Advances in Clinical Chemistry最新文献

The physin family of proteins, synaptophysin (SYP), synaptophysin like 1 (SYPL1), synaptophysin like 2 (SYPL2) and synaptoporin (SYNRP), are tetratransmembrane transport vesicle proteins distributed throughout the digestive system. Of these, SYP is a required marker for histopathologic identification of neuroendocrine neoplasms (NENs), especially in gastroenteropancreatic NENs (GEP-NENs). Recently, bloodstream SYP, i.e., on platelets and circulating tumor cells, has been correlated to clinicopathologic features of GEP-NENs and may have prognostic significance. Serum SYPL1 also represents a promising biomarker for colorectal cancer. This chapter provides an overview of physin structures and potential use as diagnostic, prognostic and therapeutic tools for digestive tract neoplasms.

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.

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.

In recent years, the comprehensive analysis of saliva, i.e., salivaomics, has played an increasing role in biomarker discovery for disease detection in general and cancer specifically. Saliva is a readily accessible, non-invasive and low-cost specimen that can be used to detect biomarkers of clinical relevance. Saliva-based "omics" technologies, which include proteomics, transcriptomics, metabolomics and microbiomics, have rapidly evolved and may be applicable in point-of-care detection, liquid biopsy and nanoscience. Advances in analytical methods has increased the scope and application of salivaomics from solely the oral cavity to the entire physiologic system, and accordingly to personalized medicine. In this chapter, we highlight recent advances in analytical approaches to identify and detect biomarkers in saliva and their potential use as diagnostic, prognostic and therapeutic markers with a focus on cancer.

Metabolomics is a powerful tool of omics that permits the simultaneous identification of metabolic perturbations in several autoimmune and chronic diseases. Several parameters can affect a metabolic profile, from the population characteristics to the selection of the analytical method. In the current chapter, we summarize the main analytical methods and results of the metabolic profiling of fatty and organic acids performed in human metabolomic studies for asthma, COPD, psoriasis and Hashimoto's thyroiditis. We discuss the most significant metabolic alterations associated with these diseases, after comparison of either a single patient's group with healthy controls or several patient's subgroups of different disease severity and phenotype with healthy controls or of a patient's group before and after treatment. Finally, we present critical metabolic patterns that are associated with each disease and their potency for the unraveling of disease pathogenesis, prediction, diagnosis, patient stratification and treatment selection.

Parathyroid hormone is an essential regulator of extracellular calcium and phosphate. PTH enhances calcium reabsorption while inhibiting phosphate reabsorption in the kidneys, increases the synthesis of 1,25-dihydroxyvitamin D, which then increases gastrointestinal absorption of calcium, and increases bone resorption to increase calcium and phosphate. Parathyroid disease can be an isolated endocrine disorder or part of a complex syndrome. Genetic mutations can account for diseases of parathyroid gland formulation, dysregulation of parathyroid hormone synthesis or secretion, and destruction of the parathyroid glands. Over the years, a number of different options are available for the treatment of different types of parathyroid disease. Therapeutic options include surgical removal of hypersecreting parathyroid tissue, administration of parathyroid hormone, vitamin D, activated vitamin D, calcium, phosphate binders, calcium-sensing receptor, and vitamin D receptor activators to name a few. The accurate assessment of parathyroid hormone also provides essential biochemical information to properly diagnose parathyroid disease. Currently available immunoassays may overestimate or underestimate bioactive parathyroid hormone because of interferences from truncated parathyroid hormone fragments, phosphorylation of parathyroid hormone, and oxidation of amino acids of parathyroid hormone.

Accurate, rapid and simple detection methods are required to facilitate early diagnosis of various disorders including infectious and lifestyle diseases as well as cancer. These detection approaches reduce the window of infection, i.e., the period between infection and reliable detection. Optimally, these methods should target protein as an indicator of pathogenic microbes as well as other biomarkers. For example, although nucleic acid is easily detected by polymerase chain reaction (PCR), these markers are also present in dead microbes, and, in the case of mRNA, it is not known whether this target was successfully translated. Accordingly, early diagnostic approaches require the development of ultrasensitive protein detection methods. In this chapter, we introduce an ultrasensitive enzyme-linked immunosorbent assay (ELISA) which combines a traditional sandwich-based immunoassay with thionicotinamide adenine dinucleotide (thio-NAD) cycling. The performance characteristics of this unique approach are reviewed as well as its potential role in providing a novel and ultrasensitive diagnostic tool in the clinical laboratory.

The field of diagnostics using invasive blood testing represents the majority of diagnostic tests used as part of routine health monitoring. The relatively recent introduction of salivary diagnostics has lead to a major paradigm shift in diagnostic analyses. Additionally, in this era of big data, oral fluid testing has shown promising outcomes in a number of fields, particularly the areas of genomics, microbiomics, proteomics, metabolomics, and transcriptomics. Despite the analytical challenges involved in the interpretation of large datasets generated from biochemical studies involving bodily fluids, including saliva, many studies have identified novel oral biomarkers for diagnosing oral and systemic diseases. In this regard, oral biofluids, including saliva, gingival crevicular fluid (GCF), peri-implant crevicular fluid (PICF), dentinal tubular fluid (DTF), are now attracting increasing attention due to their important attributes, such as noninvasive sampling, easy handling, low cost, and more accurate diagnosis of oral diseases. Recently, the utilization of salivary diagnostics to evaluate systemic diseases and monitor general health has increased in popularity among clinicians. Saliva contains a wide range of protein, DNA and RNA biomarkers, which assist in the diagnosis of multiple diseases and conditions, including cancer, cardiovascular diseases (CVD), auto-immune and degenerative diseases, respiratory infections, oral diseases, and microbial (viral, bacterial and fungal) diseases. Moreover, due to its noninvasive nature and ease-of-adoption by children, it is now being used in mass screening programs, oral health-related studies and clinical trials in support of the development of therapeutic agents. The recent advent of highly sensitive technologies, such as next-generation sequencing, mass spectrometry, highly sensitives ELISAs, and homogeneous immunoassays, suggests that even small quantities of salivary biomarkers are able to be assayed accurately, providing opportunities for the development of many future diagnostic applications (including emerging technologies, such as point-of-care and rapid molecular technologies). The present article explores the omics and biochemical compositions of various oral biofluids with important value in diagnostics and monitoring.