Advances in Clinical Chemistry最新文献

There is growing demand for novel biomarkers that detect early stage disease as well as monitor clinical management and therapeutic strategies. Exosome analysis could provide the next advance in attaining that goal. Exosomes are membrane encapsulated biologic nanometric-sized particles of endocytic origin which are released by all cell types. Unfortunately, exosomes are exceptionally challenging to characterize with current technologies. Exosomes are between 30 and 200nm in diameter, a size that makes them out of the sensitivity range to most cell-oriented sorting or analysis platforms, i.e., traditional flow cytometers. The most common methods for targeting exosomes to date typically involve purification followed by the characterization and the specific determination of their cargo. The whole procedure is time consuming, requiring thus skilled personnel as well as laboratory facilities and benchtop instrumentation. The most relevant methodology for exosome isolation, characterization and quantification is addressed in this chapter, including the most up-to-date approaches to explore the potential usefulness of exosomes as biomarkers in liquid biopsies and in advanced nanomedicine.

Alzheimer's disease (AD) characterization has progressed from being indexed using clinical symptomatology followed by neuropathological examination at autopsy to in vivo signatures using cerebrospinal fluid (CSF) biomarkers and positron emission tomography. The core AD biomarkers reflect amyloid-β plaques (A), tau pathology (T) and neurodegeneration (N), following the ATN schedule, and are now being introduced into clinical routine practice. This is an important development, as disease-modifying treatments are now emerging. Further, there are now reproducible data on CSF biomarkers which reflect synaptic pathology, neuroinflammation and common co-pathologies. In addition, the development of ultrasensitive techniques has enabled the core CSF biomarkers of AD pathophysiology to be translated to blood (e.g., phosphorylated tau, amyloid-β and neurofilament light). In this chapter, we review where we stand with both core and novel CSF biomarkers, as well as the explosion of data on blood biomarkers. Also, we discuss potential applications in research aiming to better understand the disease, as well as possible use in routine clinical practice and therapeutic trials.

Amyotrophic lateral sclerosis (ALS) is a relatively rare but fatal neurodegenerative disease with the progressive loss of both upper and lower motor neurons. Although electromyography, imaging and multi-omics technologies have suggested numerous functional, structural, circulating and microbiota markers for ALS, no clinically validated markers have, as yet, been identified. Here we summarize the advances to characterize markers underlying ALS pathophysiology as well as their potential use in diagnosis, prognosis and therapy.

Major Depressive Disorder (MDD) or depression is a pathological mental condition affecting millions of people worldwide. Identification of objective biological markers of depression can provide for a better diagnostic and intervention criteria; ultimately aiding to reduce its socioeconomic health burden. This review provides a comprehensive insight into the major biomarker candidates that have been implicated in depression neurobiology. The key biomarker categories are covered across all the "omics" levels. At the epigenomic level, DNA-methylation, non-coding RNA and histone-modifications have been discussed in relation to depression. The proteomics system shows great promise with inflammatory markers as well as growth factors and neurobiological alterations within the endocannabinoid system. Characteristic lipids implicated in depression together with the endocrine system are reviewed under the metabolomics section. The chapter also examines the novel biomarkers for depression that have been proposed by studies in the microbiome. Depression affects individuals differentially and explicit biomarkers identified by robust research criteria may pave the way for better diagnosis, intervention, treatment, and prediction of treatment response.

The analysis of salivary biomarkers has gained interest and is advantageous for simple, safe, and non-invasive testing in diagnosis as well as treatment. This chapter explores the importance of saliva biomarkers and summarizes recent advances in biosensor fabrication. The identification of diagnostic, prognostic and therapeutic markers in this matrix enables more rapid and frequent testing when combined with the use of biosensor technology. Challenges and future goals are highlighted and examined.

Globally, tuberculosis (TB) was the leading cause of death from a single infectious agent until the coronavirus (COVID-19) pandemic. In 2020, an estimated 10 million people fell ill with TB and a total of 1.5 million people died from the disease. About one-quarter of the global population, almost two billion people, is estimated to be latently infected with Mycobacterium tuberculosis (MTB). Although latent TB infection (LTBI) is asymptomatic and noncontagious, about 5-10% of LTBI patients have a lifetime risk of progression to active TB. The diagnosis and treatment of active cases are extremely vital for TB control programs. However, achieving the End TB goal of 2035 without the ability to identify and treat the pool of latently infected individuals will be a big challenge. To do so, improved technology to provide more accurate diagnostic tools and accessibility are crucial. Therefore, this chapter covers the current WHO-endorsed tests and advances in diagnostic and screening tests for active and latent TB.

We are currently experiencing a rapidly developing era in terms of translational and clinical medical sciences. The relatively mature state of nucleic acid examination has significantly improved our understanding of disease mechanism and therapeutic potential of personalized treatment, but misses a large portion of phenotypic disease information. Proteins, in particular phosphorylation events that regulates many cellular functions, could provide real-time information for disease onset, progression and treatment efficacy. The technical advances in liquid chromatography and mass spectrometry have realized large-scale and unbiased proteome and phosphoproteome analyses with disease relevant samples such as tissues. However, tissue biopsy still has multiple shortcomings, such as invasiveness of sample collection, potential health risk for patients, difficulty in protein preservation and extreme heterogeneity. Recently, extracellular vesicles (EVs) have offered a great promise as a unique source of protein biomarkers for non-invasive liquid biopsy. Membranous EVs provide stable preservation of internal proteins and especially labile phosphoproteins, which is essential for effective routine biomarker detection. To aid efficient EV proteomic and phosphoproteomic analyses, recent developments showcase clinically-friendly EV techniques, facilitating diagnostic and therapeutic applications. Ultimately, we envision that with streamlined sample preparation from tissues and EVs proteomics and phosphoproteomics analysis will become routine in clinical settings.

TRPV6 is a Transient Receptor Potential Vanilloid (TRPV) cation channel with high selectivity for Ca²⁺ ions. First identified in 1999 in a search for the gene which mediates intestinal Ca²⁺ absorption, its far more extensive repertoire as a guardian of intracellular Ca²⁺ has since become apparent. Studies on TRPV6-deficient mice demonstrated additional important roles in placental Ca²⁺ transport, fetal bone development and male fertility. The first reports of inherited deficiency in newborn babies appeared in 2018, revealing its physiological importance in humans. There is currently strong evidence that TRPV6 also contributes to the pathogenesis of some common cancers. The recently reported association of TRPV6 deficiency with non-alcoholic chronic pancreatitis suggests a role in normal pancreatic function. Over time and with greater awareness of TRPV6, other disease-associations are likely to emerge. Powerful analytical tools have provided invaluable insights into the structure and operation of TRPV6. Its roles in Ca²⁺ signaling and carcinogenesis, and the use of channel inhibitors in cancer treatment are being intensively investigated. This review first briefly describes the biochemistry and physiology of the channel, and analytical methods used to investigate these. The focus subsequently shifts to the clinical disorders associated with abnormal expression and the underlying pathophysiology. The aims of this review are to increase awareness of this channel, and to draw together findings from a wide range of sources which may help to formulate new ideas for further studies.