Advances in Clinical Chemistry最新文献

Exosomes are tiny membrane-enveloped vesicles of endosomal origin, typically 40-120nm in diameter, produced by most cells in both normal and pathological situations. These exosomes can be isolated from all biofluids, including urine. In this context, many researchers have focused on the analysis of urinary exosomes because urine can be collected in large quantities, regularly, and with minimal effort. Exosomes contain phospholipids, cholesterol, proteins, glycoconjugates, nucleic acids, and metabolites. Because all organs and tissues produce exosomes, their molecular cargo can provide first-hand information about the physiological and biological state of the site of origin. Many potential disease biomarker candidates have already been identified in urinary exosomes. In this chapter, we performed a bibliometric analysis of the keywords "exosome(s)" and "urine" to identify related terms, diseases and molecular/biological processes, and other related terms. This yielded interesting results suggesting that exosomes in urine may play a role in the pathogenesis of various diseases. Moreover, this chapter discusses exosomes isolation and characterization methodologies and highlight the importance of urinary exosomes and their role in the diagnosis, prognosis and therapy of various diseases. We offer a bibliometric approach and an in-depth analysis on several exosomes' isolation techniques, diagnostic potential for urogenital and specific non-urogenital diseases, as well as an overview of miRNAs significance on urinary exosomes, conferring a more complete status to this review, something that was still lacking in the current literature.

Myostatin is a member of the transforming growth factor (TGF)-β superfamily. It is expressed by animal and human skeletal muscle cells where it limits muscle growth and promotes protein breakdown. Its effects are influenced by complex mechanisms including transcriptional and epigenetic regulation and modulation by extracellular binding proteins. Due to its actions in promoting muscle atrophy and cachexia, myostatin has been investigated as a promising therapeutic target to counteract muscle mass loss in experimental models and patients affected by different muscle-wasting conditions. Moreover, growing evidence indicates that myostatin, beyond to regulate skeletal muscle growth, may have a role in many physiologic and pathologic processes, such as obesity, insulin resistance, cardiovascular and chronic kidney disease. In this chapter, we review myostatin biology, including intracellular and extracellular regulatory pathways, and the role of myostatin in modulating physiologic processes, such as muscle growth and aging. Moreover, we discuss the most relevant experimental and clinical evidence supporting the extra-muscle effects of myostatin. Finally, we consider the main strategies developed and tested to inhibit myostatin in clinical trials and discuss the limits and future perspectives of the research on myostatin.

Exosomes have evolved into novel candidates as diagnostic tools due to their composition of proteins and nucleic acids and ability to cross hypoxic regions, the systemic circulation and blood vessel barriers. Exosomes are nano-sized extracellular vesicles that contain information from their source cells and are found in almost all body fluids. In this chapter, we have focused on basic biogenesis, contents, and functions of these unique particles, and provide a comprehensive discussion on their usefulness as novel diagnostic tools in various diseases. In addition, these unique features make them potential candidates for development of advanced therapeutics and monitoring thereof.

Quantum dots (QDs) are crystalline inorganic semiconductor nanoparticles a few nanometers in size that possess unique optical electronic properties vs those of larger materials. For example, QDs usually exhibit a strong and long-lived photoluminescence emission, a feature dependent on size, shape and composition. These special optoelectronic properties make them a promising alternative to conventional luminescent dyes as optical labels in biomedical applications including biomarker quantification, biomolecule targeting and molecular imaging. A key parameter for use of QDs is to functionalize their surface with suitable (bio)molecules to provide stability in aqueous solutions and efficient and selective tagging biomolecules of interest. Researchers have successfully developed biocompatible QDs and have linked them to various biomolecule recognition elements, i.e., antibodies, proteins, DNA, etc. In this chapter, QD synthesis and characterization strategies are reviewed as well as the development of nanoplatforms for luminescent biosensing and imaging-guided targeting. Relevant biomedical applications are highlighted with a particular focus on recent progress in ultrasensitive detection of clinical biomarkers. Finally, key future research goals to functionalize QDs as diagnostic tools are explored.

Long noncoding RNAs (lncRNAs) are defined as noncoding RNA transcripts with a length greater than 200 nucleotides. Research over the last decade has made great strides in our understanding of lncRNAs, especially in the biology of their role in cancer. In this article, we will briefly discuss the biogenesis and characteristics of lncRNAs, then review their molecular and cellular functions in cancer by using prostate and breast cancer as examples. LncRNAs are abundant, diverse, and evolutionarily, less conserved than protein-coding genes. They are often expressed in a tumor and cell-specific manner. As a key epigenetic factor, lncRNAs can use a wide variety of molecular mechanisms to regulate gene expression at each step of the genetic information flow pathway. LncRNAs display widespread effects on cell behavior, tumor growth, and metastasis. They act intracellularly and extracellularly in an autocrine, paracrine and endocrine fashion. Increased understanding of lncRNA's role in cancer has facilitated the development of novel biomarkers for cancer diagnosis, led to greater understanding of cancer prognosis, enabled better prediction of therapeutic responses, and promoted identification of potential targets for cancer therapy.

Nonalcoholic fatty liver disease (NAFLD) is a chronic disease of worldwide impact. The disease process begins with steatosis, i.e., fat accumulation in the liver, and proceeds to nonalcoholic steatohepatitis (NASH). Liver biopsy is the gold standard for NASH diagnosis, but the procedure is invasive, expensive, error prone and poses considerable risk. Unfortunately, there are currently no precise FDA-approved therapies for NAFLD, the only options being lifestyle change and symptomatic treatment. Recently, much research has focused on the identification of molecular mechanisms that could be translated into novel diagnostics and therapeutics. With the advent of high throughput genomics and transcriptomics, noncoding RNAs, including long non-coding RNAs (lncRNAs) have been identified as key players of NAFLD pathogenesis and have accordingly attracted much attention as potential diagnostics and therapeutics. In this chapter, we reviewed various lncRNAs and their functions at different stages of NAFLD. We also highlighted how these unique molecules can be developed as stage-specific non-invasive diagnostic biomarkers for NAFLD.

Amino acids are crucial building blocks of living organisms. Together with their derivatives, they participate in many intracellular processes to act as hormones, neuromodulators, and neurotransmitters. For several decades amino acids have been studied for their potential as markers of various diseases, including inflammatory bowel diseases. Subsequent improvements in sample pretreatment, separation, and detection methods have enabled the specific and very sensitive determination of these molecules in multicomponent matrices-biological fluids and tissues. The information obtained from targeted amino acid analysis (biomarker-based analytical strategy) can be further used for early diagnostics, to monitor the course of the disease or compliance of the patients. This review will provide an insight into current knowledge about inflammatory bowel diseases, the role of proteinogenic amino acids in intestinal inflammation and modern analytical techniques used in its diagnosis and disease activity monitoring. Current advances in the analysis of amino acids focused on sample pretreatment, separation strategy, or detection methods are highlighted, and their potential in clinical laboratories is discussed. In addition, the latest clinical data obtained from the metabolomic profiling of patients suffering from inflammatory bowel diseases are summarized with a focus on proteinogenic amino acids.