Project description:Chronic inflammation is a potential systemic risk factor for many bladder dysfunctions, including interstitial cystitis (IC). However, the underlying mechanism through which a healthy bladder protects itself from inflammatory triggers remains unknown. In this study, we identified odor compounds in urine obtained from IC patients and healthy controls. Using comprehensive solid-phase microextraction-gas chromatography-time-of-flight-mass spectrometry (SPME-GC-TOF-MS) profiling and bioinformatics, we found that levels of urinary volatile metabolites, such as menthol, were significantly reduced in IC patients, compared to healthy controls. In an attempt to understand the mechanistic meaning of our volatile metabolites data and the role of menthol in the immune system, we performed two independent experiments: (a) cytokine profiling, and (b) DNA microarray. Our findings suggest that lipopolysaccharide (LPS)-stimulated inflammatory events, such as the production and secretion of inflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β) and the activation of NF-κB and associated proteins within a large signaling network (e.g., Akt, TLR1, TNFAIP3, and NF-κB), are suppressed by the presence of menthol. These findings broaden our knowledge on the role of urinary menthol in suppressing inflammatory events and provide potential new strategies for alleviating both the odor and inflammation associated with IC.
Project description:BackgroundVolatile organic compounds (VOCs) are associated with adverse respiratory outcomes at high occupational exposures. However, whether exposure levels found in the general population have similar effects is unknown.MethodsWe analyzed data on 1342 adult participants in the 2011-2012 National Health and Nutrition Examination Survey aged ≥18 years old who had urinary VOC metabolites and spirometry measurements available. Linear regression models adjusting for covariates were fitted to estimate the associations of VOC exposures levels and spirometry outcomes, while accounting for survey design and sampling weights to generate nationally representative estimates.ResultsThe urinary metabolites for xylene, acrylamide, acrolein, 1,3-butadiene, cyanide, toluene, 1-bromopropane, acrylonitrile, propylene oxide, styrene, ethylbenzene, and crotonaldehyde in our analysis were all detected in >75% of participants. Forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio % was lower with urinary metabolites of acrylamide (β: -2.65, 95% CI: -4.32, -0.98), acrylonitrile (β: -1.02, 95% CI: -2.01, -0.03), and styrene (β: -3.13, 95% CI: -5.35, -0.90). FEV1% predicted was lower with the urinary metabolites of acrolein (β: -7.77, 95% CI: -13.29, -2.25), acrylonitrile (β: -2.05, 95% CI: -3.77, -0.34), propylene oxide (β: -2.90, 95% CI: -5.50, -0.32), and styrene (β: -4.41, 95% CI: -6.97, -1.85).ConclusionsThis is the first study of a representative sample of the U.S. adult population to reveal associations of acrylonitrile, propylene oxide, and styrene urinary metabolites with reduced lung function at non-occupational exposures. Results also support previous evidence of acrylamide and acrolein's association with adverse respiratory outcomes.
Project description:Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multi-center, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool.
Project description:We aimed to identify urinary exosomal ncRNAs as novel biomarkers for diagnosis of Chronic Kidney Disease (CKD) for this, we examined 15 exosomal ncRNA profiles in urine samples from CKD patients from four different stages (I, II, III and IV) and compared them to 10 healthy controls. We identified a significant number of novel, differentially expressed ncRNAs in CKD patients compared to healthy, which might be employed as early diagnostic markers in CKD in the future.
Project description:Endoscopic evaluation is mandatory in establishing the diagnosis of pediatric inflammatory bowel disease (IBD), but unfortunately carries a high burden on patients. Volatile organic compounds (VOC) have been proposed as alternative, noninvasive diagnostic biomarkers for IBD. The current study aimed to assess and compare the potential of fecal and urinary VOC as diagnostic biomarkers for pediatric IBD in an intention-to-diagnose cohort. In this cohort study, patients aged 4-17 years, referred to the outpatient clinic of a tertiary referral center under suspicion of IBD, were eligible to participate. The diagnosis was established by endoscopic and histopathologic assessment, participants who did not meet the criteria of IBD were allocated to the control group. Participants were instructed to concurrently collect a fecal and urinary sample prior to bowel lavage. Samples were analyzed by means of gas chromatography-ion mobility spectrometry. In total, five ulcerative colitis patients, five Crohn's disease patients, and ten age and gender matched controls were included. A significant difference was demonstrated for both fecal (p-value, area under the curve; 0.038, 0.73) and urinary (0.028, 0.78) VOC profiles between IBD and controls. Analysis of both fecal and urinary VOC behold equal potential as noninvasive biomarkers for pediatric IBD diagnosis.
Project description:Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that are associated with birth defects, leukemia, neurocognitive deficits, reproductive impairment and cancer in humans exposed to these compounds. Exposure to VOCs can be assessed by measuring their metabolites in urine. Little is known, however, about the temporal variability in urinary VOC metabolite (VOCM) concentrations within- and between-individuals. In this study, we determined the variability in the concentrations of 38 VOCMs in urine samples collected from 19 healthy individuals across a period of 44 days. We also measured seven biomarkers of oxidative stress (lipid, protein and DNA damage) in urine to assess the relationship of VOC exposure to oxidative stress. Seventeen VOCMs had detection frequencies (DFs) of >60% in urine, and we limited further data analysis to those compounds. The creatinine-adjusted geometric mean concentrations of VOCMs ranged from 2.70 μg/g to 327 μg/g in spot and 2.60 μg/g to 551 μg/g in first morning void (FMV) urine samples. Calculation of the intra-class correlation coefficients (ICCs) for 17 VOCM concentrations to assess their predictability and repeatability in urinary measurements showed ranges of 0.080-0.425 in spot and 0.050-0.749 in FMV urine samples, revealing notable within-individual variability. Our results suggest that taking only single measurements of VOCM concentrations in urine in epidemiological investigations may lead to exposure misclassification. In addition, VOCM concentrations were significantly and positively correlated with oxidative stress biomarkers. This study thus provides important information for formulating sampling strategies in the biomonitoring of VOC exposure in human populations.
Project description:Accurate prediction of preterm birth is currently challenging, resulting in unnecessary maternal hospital admittance and fetal overexposure to antenatal corticosteroids. Novel biomarkers like volatile organic compounds (VOCs) hold potential for predictive, bed-side clinical applicability. In a proof of principle study, we aimed to assess the predictive potential of urinary volatile organic compounds in the identification of pregnant women at risk for preterm birth. Urine samples of women with a high risk for preterm birth (≧24 + 0 until 36 + 6 weeks) were collected prospectively and analyzed for VOCs using gas chromatography coupled with an ion mobility spectrometer (GS-IMS). Urinary VOCs of women delivering preterm were compared with urine samples of women with suspicion of preterm birth collected at the same gestation period but delivering at term. Additionally, the results were also interpreted in combination with patient characteristics, such as physical examination at admission, microbial cultures, and placental pathology. In our cohort, we found that urinary VOCs of women admitted for imminent preterm birth were not significantly different in the overall group of women delivering preterm vs. term. However, urinary VOCs of women admitted for imminent preterm birth and delivering between 28 + 0 until 36 + 6 weeks compared to women with a high risk for preterm birth during the same gestation period and eventually delivering at term (>37 + 0 weeks) differed significantly (area under the curve: 0.70). In addition, based on the same urinary VOCs, we could identify women with a confirmed chorioamnionitis (area under the curve: 0.72) and urinary tract infection (area under the curve: 0.97). In conclusion, urinary VOCs hold potential for non-invasive, bedside prediction of preterm birth and on the spot identification of intra-uterine infection and urinary tract infections. We suggest these observations are further explored in larger populations.
Project description:The analysis of urinary volatile organic compounds (VOCs) is a promising field of research with the potential to discover new biomarkers for cancer early detection. This systematic review aims to summarise the published literature concerning cancer-associated urinary VOCs. A systematic online literature search was conducted to identify studies reporting urinary VOC biomarkers of cancers in accordance with the recommendations of the Cochrane Library and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Thirteen studies comprising 1266 participants in total were included in the review. Studies reported urinary VOC profiles of five cancer subtypes: prostate cancer, gastrointestinal cancer, leukaemia/lymphoma, lung cancer, and bladder cancer. Forty-eight urinary VOCs belonging to eleven chemical classes were identified with high diagnostic performance. VOC profiles were distinctive for each cancer type with limited cross-over. The metabolic analysis suggested distinctive phenotypes for prostate and gastrointestinal cancers. The heterogenicity of study design, methodological and reporting quality may have contributed to inconsistencies between studies. Urinary VOC analysis has shown promising performance for non-invasive diagnosis of cancer. However, limitations in study design have resulted in inconsistencies between studies. These limitations are summarised and discussed in order to support future studies.
Project description:We report for the first time movement of Correia Repeat Enclosed Elements, through inversion of the element at its chromosomal location. Analysis of Ion Torrent generated genome sequence data from Neisseria gonorrhoeae strain NCCP11945 passaged for 8 weeks in the laboratory under standard conditions and stress conditions revealed a total of 37 inversions: 24 were exclusively seen in the stressed sample; 7 in the control sample; and the remaining 3 were seen in both samples. These inversions have the capability to alter gene expression in N. gonorrhoeae through the previously determined activities of the sequence features of these elements. In addition, the locations of predicted non-coding RNAs were investigated to identify potential associations with CREE. Associations varied between strains, as did the number of each element identified. The analysis indicates a role for CREE in disrupting ancestral regulatory networks, including non-coding RNAs. RNA-Seq was used to examine expression changes related to Correia repeats in the strain
Project description:A549 cells were grown at air liquid interphase (ALI) and exposed to airborne formaldehyde for three days. An exposure platform was developed for this purpose, which provided the volatile analyte in a humidified atmosphere. The platform was composed of a reference and an exposure chamber. Treatments/ Sample code: (A) 0 ppm (not = no treatment) in the exposure chamber and control cells in the reference chamber (co); (B) 0.1 ppm (01 FA) in the exposure chamber and control cells in the reference chamber (co); and (C) 0.5 ppm (05FA) in the exposure chamber and control cells in the reference chamber (co)