Urinary Levels Research Articles

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.

DaiTongXiao improves gout nephropathy by inhibiting inflammatory response through the TLR4/MyD88/NF-κB pathway.

Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties. Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression. Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and β2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type Ⅳ (COL-Ⅳ). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) -18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and IL-1β in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue. Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/ NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression.

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-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 KO (PD-Cre-Npr1 f/-) mice were fed a normal-, low-, or high-salt diet for 4 wk. Podocytes isolated from HT and KO male and female mice showed complete absence of Npr1 mRNA and NPRA protein compared with WT mice. BP, plasma creatinine, plasma sodium, urinary protein, and albumin/creatinine ratio were significantly increased, whereas plasma total protein, albumin, creatinine clearance, and urinary sodium levels were significantly reduced in the HT and KO male and female mice compared with WT mice. These changes were significantly greater in males than in females. On a normal-salt diet, glomerular filtration rate was significantly decreased in PD Npr1 HT and KO male and female mice compared with WT mice. Immunofluorescence of podocin and synaptopodin was also significantly reduced in HT and KO mice compared with 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.NEW & NOTEWORTHY Our results demonstrate that the podocyte-specific deletion of Npr1 showed increased blood pressure (BP) and altered biomarkers of renal functions, with greater magnitudes in animals fed a high-salt diet in a sex-dependent manner. The results suggest a direct and sex-dependent effect of Npr1 ablation in podocytes on the regulation of BP and renal function and reveal that podocytes may be considered an important target for the ANP-BNP/NPRA/cGMP signaling cascade.

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.

Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy

BackgroundThe TESTING trial demonstrated that corticosteroids reduce the risk of kidney failure in IgA nephropathy (IgAN) patients but increase the risk of serious adverse events. Reliable noninvasive biomarkers are needed to identify patients who would benefit most from corticosteroid therapy. Previous studies suggest glomerular macrophage infiltration is associated with the response to immunosuppressive therapy in IgAN and urinary soluble CD163(u-sCD163, a marker of M2c macrophage) is correlated with clinical remission in vasculitis. This study aims to investigate the association between u-sCD163 and response of steroids therapy in IgAN. MethodsWe measured u-sCD163 in patients from a large IgAN cohort including China participants of the TESTING trial. The correlation of baseline or serial u-sCD163 and their response of corticosteroids therapy or kidney outcomes were investigated. ResultsIn cross-sectional analysis, u-sCD163 levels correlated with kidney macrophage infiltration, especially in crescentic areas, and with active lesions. Subgroup analysis of the TESTING cohort showed higher levels u-sCD163 were associated with greater benefits from corticosteroids therapy in proteinuria remission [OR, 35.56 (95% CI, 7.62-292.34) vs 3.94 (95% CI, 1.39-12.93), p for interaction 0.036]. Corticosteroids therapy significantly reduced u-sCD163 levels at 6th month compared to placebo group [79% (IQR 58%,91%) vs 37% (-11%,58%), P<0.001]. There was no difference in the suppressive effects on u-sCD163 by either dosage of corticosteroids (full and reduced-dose). The suppression of u-sCD163 was significantly associated with a reduced risk of kidney progression events (adjusted HR 0.52,95% CI 0.30 to 0.93, P=0.027). ConclusionsU-sCD163 is a reliable noninvasive biomarker associated with active pathological lesions in IgAN and can guide glucocorticoid therapy.

Impact of oral melatonin supplementation on urine and serum melatonin concentrations and quality-of-life measures in persons with relapsing multiple sclerosis

IntroductionMelatonin is an antioxidant and anti-inflammatory agent that modulates the immune system by scavenging free radicals, reducing the upregulation of pro-inflammatory cytokines, and reducing transendothelial cell migration. Therefore, melatonin may play a role in regulating multiple sclerosis (MS) disease activity. However, little is known about how melatonin supplementation effects individuals with MS. ObjectiveDetermine if there was a dose-dependent elevation in urine and serum melatonin concentrations. Determine if melatonin supplementation had an impact on patient reported outcomes. MethodsThis was a randomized, dose-blinded exploratory study. Adults (age 18–65) with relapsing forms of multiple sclerosis (RMS) treated with a stable dose of oral disease modifying therapy for at least 6 months were randomized into melatonin 3 mg or 5 mg daily. Urinary and serum melatonin levels and modified fatigue impact scale (MFIS), multiple sclerosis impact scale (MSIS-29), and Pittsburgh sleep quality index (PSQI), patient determined disease steps (PDDS) and performance scales (PS) were measured at baseline, 3, 6, and 12 months. Urinary and serum melatonin analyses was performed to estimate mean concentrations and their differences between treatment arms over time by a repeated measures linear mixed model. The model included treatment, assessment time, and treatment × time interaction. ResultsThirty patients, randomized 1:1, were analyzed in an intent to treat population. Twenty-three completed the study. The repeated measures linear mixed model analysis of all timepoints revealed higher melatonin concentrations in patients on 5 mg compared to 3 mg melatonin for both urinary 6-SMT (p = 0.03) and serum melatonin (p = 0.04). MFIS, MSIS-29, PSQI, and PDSS-PS scores did not significantly change from baseline to month 12. No significant differences in these measures were seen between the two doses. Five patients stopped melatonin (three on 5 mg and two on 3 mg) due to adverse events, including one patient who developed focal spongiotic dermatitis. One patient experienced three consecutive serious adverse events that were unrelated to melatonin supplementation. ConclusionsThe 5 mg melatonin supplementation group had higher concentrations of urinary 6-SMT and serum melatonin compared to the 3 mg group over 12 months of treatment. There was a correlation between 6-SMT and serum melatonin concentrations. This suggests that measuring serum melatonin is a reliable alternative to measuring urinary 6-SMT. However, no differences in clinical benefit between the two dosage groups were demonstrated in the patient reported outcomes. Trial Registration NumberNCT03498131

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.

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.

Evaluation of the Protective Effects of Vitamins E and D on Oxidative Stress and Inflammation Caused by Tamoxifen in the Renal Tissue of Female Wistar Rats

Background: Tamoxifen is an effective drug for breast cancer treatment and its side effects are the production of reactive oxygen species and kidney damage. As antioxidants, vitamins E and D may help decrease kidney dysfunction. Objectives: In the present study, the protective effects of vitamins E and D on renal toxicity caused by tamoxifen in female Wistar rats were investigated. Materials and Methods: Twenty-five adult female rats weighing 180-200 were randomly divided into five groups with 5 rats. Group C, T, TE, TD, and TED were treated with olive oil, tamoxifen, tamoxifen + vitamin E, tamoxifen +vitamin D, and tamoxifen + both vitamins for four weeks. ELISA Kits measured the oxidant and antioxidant tests and TNF-α in kidney tissue. The spectrophotometric method measured urea, uric acid, and creatinine in serum and urine. Results: Tamoxifen significantly decreased the weight of rats, GPx, CAT, SOD levels and increased TNF-α, urinary creatinine level and, serum uric acid, urea levels (P &lt; 0.05). But, treatment with vitamin D and simultaneous administration of vitamins led to a significant decrease in the level of (TNF-α) compared to the tamoxifen group (p &lt; 0.01). Also, the histopathology results showed that the simultaneous administration of vitamins has significantly resolved the damage caused by the use of tamoxifen. Conclusion: The present study's findings showed that using vitamins E and D prevents kidney damage through antioxidant and anti-inflammatory effects. In addition, using vitamins E and D probably showed stronger synergistic effects against kidney damage.

The diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in assessing kidney function in severe hydronephrosis.

Up to now, there is no perfect indicator to evaluate the renal function of severe hydronephrosis, which poses difficulties in the selection of clinical treatment decisions. This study investigates the role of neutrophil gelatinase-associated lipocalin (NGAL) in urine drained from the nephrostomy tube shortly after nephrostomy to evaluate the renal function of patients with severe hydronephrosis caused by ureteral obstruction. The clinical data, and blood and urine samples of 24 patients with severe hydronephrosis due to ureteral obstruction were retrospectively collected. The NGAL in the urine drained from the nephrostomy tube on the morning of the first day after the procedure was measured. The glomerular filtration rate (GFR) was determined using a nuclear scan, and the clearance rate of creatinine was calculated based on nephrostomy drainage. The correlation between the NGAL level, urine volume post-nephrostomy, affected side GFR, and creatinine clearance rate (Ccr) was assessed. Moreover, the relationship between the urinary NGAL levels and prognosis was analyzed based on whether the patients underwent nephrectomy. There was a significant correlation between the urine NGAL from the nephrostomy of the affected side and the Ccr and urine volume post-nephrostomy (both P<0.05). Compared with the patients in the kidney preservation group, those who underwent nephrectomy had significantly increased NGAL levels, and significantly reduced Ccrs and nephrostomy drainage urine output. Through the receiver operating characteristic (ROC) curve evaluation, the efficacy of NGAL in predicting nephrectomy was found to be superior to both the Ccr and urine output, with an area under the curve (AUC) of 0.845. The NGAL in the urine shortly after nephrostomy may indicate severe renal functional deterioration.

Stable transduction of the neonatal mouse liver using a hybrid rAAV/sleeping beauty transposon gene delivery system.

Conventional adeno-associated viral (AAV) vectors, while highly effective in quiescent cells such as hepatocytes in the adult liver, confer less durable transgene expression in proliferating cells owing to episome loss. Sustained therapeutic success is therefore less likely in liver disorders requiring early intervention. We have previously developed a hybrid, dual virion approach, recombinant AAV (rAAV)/piggyBac transposon system capable of achieving stable gene transfer in proliferating hepatocytes at levels many fold above conventional AAV vectors. An alternative transposon system, Sleeping Beauty, has been widely used for ex vivo gene delivery; however liver-targeted delivery using a hybrid rAAV/Sleeping Beauty approach remains relatively unexplored. We investigated the capacity of a Sleeping Beauty (SB)-based dual rAAV virion approach to achieve stable and efficient gene transfer to the newborn murine liver using transposable therapeutic cassettes encoding coagulation factor IX or ornithine transcarbamylase (OTC). At equivalent doses, rAAV/SB100X transduced hepatocytes with high efficiency, achieving stable expression into adulthood. Compared with conventional AAV, the proportion of hepatocytes transduced, and factor IX and OTC activity levels, were both markedly increased. The proportion of hepatocytes stably transduced increased 4- to 8-fold from <5%, and activity levels increased correspondingly, with markedly increased survival and stable urinary orotate levels in the OTC-deficient Spfash mouse following elimination of residual endogenous murine OTC. The present study demonstrates the first in vivo utility of a hybrid rAAV/SB100X transposon system to achieve stable long-term therapeutic gene expression following delivery to the highly proliferative newborn mouse liver. These results have relevance to the treatment of genetic metabolic liver diseases with neonatal onset.

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.