispose and affect CKD progression. We discuss how the kidney can be used as a model to understand the impact of the exposome in health and chronic kidney disease and how this might be manipulated to improve health span.Notably, we discuss the manipulation of the foodome to mitigate acceleration of ageing processes by phosphate and to explore use of emerging senotherapies. A range of senotherapies, for removing senescent cells, diminishing inflammatory burden and either directly targeting Nrf2, or manipulating it indirectly via modification of the microbiome are discussed.

The human ovarian reserve is defined by the number of non-growing follicles (NGFs) in the ovary, with the age-related decline in NGF population determining age at menopause for healthy women. In this chapter, the concept of ovarian reserve is explored in detail, with a sequence of models described that in principle allow any individual to be compared to the general population. As there is no current technology that can count the NGFs in a living ovary, we move our focus to biomarkers for the ovarian reserve. Using serum analysis and ultrasound it is possible to measure anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and ovarian volume (OV) and to count numbers of antral follicles (AFC). These are compared, with ovarian volume being the closest to a true biomarker for a wide range of ages and with AMH and AFC being the most popular for post-pubertal and pre-menopausal ages. The study of genetic and subcellular biomarkers for the ovarian reserve has produced less concrete results. Recent advances are described and compared in terms of limitations and potential. The chapter concludes with an overview of the future study indicated by our current knowledge and by current controversy in the field.