OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Cardiac surgery-related acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery in adults. Currently, there is no specific examination method, and the diagnosis relying on serum creatinine and urine volume changes is of hysteresis. Biomarkers with the potential to predict CSA-AKI have become the focus in recent years. Clinical studies have shown that neutrophil gelatinase related lipid transporters and cell cycle inhibitors are of high diagnostic value; liver fatty acid binding protein can be used to assist in the diagnosis of CSA-AKI; microRNAs help to assess the poor prognosis of patients; the combined application of biomarkers may be used to predict the occurrence of CSA-AKI. CSA-AKI biomarkers provide the possibility for early clinical diagnosis and timely intervention, and are expected to become a new breakthrough in the diagnosis and treatment of CSA-AKI.
Acute Kidney Injury ; blood ; diagnosis ; etiology ; urine ; Adult ; Biomarkers ; analysis ; blood ; Cardiac Surgical Procedures ; adverse effects ; Creatinine ; blood ; Humans

OBJECTIVES: To study the urinary metabolic profile in rats with deep venous thrombosis （DVT） based on metabolomics and to screen out small molecular biomarkers for the diagnosis and forensic identification of DVT. METHODS: Inferior vena cava of rats was ligated to construct DVT models. The rats were randomly divided into three groups： DVT, sham, and control groups, 10 in each group. The urine of DVT and sham rats was collected during 24 hours in the metabolic cage at 48 hours after operating, meanwhile, 24 hours urine was collected in control group. The metabolic profile was analyzed by nuclear magnetic resonance. SIMCA-P 14.1 software was used for pattern recognition. The variable importance in projection （VIP） value from orthogonal PLS-DA （OPLS-DA） model combined with Mann-Whitney U test were used to search the different metabolites in the urine. RESULTS: The metabolic profiles of urine from DVT, sham, and control groups had significant differences. The DVT, sham, and control groups could be distinguished by the partial least squares method-discriminant analysis （PLS-DA） model. Compared with the urine of the rats in control groups, the levels of leucine, glutamine, creatine, creatinine and sucrose in the urine of DVT rats were up-regulated, and the levels of 3-hydroxybutyrate, lactate, acetone, α-oxoglutarate, citrate and hippurate were down-regulated. CONCLUSIONS The different metabolites in the urine of DVT rats are expected to become its candidate biomarkers. The results can provide a research basis for the diagnosis, treatment and forensic identification of DVT.
Animals ; Biomarkers/blood* ; Discriminant Analysis ; Humans ; Magnetic Resonance Spectroscopy/methods* ; Metabolome ; Metabolomics/methods* ; Nuclear Magnetic Resonance, Biomolecular/methods* ; Rats ; Rats, Sprague-Dawley ; Urine/chemistry* ; Venous Thrombosis/urine*

Case reports of indium-related lung disease in workers have raised public concern to the human toxicity of indium (In) and its compounds. However, studies evaluating the exposure or health of workers in In smelting plants are rare. Therefore, in this study, we focused on four In smelting plants, with the main objective of characterizing In in smelter plants in China and discussing the potential exposure biomarkers of In exposure. We recruited 494 subjectsat four In smelting plants in China. Personal air samples, first morning urine and spot blood samples were collected. In concentrations in samples were analyzed using inductively coupled plasma mass spectrometry. In concentrations in air samples did not exceed the permissible concentration-time weighed average, but the smelter workers had a higher internal exposure to In. Positive correlations were observed between the air In and urine In concentrations, and between the air In and blood In concentrations. This study provides basic data for the following In exposure and health risk assessment.
Adult ; Air Pollutants, Occupational ; blood ; urine ; Biomarkers ; blood ; urine ; China ; Environmental Monitoring ; Female ; Humans ; Indium ; blood ; urine ; Male ; Mass Spectrometry ; Metallurgy ; Middle Aged ; Occupational Exposure ; Young Adult

Precision medicine is becoming the goal of translational research on colorectal cancer. Accurate molecular subtyping contributes to better guidance of clinical practice. The current TNM staging system of colorectal cancer is inadequate in terms of guiding clinical practice, such as the underestimation of prognosis of with stage II( and III( colorectal cancer TNM staging, and identification of high-risk and low-risk patients with stage II( colorectal cancer. Researchers from Europe and US have proposed a number of molecular subtypings with clinicopathological phenotypes and molecular phenotypes, which has certain practical significance and is beneficial to the choice of treatment regimen and targeted drugs. But the current results of subtyping research require further validations by clinical large scale multi-center trials. Based on precision medicine, molecular subtyping gradually reveals its clinical significance and is optimized through combining genomics with various clinical phenotypes, indicating its guidance for clinical practice, which is the inevitable course of precision medicine accomplishment. In recent years, there have been many new advances in colorectal cancer liver metastasis treatment. The prognosis of colorectal cancer patients undergoing resection of liver metastasis lesion is similar to those with stage III(. Early recurrence within 6 months after translational treatment and resection occurred in about one third of the patients with initially unresectable liver metastasis, and the overall survival was poor. Thus, an evaluation system should be established in order to avoid the strong therapy and strive for better quality of life in some patients. Individualized treatment for colorectal cancer is emphasized increasingly. Body fluid (peripheral blood and urine) marker detection is a recent research hotspot, including serum protein(polypeptide), plasma miRNA, circulating tumor cells and circulating nucleic acid.
Biomarkers, Tumor ; blood ; urine ; Colorectal Neoplasms ; diagnosis ; pathology ; therapy ; Humans ; Liver Neoplasms ; secondary ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Precision Medicine ; Prognosis ; Quality of Life ; Translational Medical Research

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.
Adult ; Biomarkers/blood ; Body Mass Index ; C-Reactive Protein/analysis ; Chemokines/*blood ; Creatinine/blood/urine ; Diabetes Mellitus, Type 2/*blood/diagnosis ; Female ; Humans ; Insulin/blood ; Intercellular Signaling Peptides and Proteins/*blood ; Intra-Abdominal Fat/*pathology ; Linear Models ; Lipocalins/blood ; Male ; Middle Aged ; Obesity/complications ; Triglycerides/blood

BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% +/- 26.1% (p < 0.001) in the regular-dose group and -21.1% +/- 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.
Adult ; Angiotensin II Type 1 Receptor Blockers/*administration & dosage/adverse effects ; Biomarkers/urine ; Blood Pressure ; Creatinine/urine ; Female ; Glomerulonephritis, IGA/diagnosis/*drug therapy/physiopathology/urine ; Humans ; Male ; Middle Aged ; Prospective Studies ; Proteinuria/diagnosis/*drug therapy/physiopathology/urine ; Republic of Korea ; Time Factors ; Treatment Outcome ; Valsartan/*administration & dosage/adverse effects

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.
Biomarkers ; blood ; urine ; Chemical and Drug Induced Liver Injury ; diagnosis ; Humans ; Sensitivity and Specificity

Our study explored the dynamic changes in and the relationship between the DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the DNA repair marker 8-hydroxyguanine DNA glycosidase 1 (hOGG1) according to the length of occupational employment in nickel smelting workers. One hundred forty nickel-exposed smelting workers and 140 age-matched unexposed office workers were selected from the Jinchang cohort. The 8-OHdG levels in smelting workers was significantly higher than in office workers (Z=-8.688, P<0.05) and the 8-OHdG levels among nickel smelting workers in the 10-14 y employment length category was significantly higher than among all peers. The hOGG1 levels among smelting workers were significantly lower than those of non-exposed workers (Z=-8.948, P<0.05). There were significant differences between employment length and hOGG1 levels, with subjects employed in nickel smelting for 10-14 y showing the highest levels of hOGG1. Correlation analysis showed positive correlations between 8-OHdG and hOGG1 levels (r=0.413; P<0.01). DNA damage was increased with employment length among nickel smelting workers and was related to the inhibition of hOGG1 repair capacity.
Biomarkers ; Case-Control Studies ; Cohort Studies ; DNA Damage ; drug effects ; DNA Glycosylases ; blood ; DNA Repair ; Deoxyadenosines ; blood ; Humans ; Male ; Metallurgy ; Nickel ; toxicity ; urine ; Occupational Exposure ; adverse effects ; Time Factors

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.
Acute-Phase Proteins/*urine ; Adult ; Biomarkers/blood/urine ; Biopsy ; Chi-Square Distribution ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology/*urine ; Humans ; Kaplan-Meier Estimate ; Kidney/*metabolism/pathology/physiopathology ; Lipocalins/*blood/*urine ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood/*urine ; Retrospective Studies ; Risk Factors ; Young Adult