Urinary biomarkers for prostate cancer： a review

Although the routine use of serum prostate-specific antigen （PSA） testing has undoubtedly increased prostate cancer （PCa） detection, one of its main drawbacks is its lack of specificity. As a consequence, many men undergo unnecessary biopsies or treatments for indolent tumours. PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour. Since PCa is a heterogeneous disease, a panel of tumour markers is fundamental for a more precise diagnosis. Several biomarkers are promising due to their specificity for the disease in tissue. However, tissue is unsuitable as a possible screening tool. Since urine can be easily obtained in a non-invasive manner, it is a promising substrate for biomarker testing. This article reviews the biomarkers for the non-invasive testing of PCa in urine.

Association of Increased Urine Brain Derived Neurotrophic Factor with Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia

Urinary brain-derived neurotrophic factor（BDNF）, an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia（BPH）. We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms（LUTS） in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score（IPSS） was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity（DO） in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine（Cr） levels. Seventy-six BPH patients were divided into moderate LUTS group（n=51, 720） according to the IPSS. Of the 76 BPH patients, DO was present in 34（44.7%） according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS（8.29±3.635, P〈0.0001） and severe LUTS（11.8±6.44, P〈0.0001） than normal controls（1.71±0.555）. Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS（11.8±6.44 vs. 8.29±3.635, P=0.000）. The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker

Blueberry Extract Reduces Oxidative Stress in Patients with Metabolic Syndrome

Oxidative stress is a health condition that could potentially harm the patient, and it is defined as the lack of balance between the production of oxygen free radicals, which rises, and antioxidant defenses, which are in decrease. Metabolic syndrome implies a variety of risk factors that are based on abdominal obesity and insulin resistance. Moreover, the importance of metabolic syndrome is emphasized due to the fact that it presents an increase in oxidative stress, which is produced by the sum of alterations that each risk factor produces within the metabolic syndrome pathology. Reducing oxidative stress in these patients is currently one of the most interesting challenges of cardiovascular and metabolic therapeutics, because it is a molecular biology alteration that is not generally diagnosed and, therefore, not treated. The increasing incidence of overweight and obesity cause an increase in the incidence of metabolic syndrome, thus turning into a huge problem that keeps growing at alarming proportions. This syndrome＇s incidence oscillates between 20 and 40%, depending on the gender, age, ethnic group, and diagnostic criteria used for the definition of the disease. Prospective studies show that metabolic syndrome doubles the risk of cardiovascular disease and causes a five-fold increase in the risk of developing type 2 diabetes. With the aim of decreasing the oxidative stress caused by metabolic syndrome, we investigated the effect of antioxidant protection in DNA repair and cell membranes through the use of blueberry extract, which is the fruit with the highest antioxidant capacity, in patients with metabolic syndrome. Thirty patients were studied for a period of 6 months of intervention, and it could be demonstrated that they showed a highly significant decrease in the damage produced to the DNA, which was measured by the urinary excretion of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） and the damage caused to the vascular endothelium and cell membranes, which was measured through the urinary excretion of F2-isoprostane. Based on our knowledge, this investigation is the first one to show that lyophilized blueberry extract （BlueKing~） as a dietary supplement, with meals, is an additional therapeutic tool of great value for the treatment of oxidative stress through DNA and cell membrane protection in patients with metabolic syndrome.

Nitro-PAH exposures of occupationally-exposed traffic workers and associated urinary 1-nitropyrene metabolite concentrations

The assessment of occupational exposure to diesel exhaust（DE） is important from an epidemiological perspective. Urinary biomarkers of exposure have been proposed as a novel approach for measuring exposure to DE. In this study, we measured the concentrations of two urinary metabolites of 1-nitropyrene（1NP）, a nitrated polycyclic aromatic hydrocarbon that has been suggested as a molecular marker of diesel particulate matter. These two metabolites, 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were determined in urine samples（10 m L） from a small group of workers who were occupationally-exposed to vehicle exhaust in Trujillo, Peru, before and after their workshifts. Workshift exposures to1 NP, as well as PM_（2.5）, 2-nitropyrene and 2-nitrofluoranthene, were also measured.Exposures to 1NP were similar in all studied workers, averaging 105 ± 57.9 pg/m^3（±standard deviation）. Median urinary concentrations of the average of the pre- and post-exposure samples for 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were found to be 3.9 and 2.3 pg metabolite/mg creatinine, respectively in the group of occupationally-exposed subjects（n = 17） studied. A direct relationship between workshift exposure to 1NP and urinary 1NP metabolites concentrations was not observed. However,the 1NP exposures and the creatinine-corrected urinary concentrations of the hydroxynitropyrene metabolites in these Peruvian traffic workers were similar to occupationally-exposed taxi drivers in Shenyang, China, and were higher than biomarker levels in office workers from Trujillo without occupational exposure to vehicle exhaust.This study provides further evidence that urinary metabolites of 1NP are associated with exposure to DE and may serve as a useful exposure biomarker.

Collection and preservation of urinary proteins, using a fluff pulp diaper

Change is the most fundamental property of a biomarker. In contrast to the blood, which is under homeostatic controls, urine reflects changes in the body earlier and is more sensitive, thus making it a better biomarker source. Moreover, drawing blood from infants and toddlers is difficult and not tolerated well. For patients limited by language, communicating their chief complaint is difficult. Thus, monitoring biomarkers in urine can provide valuable clues for the diagnosis of diseases, especially pediatric diseases. Collecting urine from young children and some adult patients is more challenging than collecting it from healthy adults.Here, we propose a method that uses a fluff pulp diaper to collect urine. Urinary proteins are then eluted and adsorbed onto a piece of nitrocellulose membrane, which can be dried and stored in a vacuum bag. SDS-PAGE and LC-MS/MS analysis indicated that this method is reproducible, and similar proteins were identified as those obtained by an acetone precipitation method. With this simple and economical method, it is possible to collect and preserve urine samples from infants, toddlers, and patients with special needs, even for large-scale biomarker studies.