Gene Ontology (GO)-Driven Inference of Candidate Proteomic Markers Associated with Muscle Atrophy Conditions.

Skeletal muscle homeostasis is essential for the maintenance of a healthy and active lifestyle. Imbalance in muscle homeostasis has significant consequences such as atrophy, loss of muscle mass, and progressive loss of functions. Aging-related muscle wasting, sarcopenia, and atrophy as a consequence of disease, such as cachexia, reduce the quality of life, increase morbidity and result in an overall poor prognosis.

Urinary proteomics predict onset of microalbuminuria in normoalbuminuric type 2 diabetic patients, a sub-study of the DIRECT-Protect 2 study.

Background: Early prevention of diabetic nephropathy is not successful as early interventions have shown conflicting results, partly because of a lack of early and precise indicators of disease development. Urinary proteomics has shown promise in this regard and could identify those at high risk who might benefit from treatment. In this study we investigate its utility in a large type 2 diabetic cohort with normoalbuminuria.

Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study.

Background: Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure.

In vitro studies on the stability in the proximal gastrointestinal tract and bioaccessibility in Caco-2 cells of chlorogenic acids from spent coffee grounds.

Spent coffee grounds are a potential commercial source of substantial amounts of chlorogenic acids (CGAs). The aim of this study was to evaluate the stability of spent coffee CGAs using in vitro simulated gastroduodenal digestion and to investigate their potential absorption using an in vitro Caco-2 model of human small intestinal epithelium. During in vitro digestion, lactones were partially degraded while caffeoylquinic and feruloylquinic acids were much more stable.

Urinary proteomic biomarkers to predict cardiovascular events.

Purpose: We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here, we evaluate the potential of a urinary proteomic panel as a predictor of CAD in the hypertensive atherosclerotic cardiovascular disease (HACVD) substudy population of the Anglo-Scandinavian Cardiac Outcomes Trial study.

Experimental Design: Thirty-seven cases with primary CAD endpoint were matched for sex and age to controls who had not reached a CAD endpoint during the study.

Methods in capillary electrophoresis coupled to mass spectrometry for the identification of clinical proteomic/peptidomic biomarkers in biofluids.

Proteomic biomarkers hold the promise of enabling assessment of patients according to a pathological condition aiming at improvements in diagnosis, prognosis, in general clinical patient management. Capillary electrophoresis coupled to an electrospray ionization time-of-flight mass spectrometer (CE-MS) allows the detection of thousands of small proteins and peptides in various biofluids, in a single, reproducible and time-limited step, enabling the simultaneous comparison of multiple individual proteins and peptides in biomarker discovery, but also in clinical applications. The reliability of the CE-MS platform, together with the use of a validated approach for data processing and mining is, to date, the most advanced technique for biomarker discovery of clinical significance.

Identification of urinary peptide biomarkers associated with rheumatoid arthritis.

Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides.

Impact of dose on the bioavailability of coffee chlorogenic acids in humans.

Single servings of coffee beverage containing low (412 μmol), medium (635 μmol) and high (795 μmol) amounts of chlorogenic acids were administered to eleven healthy volunteers in a double-blind randomised controlled trial. Analysis of plasma and urine collected for 24 h revealed the presence of 12 metabolites in plasma and 16 metabolites in urine, principally in the form of sulphates, and to a lesser extent glucuronides of caffeic, ferulic, dihydrocaffeic and dihydroferulic acids, as well as intact feruloylquinic and caffeoylquinic acids, and sulphated caffeoylquinic acid lactones. Median values of peak plasma concentrations after increasing doses of chlorogenic acids were 1088, 1526 and 1352 nM.

Classical MALDI-MS versus CE-based ESI-MS proteomic profiling in urine for clinical applications.

Human urine is an attractive and informative biofluid for medical diagnosis, which has been shown to reflect the (patho)-physiology of not only the urogenital system, but also others such as the cardiovascular system. For this reason, many studies have concentrated on the study of the urine proteome, aiming to find relevant biomarkers that could be applied in a clinical setting. However, this goal can only be achieved after reliable quantitative and qualitative analysis of the urinary proteome.

Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men.

Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits.

Fetal urinary peptides to predict postnatal outcome of renal disease in fetuses with posterior urethral valves (PUV).

Bilateral congenital abnormalities of the kidney and urinary tract (CAKUT), although are individually rare diseases, remain the main cause of chronic kidney disease in infants worldwide. Bilateral CAKUT display a wide spectrum of pre- and postnatal outcomes ranging from death in utero to normal postnatal renal function. Methods to predict these outcomes in utero are controversial and, in several cases, lead to unjustified termination of pregnancy.

Improving peptide relative quantification in MALDI-TOF MS for biomarker assessment.

Proteomic profiling by MALDI-TOF MS presents various advantages (speed of analysis, ease of use, relatively low cost, sensitivity, tolerance against detergents and contaminants, and possibility of automation) and is being currently used in many applications (e.g. peptide/protein identification and quantification, biomarker discovery, and imaging MS).

Recent advances in capillary electrophoresis coupled to mass spectrometry for clinical proteomic applications.

Proteome analysis using capillary electrophoresis coupled to mass spectrometry (CE-MS) has been used in a number of clinical applications in the past years. The main focus of CE-MS-based studies has been on the investigation of urine, due to the stability of the urinary proteome, ease of collection, and also the low molecular weight range of the urinary proteome, mostly peptides below 30 kDa. The reproducibility of this approach has enabled analysis of over 20 000 samples in a comparable way, giving enormous statistical power to any additional study involving this methodological setup.

Colonic catabolism of dietary phenolic and polyphenolic compounds from Concord grape juice.

After acute ingestion of 350 ml of Concord grape juice, containing 528 μmol of (poly)phenolic compounds, by healthy volunteers, a wide array of phase I and II metabolites were detected in the circulation and excreted in urine. Ingestion of the juice by ileostomists resulted in 40% of compounds being recovered intact in ileal effluent. The current study investigated the fate of these undigested (poly)phenolic compounds on reaching the colon.

Absorption, disposition, metabolism, and excretion of [3-(14)C]caffeic acid in rats.

Male Sprague-Dawley rats ingested 140 × 10(6) dpm of [3-(14)C]trans-caffeic acid, and over the ensuing 72 h period, body tissues, plasma, urine, and feces were collected and the overall levels of radioactivity determined. Where sufficient radioactivity had accumulated, samples were analyzed by HPLC with online radioactivity and tandem mass spectrometric detection. Nine labeled compounds were identified, the substrate and its cis isomer, 3'-O- and 4'-O-sulfates and glucuronides of caffeic acid, 4'-O-sulfates and glucuronides of ferulic acid, and isoferulic acid-4'-O-sulfate.

Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans.

The in vitro gastrointestinal stability of (poly)phenolic compounds in Concord grape juice was compared with recoveries in ileal fluid after the ingestion of the juice by ileostomists. Recoveries in ileal fluid indicated that 67% of hydroxycinnamate tartarate esters, and smaller percentages of the intake of other (poly)phenolic compounds, pass from the small intestine to the colon. The juice was also ingested by healthy subjects with an intact functioning colon.

Espresso coffees, caffeine and chlorogenic acid intake: potential health implications.

HPLC analysis of 20 commercial espresso coffees revealed 6-fold differences in caffeine levels, a 17-fold range of caffeoylquinic acid contents, and 4-fold differences in the caffeoylquinic acid : caffeine ratio. These variations reflect differences in batch-to-batch bean composition, possible blending of arabica with robusta beans, as well as roasting and grinding procedures, but the predominant factor is likely to be the amount of beans used in the coffee-making/barista processes. The most caffeine in a single espresso was 322 mg and a further three contained >200 mg, exceeding the 200 mg day(-1) upper limit recommended during pregnancy by the UK Food Standards Agency.

Identification of (poly)phenolic compounds in concord grape juice and their metabolites in human plasma and urine after juice consumption.

Analysis of Concord grape juice by HPLC with ESI-MS(n), PDA, and fluorescence detection resulted in the identification and quantification of 60 flavonoids and related phenolic compounds, which were present at an overall concentration of 1508 ± 31 μmol/L. A total of 25 anthocyanins were detected, which were mono- and di-O-glucosides, O-acetylglucosides, O-p-coumaroyl-O-diglucosides, and O-p-coumaroylglucosides of delphinidin, cyanidin, petunidin, peonidin, and malvidin. The anthocyanins represented 46% of the total phenolic content of the juice (680 μmol/L).

First synthesis, characterization, and evidence for the presence of hydroxycinnamic acid sulfate and glucuronide conjugates in human biological fluids as a result of coffee consumption.

A systematic investigation of the human metabolism of hydroxycinnamic acid conjugates was carried out. A set of 24 potential human metabolites of coffee polyphenols has been chemically prepared, and used as analytical standards for unequivocal identifications. These included glucuronide conjugates and sulfate esters of caffeic, ferulic, isoferulic, m-coumaric and p-coumaric acids as well as their dihydro derivatives.

Bioavailability of coffee chlorogenic acids and green tea flavan-3-ols.

This paper reviews recent human studies on the bioavailability of chlorogenic acids in coffee and green tea flavan-3-ols in which the identification of metabolites, catabolites and parent compounds in plasma, urine and ileal fluid was based on mass spectrometric methodology. Both the chlorogenic acids and the flavan-3-ols are absorbed in the small intestine and appear in the circulatory system predominantly as glucuronide, sulfate and methylated metabolites. Even when absorption occurs in the small intestine, feeding studies with ileostomists reveal that substantial amounts of the parent compounds and some of their metabolites appear in ileal fluid indicating that in volunteers with a functioning colon these compounds will pass to the large intestine where they are subjected to the action of the colonic microflora.

Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy.

The intestinal absorption and metabolism of 385 micromol chlorogenic acids following a single intake of 200 mL of instant coffee by human volunteers with an ileostomy was investigated. HPLC-MS(3) analysis of 0-24h post-ingestion ileal effluent revealed the presence of 274+/-28 micromol of chlorogenic acids and their metabolites accounting for 71+/-7% of intake. Of the compounds recovered, 78% comprised parent compounds initially present in the coffee, and 22% were metabolites including free and sulfated caffeic and ferulic acids.

Green tea flavan-3-ols: colonic degradation and urinary excretion of catabolites by humans.

Following the ingestion of green tea, substantial quantities of flavan-3-ols pass from the small to the large intestine (Stalmach et al. Mol. Nutr.

In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans.

Hydroxycinnamic acids are a class of phenolic antioxidants found widely in dietary plants. Their biotransformation in the human organism primarily involves Phase II conjugation reactions. In this study, activities of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) towards major dietary hydroxycinnamic acids (caffeic, dihydrocaffeic, dihydroferulic, ferulic and isoferulic acids) were investigated.

Absorption, metabolism, and excretion of green tea flavan-3-ols in humans with an ileostomy.

Green tea containing 634 micromol of flavan-3-ols was ingested by human subjects with an ileostomy. Ileal fluid, plasma, and urine collected 0-24 h after ingestion were analysed by HPLC-MS. The ileal fluid contained 70% of the ingested flavan-3-ols in the form of parent compounds (33%) and 23 metabolites (37%).

Bioavailability of C-linked dihydrochalcone and flavanone glucosides in humans following ingestion of unfermented and fermented rooibos teas.

High-performance liquid chromatography-mass spectrometry (HPLC-MS(n)) detected aspalathin and nothofagin, C-glycosides of apigenin and luteolin, and four eriodictyol-C-glycoside isomers in unfermented and fermented rooibos teas. The fermented drink contained 10-fold higher levels of aspalathin and nothofagin and a 4-fold lower eriodictyol-C-glycoside content than the fermented tea. The total flavonoid contents in 500 mL servings of the teas were 84 (fermented) and 159 mumol (unfermented).