Advances in clinical chemistry最新文献

Gel electrophoresis is a key technique of modern biochemistry and frequently used for efficient protein separation prior to top-down proteomics. For comparative studies, differential fluorescent tagging can be employed to avoid gel-to-gel variations, which has been extensively used in two-dimensional difference gel electrophoresis (2D-DIGE). This chapter reviews recent advances in 2D-DIGE and focuses on comparative proteomic studies. Strategies to improve the sensitivity of this gel-based method, as well as a discussion of its bioanalytical advantages versus technical limitations are provided. The general suitability of 2D-DIGE for the large-scale screening of cellular systems and biofluids to support biomarker discovery is explored.

Volatile organic compounds (VOCs) of biological origin represent a promising source of noninvasive biomarkers for a wide range of biomedical applications. These compounds can be detected in various sample types, including breath, urine, blood, sweat, and more. The scientific exploration of VOCs, known as volatilomics, has its roots in the 1970's with research focusing on identifying novel biomarkers for cancers, metabolic disorders, and infectious diseases. This chapter explores the breadth of viable biological samples for VOC analysis and highlights recent technological advancements in both sampling and analytical techniques. We also delve into sophisticated data processing strategies and methods for selecting high-confidence biomarkers. State-of-the-art studies in VOC discovery are reviewed, with particular attention to the most investigated diseases and sample types. Additionally, we examine ongoing efforts and initiatives aimed at addressing key challenges in the field, such as elucidating the biological origins of VOCs and achieving robust clinical validation. Finally, we present innovative approaches for early and at-home disease detection, including the development of synthetic breath-based biomarkers, which hold significant potential for future clinical applications.

Autoimmune disease (AD), characterized by abnormal immune system function, leads to self-attack against cells, tissues and organs resulting in increased morbidity and mortality thus contributing to healthcare and socioeconomic expense worldwide. As the population ages, there is increased demand for novel analytical tools enabling early AD diagnosis that facilitates timely therapeutic and lifestyle intervention. Advances in biosensor technology have provided a more rapid and less costly alternative to traditional laboratory testing. In the field of AD, biosensors have been developed to target primary indices such as specific autoantibodies or secondary markers, such as proinflammatory cytokines. This article explores the use of biosensor technology in various AD including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, etc. Other biosensors based on molecular and cellular AD targets are also explored including those for type 1 diabetes mellitus. Biosensors developed for quantifying and monitoring efficacy of drugs against AD are highlighted. We conclude with an overview of emerging biosensor technologies and future perspectives.

Advancements in clinical chemistry have major implications in terms of public health, prompting many clinicians to seek out chemical information to aid in diagnoses and treatments. While mass spectrometry (MS) and hyphenated-MS techniques such as LC-MS or tandem MS/MS have long been the analytical methods of choice for many clinical applications, these methods routinely demonstrate difficulty in differentiating between isomeric forms in complex matrices. Consequently, ion mobility spectrometry (IM), which differentiates molecules on the basis of size, shape, and charge, has demonstrated unique advantages in the broad application of stand-alone IM and hyphenated IM instruments towards clinical challenges. Here, we highlight representative IM applications and approaches and describe contemporary commercial offerings of IM technology and how these can be, or are currently being, applied to the field of clinical chemistry.

This chapter reviews the emerging role of metabolomics in nephrotic syndrome (NS), a kidney disorder characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Metabolomics provides valuable insights into the complex metabolic changes associated with NS, including disruptions in lipid, amino acid, and energy metabolism and oxidative stress markers. Through untargeted and targeted approaches, metabolomics enables the discovery of novel potential biomarkers that could enhance diagnosis, monitor disease progression, and personalize treatment strategies. Despite challenges such as methodological variability and the need for extensive computational resources, advancements in metabolomics technology and data integration are poised to improve our understanding of NS. Integrating metabolomics with genomics and proteomics may enable a comprehensive molecular profile of NS, offering new opportunities for precision medicine and improved patient outcomes.

Proteomics using gel electrophoresis (GE) for efficient protein separation prior to mass spectrometry is a frequently employed and proteoform-centric analysis tool of biomedical chemistry. Isolated molecular species can be visualized by various protein staining techniques and their characterization being combined with protein interaction analyses and the determination of dynamic post-translational modifications. This chapter describes the bioanalytical usefulness of one-dimensional GE (1D-GE) approaches, including the gel electrophoresis liquid chromatography (GeLC) mass spectrometry method, as well as commonly used two-dimensional gel electrophoresis (2D-GE) techniques, including fluorescence difference GE (DIGE) for sophisticated comparative studies. The ways in which advanced protein identification and gel-based proteomics can help to discover novel biomarker candidates is discussed.

Underrepresented k-mer sequences, provide insights into evolutionary constraints, molecular mechanisms, and organismal fitness. Analysis of these sequences have broad applications across genomics and proteomics, such as in biomarker development, cancer diagnostics, phylogenetic analysis, synthetic biology and novel drug discovery. Absent sequences (nullomers and neomers) show promise for cancer detection and tissue-of-origin identification using nucleic acids derived from liquid biopsies, while quasi-primes serve as genomic fingerprints that offer potential for evolutionary studies for understanding trait evolution, and in metagenomics, as biomarkers of organismal presence. The chapter also discusses computational challenges associated with analyzing absent sequences and highlights available k-mer based resources and databases. With the continuous expansion of genomic and proteomic data, absent sequences present an innovative framework for addressing fundamental biological questions and advancing applications in basic and translational research.

Aminopeptidase N (CD13) is a multifunctional protein recognized for its diverse roles as an enzyme, receptor, and signalling molecule, attributes that have earned it classification as a "moonlighting" protein. Its involvement in key biological processes such as inflammation, angiogenesis, cell migration, tissue invasion, and the propagation and survival of cancer cells has spurred significant interest in its potential as a therapeutic target. This interest extends beyond oncology to include conditions such as hypertension and rheumatoid arthritis. Consequently, substantial research efforts have been directed toward exploring strategies for leveraging CD13 in clinical interventions. This chapter comprehensively reviews this protein with the aim of improving current understanding of this protein, with a particular focus on its tissue-specific expression and functional roles. Special attention is given to the physiological and pathological diversity of CD13 activity, which offers critical insights into opportunities for selective targeting and disease-specific therapeutic applications.