Urinary Levels Research Articles

Cadmium, arsenic, and mercury urine levels of an environmental exposed Brazilian population

Cadmium, arsenic, and mercury urine levels of an environmental exposed Brazilian population

Fufang Zhenzhu Tiaozhi (FTZ) capsule ameliorates diabetic kidney disease in mice via inhibiting the SGLT2/glycolysis pathway

Ethnopharmacological relevanceFufang Zhenzhu Tiaozhi (FTZ) capsule is a hospital preparation of a patented traditional Chinese medicine compound. FTZ has been clinically used for nearly 13 years in the treatment of diabetes and glycolipid metabolic diseases. With the significant benefits of SGLT2 inhibitor in patients with diabetic kidney disease (DKD), it provides a research avenue to explore the mechanism of FTZ in treating this disease based on glycolysis pathway. Aim of the studyTo explore the pharmacological characteristics of FTZ in DKD mice and its impact on the glycolysis pathway. Materials and methodsWe induced a DKD model in C57BL/6 mice by injection of streptozotocin (STZ) combined with long-term high-fat diet. We administered three doses of FTZ for 12 weeks of treatment. Kidney function, blood lipid levels, glucose tolerance, and key glycolytic enzymes were evaluated. Renal pathological changes were observed using HE, MASSON, and PAS staining. The potential targets of the active ingredients of FTZ in the glycolysis pathway were predicted using network pharmacology and molecular docking. Validation was performed using immunohistochemistry and Western blotting. ResultsFTZ effectively reduces blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, 24 h proteinuria, serum creatinine, blood urea nitrogen, and increases urinary glucose levels. Glucose tolerance and renal pathological changes were significantly improved by FTZ treatment. Pinusolidic acid, a component of FTZ, shows good binding affinity with three active pockets of SGLT2. WB and immunohistochemistry revealed that FTZ significantly inhibits the expression of SGLT2 and its glycolytic related proteins (GLUT2/PKM2/HK2). Hexokinase, pyruvate kinase, and lactate dehydrogenase in the kidney were also significantly inhibited by FTZ in a dose-dependent manner. ConclusionFTZ may alleviate the progression of DKD by inhibiting the activation of the SGLT2/glycolytic pathway. Our study provides new insights into the clinical application of FTZ in DKD.

Urinary metals and their associations with DNA oxidative damage among e-waste recycling workers in Hong Kong

Recycling electronic waste (e-waste) poses risks of metal exposure, potentially leading to health impairments. However, no previous study has focused on this issue in Hong Kong. Therefore, from June 2021 to September 2022, this study collected urine samples from 101 e-waste workers and 100 office workers in Hong Kong to compare their urinary levels of metals using ICP-MS. Among the 15 included metals (with detection rates above the 70 % threshold), eight showed significantly higher urinary concentrations (unit: μg/g creatinine) in e-waste workers compared to office workers: Li (25.09 vs. 33.36), Mn (1.78 vs. 4.15), Ni (2.10 vs. 2.77), Cu (5.81 vs. 9.23), Zn (404.35 vs. 431.52), Sr (151.33 vs. 186.26), Tl (0.35 vs. 0.43), and Pb (0.69 vs. 1.16). E-waste workers in Hong Kong generally exhibited lower metal levels than those in developing regions but higher than their counterparts in developed areas. The urine level of 8-hydroxy-2-deoxyguanosine (8-OHdG) was determined by HPLC-MS/MS, and no significant difference was found between the two groups. Multiple linear regression models revealed no significant association between individual metal and urinary 8-OHdG concentrations. However, the metal mixture was identified to marginally elevate the 8-OHdG concentrations (1.12, 95 %CI: 0.04, 2.19) by quantile g‑computation models, with Mn and Cd playing significant roles in such effect. In conclusion, while the metal levels among Hong Kong e-waste workers compared favorably with their counterparts in other regions, their levels were higher than those of local office workers. This underscores the need for policymakers to prioritize attention to this unique industry.

Calibration of 24-h urinary sodium excretion estimates from fasting morning urine in Chinese populations: a comparative analysis of 2 calibration models and a locally developed model

BackgroundSpot urine collection offers a convenient alternative to the more cumbersome 24-h urine collection. However, the widely recognized estimation models, such as Tanaka and International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT), have not been adequately adapted for widespread use in the general Chinese population. ObjectivesThis study was designed to evaluate the precision of the Tanaka and INTERSALT calibration models, alongside a locally Zhejiang Province-formulated model, in predicting 24-h urinary sodium (24-hUNa) excretion among the Chinese population. MethodsThe study comprised 1424 participants, aged 18–69 y, who provided both comprehensive 24-h urine and fasting morning urine samples. The researchers assessed the accuracy of the measured 24-hUNa against the estimates obtained from the Tanaka, INTERSALT, and Zhejiang models. This evaluation was conducted at both population and individual levels, employing a range of statistical techniques, including bias analysis, correlation coefficients, intraclass correlation coefficients, receiver operating characteristic curves, Bland–Altman plots, as well as relative and absolute difference calculations, and misclassification rates. ResultsThe measured average 24-hUNa excretion was found to be 165.7 ± 71.5 mmol/24-h. Notably, there was a significant deviation between the estimated and measured values for the Tanaka-adjusted model [−11.7 mmol, 95% confidence interval (CI): −16.7, −6.7 mmol/24-h], indicating a statistically significant difference. In contrast, the deviations for the INTERSALT-adjusted model (0.6 mmol, 95% CI: −4.2, 5.4 mmol/24-h) and the Zhejiang model (0.2 mmol, 95% CI: −4.6, 5.0 mmol/24-h) were nonsignificant. The correlation coefficients for the models were 0.303, 0.398, and 0.391, respectively, with the INTERSALT-adjusted and Zhejiang models showing superior performance at the population level. ConclusionsThe 3 evaluation models may serve as effective, low-burden alternatives for assessing urinary sodium levels in the population. However, to enhance the accuracy and reliability of predictions at the individual level, further repeated measurements are necessary to minimize measurement errors and augment the validity of the estimations.

РОЛЬ ИММУННОГО ОТВЕТА В РАЗВИТИИ ГИПОКСИЧЕСКИХ ОСЛОЖНЕНИЙ РЕСПИРАТОРНЫХ ИНФЕКЦИЙ НИЖНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ У ДЕТЕЙ

Pneumonia is one of the most common severe infectious diseases in pediatric practice. Hypoxia is common in children with pneumonia and is one of the main predictors of poor outcome. The role of the central link in the cellular response to hypoxia is played by the family of hypoxia-inducible factors (HIF). HIF-1α is the key regulator of both T- and B-lymphocyte functions. The processes of their maturation are accompanied by the formation of circular DNA fragments, TREC (T-cell Receptor Excision Circle) and KREC (Kappa-deleting Recombination Excision Circle). TREC and KREC are unable to replicate and serve as markers for naive lymphocyte production. In its turn, HIF-1α can be used as a marker for cellular hypoxia. The use of TREC and KREC in assessing the immune system in patients with various immunological and infectious pathologies has already been described. At the same time, HIF-1α has so far been little studied as yet. The purpose of this research was to analyze the scientific bibliographical data on the HIF-1α assessment as a marker for hypoxia as well as the quantitative level of TREC and KREC as markers for the adaptive immune response; to study the bibliographical sources on the effect of hypoxia on the immune response, including as part of lower respiratory tract infections. Methods used: bibliographical research in Scopus, PubMed and Google Scholar with keywords “TREC,” “KREC,” “HIF,” “hypoxia,” “pneumonia,” “immune response,” that was then followed by the search results’ systematization, analysis and synthesis. Results: the analysis of bibliographical sources had allowed the Authors to conclude that there is a possible close connection between acute hypoxia and the formation of an adequate immune response in infectious pathologies. Research in this area is still extremely scarce. At the same time, the prospects for this area determine the need for further fundamental and clinical research. Conclusion: it is of a great scientific and clinical interest to be able to non-invasively assess the degree of acute hypoxia during an ongoing infectious disease by examining urinary HIF-1α levels. Particularly promising is the assessment of the HIF-1α level not only as a regulator of tissue adaptation to acute hypoxia, but also as a modulator of the immune response. Taking into consideration the analyzed data, both TREC and KREC appear to be the optimal markers characterizing the functional state of the adaptive immune system.

Salivary proteomic signatures in severe dental fluorosis

The relationship between dental fluorosis and alterations in the salivary proteome remains inadequately elucidated. This study aimed to investigate the salivary proteome and fluoride concentrations in urine and drinking water among Thai individuals afflicted with severe dental fluorosis. Thirty-seven Thai schoolchildren, aged 6–16, were stratified based on Thylstrup and Fejerskov fluorosis index scores: 10 with scores ranging from 5 to 9 (SF) and 27 with a score of 0 (NF). Urinary and water fluoride levels were determined using an ion-selective fluoride electrode. Salivary proteomic profiling was conducted via LC–MS/MS, followed by comprehensive bioinformatic analysis. Results revealed significantly elevated urinary fluoride levels in the SF group (p = 0.007), whereas water fluoride levels did not significantly differ between the two cohorts. Both groups exhibited 104 detectable salivary proteins. The NF group demonstrated notable upregulation of LENG9, whereas the SF group displayed upregulation of LDHA, UBA1, S100A9, H4C3, and LCP1, all associated with the CFTR ion channel. Moreover, the NF group uniquely expressed 36 proteins, and Gene Ontology and pathway analyses suggested a link with various aspects of immune defense. In summary, the study hypothesized that the CFTR ion channel might play a predominant role in severe fluorosis and highlighted the depletion of immune-related salivary proteins, suggesting compromised immune defense in severe fluorosis. The utility of urinary fluoride might be a reliable indicator for assessing excessive fluoride exposure.

Nanoengineered Nonenzymatic Paper-Based Fluorescent Platform for Pre-Dilution-Free and Visual Real-Time Home Monitoring of Urea for Early Warning of Abnormal Nitrogen-Based Unhealthy Issues.

Distorted urea levels indicate several liver, kidney, or metabolic diseases; however, traditional clinical urea detection relies on urease-based methods enslaved to well-known limitations of high-price, unstable properties, complicated sample pretreatment and analysis procedures, and difficult visual real-time monitoring. Herein, nonenzymatic paper-based fluorescent materials (UFP-BP) are strategically integrated with an on-demand fluorescent-sensor (UFP) self-aggregated nanoparticle on commercial filter paper for pre-dilution-free and visual real-time urea monitoring. The UFP is synthesized and self-aggregated into the fluorescent nanoparticles for selective urea recognition. Then, the nanoparticles are interstitially loaded on filter paper to nanoengineer the UFP-BP, achieving selective quantitative urea detection in the normal concentration range (10-1000mm). UFP and UFP-BP can successfully monitor urea levels in real rat urine, artificial simulants, and milk. The proposed sensing platform, integrated with smartphones, offers accurate, quantitative, nonenzymatic, noninvasive, pre-dilution-free, on-site, rapid, low-cost, easy-to-operate, real-time visual urea detection in food samples and human body fluids. The designed sensing system can provide early warnings of abnormal nitrogen-based health issues.

Wilson's disease in Sardinian population: The experience of a pediatric referral center.

Wilson's disease (WD) in children and adolescents is predominantly asymptomatic or oligo-symptomatic. The symptoms are nonspecific and difficult to distinguish from other hepatic or neuropsychiatric disorders. In this study, we present the experience of a pediatric referral center for WD diagnosis and treatment. We retrospectively analyzed clinical and laboratory data from 99 patients with WD of Sardinian origin, including physical examination, laboratory biochemical testing, liver biopsy, and genetic analysis. Patients were prevalently oligo-symptomatic or asymptomatic. The median age of diagnosis was 8.78 years. Ceruloplasmin values were lower than normal values in all analyzed patients. Twenty-four-hour urinary copper levels were higher than 40 μg/24-h in 92/96 patients. In all analyzed patients with the exception of one, liver copper was higher than 250 μg/g of dry weight but all had >75 μg/g of dry weight. Statistical analysis showed correlation between the age at diagnosis, serum copper, and 24-h urinary copper. Correlation was also found between serum copper and 24-h urinary copper. Molecular analysis of ATP7B gene allowed complete characterization in all the analyzed patients. A high index of clinical suspicion and biochemical tests including liver tests, serum ceruloplasmin, and basal 24-h urinary copper excretion and genotype determination are key to WD diagnosis. The long experience that a referral center for WD possesses is an important factor in making WD diagnosis a more accurate process. Studies in animal models on WD could be used as a guide to further investigate the molecular mechanisms that regulate copper metabolism and influence the natural history of WD.

A comprehensive investigation of biochemical status in patients with telogen effluvium: Analysis of Hb, ferritin, vitamin B12, vitamin D, thyroid function tests, zinc, copper, biotin, and selenium levels.

The etiology of telogen effluvium (TE) includes situations that may cause physiological stress, surgical trauma, inflammatory, infectious, iatrogenic causes, medications and nutritional deficiencies. TE has been associated with iron deficiency, vitamin B12 deficiency and thyroid diseases. In recent years, the use of over-the-counter food supplements containing vitamins and minerals such as biotin, vitamin D, zinc (Zn), copper (Cu) and selenium (Se) has been increasing in TE patients. The aim of this study is to investigate whether there are differences in nutritional status, vitamin and mineral levels by comparing individuals with TE and a control group. This case-control study included 90 female patients diagnosed with chronic telogen effluvium (CTE), and 90 female controls volunteered to participate in the study who consulted for reasons other than TE. Both groups aged 18 and over and applied to dermatology polyclinic between 01.09.2022 and 01.09.2023. A detailed anamnesis was taken from all patients, a hair pull test was performed, and TE was diagnosed after a dermoscopic examination was performed on all areas of the scalp. Then, serum vitamin D, Zn, Cu, Se levels and biotin levels in serum and urine were measured. Hemoglobin (Hb), ferritin, vitamin B12 and thyroid function tests were retrospectively scanned from the hospital database. It was determined that Zn levels were significantly lower in CTE patients than in controls. Se levels were found to be significantly higher in patients than in controls. There was no difference in Hb, ferritin, vitamin B12, thyroid function tests, vitamin D, Cu levels, serum and urine biotin levels between the two groups. Zn, Cu/Zn and Se levels were found to have statistically significant diagnostic performance in predicting the diagnosis of CTE. Cu/Zn ratio and Se value were found to be significant predictors of CTE. This study shows us that nutritional deficiencies are not as common as thought in patients diagnosed with TE. Other causes that may cause TE should be investigated by a detailed anamnesis and a good physical examination. After all, tests for suspected conditions should be performed and individualized treatment options should be created for each patient.

The association between renal medullary and cortical fibrosis, stiffness, and concentrating capacity: an observational, single-center cross-sectional study.

Fibrosis is a common final pathway leading to end-stage renal failure. As the renal medulla and cortex contain different nephron segments, we analyzed the factors associated with the progression of renal medullary and cortical fibrosis. A total of 120 patients who underwent renal biopsy at Kawashima Hospital between May 2019 and October 2022 were enrolled in this retrospective study. Renal medullary and cortical fibrosis and stiffness were evaluated using Masson's trichrome staining and shear wave elastography, respectively. Maximum urine osmolality in the Fishberg concentration test was also examined. Medullary fibrosis was positively correlated with cortical fibrosis (p < 0.0001) and log-converted urinary β2-microglobulin (MG) (log urinary β2-MG) (p = 0.022) and negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.0002). Cortical fibrosis also correlated with log urinary β2-MG, eGFR, and maximum urine osmolality. Multivariate analysis revealed that cortical fibrosis levels (odds ratio [OR]: 1.063) and medullary stiffness (OR: 1.089) were significantly associated with medullar fibrosis (≧45%). The severe fibrosis group with both medullary fibrosis (≧45%) and cortical fibrosis (≧25%) had lower eGFR and maximum urine osmolality values and higher urinary β2-MG levels than the other groups. Patients with disorders involving both renal medullary and cortical fibrosis had decreased maximum urine osmolality but had no abnormalities in the urinary concentrating capacities with either condition. Renal medullary and cortical fibrosis were positively correlated with urinary β2-MG, but not with urinary N-acetyl-beta-D-glucosaminidase.

Cross-sectional and longitudinal associations of PAHs exposure with serum uric acid and hyperuricemia among Chinese urban residents: The potential role of oxidative damage

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-μmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 μmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms.

Podocyte Cell-Specific Npr1 is Required for Blood Pressure and Renal Homeostasis in Male and Female Mice: Role of Sex-Specific Differences.

Atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA), stimulating natriuresis and diuresis and reducing blood pressure (BP), but the role of ANP/NPRA signaling in podocytes (highly specialized epithelial cells covering the outer surfaces of renal glomerular capillaries) remains unclear. This study aimed to determine the effect of conditional deletion of podocyte (PD)-specific Npr1 (encoding NPRA) gene knockout (KO) in male and female mice. Tamoxifen-treated wild-type control (PD Npr1 f/f; WT), heterozygous (PD-Cre-Npr1 f/+; HT), and knockout (PD-Cre-Npr1 f/-; KO) mice were fed a normal-, low-, or high-salt diet for 4 weeks. Podocytes isolated from HT and KO male and female mice showed complete absence of Npr1 mRNA and NPRA protein compared to WT mice. BP, plasma creatinine, plasma sodium, urinary protein, and albumin/creatinine ratio were significantly increased, while plasma total protein, albumin, creatinine clearance, and urinary sodium levels were significantly reduced in the HT and KO male and female mice compared to WT mice. These changes were significantly greater in males than females. On a normal-salt diet, glomerular filtration rate (GFR) was significantly decreased in PD Npr1 HT and KO male and female mice compared with WT mice. Immunofluorescence of podocin and synaptopodin were also significantly reduced in HT and KO mice compared to WT mice. These observations suggest that in podocytes, ANP/NPRA signaling may be crucial in the maintenance and regulation of glomerular filtration and BP and serve as a biomarker of renal function in a sex-dependent manner.

Cystatin C: diagnostic and prognostic value in acute kidney injury

Acute kidney injury (AKI) is a life-threatening condition that occupies one of the leading places in the structure of mortality in intensive care units. AKI markers common in clinical practice are characterized by a number of disadvantages: serum creatinine – late response to damage to the kidney tubules, an increase in damage to more than 50% of nephrons; urine volume – limited diagnostic value and overdiagnosis of AKI in dehydration, the impossibility of assessing on the basis of a single measurement, as well as the need for regular and frequent dynamic monitoring. The review considers the diagnostic and prognostic possibilities of cystatin C (CysC) in AKI. The results of 55 researches were analyzed. The influence of a number of physiological conditions and non-renal diseases on blood serum and urinary CysC levels were shown. These indicators proved to be highly sensitive and specific biomarkers for AKI diagnosis and prognosis, allowing the specialists to verify renal dysfunction at an early stage of development, ahead of structural changes, and thereby to timely correct treatment, including withdrawal of nephrotoxic drugs and initiation of nephroprotection therapy.

Aflatoxin M1 levels in urine and breast milk of lactating mothers in Kuala Lumpur, Malaysia

Aflatoxins are carcinogens that can contaminate food and affect various body organs especially liver and kidney. When consumed, aflatoxin B1 (AFB1) is partially metabolised into aflatoxin M1 (AFM1), which is excreted in the urine.Breast milk may also contain AFM1 due to maternal dietary intake from contaminated food. This cross-sectional study aimed to determine the levels of AFM1 in both urine and breast milk among breastfeeding mothers (n = 256). The mother’s demographic information was collected during recruitment. Mothers were then scheduled for an appointment to provide a morning urine sample along with five to ten mL samples of breast milk. AFM1 levels in both samples were analysed using an enzyme-linked immunosorbent assay (ELISA). Spearman’s rho and Chi-square were used to determine the associations between mean levels of AFM1 in urine and breast milk. Findings show 68.0% of urine samples were contaminated with AFM1 (mean levels = 0.08 ± 0.04 ng/mL), while 14.8% of breast milk samples had AFM1 (mean levels = 5.94 ± 1.81 ng/kg). Urine AFM1 levels were not significantly associated with AFM1 levels in breast milk (p > 0.05). This study can act as a baseline for future research examining long-term aflatoxin exposure among both mothers and infants.

Urinary D-amino acid profiles in cats with chronic kidney disease.

Chronic kidney disease (CKD) is highly prevalent in domestic cats. This study aimed to compare urinary D-amino acid levels between control and CKD-afflicted cats as a novel noninvasive method for assessing CKD. Cats were divided into control and CKD stage II groups in accordance with the International Renal Interest Society guidelines. The urinary DL-amino acid levels of the cats were analyzed using chiral tandem liquid chromatography-tandem mass spectrometry, and their medical records were investigated. The CKD group had considerably lower urinary D-amino acid concentrations and enantiomeric ratios than the control group. The total urinary D-amino acid contents significantly correlated with blood parameters (creatinine and urea nitrogen). These findings may contribute towards the detection of CKD stage II in domestic cats.

Urinary NGAL in gastrointestinal diseases can be used as an indicator of early infection in addition to acute kidney injury marker.

Neutrophil gelatinase-associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child-Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases.

Short occupational exposure to glyphosate and its biomonitoring via urinary levels of glyphosate and metabolite AMPA (Amino-MethylPhosphonic acid), in Italian vineyard workers

Glyphosate, an herbicide largely used in various contexts, can have adverse effects on human health. Although it is currently the most applied pesticide worldwide, few studies evaluated the extent of human exposure via biomonitoring. To expand such information, biological monitoring of exposure to glyphosate was conducted.The study has a before-and-after design to demonstrate the immediate impact of short-term interventions. Accordingly, the urine concentrations of glyphosate and its main biodegradation product (amino-methylphosphonic acid- AMPA) were measured before and the day after the single herbicide application in 17 male winegrowers. Urine samples were analyzed by high performance liquid chromatography coupled with a triple quadrupole mass spectrometer equipped with an electrospray ionization source.Glyphosate and AMPA were not detectable in pre-application urine samples (limit of quantification for glyphosate (LOQG) was 0.1 μg/L; limit of quantification for AMPA (LOQAMPA) was 0.5 μg/L). After application, glyphosate urinary levels were above LOQG in all workers. The median, min, and max values were 2.30, 0.51, and 47.2 μg/L, respectively. The same values were found for 50 %, 5 % and 95 % percentiles. After assigning numerical values, such as one half the LOQ, to each of the non-detects, the “z” of Wilcoxon matched-pairs signed-ranks test was −3.62 (p = 0.0003), suggesting the pre-application values being significantly lower than the post-application urinary glyphosate concentration. A similar analysis was not feasible with AMPA urinary levels, which were detectable only in 3 workers, after application. 12 (71 %) workers were significantly exposed to glyphosate, but adherence to the adoption of personal protective equipment was good: 14 (82 %) workers used gloves, 13 (76 %) used overalls and 13 (76 %) facial masks.Our data show that glyphosate can be absorbed by the workers after a single application and confirms the usefulness of biomonitoring in exposed workers. Further studies are needed in larger working populations and with multiple glyphosate applications, as well as to evaluate the correlations of glyphosate urine levels with exposure questionnaire data, in order to assess the actual relevance of risk and protection factors.

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.

An epigenome-wide study of selenium status and DNA methylation in the Strong Heart Study

BackgroundSelenium (Se) is an essential nutrient linked to adverse health endpoints at low and high levels. The mechanisms behind these relationships remain unclear and there is a need to further understand the epigenetic impacts of Se and their relationship to disease. We investigated the association between urinary Se levels and DNA methylation (DNAm) in the Strong Heart Study (SHS), a prospective study of cardiovascular disease (CVD) among American Indians adults. MethodsSelenium concentrations were measured in urine (collected in 1989–1991) using inductively coupled plasma mass spectrometry among 1,357 participants free of CVD and diabetes. DNAm in whole blood was measured cross-sectionally using the Illumina MethylationEPIC BeadChip (850 K) Array. We used epigenome-wide robust linear regressions and elastic net to identify differentially methylated cytosine-guanine dinucleotide (CpG) sites associated with urinary Se levels. ResultsThe mean (standard deviation) urinary Se concentration was 51.8 (25.1) μg/g creatinine. Across 788,368 CpG sites, five differentially methylated positions (DMP) (hypermethylated: cg00163554, cg18212762, cg11270656, and hypomethylated: cg25194720, cg00886293) were significantly associated with Se in linear regressions after accounting for multiple comparisons (false discovery rate p-value: 0.10). The top hypermethylated DMP (cg00163554) was annotated to the Disco Interacting Protein 2 Homolog C (DIP2C) gene, which relates to transcription factor binding. Elastic net models selected 425 hypo- and hyper-methylated DMPs associated with urinary Se, including three sites (cg00163554 [DIP2C], cg18212762 [MAP4K2], cg11270656 [GPIHBP1]) identified in linear regressions. ConclusionsUrinary Se was associated with minimal changes in DNAm in adults from American Indian communities across the Southwest and the Great Plains in the United States, suggesting that other mechanisms may be driving health impacts. Future analyses should explore other mechanistic biomarkers in human populations, determine these relationships prospectively, and investigate the potential role of differentially methylated sites with disease endpoints.

Styrene and ethylbenzene exposure and type 2 diabetes mellitus: A longitudinal gene–environment interaction study

Styrene and ethylbenzene (S/EB) are identified as hazardous air contaminants that raise significant concerns. The association between S/EB exposure and the incidence of type 2 diabetes mellitus (T2DM), and the interaction between genes and environment, remains poorly understood. Our study consisted of 2,219 Chinese adults who were part of the Wuhan-Zhuhai cohort. A follow-up assessment was conducted after six years. Exposure to S/EB was quantified by determining the concentrations of urinary biomarkers of exposure to S/EB (UBE-S/EB; urinary phenylglyoxylic acid level plus urinary mandelic acid level). Logistic regression models were constructed to investigate the relations of UBE-S/EB and genetic risk score (GRS) with T2DM prevalence and incidence. The interaction effects of UBE-S/EB and GRS on T2DM were investigated on multiplicative and additive scales. UBE-S/EB was dose-dependently and positively related to T2DM prevalence and incidence. Participants with high levels of UBE-S/EB [relative risk (RR) ​= ​1.930, 95% confidence interval (CI): 1.157–3.309] or GRS (1.943, 1.110–3.462) demonstrated the highest risk of incident T2DM, in comparison to those with low levels of UBE-S/EB or GRS. Significant additive interaction between UBE-S/EB and GRS on T2DM incidence was discovered with relative excess risk due to interaction (95% CI) of 0.178 (0.065–0.292). The RR (95% CI) of T2DM incidence was 2.602 (1.238–6.140) for individuals with high UBE-S/EB and high GRS, compared to those with low UBE-S/EB and low GRS. This study presented the initial evidence that S/EB exposure was significantly related to increased risk of T2DM incidence, and the relationship was interactively aggravated by genetic predisposition.