Urinary Metabolite Levels Research Articles

Association of urinary volatile organic compounds and chronic kidney disease in patients with diabetes: real-world evidence from the NHANES.

Chronic kidney disease (CKD) is common in patients with diabetes mellitus (DM). Volatile organic compounds (VOCs) are widespread pollutants that may impact DM development. This study aims to explore the association between urinary VOC metabolites and CKD in patients with DM. Adult National Health and Nutrition Examination Survey (NHANES) 2011 to 2018 participants with DM were included in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Multivariable regression models were used to analyze the associations between urinary VOC metabolites and CKD. A total of 1,295 participants with DM and a mean age of 59 years were included. After adjustment for demographic and clinical characteristics, elevated levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) (tertile 2: adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI): 1.15-2.85, p = 0.012), N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) (tertile 2: aOR = 1.84, 95% CI: 1.10-3.08, p = 0.021), DHBMA (tertile 3: aOR = 1.93, 95% CI: 1.12-3.35, p = 0.020), and phenylglyoxylic acid (PGA) (tertile 3: aOR = 1.71, 95% CI: 1.11-2.63, p = 0.017) were significantly associated with increased likelihood of CKD. Specific urinary VOC metabolite levels are positively associated with an increased risk of CKD in patients with DM. These findings suggest that monitoring urinary VOC metabolites could be important for the prevention and management of CKD in this population. Future longitudinal studies should focus on establishing causality and elucidating the underlying mechanisms of these associations.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) elicited dose-dependent shifts in the murine urinary metabolome associated with hepatic AHR-mediated differential gene expression.

Epidemiological evidence suggests an association between dioxin and dioxin-like compound (DLC) exposure and human liver disease. The prototypical DLC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to induce the progression of reversible hepatic steatosis to steatohepatitis with periportal fibrosis and biliary hyperplasia in mice. Although the effects of TCDD toxicity are mediated by aryl hydrocarbon receptor (AHR) activation, the underlying mechanisms of TCDD-induced hepatotoxicity are unresolved. In the present study, male C57BL/6NCrl mice were gavaged every 4 days for 28 days with 0.03 - 30 μg/kg TCDD and evaluated for liver histopathology and gene expression as well as complementary 1-dimensional proton magnetic resonance (1D- 1H NMR) urinary metabolic profiling. Urinary trimethylamine (TMA), trimethylamine N-oxide (TMAO), and 1-methylnicotinamide (1MN) levels were altered by TCDD at doses ≤ 3 μg/kg; other urinary metabolites, like glycolate, urocanate, and 3-hydroxyisovalerate, were only altered at doses that induced moderate to severe steatohepatitis. Bulk liver RNA-seq data suggested altered urinary metabolites correlated with hepatic differential gene expression corresponding to specific metabolic pathways. In addition to evaluating whether altered urinary metabolites were liver-dependent, published single-nuclear RNA-seq (snRNA-seq), AHR ChIP-seq, and AHR knockout gene expression datasets provide further support for hepatic cell-type and AHR-regulated dependency, respectively. Overall, TCDD-induced liver effects were preceded by and occurred with changes in urinary metabolite levels due to AHR-mediated changes in hepatic gene expression.

Toxicokinetic model of the pyrethroid pesticide lambda-cyhalothrin, main exposure route and dose reconstruction predictions in agricultural workers.

A toxicokinetic model of the pyrethroid insecticide lambda-cyhalothrin (LCT) was developed to relate absorbed doses to urinary cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) metabolite levels used as a biomarker of exposure. The model then served to reconstruct absorbed doses in agricultural workers and their probability of exceeding the EFSA Acceptable occupational Exposure Level (AOEL). The toxicokinetic model was able to reproduce the temporal profiles of CFMP in the urine of operators spraying pesticides using the optimized model parameters (adjusted to human volunteer data). Modeling also showed that simulation of an inadvertent oral exposure mainly was the exposure scenario giving the best fit to CFMP urinary time-course data in applicators. With the dermal model parameters optimized from data in volunteers, simulation of a dermal exposure in applicators did not allow to reproduce the observed peak excretions and urinary metabolite levels; extremely high applied dermal doses would be required but still simulated dermal penetration rate would remain too slow. Simulation of an inhalation exposure allowed to reproduce the observed time-courses, but with unrealistic air concentrations. For applicators with the highest urinary concentrations, there was a probability of exceeding the AOEL at some points during the biomonitoring period [>50% probability of exceeding for 27% of 24-h samples]; for non-applicator workers the probability of exceeding the AOEL value was very low [corresponding value of 5%]. Furthermore, the median [95% CI] estimates of 10 000 Monte Carlo simulations led to a biological reference value corresponding to the AOEL of 116 [113-119] ng/kg bw/d and 7.5 [7.3-7.7] μg/L. Overall, 7% of applicators and 1% of workers performing weeding and strawberry picking had a probability of exceeding this biological reference value. As a next step, it would be interesting to apply these methods to multiple exposure to various contaminants.

Exposure to Phthalates and Alternative Plasticizers in Patients with Impaired Kidney Function in Korea: Temporal Trend during 2011-2020 and Its Association with Chronic Kidney Disease.

Phthalates are chemical risk factors of chronic kidney disease (CKD); however, little is known about temporal trends of phthalate exposure and associated health risks among CKD patients. Such information is even scarce for alternative plasticizers. CKD patients were recruited from 2011 to 2020 in Korea (n = 200) and assessed for the temporal changes of both traditional and alternative plasticizer exposure. Their associations with kidney dysfunction were also investigated. In CKD patients, urinary levels of DEP, BBzP, and DEHP metabolites declined significantly during this period, while those of the DEHTP metabolite increased. The level of DEHP metabolites showed a negative association with the estimated glomerular filtration rate (eGFR) in multiple association models, but additional eGFR subgroup analysis failed to show consistent results. Associations between phthalate exposure and eGFR were influenced by the severity of kidney dysfunction: DEHP and BBzP exposure showed negative associations with eGFR only among the patients with moderate kidney dysfunction (eGFR 30-59 mL/min/1.73 m2). Changing associations by CKD severity may be explained by negative correlations between eGFR and both urinary creatinine concentration and specific gravity. Our observations show that DEHTP has rapidly replaced DEHP and exposure to several phthalates adversely influences kidney function even among CKD patients.

Microfluidic Wearable Electrochemical Sensor Based on MOF-Derived Hexagonal Rod-Shaped Porous Carbon for Sweat Metabolite and Electrolyte Analysis.

Wearable sensors enable the noninvasive continuous analysis of biofluid, which is of great importance for healthcare monitoring. In this work, a wearable sensor was seamlessly integrated with a microfluidic chip which was prepared by a three-dimensional printing technology for noninvasive and multiplexed analysis of metabolite and electrolytes in human sweat. The microfluidic chip could enable rapid sampling of sweat, which avoids the sweat evaporation and contamination. Using a Zn metal-organic framework as a sacrificial template, the hexagonal rod-shaped porous carbon nanorod (PCN) with high porosity, a large specific surface area, and excellent conductivity was synthesized and exhibited the robust electrocatalytic ability of uric acid (UA) oxidation. Therefore, the PCN-based sensor showed high sensitivity and good selectivity of UA with a wide linear range of 10-200 μM and a low detection limit of 4.13 μM. Meanwhile, the potentiometry-based ion-selective electrode was constructed for detection of pH and K+, respectively, with good sensitivity, selectivity, reproducibility, and stability. In addition, the testing under different bending states demonstrated that mechanical deformation had little effect on the electrochemical performance of the wearable sensors. Furthermore, we evaluated the utility of the wearable sensor for multiplexed real-time analysis of UA, pH, and K+ in sweat during aerobic exercise, and the effect of the amount of consumed purine-rich foods on uric acid metabolite levels in sweat and urine was further investigated. The relationship between urine UA and sweat UA was obtained. Overall, this wearable sensor enables multiple electrolyte and metabolite analysis in different noninvasive biofluids, suggesting its potential application in personalized disease prevention.

Phthalate Exposure and Pediatric Asthma: A Case Control Study Among Egyptian Children

Background: Phthalates, which are diesters of phthalic acid, are commonly used as plasticizers and additives in various consumer products. Several phthalates have been identified as substances of high concern. Exposure to phthalate esters (PAEs) has been linked to asthma in children, but the specific impacts of PAEs on asthmatic children were not well understood. Objective: The objective of this study was to compare urinary phthalate concentrations in asthmatic and non-asthmatic children and to identify potential sources of exposure as risk factors for asthma. Methods: A case control study was conducted for 100 Egyptian children aged 8-16 years (50 asthmatics and 50 healthy controls). Asthma was identified using GINA guidelines. Socio-demographic and probable risk factors were assessed, in addition to measuring phthalate levels in urine samples using high-performance liquid chromatography. Results and conclusion: Mean urinary Mono-methyl as well as Mono-benzyl levels were highly significant in asthmatic children compared to control group (895.26ng/ mL vs 548.55 ng/mL and 13.5 ng/mL vs 2.07 ng/mL respectively) (p= 0.001). The number of asthmatic children living in houses painted with non-plastic paint was significantly lower (P&lt;0.05) than children living in houses painted with other paints. No association between floor type and asthma was reported. The frequent use of personal care products and plastic painting of walls were identified by multiple logistic regression analysis as the highly significant predictors of asthma in the studied subjects. The declared higher levels of urinary phthalate metabolites (Mono-methyl and Mono-benzyl) in Egyptian asthmatic children may reveal the probable risk of phthalate exposure in triggering bronchial asthma.

Phthalate exposure as a hidden risk factor for uterine leiomyoma in adult women: Accumulated evidence from observational studies

BackgroundThere is evidence that exposure to phthalate in women may increase the risk of uterine leiomyomas. Whereas, the association between exposure to phthalate and the incidence of uterine leiomyoma remained inconclusive. MethodsA meta-analysis was performed to evaluate their relationship. Literature eligible for inclusion was found in PubMed, EMBASE, Web of Science, and WanFang Medical Database. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the risk for effect estimate for each phthalate. ResultsA total of fourteen observational studies with 5777 subjects of adult women were included in this study. In the pooled analysis, we found an elevated risk of uterine leiomyoma among women who were exposed to higher levels of di-2-ethylhexyl phthalate (DEHP) (OR 1.61, 95 % CI: 1.18–2.20), as estimated indirectly from the molar summation of its urinary metabolite concentrations. In addition, a positive association was observed between the occurrence of uterine leiomyoma and exposure to low molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.00–1.15), as well as high molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.01–1.15), as quantified by integrating the effect estimates of individual metabolite from each study. Urinary levels of DEHP metabolites, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, monoethyl phthalate, and monomethyl phthalate were not appreciably correlated with the risk of uterine leiomyoma. ConclusionOur results indicated that exposure to DEHP, and co-exposure to high or low molecular weight phthalate mixture might be potential risk factors for uterine leiomyoma in adult women. Owing to the indirect estimation of association, when interpreting these findings, cautions should be taken.

Association of prenatal urinary phthalate metabolite levels on the newborn metabolome and neurodevelopmental outcomes among African Americans

Association of prenatal urinary phthalate metabolite levels on the newborn metabolome and neurodevelopmental outcomes among African Americans

Maternal symptoms of depression and anxiety as modifiers of the relationship between prenatal phthalate exposure and infant neurodevelopment in the Atlanta African American maternal-child cohort

BackgroundPrenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment. Study designOur analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8–14 weeks and 24–32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety. ResultsHigher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: β = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, β = −0.30, 95% CI = −0.73, 0.12 for low; MEOHP: β = 0.60, 95% CI = −0.03, 1.23 for high, β = −0.12, 95% CI = −0.58, 0.33 for low; MEHHP: β = 0.54, 95% CI = −0.04, 1.11 for high, β = −0.11, 95% CI = −0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide. ConclusionOur results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

Effect of polycyclic aromatic hydrocarbon exposure on amnestic mild cognitive impairment and Alzheimer’s disease: A matched case-control study

There is an emerging body of evidence concerning the neurological effect of air pollutants on cognitive function and increased risk of neurodegeneration. Although previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) are neurotoxic, the effect of PAHs exposure on neurodegeneration remains unclear. This study aimed to investigate the association between PAH exposure and the risk of developing amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). For this matched case-control cross-sectional study, we recruited patients aged ≥50 years diagnosed with aMCI and AD from the Samsung Medical Center, Seoul, Korea, between 2014 and 2019. For each patient, we randomly selected four cognitively healthy controls through frequency matching based on sex, age group, and education level. Urinary levels of four PAH metabolites, 1-hydroxypyrene (1-OHP), 1-hydroxyphenanthrene (1-OHPhe), 2-hydroxyfluorene (2-OHFlu), and 2-naphthol (2-NAP), were measured. A conditional logistic regression model was used to evaluate the association, adjusting for potential confounders. A total of 212 patients with aMCI with 848 matched controls, and 267 patients with AD with 1068 matched controls were included in the analyses to estimate the risk of PAH exposure. We found that elevated urinary levels of PAH metabolites (specifically, 1-OHP and 2-NAP) were significantly associated with an increased risk of aMCI and AD. An increase of one unit in log-transformed level of urinary 1-OHP was associated with a 1.15- and 1.16-times higher risk of aMCI and AD, respectively. An increase of one unit in log-transformed level of urinary 2-NAP was associated with a 1.11- and 1.13-times higher risk of aMCI and AD, respectively. These findings indicate that PAH exposure may increase the risk of aMCI and AD, especially for the elderly population. Considering the widespread distribution of PAHs in the environment, reducing PAH exposure may be an effective strategy for the prevention of neurodegenerative diseases.

Exposure to organophosphate esters and early menopause: A population-based cross-sectional study

Organophosphate esters (OPEs), increasingly used as new flame retardants and plasticizers in various products, have been found to have reproductive toxicity with overt endocrine disruption potential, yet the relationship between OPEs and early menopause remains unexplored. In the present study, we included 2429 women who participated in the U.S. National Health and Nutrition Examination Survey data (2011–2020) and had data of five urinary OPE metabolite levels and information of menopause characteristics, to investigate the associations of OPEs exposure with premature ovarian insufficiency (POI) and age of menopause. Multivariable adjusted linear and logistic regression were used to assess the associations of urinary OPE metabolites with age of menopause and POI, respectively. Quantile g computation (QGC) models were used to assess the relative contribution of individual metabolites to associations of OPE metabolites mixture. After adjusting for covariates, urinary bis(2-chloroethyl) phosphate (BCEP) concentration was inversely associated with menopause age (β = - 0.21; 95% confidence interval (CI): 0.41, - 0.002). Higher urinary BCEP level (>median) was associated with earlier age at menopause (β = −1.14, 95% CI: 1.83, - 0.46), and elevated odds of having POI (OR = 1.93; 95% CI: 1.02, 3.66). These associations were robust to the further adjustment of cardiometabolic diseases and related traits (e.g., body mass index). Further QGC analyses confirmed that BCEP was the dominant metabolite contributing most to the associations of OPEs mixture with age of menopause (weight = 49.5%) and POI (weight = 75.1%). No significant associations were found for the other four OPE metabolites. In this cross-sectional study, urinary BCEP level was associated with earlier menopause and increased odds of POI, highlighting the potential negative impacts of this chemical and its parent compound tris(2-chloroethyl) phosphate on ovarian function. Further studies are required to validate our findings and reveal potential underlying mechanisms.

Protective signature of xanthohumol on cognitive function of APP/PS1 mice: a urine metabolomics approach by age.

Alzheimer's disease (AD) has an increasing prevalence, complicated pathogenesis and no effective cure. Emerging evidences show that flavonoid compounds such as xanthohumol (Xn) could play an important role as a dietary supplement or traditional Chinese herbal medicine in the management of diseases such as AD. This study aims to analyze the target molecules of Xn in the prevention and treatment of AD, and its potential mechanism from the perspective of metabolites. APP/PS1 mice 2- and 6-months old were treated with Xn for 3months, respectively, the younger animals to test for AD-like brain disease prevention and the older animals to address therapeutic effects on the disease. Memantine (Mem) was selected as positive control. Behavioral tests were performed to assess the course of cognitive function. Urine samples were collected and analyzed by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) coupled with online Compound Discoverer software. Morris Water Maze (MWM) tests showed that Xn, like Mem, had a therapeutic but not a preventive effect on cognitive impairment. The expression levels of urinary metabolites appeared to show an opposite trend at different stages of Xn treatment, downregulated in the prevention phase while upregulated in the therapy phase. In addition, the metabolic mechanisms of Xn during preventive treatment were also different from that during therapeutic treatment. The signaling pathways metabolites nordiazepam and genistein were specifically regulated by Xn but not by Mem in the disease prevention stage. The signaling pathway metabolite ascorbic acid was specifically regulated by Xn in the therapeutic stage. In conclusion, dietary treatment with Xn altered the urinary metabolite profile at different stages of administration in APP/PS1 mice. The identified potential endogenous metabolic biomarkers and signal pathways open new avenues to investigate the pathogenesis and treatment of AD.

Association between organophosphorus pesticides and obesity among American adults

ObjectiveTo investigate any connections between urinary organophosphorus pesticide (OPP) metabolites and adiposity measures.MethodsIn this study, data from the National Health and Nutrition Examination Survey (NHANES) projects from 2003 to 2008, 2011 to 2012, and 2015 to 2018 were analysed. Obesity was defined as a body mass index (BMI) of 30 kg/m² or higher. Abdominal obesity was defined as a waist circumference (WC) over 102 cm for men and 88 cm for women. Four urinary OPP metabolites (dimethyl phosphate [DMP], diethyl phosphate [DEP], dimethyl phosphorothioate [DMTP], and diethyl phosphorothioate [DETP]) and adiposity measures were examined using multiple linear regression and logistic regression analyses. The correlations between a variety of urinary OPP metabolites and the prevalence of obesity were investigated using weighted quantile sum regression and quantile g-computation regression.ResultsIn this analysis, a total of 9,505 adults were taken into account. There were 49.81% of male participants, and the average age was 46.00 years old. The median BMI and WC of the subjects were 27.70 kg/m2 and 97.10 cm, respectively. Moreover, 35.60% of the participants were obese, and 54.42% had abdominal obesity. DMP, DMTP, and DETP were discovered to have a negative correlation with WC and BMI in the adjusted models. DMP (OR = 0.93 [95% CI: 0.89–0.98]), DEP (OR = 0.94 [95% CI: 0.90–0.99]), DMTP (OR = 0.91 [95% CI: 0.86–0.95]), and DETP (OR = 0.85 [95% CI: 0.80–0.90]) exhibited negative associations with obesity prevalence. Similar correlations between the prevalence of abdominal obesity and the urine OPP metabolites were discovered. Moreover, the mixture of urinary OPP metabolites showed negative associations with adiposity measures, with DMTP and DETP showing the most significant effects.ConclusionTogether, higher levels of urinary OPP metabolites in the urine were linked to a decline in the prevalence of obesity.

Exposure to Volatile Organic Compounds May Contribute to Atopic Dermatitis in Adults.

Volatile organic compounds (VOC) are major indoor air pollutants. Previous studies reported an association between VOC exposure and allergic diseases. Here, we aimed to explore the relationship between VOC exposure and atopic dermatitis (AD) in adults. We prospectively enrolled 31 adult AD patients and 11 healthy subjects as controls. Urine metabolite levels of VOCs, including 1.3-butadiene, acrylamide, benzene, toluene, and xylene, were all determined with liquid chromatography-mass spectrometry. The relationship between AD and log-transformed urine levels of VOC metabolites were examined using a multivariate linear regression model adjusted for age and sex. We also treated mouse bone marrow-derived cells (BMMCs) with 1,3-butadiene and toluene and measured the release of β-hexosaminidase. Our results demonstrated that creatinine-corrected urine levels of N-Acetyl-S- (3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), and N-Acetyl-S-(benzyl)-L-cysteine (BMA) were all elevated in AD patients compared with controls. In a multivariate linear regression model, creatinine-corrected urine levels of BMA (a toluene metabolite) and DHBMA (a 1,3-butadiene metabolite) appeared elevated in AD patients, although statistical significance was not reached after correction for multiple comparisons. In addition, 1,3-butadiene and toluene could stimulate BMMCs to degranulate as much as compound 48/80. Some VOCs, such as 1,3-butadiene and toluene, might be associated with AD pathogenesis in adults.

Seasonal variation in urinary PAH metabolite levels and associations with neonatal birth outcomes.

Previous studies have demonstrated that exposure to polycyclic aromatic hydrocarbons (PAHs) can affect maternal and infant health. However, the conclusions regarding the effects of seasonal PAH exposure on maternal and infant health have been inconsistent. To further elucidate this issue, this study included data from 2282 mother-infant pairs in the Zuni birth cohort. The objective was to investigate the association between maternal late-pregnancy urinary PAH metabolite concentrations and neonatal birth outcomes during the heating and non-heating seasons. The results demonstrated that PAH exposure in Zunyi was primarily dominated by 2-OHNAP and 1-OHNAP and that the concentrations of PAH metabolites were significantly higher during the heating season. Furthermore, PAH metabolite exposure was found to affect neonatal birth weight, birth length, and parity index with seasonal differences. Further dose-effect analyses revealed nonlinear relationships and seasonal differences between PAH metabolites and neonatal birth weight, birth length, and parity index. Bayesian kernel mechanism regression modeling demonstrated that the inverted U-shaped relationship between PAH metabolites and neonatal birth weight and parity index was exclusive to the heating season. Consequently, it can be posited that maternal exposure to PAH metabolites during late pregnancy exerts a detrimental influence on neonatal growth and development, which is further compounded by the use of heating fuels. This highlights the necessity to either control or alter the use of heating fuels during pregnancy.

Urinary polycyclic aromatic hydrocarbon metabolites and hyperlipidemia: NHANES 2007-2016.

The relationships between urinary polycyclic aromatic hydrocarbon (PAH) metabolites and hyperlipidemia have not been thoroughly studied. The primary goal of this research focused on investigating the linkage between PAH metabolite concentrations in urine and hyperlipidemia prevalence within US adults. A cross-sectional analysis was conducted using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Logistic regression models were used to assess correlations between urinary PAH metabolite levels and the risk of hyperlipidemia, while restricted cubic spline models were used to examine dose‒response relationships. Subgroup and interaction analyses were performed to further elucidate these associations. Weighted quantile sum (WQS) regression analyzed the cumulative impact of various urinary PAH metabolites on hyperlipidemia risk. This study included 7,030 participants. Notably, individuals in the highest quintile of urinary PAH metabolite concentrations exhibited a significantly elevated prevalence of hyperlipidemia, even after comprehensive adjustments (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.01-1.75). Moreover, elevated levels of 1-hydroxyphenanthrene and 2-hydroxynaphthalene in the fourth quintile and 2-hydroxyfluorene in the third, fourth, and fifth quintiles demonstrated positive correlations with the prevalence of hyperlipidemia. These associations persisted across subgroup analyses. Additionally, a positive correlation between the urinary PAH metabolite mixture and hyperlipidemia (positive model: OR = 1.04, 95% CI: 1.00-1.09) was observed in the WQS model, and 2-hydroxynaphthalene showed the most substantial contribution. The cross-sectional analysis identified a significant correlation between urinary PAH metabolite and hyperlipidemia prevalence within the US demographic, with 2-hydroxynaphthalene being the predominant influencer. These findings underscore the need to mitigate PAH exposure as a preventive measure for hyperlipidemia.

Sleep characteristics in underweight young females across their menstrual cycles: A sleep-monitoring survey study with preliminary results.

This study investigated the association between underweight and sleep in young females across their menstrual cycles. A lifestyle-monitoring survey was conducted among 38 female university students aged 18-24 years in Japan from January to December 2023. Sleep data from 28 participants were analysed. Participants were categorized into underweight (n = 10) and control (n = 18) groups based on a baseline body mass index cut-off of 18.5 kg m-2. Sleep parameters were assessed using a daily sleep questionnaire, sleep sensor mats, and urinary melatonin metabolites across their menstrual cycles. The results indicated no significant differences in sleep patterns between the underweight and control groups or menstrual cycle phases, as assessed using both the daily sleep questionnaire and the sleep sensor mats. However, underweight participants experienced more difficulty maintaining sleep during the follicular phase. Body mass index significantly correlated with sleep efficiency (rs = 0.52) and wake after sleep onset (rs = -0.56). While urinary melatonin metabolite levels did not differ significantly between the groups or menstrual cycle phases, decreased levels during the luteal phase were more prevalent in the underweight group (7 of 10 participants) than in the control group (3 of 13 participants). This study suggests an association between underweight and sleep quality, especially nocturnal awakening, in young females. These findings underscore the importance of considering sleep quality in the management of underweight young females to improve their overall health outcomes.

Prenatal arsenic metabolite exposure is associated with increased newborn mitochondrial DNA copy number: evidence from a birth cohort study.

While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether maternal urinary arsenic metabolite levels in different trimesters were related to neonatal cord blood mtDNAcn. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters. We determined cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each one-unit increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the third trimester was related to 8.43% (95% CI 1.13%, 16.26%) and 12.15% (95% CI 4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the third trimester with mtDNAcn (DMA percent changes (%Δ) = 25.60 (95% CI 6.73, 47.82), for the highest vs the lowest tertile (P = 0.02); TAs %Δ = 40.31 (95% CI 19.25, 65.10), for the highest vs the lowest tertile (P = 0.0002)). These findings may prove the relationships between prenatalarsenic species levelsand neonatalmitochondrial dysfunction.

#2194 Targeted metabolomics analysis identifies a specific metabolomic profile in patients with early chronic kidney disease

Abstract Background and Aims The complex interconnections between various metabolites and the kidney play a major role in the pathogenesis of chronic kidney disease (CKD). Hence, by the assessment of the relationship between metabolites and the kidney, more accurate biomarkers could be discovered to prevent and detect CKD at an early stage. The primary goal of this study was to find new serum and urine biomarkers for the diagnosis of early CKD by conducting a metabolomic profiling through targeted metabolomics of both blood and urine in patients with CKD. Method This cross-sectional study comprised 80 patients with CKD who were categorized into six subgroups (G1-G6) based on their eGFR according to the KDIGO Guidelines. Additionally, 20 healthy individuals were included as healthy control participants (group C). Ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry was used to perform serum and urine metabolomic profiling. The 6 metabolites evaluated by this study were selected based on the results of a previous untargeted analysis research. Both blood and urine samples underwent multivariate analysis, which was subsequently followed by univariate analysis and quantitative analysis. Initially, the PLSDA score plot and VIP score were utilized. The application of the cross-validation procedure to the initial set of 6 molecules provided outstanding results, including high accuracy, high R² values, and a significant Q2 value. Hence, the model might be deemed as predictive. Random Forest analysis was utilized to conduct biomarker analysis and prediction. The specificity and sensitivity of the compounds identified as possible biomarkers were assessed using the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC). Results There were strong positive correlations between eGFR and serum levels of Arginine (p &amp;lt; 0.05) and L-Acetylcarnitine (p &amp;lt; 0.05). Of note, the amounts of L-Methionine, L-Phenylalanine, Kynurenic acid, and Indoxyl sulfate in serum showed a progressive increase from group C to subgroups G1-G5. Furthermore, L-Methionine, L-Phenylalanine, Kynurenic acid, and Indoxyl sulfate exhibited a negative correlation with eGFR (p &amp;lt; 0.05). In addition, there was a positive correlation between the levels of urine Arginine, L-Methionine, and L-Phenylalanine and eGFR (p &amp;lt; 0.05). Urine levels of Kynurenic acid, Indoxyl sulfate, and L-Acetylcarnitine were higher in groups G4 and G5, as compared to groups G1-G3b and C, respectively. The urinary concentrations of Indoxyl sulfate, Kynurenic acid, Indoxyl sulfate, and L-Acetylcarnitine exhibited a negative correlation with eGFR (p &amp;lt; 0.05). Conclusion The current study shows that serum and urinary metabolites levels in patients with CKD display an alteration in production, secretion, and excretion in all CKD stages. There was demonstrated a distinct metabolomic profile in the course of CKD which points to novel biomarkers useful for the diagnosis and progression evaluation of CKD from its early stages.

Estimated daily intake and cumulative risk assessment of organophosphate esters and associations with DNA damage among e-waste workers in Hong Kong

Organophosphate esters (OPEs) are extensively used as additives in various products, including electronic equipment, which becomes e-waste when obsolete. Nevertheless, no study has evaluated OPEs exposure levels and the related health risks among e-waste workers in Hong Kong. Therefore, 201 first-spot morning urine samples were collected from 101 e-waste workers and 100 office workers to compare eight urinary OPE metabolites (mOPEs) levels in these groups. The concentrations of six mOPEs were similar in e-waste workers and office workers, except for significantly higher levels of diphenyl phosphate (DPHP) in e-waste workers and bis(1-chloro-2propyl) phosphate (BCIPP) in office workers. Spearman correlation analysis showed that most non-chlorinated mOPEs were correlated with each other in e-waste workers (i.e., nine out of ten pairs, including di-p-cresyl phosphate (DpCP) and di-o-cresyl phosphate (DoCP), DpCP and bis(2-butoxyethyl) phosphate (BBOEP), DpCP and DPHP, DpCP and dibutyl phosphate (DBP), DoCP and BBOEP, DoCP and DPHP, DoCP and DBP, BBOEP and DPHP, DPHP and DBP), indicating that handling e-waste could be the exposure source of specific OPEs. The median values of estimated daily intake (EDI) and hazard quotient (HQ) suggested that the health risks from OPEs exposures were under the recommended thresholds. However, linear regression models, Quantile g-computation, and Bayesian kernel machine regression found that urinary mOPEs elevated 8-hydroxy-2-deoxyguanosine (8-OhdG) levels individually or as a mixture, in which DPHP contributed prominently. In conclusion, although e-waste might not elevate the internal OPEs levels among the participating Hong Kong e-waste workers, attention should be paid to the potential DNA damage stimulated by OPEs under the currently recommended thresholds.