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The evidence is increasing that prenatal air pollutant exposure contributes to elevated oxidative stress in children, but the underlying mechanism is unclear. A pilot study was conducted in China to explore the associations between prenatal ambient air pollution exposure and superoxide dismutase 2 (SOD2) promoter methylation in maternal and cord blood. After detection and analyses, SOD2 promoter methylation levels in umbilical cord blood were elevated as maternal SOD2 promoter methylation levels increased. In addition, the SOD2 promoter methylation levels in umbilical cord blood were positively associated with the particulate matter 10 (PM10) exposure concentrations during the entire pregnancy and the second trimester. In maternal peripheral blood, the SOD2 promoter methylation levels were positively associated with the exposure concentrations of PM10 (during the entire pregnancy and the second trimester) and nitrogen dioxide (NO2) (during the first trimester of pregnancy), whereas the levels were negatively associated with the exposure concentrations of NO2 during the third trimester of pregnancy. Additionally, interaction analyses revealed that the maternal SOD2 promoter methylation level and sulfur dioxide (SO2) exposure (during the entire pregnancy and the third trimester), as well as NO2 exposure (during the third trimester of pregnancy), had an interaction effect on the SOD2 promoter methylation level in umbilical cord blood. Furthermore, mediation analysis revealed that the associations between SOD2 promoter methylation in umbilical cord blood and PM10 exposure during the entire pregnancy and the second trimester were partly mediated by maternal SOD2 promoter methylation. In conclusion, prenatal exposure to air pollutants was significantly associated with SOD2 promoter methylation levels in umbilical cord blood, and this association may be affected by SOD2 promoter methylation levels in maternal peripheral blood. These associations may be one of the mechanisms by which prenatal air pollutant exposure leads to oxidative stress in newborns.

To evaluate the effects of CREB1 gene polymorphisms and long-term exposure to fluoride on thyroid function of children.A total of 424 children (including 226 boys and 198 girls) aged 7-12 years old were enrolled in Kaifeng, China by cross-sectional study in 2017. The concentrations of urinary fluoride (UF) and creatinine (UCr) were measured using fluoride ion-selective electrode assay and creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted UF (CUF) was calculated. Children were divided into high fluoride exposure group (HFG, CUF1.41 mg/L) and low fluoride exposure group (LFG, CUF ≤1.41 mg/L) according to the median concentration of CUF (1.41 mg/L). The serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyronine (TT4) levels were detected by the radiation immunoassay. The B-mode ultrasound was performed to test the thyroid volume (Tvol). Genotyping of CREB1 gene was conducted by a custom-by-design 48-plex SNPscan™ Kit. Associations between CUF concentration, CREB1 single nucleotide polymorphisms (SNPs) and thyroid function were assessed by multiple linear regression models.Negative and positive associations between serum TT4 level (β = -0.721, 95%CI: -1.209, -0.234) and Tvol (β = 0.031, 95%CI: 0.011, 0.050) and CUF concentration were observed respectively. Children carrying CREB1 rs11904814 TG and rs2254137 AC genotypes had lower TT3 levels (P 0.05). Children in HFG carrying rs11904814 TT, rs2253206 GG genotypes and rs6740584 C allele easily manifested lower serum TT4 levels (P 0.05). Moreover, interactions between excessive fluoride exposure and CREB1 SNPs on Tvol were observed, and the interaction among different loci of CREB1 gene could modify serum TT3 level (P 0.05, respectively).Fluoride could alter children's serum TT4 levels and Tvol. Interactions between fluoride exposure and CREB1 polymorphisms may modify thyroid volume of children.

The health risks to populations induced by lead (Pb) and high-fat diets (HFD) have become a global public health problem. Pb and HFD often co-exist and are co-occurring risk factors for cognitive impairment. This study investigates effect of combined Pb and HFD on cognitive function, and explores the underlying mechanisms in terms of regulatory components of synaptic plasticity and insulin signaling pathway. We showed that the co-exposure of Pb and HFD further increased blood Pb levels, caused body weight loss and dyslipidemia. The results from Morris water maze (MWM) test and Nissl staining disclosed that Pb and HFD each contributed to cognitive deficits and neuronal damage and combined exposure enhanced this toxic injury. Pb and HFD decreased the levels of synapsin-1, GAP-43 and PSD-95 protein related to synaptic properties and SIRT1, NMDARs, phosphorylated CREB and BDNF related to synaptic plasticity regulatory, and these decreases was greater when combined exposure. Additionally, we revealed that Pb and HFD promoted IRS-1 phosphorylation and subsequently reduced downstream PI3K-Akt kinases phosphorylation in hippocampus and cortex of rats, and this process was aggravated when co-exposure. Collectively, our data suggested that combined exposure of Pb and HFD enhanced cognitive deficits, pointing to additive effects in rats than the individual stress effects related to multiple signaling pathways with CREB-BDNF signaling as the hub. This study emphasizes the need to evaluate the effects of mixed exposures on brain function in realistic environment and to better inform prevention of neurological disorders via modulating central pathway, such as CREB/BDNF signaling.

Bioaerosols containing pathogens released from wastewater treatment plants (WWTP) may pose potential health risks to workers on-site and residents downwind. In this study, sampling points were set up in the wastewater treatment facility to investigate the generation pattern of bioaerosols in the aeration tank section. High-throughput sequencing was utilized to assay the intestinal bacteria population, while the health risks associated with airborne bacteria were estimated based on average daily dose rates. The contribution of wastewater to bioaerosols was evaluated using the traceability analysis. As the rotational speed increased from 200 rpm to 800 rpm, the concentration of culturable bacteria increased from 397 CFU/m

Prenatal exposure to air pollutants is believed to be associated with adverse birth outcomes. However, the potential mechanisms, especially the epigenetic modified effects, still remain unclear. This study was designed to explore the association of air pollution, H19/DMR methylation levels, and birth weight and length. A total of 527 mother-infant pairs were recruited from Houzhai Center Hospital, Zhengzhou. Air pollution data during the study period was collected. The methylation at H19 promoter region and H19 DMR in maternal and cord bloods were determined using real-time PCR analysis. Ridge regression was used to analyze the association of air pollutants exposure during gestation with H19/DMR methylation and birth weight and length respectively. Results showed that prenatal exposure to NO2 was associated with higher H19 methylation in cord blood. Whereas SO2 and PM10 exposure were associated with lower H19 and H19 DMR methylation respectively. After stratification by pregnancy trimesters, the association of H19 methylation in cord blood with PM10 exposure also was found. Furthermore, prenatal exposures to air pollutants also were associated with birth weight and length. Specifically, with the increase of maternal SO2 exposure during the entire pregnancy, birth weight and length significantly decreased. While birth weight and birth length were significantly increased with NO2 exposure. The stratified analysis also found the associations between PM10 exposure and birth sizes in different trimesters. In conclusion, the gene methylation level in cord blood might be associated with prenatal environmental exposures. Birth weight and length were associated with both prenatal environmental exposures and genetic factors.

Background A low serum vitamin D concentration is associated with an increased risk of type 2 diabetes mellitus (T2DM). Recently, several single nucleotid polymorphisms (SNPs) have been identified which influence vitamin D levels. If a causal relationship exists between vitamin D concentrations and T2DM, one would expect a similar association between the newly identified SNPs and T2DM risk. Therefore, this study investigated the association between four SNPs of cytochrome P450 family 2, subfamily R, peptide 1 (CYP2R1) gene, serum 25(OH)D3 levels and T2DM. Methods Three hundred and ninety-seven patients with confirmed T2DM, as well as 397 age- and gender-matched controls were enrolled in this case-control study. Genotyping was performed by TaqMan probe assays. Kruskal-Wallis one-way analysis and muitiple logistic regression analysis were performed to identify the possible risk genotype for vitamin D levels and T2DM, respectively. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-environment interactions. Results The serum 25(OH)D3 levels were significant lower in the T2DM group. Significant differences were observed between patients and controls in terms of the genotype distributions of rs1993116 (P = 0.048) and rs10766197 (P = 0.024). Similarly, rs1993116 and rs10766197 polymorphisms were found to be significantly associated with T2DM risk. AG + GG genotype carriers of the rs1993116 and rs10766197 polymorphisms could have an increased risk of developing T2DM compared with AA carriers, the OR and 95% CI were 1.64 (1.09–2.46) and 1.76 (1.18–2.65), respectively. However, none of the tested SNPs were independently associated with serum 25(OH)D3 levels (P > 0.059). Gene-gene and gene-environment interaction analyses indicated that rs12794714-rs10766197 and rs12794714-vitamin D deficiency (VDD) models successfully predicted T2DM risk (P Conclusions Rs1993116 and rs10766197 polymorphisms of CYP2R1 gene may be novel genetic markers for T2DM in China. Given the lack of association between SNPs and serum 25(OH)D3 levels, well-designed future studies should be conducted with larger sample sizes in rural areas of China.

Aims Association between T2DM and vitamin D was found in many epidemiologic reports. And 24-hydroxylase encoded by CYP24A1 is the very enzyme that degrades the active vitamin D metabolite. We aimed to investigate the association between rs4809957 in CYP24A1 and T2DM, as well as vitamin D level. Methods A total of 419 pedigrees containing 1556 participants were included. T2DM diagnosis, 25(OH)D measurement and genotyping of rs4809957 were conducted for all the individual. Then association between rs4809957 and T2DM, as well as 25(OH)D level, was investigated by family-based association test (FBAT) and 1:1 matched case-control study. Results The FBAT results revealed that there was transmission disequilibrium for allele G in T2DM families by both additive model ( Z = 2.183, P = 0.029049) and recessive model ( Z = 2.236, P = 0.025347). Allele G was also associated with 25(OH)D level in both additive model ( Z = 2.549, P = 0.010811) and dominant model ( Z = 2.012, P = 0.044187). On the other hand, results of case-control study suggested that vitamin D deficiency was a risk factor for T2DM ( OR 1.987; 95% CI 1.331–2.964; P = 0.001). Further stratified analysis revealed that vitamin D deficiency increased T2DM risk in women ( OR 2.347; 95% CI 1.373–4.012; P = 0.002), instead of men ( OR 1.600; 95% CI 0.874–2.931; P = 0.127). In addition, T2DM patients with GG and AG genotypes were more susceptible to vitamin D deficiency than the control ( P = 0.006 and P = 0.038, respectively). Conclusion There was transmission disequilibrium for allele G of rs4809957 in T2DM families, which was linked to vitamin D deficiency.

Due to the poor living and healthcare conditions, preterm birth (PTB) in rural population is a pressing health issue. However, PTB studies in rural population are rare. To explore the effects of air pollutants on PTB in rural population, we collected 697,316 medical records during 2014–2016 based on the National Free Preconception Health Examination Project. Logistic regression models were used to estimate the association between air pollutants and PTB and the modifying effects of demographic characteristics. Relative contribution and principal component analysis-generalized linear model (PCA-GLM) analysis were used to explore the most significant air pollutant and gestational period. Our results demonstrated that PTB risk is positively associated with exposure to air pollutants including PM10, PM2.5, SO2, NO2, and CO, while negatively associated with O3 exposure (P

To identify the role of the Hippo signaling pathway in the extracellular matrix degradation of chondrocytes induced by fluoride exposure. Environmental response genes (ERGs) of bone injury induced by fluoride exposure were obtained from the Comparative Toxicogenomics Database, and annotated by STRING for KEGG pathway enrichment analysis. The CCK-8 kit was used to measure the proliferation of ATDC5 cells. The malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-PX) levels in ATDC5 cells were measured using oxidative stress detection kit. Western blot analysis was used to measure the p-MST1/2, p-LATS1/2, and p-YAP/YAP1 expression levels in the Hippo pathway and the COL2A1, ACAN and MMP13 expression levels in the cartilage matrix. Localizations of YAP1 and COL2A1 proteins in chondrocytes were performed using cell immunofluorescence. Continuous data from the multiple groups were compared using one-way analysis of variance, and then the differences between groups were tested with Dunnett's t-test, with the test level α = 0.05. The 145 ERGs of bone injury induced by fluoride exposure were identified, and KEGG enrichment analysis revealed Hippo signaling pathways significantly related to bone injury. A CCK-8 assay revealed that the viability of the ATDC5 cells was significantly decreased with increased fluorine concentration. The MDA content in 20 mg/L sodium fluoride (NaF) exposure group was significantly higher than that in the control group, the T-SOD, T-AOC and GSH-PX activities in 15 and 20 mg/L NaF exposure groups were significantly lower than those in the control group (P

This study examined the neuroprotective properties of resveratrol (Res) and its target sirtuin1 (SIRT1) against lead (Pb)-mediated toxicity and discovered that both resveratrol treatment and SIRT1 overexpression restored blocked autophagic flux as well as reduced β-amyloid (Aβ) contents. Four-week-old male C57BL/6 mice were employed to consumed 0.2% Pb(Ac)2 solution or deionized water for 3 months followed by 12 months of Res (50 mg/kg BW) or vehicle gavage. In in vitro study, SH-SY5Y cells were pretreated with the SIRT1 activator SRT1720 (2 μM) or the inhibitor EX527 (2 μM) for 2 h, then 25 μM of Pb(Ac)2 was added and incubated for 48 h. Western blotting, RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and Lyso-Tracker Red Staining were next used to estimate the potential alterations of the autophagic pathway as well as BACE1-mediated amyloid processing in response to Pb exposure, respectively. Our data revealed that Res treatment or SIRT1 activation resisted the induction of autophagy by Pb exposure through inhibition of LC3 and Beclin-1 expression and promoted the degradation of Aβ and Tau phosphorylation. Besides, the SIRT1 activator (SRT1720) downregulated the expression of BACE1, the rate-limiting enzyme for Aβ production, by inhibiting the activation of nuclear factor-κB (NF-κB) in Pb-treated SH-SY5Y cells, which resulted in reduced Aβ production. Collectively, we verified the role of Res-SIRT1-autophagy as well as the SIRT1-NF-κB-BACE1 pathway in Pb-induced neuronal cell injury by in vivo or in vitro models. Our findings further elucidate the important role of SIRT1 and Res in counteracting Pb neurotoxicity, which may provide new interventions and targets for the subsequent treatment of neurodegenerative diseases.

Lead (Pb) exposure damages synaptic structural plasticity that results in cognitive impairment. Resveratrol, a natural polyphenolic compound, is one of the most potent agonists of silencing information regulator 1 (SIRT1) discovered to date. However, the effects of SIRT1 on synaptic functional plasticity in early life Pb exposure are not well studied. Herein, the purpose of this study is to investigate the expression of synaptic markers and SIRT1 in rats exposed to Pb and to evaluate the regulatory effect of resveratrol during this process. The Pb exposed male SD pups were treated with resveratrol (50 mg/kg/d) or EDTA (150 mg/kg/d) followed by hippocampal and blood sampling for analysis at postnatal day 21 (PND21). In the Morrris water maze test, resveratrol treatement protected the rats against Pb-induced impairment of learning and memory (P0.05). Resveratrol also enhanced the expression of brain-derived neurotrophic factor (BDNF, P 0.001 vs 0.2% Pb group), and reversed the effects of Pb exposure on SIRT1(P 0.001 vs 0.2% Pb group). The DG, CA1 and CA3 regions of the hippocampus showed a considerable increase in the expression of pre- and postsynaptic proteins (P 0.001 vs 0.2% Pb group). In conclusion, our study demonstrated that resveratrol, through the activation of SIRT1, played a protective role against Pb-induced defects in synaptic plasticity, and suggested a new potential adjuvant treatment for Pb poisoning.

Antibiotic resistance (AR) has become a potential concern to public health. It is mainly associated with the overuse and misuse of antibiotics in the environment. Several factors influence the development and dissemination of antibiotic resistance genes (ARGs); however, the relative contribution of these factors has been scarcely characterized. To study the impact of each factor, we examined the effects of five antibiotics, eight heavy metals, five physicochemical properties, and bacterial community on the abundance of 310 ARGs in agricultural soils collected near a smelter. Tetracycline was found in the highest levels of all the samples compared to the other four antibiotics, with the most severe contamination (1738.534 μg/kg) occurring in the sample farthest from the plant (2556 m), whereas the highest copy number of ARGs (sulfonamide resistance genes, 3.63 × 10−1 copies/16SrRNA) and the worst heavy metal pollution (Cd, 18.900 mg/kg; Pb, 1938.000 mg/kg) were detected in the sample closet to the plant (741 m). Pearson and Spearman rank correlation analysis showed that the abundance of 84 ARGs was impacted by these four factors in the soil. The bacterial phyla contributed to 79.76% of ARGs variation, whereas antibiotics, heavy metals, and physicochemical properties contributed 4.76%, 1.19%, and 3.57%, respectively. Bacterial community was the main factor influencing the distribution of ARGs. Antibiotics and heavy metals may affect the distribution of ARGs not only by themselves but also by influencing the structure of bacterial community in the soil. The research provides insights into the different contributions of factors to AR control.

The development and exacerbation of asthma are mainly attributed to inflammatory reactions caused by allergens. However, less is known about the development of asthma caused by microbial disorders in the oropharynx and induced by environmental factors. Here, the metagenome of the oropharyngeal microbiome of adults with asthma was analysed to identify their association with air pollutants. Oropharyngeal swabs from patients with asthma were collected in two winters (W1 and W2) with different environmental factor exposures. The bacterial composition and community structure of the oropharynx were analysed through high-throughput sequencing. After analysis, the α-diversity and β-diversity exhibited significant differences between the two groups. LEfSe analysis detected 8 significantly different phyla and 11 significantly different genera between the W1 and W2 groups. Multiple linear regression analyses found that the asthma status might contribute to the alteration of microbial composition. Redundancy analysis showed that NO2 was the only environmental factor that significantly affected the microbial community structure of the oropharynx. The different genera associated with NO2 were Rothia, Actinomyces, Fusobacterium and Leptotrichia. The altered taxa related to PM2.5 were Cupriavidus and Acinetobacter. Actinobacillus and Prevotella showed a highly positive correlation with O3. Moreover, network analysis was carried out to explore the co-occurrence relationships of the main genera, and PICRUSt was conducted to predict bacterial functions. This study showed that environmental factors might cause alteration in the oropharyngeal flora, which might be a potential risk factor of asthma.

Meteorological conditions during pregnancy can affect birth outcome, which has been linked to the H19/H19-differentially methylated region (DMR). However, the detailed mechanisms underlying this association are unclear. This was investigated in the present study to provide epidemiological evidence for elucidating the pathogenesis of adverse birth outcomes. A total of 550 mother-newborn pairs were recruited in Zhengzhou, China from January 2010 to January 2012. Meteorological data including temperature (T), relative humidity (RH), and sunshine duration (SSD) were obtained from the China Meteorological Data Sharing Service System. Bisulfite sequencing PCR was performed to determine the methylation levels of H19/H19-DMR using genomic DNA extracted from maternal peripheral and umbilical cord blood. The results showed that H19-DMR methylation status in cord blood was positively associated with that in maternal blood. Neonatal H19-DMR methylation was negatively associated with T and RH during the first trimester and positively associated with these variables during the third trimester. There was a positive correlation between neonatal H19-DMR methylation and SSD during the second trimester and a negative correlation during the third trimester. Similar associations were observed between maternal H19-DMR methylation and prenatal meteorological conditions. We also observed significant interaction effects of maternal H19/H19-DMR methylation and most prenatal meteorological factors on neonatal methylation, and found that changes in the methylation status of maternal H19-DMR were responsible for the effects of prenatal meteorological conditions on neonatal methylation. In summary, neonatal H19-DMR methylation was significantly associated with prenatal meteorological conditions, which was modified and mediated by maternal H19-DMR methylation changes. These findings provide insights into the relationship between meteorological factors during pregnancy and adverse birth outcomes or disease susceptibility in offspring, and can serve as a reference for environmental policy-making.

Excessive fluoride exposure is known to contribute to reproductive system dysfunction, ultimately leading to pathological damage and apoptosis in cells. Although both oxidative and endoplasmic reticulum (ER) stresses have been implicated in fluorosis, the signaling pathways and their roles in sodium fluoride (NaF)-induced apoptosis of Sertoli cells have been sparsely described. In this study, oxidative damage, ER stress, and apoptosis were analyzed after Sertoli cells were treated with varying doses of NaF for 24hr. Moreover, the antioxidant N-acetylcysteine (NAC) and pro-apoptotic transcription factor CHOP knockdown were used to clarify the precise interplay between reactive oxygen species (ROS), ER stress and their roles in NaF-induced apoptosis in Sertoli cells. The present study indicated that NaF significantly decreased cell viability and induced apoptosis in Sertoli cells. In addition, NaF exposure facilitated the accumulation of ROS and increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in Sertoli cells. Treatment with NAC caused remarkable recovery from these NaF-induced responses. Meanwhile, excessive NaF triggered ER stress as evidenced by up-regulated glucose-regulated protein 78 kDa (GRP78), PKR-like ER kinase (PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) and CCAAT/enhancer-binding protein-homologous protein (CHOP), without affecting total eukaryotic translation initiation factor 2α (eIF2α). NAC effectively blocked the activation of ER stress, suggesting that NaF-induced ROS is an early event that triggers ER stress. Taken together, the results demonstrate that the ROS-mediated ER stress pathway is the crucial mechanistic event involved in NaF-induced apoptosis of Sertoli cells.

Excessive fluoride intake has been shown to affect dentin and cementum mineralization throughout life. Some studies indicated that a HindIII polymorphism, of osteocalcin (OC) gene, was associated with bone metabolism-related diseases. Therefore, it is possible that the variation in OC genotypes will be associated with dental fluorosis (DF) status and/or serum caciotropic hormone level. A case-control study was conducted among children aged 8-12 years in Henan Province, PR China to investigate the association between dental fluorosis, serum calciotropic hormone level, and polymorphisms in the OC gene. HindIII polymorphism in OC gene was genotyped using the PCR-RFLP procedure. OC and calcitonin (CT) level in serum was detected using radioimmunoassay. No significant difference was observed for OC HindIII genotypes among the cases with dental fluorosis, the controls from endemic fluorosis area (EFA) and the controls from non-endemic fluorosis area (NEFA). A significant negative correlation was observed between serum calcium and OC level. No significant relationship was found between OC HindIII polymorphisms and the level of OC and CT. In conclusion, OC HindIII polymorphisms may not be a useful genetic marker for differential risk of dental fluorosis among children in PR China.