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.

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.

Noncoding RNA miR-205-5p mediates osteoporosis pathogenesis and osteoblast differentiation by regulating RUNX2.

As a kind of noncoding RNAs, microRNAs (miRNAs) play important roles in disease pathogenesis by regulating gene expression. However, the molecular mechanism of miRNAs in osteoporosis remains largely unknown. In the present study, we aim to explore the genome-wide miRNAs expression profile and the regulatory mechanism of miR-205-5p in osteoporosis. A total of 72 differentially expressed miRNAs were identified in osteoporosis via microarray technology and bioinformatics analysis. We focused on one of the abnormally expressed miRNAs, miR-205-5p, which was previously unknown in osteoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that miR-205-5p was upregulated in osteoporosis samples and its expression was gradually decreased during osteogenic differentiation. Besides, miR-205-5p overexpression could inhibit the activity of osteoblast markers, including collagen, type I, α 1 (COL1A1) and alkaline phosphatase (ALP) while miR-205-5p inhibition showed the opposite results. Moreover, bioinformatics analysis identified the potential targets of miR-205-5p, including runt-related transcription factor 2 (RUNX2), SMAD1 and BCL6, etc. The dual-luciferase reporter assay confirmed RUNX2 was directly targeted by miR-205-5p. Furthermore, the rescue experiments showed that RUNX2 overexpression could significantly weaken the effect of miR-205-5p on osteoblast markers, indicating that miR-205-5p may inhibit osteogenic differentiation by targeting RUNX2.

Effect of IL-17A on the migration and invasion of NPC cells and related mechanisms.

In carcinogenesis, inflammasomes may play contradictory roles through facilitating anti-tumor immunity or inducing oncogenic factors. Their function in cancer remains poorly characterized. In this study, we explored the effect of interleukin-17A (IL-17A) on the migration and invasion activity of nasopharyngeal carcinoma (NPC) cell lines and account for related mechanisms. Our results revealed that exogenous IL-17A promoted cell migration and invasion significantly in both NPC-039 and CNE-2Z cell lines. In addition, the expression of matrix metalloproteinase-2 (MMP-2)/-9 and Vimentin could be elevated by IL-17A stimulation; meanwhile the expression of E-cadherin was decreased. The results also show that IL-17A could activate the p38 signaling pathway in IL-17A-stimulated NPC-039 and CNE-2Z cell lines. Combining treatment with a p38 inhibitor (SB203580) resulted in decreased invasion capabilities of NPC-039 and CNE-2Z cell lines. SB203580 also inhibited the expression of MMP-2/-9 and increased the expression of E-cadherin in IL-17A-stimulated NPC-039 and CNE-2Z cell lines. IL-17A also could activate NF-κB in NPC-039 and CNE-2Z cell lines. In summary, our data show that IL-17A promote the cell migration and invasion of NPC cells. The effect of IL-17A on cell migration and invasion may be mediated via regulation of the expression of MMP-2/-9 and epithelial-mesenchymal transition (EMT) via p38-NF-κB signaling pathway. Thus, IL-17A or its related signaling pathways may be a promising target for preventing and inhibiting NPC metastasis.

Effects of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes.

Endothelial dysfunction is thought to be a critical event in the pathogenesis of vasculopathy in type 2 diabetes and oxidant stress is a major etiological factor. Gliclazide, a second generation sulfonylurea, contains an azabicyclo-octyl ring, which has been described to have antioxidant properties. However, the effect of gliclazide on endothelial function is unknown. Therefore, in this study, we examined the effect of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes (diabetic group; n=33). A control group of non-diabetic subjects was also enrolled (n=25). All of the diabetic patients were treated with gliclazide for 12 weeks. Endothelial function was evaluated by flow-mediated vasodilation (FMD) before and after treatment. We also determined the number of circulating endothelial progenitor cells (EPCs), which were defined by CD45(low)/CD34(+)/VEGFR2(+) and quantified by flow cytometry, because these cells may offer a new biomarker for circulatory diseases. Oxidative stress was evaluated in terms of the serum levels of malondialdehyde, superoxide dismutase and nitric oxide. FMD, circulating EPC count and superoxide dismutase activity were significantly lower in the diabetic group than in the control group at baseline (P<0.05), and improved significantly following gliclazide treatment (P<0.05). Malondialdehyde and nitric oxide levels were higher in the diabetic group than in the control group at baseline (P<0.05), and decreased following gliclazide treatment. These results suggest that gliclazide could improve endothelial function in diabetes, which may be related to its antioxidant properties.

Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase.

AIM: To investigate whether resveratrol (RSV) can improve non-alcoholic fatty liver disease (NAFLD) and to find the possible mechanism. METHODS: Rats fed a high-fat diet were treated with RSV. The liver histology was observed. Hyperinsulinemic euglycemic clamp was performed to assess insulin sensitivity. Fat accumulation was induced in HepG2 cells, and the cells were treated with RSV. AMP-activated protein kinase (AMPK) phosphorylation levels were determined both in the animal study and cell study. RESULTS: Rats fed a high-fat diet developed abdominal obesity, NAFLD, and insulin resistance (IR), which were markedly improved by 10 weeks of RSV administration. RSV treatment prevented triacylglycerol (TG) accumulation in HepG2 cells that were incubated with high concentration of glucose and insulin. Both in vivo and in vitro studies showed that RSV treatment could promote the phosphorylation of AMPK, which in this study, suppressed 2 lipogenesis gene expressions, contributing to the improvement of NAFLD and IR. CONCLUSION: The results indicated that by reducing TG accumulation and improving IR, RSV could protect the liver from NAFLD. The activation of AMPK was involved in the mechanism. RSV has the therapeutic potential for preventing or treating NAFLD and IR-related metabolic disorders.