Advances in Clinical Chemistry最新文献

Cardiovascular disease remains the leading cause of morbidity and mortality globally. Extracellular vesicles (EVs), a group of heterogeneous nanosized cell-derived vesicles, have attracted great interest as liquid biopsy material for biomarker discovery in a variety of diseases including cardiovascular disease. Because EVs inherit bioactive components from parent cells and are able to transfer their contents to recipient cells, EVs hold great promise as potential cell-free therapeutics and drug delivery systems. However, the development of EV-based diagnostics, therapeutics or drug delivery systems has been challenging due to the heterogenicity of EVs in biogenesis, size and cellular origin, the lack of standardized isolation and purification methods as well as the low production yield. In this review, we will provide an overview of the recent advances in EV-based biomarker discovery, highlight the potential usefulness of EVs and EV mimetics for therapeutic treatment and drug delivery in cardiovascular disease. In view of the fast development in this field, we will also discuss the challenges of current methodologies for isolation, purification and fabrication of EVs and potential alternatives.

Glycosylation, one of the most common post-translational modifications in mammalian cells, impacts many biological processes such as cell adhesion, proliferation and differentiation. As the most abundant glycoprotein in human serum, immunoglobulin G (IgG) plays a vital role in immune response and protection. There is a growing body of evidence suggests that IgG structure and function are modulated by attached glycans, especially N-glycans, and aberrant glycosylation is associated with disease states. In this chapter, we review IgG glycan repertoire and function, strategies for profiling IgG N-glycome and recent studies. Mass spectrometry (MS) based techniques are the most powerful tools for profiling IgG glycome. IgG glycans can be divided into high-mannose, biantennary complex and hybrid types, modified with mannosylation, core-fucosylation, galactosylation, bisecting GlcNAcylation, or sialylation. Glycosylation of IgG affects antibody half-life and their affinity and avidity for antigens, regulates crystallizable fragment (Fc) structure and Fcγ receptor signaling, as well as antibody effector function. Because of their critical roles, IgG N-glycans appear to be promising biomarkers for various disease states. Specific IgG glycosylation can convert a pro-inflammatory response to an anti-inflammatory activity. Accordingly, IgG glycoengineering provides a powerful approach to potentially develop effective drugs and treat disease. Based on the understanding of the functional role of IgG glycans, the development of vaccines with enhanced capacity and long-term protection are possible in the near future.

Bone fragility fractures remain an important worldwide health and economic problem due to increased morbidity and mortality. The current methods for predicting fractures are largely based on the measurement of bone mineral density and the utilization of mathematical risk calculators based on clinical risk factors for bone fragility. Despite these approaches, many bone fractures remain undiagnosed. Therefore, current research is focused on the identification of new factors such as bone turnover markers (BTM) for risk calculation. BTM are a group of proteins and peptides released during bone remodeling that can be found in serum or urine. They derive from bone resorptive and formative processes mediated by osteoclasts and osteoblasts, respectively. Potential use of BTM in monitoring these phenomenon and therefore bone fracture risk is limited by physiologic and pathophysiologic factors that influence BTM. These limitations in predicting fractures explain why their inclusion in clinical guidelines remains limited despite the large number of studies examining BTM.

High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). International Guidelines recommend a large reduction in the consumption of sodium to reduce blood pressure, organ damage, and mortality. In its early stages, the symptoms of CKD are generally not apparent. CKD proceeds in a "silent" manner, necessitating the need for urinary biomarkers to detect kidney damage at an early stage. Since traditional renal biomarkers, such as serum creatinine, are not sufficiently sensitive, difficulties are associated with detecting kidney damage induced by a high salt intake, particularly in normotensive individuals. Several new biomarkers for renal tubular damage, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), vanin-1, liver-type fatty acid-binding protein (L-FABP), and monocyte chemotactic protein-1 (MCP-1), have recently been identified. However, few studies have investigated early biomarkers for CKD progression associated with a high salt diet. This chapter provides insights into novel biomarkers for CKD in normo- and hypertensive individuals with a high salt intake. Recent studies using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high salt diet identified urinary vanin-1 and NGAL as early biomarkers for renal tubular damage in SHR and WKY, whereas urinary KIM-1 was a useful biomarker for salt-induced renal injury in SHR only. Clinical studies are needed to confirm these findings.

Epigenetics examines heritable changes in DNA and its associated proteins except mutations in gene sequence. Epigenetic regulation plays fundamental roles in kidney cell biology through the action of DNA methylation, chromatin modification via epigenetic regulators and non-coding RNA species. Kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis are multistep processes associated with numerous molecular alterations even in individual kidney cells. Epigenetic alterations, including anomalous DNA methylation, aberrant histone alterations and changes of microRNA expression all contribute to kidney pathogenesis. These changes alter the genome-wide epigenetic signatures and disrupt essential pathways that protect renal cells from uncontrolled growth, apoptosis and development of other renal associated syndromes. Molecular changes impact cellular function within kidney cells and its microenvironment to drive and maintain disease phenotype. In this chapter, we briefly summarize epigenetic mechanisms in four kidney diseases including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis. We primarily focus on current knowledge about the genome-wide profiling of DNA methylation and histone modification, and epigenetic regulation on specific gene(s) in the pathophysiology of these diseases and the translational potential of identifying new biomarkers and treatment for prevention and therapy. Incorporating epigenomic testing into clinical research is essential to elucidate novel epigenetic biomarkers and develop precision medicine using emerging therapies.

Point-of-care testing (POCT) is a specific format of diagnostic testing that is conducted without accompanying infrastructure or sophisticated instrumentation. Traditionally, such rapid sample-to-answer assays provide inferior analytical performances to their laboratory counterparts when measuring cardiac biomarkers. Hence, their potentially broad applicability is somewhat bound by their inability to detect clinically relevant concentrations of cardiac troponin (cTn) in the early stages of myocardial injury. However, the continuous refinement of biorecognition elements, the optimization of detection techniques, and the fabrication of tailored fluid handling systems to manage the sensing process has stimulated the production of commercial assays that can support accelerated diagnostic pathways. This review will present the latest commercial POC assays and examine their impact on clinical decision-making. The individual elements that constitute POC assays will be explored, with an emphasis on aspects that contribute to economically feasible and highly sensitive assays. Furthermore, the prospect of POCT imparting a greater influence on early interventions for medium to high-risk individuals and the potential to re-shape the paradigm of cardiovascular risk assessments will be discussed.

Exosomes are small extracellular vesicles released by cells under physiological and pathological conditions. There is emerging evidence associating exosomes with tumorigenesis. They carry cargo (DNA, RNA, miRNA and protein) pertaining to the cell of origin and play a key role in intercellular communication, influencing several cellular processes. Moreover, exosomes can be shed and found in almost all body fluids, providing a source of biomarkers for tumor diagnosis and prognosis. In addition, the use of exosomes for cancer therapeutics is another research area that is gaining attention. This book chapter aims to explore the role of exosomes in tumor biogenesis, progression and clinical applications, comprehensively compiling the research for three tumor types, namely head and neck cancer, lung cancer and glioblastoma.