Advances in clinical chemistry最新文献

High density lipoprotein (HDL) functions are mostly mediated through a complex proteome, particularly its enzymes. HDL can provide a scaffold for the assembly of several proteins that affect each other's function. HDL particles, particularly small, dense HDL3, are rich in paraoxonase 1 (PON1), which is an important enzyme in the functionality of HDL, so the antioxidant and antiatherogenic properties of HDL are largely attributed to this enzyme. There is an increasing need to represent a valid, reproducible, and reliable method to assay HDL function in routine clinical laboratories. In this context, HDL-associated proteins may be key players; notably PON1 activity (its arylesterase activity) may be a proper candidate because its decreased activity can be considered an important risk factor for HDL dysfunctionality. Of note, automated methods have been developed for the measurement of serum PON1 activity that facilitates its assay in large sample numbers. Arylesterase activity is proposed as a preferred activity among the different activities of PON1 for its assay in epidemiological studies. The binding of PON1 to HDL is critical for the maintenance of its activity and it appears apolipoprotein A-I plays an important role in HDL-PON1 interaction as well as in the biochemical and enzymatic properties of PON1. The interrelationships between HDL, PON1, and HDL's other components are complex and incompletely understood. The purpose of this review is to discuss biochemical and clinical evidence considering the interactions of PON1 with HDL and the role of this enzyme as an appropriate biomarker for HDL function as well as a potential therapeutic target.

Congenital disorders of glycosylation (CDG) are one of the fastest growing groups of inborn errors of metabolism, comprising over 160 described diseases to this day. CDG are characterized by a dysfunctional glycosylation process, with molecular defects localized in the cytosol, the endoplasmic reticulum, or the Golgi apparatus. Depending on the CDG, N-glycosylation, O-glycosylation and/or glycosaminoglycan synthesis can be affected. Various proteins, lipids, and glycosylphosphatidylinositol anchors bear glycan chains, with potential impacts on their folding, targeting, secretion, stability, and thus, functionality. Therefore, glycosylation defects can have diverse and serious clinical consequences. CDG patients often present with a non-specific, multisystemic syndrome including neurological involvement, growth delay, hepatopathy and coagulopathy. As CDG are rare diseases, and typically lack distinctive clinical signs, biochemical and genetic testing bear particularly important and complementary diagnostic roles. Here, after a brief introduction on glycosylation and CDG, we review historical and recent findings on CDG biomarkers and associated analytical techniques, with a particular emphasis on those with relevant use in the specialized clinical chemistry laboratory. We provide the reader with insights and methods which may help them properly assist the clinician in navigating the maze of glycosylation disorders.

The detection of volatile organic compounds (VOCs) in breath has become a potential method for early cancer screening. Although this approach has attracted increasing attention from the both scientific and medical communities, it has not received appreciable traction in the clinical setting. There are two main obstacles. One involves the identification of specific biomarkers or combinations thereof especially in early cancer. The other is the lack the specialized equipment for breath analysis having the appropriate sensitivity and specificity. Using metabolomics, this chapter examines the research strategies involving gas biomarkers in cancer patient breath, cancer cell gas metabolites and synthetic biomarkers. We briefly explore gas biomarkers of seven cancers and introduce principles of detection and clinical application. Large analytical instruments and small sensor technology are highlighted. Challenges to VOC analysis are presented including clinical use, extraction and detection, miniaturization efforts and examination of metabolic VOC pathways. Finally, VOCs in cancer and in exhaled breath detection technology are summarized and future prospects explored.

Posttraumatic stress disorder (PTSD) is characterized by exposure to traumatic events and involves symptom domains such as intrusive thoughts, avoidant behaviors, negative mood, and cognitive dysfunction. The disorder can be chronic and debilitating, and the heterogenous nature and varied presentation of PTSD has afforded difficulty in determining efficacious treatment. The ability to identify biomarkers for PTSD risk, prognosis, or for the purposes of treatment, would be highly valuable. There is evidence for peripheral biomarkers related to the hypothalamic-pituitary-adrenal axis, the immune system, neurotransmitters and neurohormones, while genome and epigenome wide association studies have identified genes of interest relating to neurocircuitry, monoaminergic function, and the immune system. Importantly, however, reproducibility is a persistent issue. Considerations for future research include the need for well-powered and well-designed studies to determine directionality, in addition to considering biomarkers as they relate to symptom domains and the spectrum of symptom severity rather than dichotomous diagnostic outcomes. We conclude by recommending the staging of biological processes and PTSD symptoms, from subsyndromal to chronic, which could eventually facilitate selection of personalized treatment interventions for individuals with PTSD, in addition to serving as a future framework for biomarker data.

Over the last four decades, cardiac natriuretic peptides have changed our understanding of patients with chronic heart failure. From the discovery of the heart as an endocrine organ with its own hormones and receptors, the biochemistry and physiology of the system have been translated into useful biomarkers and drug targets in cardiovascular disease. The purpose of this review is to provide medical researchers not working in the field with a simple introduction to the system and its molecular components, its quantitative methods, and its physiology and pathophysiology. The hope is that this overview may help to broaden the knowledge of the endocrine heart with the intent that researchers in other areas of medical research will be inspired to seek new facets of the system, both in translational science and in clinical practice.

Physiologically, extracellular vesicles (EVs) have been implicated as crucial mediators of immune response, cell homeostasis, angiogenesis, cell differentiation and growth, and tissue repair. In heart failure (HF) they may act as regulators of cardiac remodeling, microvascular inflammation, micro environmental changes, tissue fibrosis, atherosclerosis, neovascularization of plaques, endothelial dysfunction, thrombosis, and reciprocal heart-remote organ interaction. The chapter summaries the nomenclature, isolation, detection of EVs, their biologic role and function physiologically as well as in the pathogenesis of HF. Current challenges to the utilization of EVs as diagnostic and predictive biomarkers in HF are also discussed.

Mitochondria, as an endosymbiont of eukaryotic cells, controls multiple cellular activities, including respiration, reactive oxygen species production, fatty acid synthesis, and death. Though the majority of functional mitochondrial proteins are translated through a nucleus-controlled process, very few of them (∼10%) are translated within mitochondria through their own machinery. Germline and somatic mutations in mitochondrial and nuclear DNA significantly impact mitochondrial homeostasis and function. Such modifications disturbing mitochondrial biogenesis, metabolism, or mitophagy eventually resulted in cellular pathophysiology. In this chapter, we discussed the impact of mitochondria and its dysfunction on several non-communicable diseases like cancer, diabetes, neurodegenerative, and cardiovascular problems. Mitochondrial dysfunction and its outcome could be screened by currently available omics-based techniques, flow cytometry, and high-resolution imaging. Such characterization could be evaluated as potential biomarkers to assess the disease burden and prognosis.

Cortisol, a stress hormone, plays a crucial role in regulating metabolic, hemodynamic, inflammatory, and behavioral processes. Its secretion is governed by the hypothalamic-pituitary-adrenal axis. However, prolonged activation of this axis and increased cortisol bioavailability in tissues can result in detrimental metabolic effects. Chronic exposure to excessive cortisol is associated with insulin resistance and visceral obesity, both significant contributors to metabolic syndrome. This review delves into the regulation of the hypothalamic-pituitary-adrenal axis, the molecular mechanisms underlying cortisol synthesis and its actions, as well as the key factors influencing cortisol bioavailability. Furthermore, it provides a summary of available clinical research data on the involvement of cortisol in metabolic syndrome, alongside a discussion on the various biomatrices used for cortisol measurement in clinical settings.