Widespread glyphosate contamination in the environment and its endocrine-disrupting potential are concerning. However, evidence of glyphosate's effects on glycemic health is limited. To examine the association between glyphosate and glucose homeostasis in the general US population, a total of 3038 individuals were enrolled from the 2013-2016 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression and restricted cubic spline curves were used to detect the associations between glyphosate and glycemic disorders. The effects of interactions between sex hormones and glyphosate on glycemic outcomes were evaluated. The results showed that glyphosate was significantly linked to increased glycated hemoglobin A1c (HbA1c) levels (
Abstract Phthalates are a group of neurotoxicants with cognitive-disrupting potentials. Given the structural diversity of phthalates, the corresponding neurotoxicity is dramatically altered. To identify the potential contributions of different phthalates on the process of cognitive impairment, data of 836 elders from the NHANES 2011–2014 cycles were used. Survey-weighted logistic regression and principal component analysis-weighted quantile sum regression (PCA-WQSR) models were applied to estimate the independent and combined associations of 11 urinary phthalate metabolites with cognitive deficit [assessed by 4 tests: Immediate Recall (IR), Delayed Recall (DR), Animal Fluency (AF), and Digit Symbol Substitution test (DSST] and to identify the potential phthalate with high weight. Laboratory mice were further used to examine the effect of phthalates on cognitive function and to explore the potential mechanisms. In logistic regression models, MBzP was the only metabolite positively correlated with four tests, with ORs of 2.53 [quartile 3 (Q3)], 2.26 (Q3), 2.89 (Q4) and 2.45 (Q2), 2.82 (Q4) for IR, DR, AF and DSST respectively. In PCA-WQSR co-exposure models, low-molecular-weight (LMW) phthalates were the only PC positively linked to DSST deficit (OR: 1.93), which was further validated in WQSR analysis (WQS OR 7 − phthalates : 1.56 and WQS OR 8 − phthalates : 1.55); consistent with the results of logistic regression, MBzP was the dominant phthalate. In mice, butyl benzyl phthalate (BBP), the parent phthalate of MBzP, dose-dependently reduced cognitive function and disrupted hippocampal neurons. Additionally, the hippocampal transcriptome analysis identified 431 differential expression genes, among which most were involved in inhibiting the neuroactive ligand‒receptor interaction pathway and activating the cytokine‒cytokine receptor interaction pathway. Our study indicates the critical role of BBP in the association of phthalates and cognitive deficits among elderly individuals, which might be speculated that BBP could disrupt hippocampal neurons, activate neuroinflammation and inhibit neuroactive receptors. Our findings provide new insight into the cognitive-disrupting potential of BBP.
People are continually and simultaneously exposed to various non-persistent pesticides as these chemicals are ubiquitously distributed in the environment. Toxicological studies have indicated the associations between non-persistent pesticides and liver fibrosis in vitro and in vivo. However, epidemical study on the deleterious effect of non-persistent pesticides on the risk of liver fibrosis is rather limited. To examine the relationship between mixed non-persistent pesticides exposure and liver fibrosis, and to identify the potential pesticides of significant importance, this study enrolled the representative individuals from the NHANES 2013-2016 survey cycles, in which urinary non-persistent pesticides were measured. Liver fibrosis was determined based on the alternative noninvasive tests Fibrosis-4 index (FIB-4) and Hepamet Fibrosis Score (HFS). Survey-weighted linear/logistic regression and Bayesian kernel machine regression (BKMR) were used to detected the independent and combined associations between non-persistent pesticides and liver fibrosis, respectively. In single exposure analysis, significant and persistent associations were identified for 3,5,6-trichloropyridinol (TCPY), para-nitrophenol (PNP), glyphosate (GLYP) and 2,4-dichlorophenoxyacetic acid (2,4-D) exposure with both continuous and dichotomous liver fibrosis outcomes. Of them, TCPY and GLYP had the highest effect estimates, with the corresponding FIB-4 coefficient (β) being 0.09 (0.05-0.13, model 3) and 0.09 (0.06-0.12, model 3), respectively. In BKMR analysis, positive associations between pesticides mixture and FIB-4 and HFS liver fibrosis were identified. The results of Posterior Inclusion Probability (PIP) further showed that GLYP, TCPY, and PNP were the main contributors to the overall effects of pesticides mixture, and the corresponding PIPs were 1.000 (1.000), 1.000 (0.914) and 0.972 (0.819) for FIB-4 (HFS) liver fibrosis, respectively. This study indicates that exposure to non-persistent pesticides mixture is associated with increased risk of liver fibrosis in humans, and provide new insight into the hepatotoxic potential of non-persistent pesticides.
Glyphosate is the most widely used herbicide in the world. This study aimed to evaluate the relationships among urinary glyphosate, all-cause mortality and cardiovascular diseases (CVD)-related mortality in the general US population of adults, and to determine the role of alkaline phosphatase (ALP), an inflammation marker that is associated with glyphosate exposure, in these relationships. Subjects from the National Health and Nutrition Examination Survey (NHANES) 2013-2018 cycles were included. Survey-weighted Cox regression analysis was applied to estimate the relationship of glyphosate with overall and CVD mortalities. Restricted cubic spline (RCS) analysis was utilized to detect the linearity of associations. The intermediary role of ALP was explored by mediation analysis. Our results found consistent and positive associations of glyphosate with all-cause mortality (HR: 1.29, 95%CI: 1.05-1.59) and CVD mortality (HR: 1.32, 95%CI: 1.02-1.70). RCS curves further validated linear and positive dose-dependent relationships between glyphosate and mortality-related outcomes. Moreover, serum ALP was identified as a mediator in these associations and explained 12.1% and 14.0% of the total associations between glyphosate and all-cause death and CVD death risk, respectively. Our study indicated that glyphosate was associated with increased all-cause and CVD mortality in humans. Increased ALP may play an essential role in these associations.
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