Reduction of haemoglobin is related to metal mixtures exposure in Chinese preschoolers: Joint effect models.

Heavy metal exposure is a known risk factor for hematologic disorders in children, yet the impact of co-exposure to multiple metals remains underexplored. This cross-sectional study investigates the relationship between urinary levels of 23 metals and haemoglobin (Hb) in 1460 Chinese preschoolers. The concentrations of the 23 urinary metals were quantified using an inductively coupled plasma mass spectrometer, while Hb levels were assessed through finger prick blood samples. To evaluate the co-exposure effects, we employed three approaches: Generalized linear regression model, joint effect models including Quantile g-Computation and Bayesian Kernel Machine Regression (BKMR). From the generalized linear regression and Quantile g-computation, urinary uranium, thallium, aluminium, iron and tungsten were correlated negatively with Hb, while urinary barium was correlated positively (all P < 0.05). Moreover, significant negative associations between metal mixtures exposure with Hb were identified in both Quantile g-computation [ß (95% CI): -0.083 (-0.132, -0.033), P = 0.0012] and BKMR [90th percentile vs. 50th percentile ß (95% CI): -0.238 (-0.368, -0.107), P < 0.001] with aluminium emerging as the primary contributor to this joint effect (weight in Quantile g-computation = 0.399, PIPs in BKMR = 0.896). These findings provide a potential explanation for environmental exposure to metals and Hb-related disease in preschoolers.

Mechanism of GW117 antidepressant action: melatonin receptor-mediated regulation of sleep rhythm.

Alterations in circadian sleep patterns constitute a salient manifestation in major depressive disorder. GW117, an emergent antidepressant, functions as an agonist for melatonin 1 and melatonin 2 (MT1/MT2) receptors, in tandem with antagonism of the serotonin (5-HT) 2C receptor. The present investigation is dedicated to elucidating the role and underlying mechanisms by which GW117 ameliorates circadian sleep disruptions. Utilizing an adapted chronic unpredictable mild stress protocol, we induced a depressive-like phenotype and perturbed circadian rhythms in rodent models. Our methodological approach integrated quantitative polymerase chain reaction (qPCR) in real-time, enzyme-linked immunosorbent assay (ELISA), and immunoblotting techniques to probe alterations in the expression of core circadian genes and homeostatic sleep markers. The impact of GW117 was assessed across various dosages (10, 20, and 40 mg/kg) on these molecular signatures. In a parallel examination, we evaluated the influence of GW117 (administered at 15, 40, and 60 mg/kg) on the sleep patterns of healthy mice. The results showed that GW117 significantly improved sleep-wake circadian rhythms, altered sleep architecture, and shortened sleep latency. Furthermore, GW117 increased the expression of several clock genes in the hypothalamus of chronic unpredictable mild stress model rats and normal mice. It also regulated circadian biomarkers, including melatonin and cortisol. Based on our findings, we propose that the beneficial effects of GW117 on sleep rhythms may be due to the melatonin system-mediated activation of the Wnt/ß-catenin signaling pathway.

Association Between Heavy Metals Exposure and Height in Chinese Preschoolers.

OBJECTIVES: This study aimed to explore the association between multiple metals' exposure and children's height. METHODS: We collected urine samples and physical measurement data of 1477 preschoolers in China. Children's actual height was measured, and whether reached target height was also assessed. Logistic regression analysis was performed to explore the association between heavy metals and height. The least absolute shrinkage and selection operator regression was used to select the urinary metals, which were highly correlated. RESULTS: In the single-metal model after adjusting for potential confounders, urinary iron, aluminum, nickel, chrome, titanium, vanadium, selenium, rubidium, and thallium levels were negatively associated with actual height. Urinary iron, aluminum, nickel, and chrome concentrations were also negatively associated with target height. CONCLUSIONS: The findings suggested that some urinary metal exposure might be associated with height in preschoolers.

Associations of exposure to multiple metals with blood pressure and hypertension: A cross-sectional study in Chinese preschool children.

Exposure to metals might be a risk factor for hypertension, which contributes largely to the global burden of disease and mortality. However, relevant epidemiological studies of associations between metals exposure with hypertension among preschoolers are limited. This study aimed to explore the associations of urine metals with blood pressure and hypertension among Chinese preschoolers. A total of 1220 eligible participants who had urine metals measurement, blood pressure measurements, and relevant covariates were included in this cross-sectional study. Urine concentrations of metals were measured by inductively coupled plasma mass spectrometer. The single and multiple metals regression models were used to investigate the associations of urine metal with blood pressure and the risk of hypertension after adjusting for potential confounders. We observed urine concentrations of chromium, iron, and barium were negatively associated with levels of systolic blood pressure, diastolic blood pressure and the risk of hypertension in the single metal model (all P-FDR adjustment <0.05). Significant associations of urine chromium concentrations with systolic blood pressure, diastolic blood pressure and the risk of hypertension were found in the multi-metal model (ß or OR (95% confidence interval) was -3.07 (-5.12, -1.02), -2.25 (-4.29, -0.22), and 0.51 (0.26, 0.97) for 3rd quartile, compared with 1st quartile, respectively). The same association was found for barium concentrations in the multi-metal model, while none of the associations among iron quartiles was significant. In addition, urine chromium, iron and barium may have joint effects on systolic blood pressure, diastolic blood pressure and hypertension. Children's age and body mass index could modify the associations of chromium, iron, and barium concentrations with blood pressure. Our findings suggested that exposure to chromium, iron, and barium was inversely associated with blood pressure and hypertension among preschool children. These findings need further validation in prospective studies.