Advances in clinical chemistry最新文献

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.

Fibrinogen is the primary precursor protein for the fibrin clot, which is the final target of blood clotting. It is also an acute phase reactant that can vary under physiologic and inflammatory conditions. Disorders in fibrinogen concentration and/or function have been variably linked to the risk of bleeding and/or thrombosis. Fibrinogen assays are commonly used in the management of bleeding as well as the treatment of thrombosis. This chapter examines the structure of fibrinogen, its role in hemostasis as well as in bleeding abnormalities and measurement thereof with respect to clinical management.

The blood-brain barrier (BBB) is a dynamic interface that regulates the exchange of molecules and cells between the brain parenchyma and the peripheral blood. The BBB is mainly composed of endothelial cells, astrocytes and pericytes. The integrity of this structure is essential for maintaining brain and spinal cord homeostasis and protection from injury or disease. However, in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, and multiple sclerosis, the BBB can become compromised thus allowing passage of molecules and cells in and out of the central nervous system parenchyma. These agents, however, can serve as biomarkers of BBB permeability and neuronal damage, and provide valuable information for diagnosis, prognosis and treatment. Herein, we provide an overview of the BBB and changes due to aging, and summarize current knowledge on biomarkers of BBB disruption and neurodegeneration, including permeability, cellular, molecular and imaging biomarkers. We also discuss the challenges and opportunities for developing a biomarker toolkit that can reliably assess the BBB in physiologic and pathophysiologic states.

Digital biomarker (DB) assessments provide objective measures of daily life tasks and thus hold promise to improve diagnosis and monitoring of Parkinson's disease (PD) patients especially those with advanced stages. Data from DB studies can be used in advanced analytics such as Artificial Intelligence and Machine Learning to improve monitoring, treatment and outcomes. Although early development of inertial sensors as accelerometers and gyroscopes in smartphones provided encouraging results, the use of DB remains limited due to lack of standards, harmonization and consensus for analytical as well as clinical validation. Accordingly, a number of clinical trials have been developed to evaluate the performance of DB vs traditional assessment tools with the goal of monitoring disease progression, improving quality of life and outcomes. Herein, we update current evidence on the use of DB in PD and highlight potential benefits and limitations and provide suggestions for future research study.

Glycosaminoglycans (GAGs) are sulfated polysaccharides comprising repeating disaccharides, uronic acid (or galactose) and hexosamines, including chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. Hyaluronan is an exception in the GAG family because it is a non-sulfated polysaccharide. Lysosomal enzymes are crucial for the stepwise degradation of GAGs to provide a normal function of tissues and extracellular matrix (ECM). The deficiency of one or more lysosomal enzyme(s) results in the accumulation of undegraded GAGs, causing cell, tissue, and organ dysfunction. Accumulation of GAGs in various tissues and ECM results in secretion into the circulation and then excretion in urine. GAGs are biomarkers of certain metabolic disorders, such as mucopolysaccharidoses (MPS) and mucolipidoses. GAGs are also elevated in patients with various conditions such as respiratory and renal disorders, fatty acid metabolism disorders, viral infections, vomiting disorders, liver disorders, epilepsy, hypoglycemia, myopathy, developmental disorders, hyperCKemia, heart disease, acidosis, and encephalopathy. MPS are a group of inherited metabolic diseases caused by the deficiency of enzymes required to degrade GAGs in the lysosome. Eight types of MPS are categorized based on lack or defect in one of twelve specific lysosomal enzymes and are described as MPS I through MPS X (excluding MPS V and VIII). Clinical features vary with the type of MPS and clinical severity of the disease. This chapter addresses the historical overview, synthesis, degradation, distribution, biological role, and method for measurement of GAGs.

Lung diseases affect pulmonary and respiratory function and are caused by bacterial viral and fungal infection as well as environmental factors. Unfortunately, symptom overlap between various pulmonary diseases often prevents clear differentiation and uncertain diagnosis. Accordingly, identification of specific markers of inflammatory activity in early disease stage could potential unveil the intrinsic molecular mechanisms of the underlying pathology. Proteomic studies aimed at understanding the genetic/environmental contributions to the development and progression of lung diseases represent a promising approach for diagnosis and treatment. The fluid phase of sputum represents a rich protein source and is frequently used in these studies. This chapter addresses causes of lung disorders, sputum composition, collection and processing as well as the clinical significance and challenges associated with the presence of interfering factors. Basics of proteomics and mass spectrometry are also described, together with the analytical approaches to investigate the sputum proteome. Finally, we explore the application of sputum proteomics in severe lung disorders including COVID-19 infection, chronic obstructive pulmonary disease, asthma, cystic fibrosis, lung cancer and tuberculosis.

Allowable total error (ATE) are performance specification limits predefined for a variety of laboratory analytes. These limits define the maximum amount of error that is allowed for an assay when judging acceptability of a new assay during method verification/validation, evaluating patient or instrument comparison data, or in designing a quality control strategy. There are several widely available resources and models that can serve as a guide in selecting ATE. They may be based on legal requirements or set by providers of proficiency testing (PT) and external quality assessment schemes (EQAS). ATE can be also determined by professional expert groups or be based on biological variation of an analyte. Because there are several resources to choose from, there have been several attempts in reaching consensus on which ATE resource should be given preference. This chapter reviews several of these resources in more detail and discusses the difference between allowable total error (ATE) and observed total analytical error (TAE).

Idiopathic inflammatory myopathies (IIM), generally referred to as myositis is a heterogeneous group of diseases characterized by muscle inflammation and/or skin involvement, diverse extramuscular manifestations with variable risk for malignancy and response to treatment. Contemporary clinico-serologic categorization identifies 5 main clinical groups which can be further stratified based on age, specific clinical manifestations and/or risk for cancer. The serological biomarkers for this classification are generally known as myositis-specific (MSAs) and myositis-associated antibodies. Based on the use of these antibodies, IIM patients are classified into anti-synthetase syndrome, dermatomyositis, immune-mediated necrotizing myopathy, inclusion body myositis, and overlap myositis. The current classification criteria for IIM requires clinical findings, laboratory measurements, and histological findings of the muscles. However, the use MSAs and myositis-associated autoantibodies as an adjunct for disease evaluation is thought to provide a cost-effective personalized approach that may not only guide diagnosis but aid in stratification and/or prognosis of patients. This review provides a comprehensive overview of contemporary autoantibodies that are specific or associated myositis. In addition, it highlights possible pathways for the detection and interpretation of these antibodies with limitations for routine clinical use.