Current state of the art for enhancing urine biomarker discovery

Abstract

Urine is a highly desirable biospecimen for biomarker analysis because it can be collected recurrently by non-invasive techniques, in relatively large volumes. Urine contains cellular elements, biochemicals, and proteins derived from glomerular filtration of plasma, renal tubule excretion, and urogenital tract secretions that reflect, at a given time point, an individual's metabolic and pathophysiologic state. High-resolution mass spectrometry, coupled with state of the art fractionation systems are revealing the plethora of diagnostic/prognostic proteomic information existing within urinary exosomes, glycoproteins, and proteins. Affinity capture pre-processing techniques such as combinatorial peptide ligand libraries and biomarker harvesting hydrogel nanoparticles are enabling measurement/identification of previously undetectable urinary proteins. Future challenges in the urinary proteomics field include a) defining either single or multiple, universally applicable data normalization methods for comparing results within and between individual patients/data sets, and b) defining expected urinary protein levels in healthy individuals.

EDTA-functionalized magnetic nanoparticles: A suitable platform for the analysis of low abundance urinary proteins

“…Furthermore, targeted proteomics studies rely heavily on the knowledge of the urinary proteome to obtain a quantifiable protein library and, thus, expansion of the known urine protein repertoire will increase the chances of creating suitable biomarker panels for a condition at scope. Several strategies have been reported, namely the use of combinatorial peptide ligand libraries, ion-exchange chromatography and immunoaffinity chromatography to enrich low-abundance proteins with biological value [4,38]. Nevertheless, these approaches require large amounts of sample, being thus impractical in large cohort studies, rapidly become expensive when dealing with large volumes and still fail to improve significantly the number of identifications or the sequence Fig.…”

“…Still, such technologies rely heavily on the knowledge of the urinary proteome, which is not fully known to date. Recently employed pre-analytical techniques based on depletion/enrichment strategies, such as solid phase adsorption, combinatory peptide ligand libraries or hydrogel nanoparticles have significantly expanded the urinary proteome to over 4400 proteins, as reviewed elsewhere [4]. Therefore, there are reasons to believe that novel fractionation strategies will extend the knowledge on this fluid composition.…”

Identification of pathogens from native urine samples by MALDI-TOF/TOF tandem mass spectrometry

“…Therefore, bacterial identification at the strain-level is still regarded as a challenge. Some of the underlying factors that compromise this method sensitivity in bacterial identification are: sample impurity substances (human proteins), the low abundance of bacterial proteins in the sample [41], insufficient coverage of urinary bacterial species in the databases, shared peptide sequences among proteins from different taxa [38] as well as insufficient data for identification after analysis [39]. Bottom-up tandem MS with growing reference database and data processing through bioinformatic analysis has made significant progress in increasing polymicrobial identification [36,30] but this is still a field being developed experimentally and far from clinical practice.…”

Curcumin protects murine lung mesenchymal stem cells from H2O2 by modulating the Akt/Nrf2/HO-1 pathway

“…[3][4][5] Mesenchymal stem cells (MSCs) are a type of adult stem cell than can repair tissues, regulate immunity, and inhibit fibrosis. 6 As such, lung MSCs (LMSCs) are considered the most effective treatment for IPF; however, they show limited survival after transplantation, which may be related to the internal environment. 7 Additionally, the harsh pulmonary microenvironment inhibits the repair of damaged tissue by autologous LMSCs.…”