Association between perfluoroalkyl and polyfluoroalkyl substances exposure and fetal overgrowth: A prospective birth cohort study conducted in China.

BACKGROUND: Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been associated with gestational diabetes mellitus, obesity or overweight in childhood, but data on fetal overgrowth outcomes including macrosomia and large for gestational age (LGA) and among gestational age diverse infants remain scarce. OBJECTIVE: To evaluate the association between maternal PFASs exposure and macrosomia and LGA, with exploration of the interaction between PFASs exposure and gestational age on fetal overgrowth. METHODS: A total of 1441 mother-infants pairs from Guangxi Zhuang Birth Cohort of China were analyzed. Nine PFASs were measured in maternal serum using ultra-high liquid performance chromatographytandem mass spectrometry. Multivaraible logistical regression and generalized additive models were performed for individual PFAS exposures, piecewise regression analysis was used to estimate the breakpoint values for the non-linear dose-response relationships. Bayesian Kernel Machine Regression was performed for PFASs mixture. RESULTS: In single pollutant models, maternal PFDA and PFOA exposure showed U-shaped relationship with macrosomia and LGA. When PFDA concentration exceeded 0.32 ng/mL was significantly positively associated with risks of LGA and macrosomia (OR=4.66, 95%CI: 1.26, 17.17; OR=14.43, 95%CI: 2.64, 79.02; respectively), while a negatively association was observed when level below 0.32 ng/mL. When PFOA concentration exceeded 1.20 ng/mL was significantly associated with increased risk of macrosomia (OR=7.75, 95%CI: 1.36, 44.06). In mixed exposure models, mixture of PFASs was positively associated with macrosomia, as well as associated with LGA when all the PFASs were at their 30th percentile or below. The maximum risk of LGA was reached when concentrations of PFUnA, PFDA, or PFBS were at the highest concentrations and the gestational age at the minimum of this study. CONCLUSIONS: Maternal exposure to PFDA, PFOA and PFASs mixture were non-monotonically associated with macrosomia and LGA, the direction of the associations depends on the level of exposure.

The association between iron status and thyroid hormone levels during pregnancy.

BACKGROUND: Iron deficiency may be a risk factor for thyroid disorder; however, the relationship between iron deficiency and thyroid disorder as well as mechanism involved remain unclear. METHODS: A hospital-based cross-sectional study was conducted to analyze the correlation between iron status and thyroid hormone levels in pregnant women. A total of 2218 pregnant women were recruited, and iron status and thyroid hormones were measured. Canonical correlation, Lasso regression, and Receiver operator characteristic (ROC) curve analysis were used to determine the association and related factors. RESULTS: There were 219 cases with iron deficiency anemia (IDA), 168 cases with iron deficiency (ID), and 1831 subjects with normal iron status. Compared with normal group, free triiodothyronine (FT3) and free thyroxine (FT4) in ID group and IDA group had a significant decreasing trend (P < 0.05), with the lowest levels in IDA group. Thyroid stimulating hormone (TSH) was significantly increased in ID group and IDA group (P < 0.05). Moreover, the proportion of hypothyroidism in both ID group and IDA group was higher than the normal group, meanwhile the proportion of hyperthyroidism was lower in both groups (P < 0.05). Serum ferritin (SF) and hemoglobin (Hb) were positively correlated with FT3 and FT4 but negatively correlated with TSH. Correlation analysis indicated that iron status was associated with thyroid hormone levels (P < 0.05). Lasso regression analysis showed that SF, Hb and other variables could be included in the prediction model of FT4. The variables selected by Lasso model were used for ROC curve analysis, and the prediction accuracy was acceptable (AUC=0.778, P < 0.05). CONCLUSION: Our study indicated that there is an association between iron status and thyroid hormone levels in pregnant women, and the level of FT4 may change with iron status. Our findings provide new ideas for regulating the thyroid hormone levels to prevent thyroid dysfunction during pregnancy.

Effects of household environmental exposure and ventilation in association with adverse birth outcomes: A prospective cohort study in rural China.

Prenatal exposure to outdoor air pollution have been associated with birth outcomes. However, there is limited evidence on the adverse effects of household indoor air pollution worldwide, much less in rural areas of China. This study aimed to explore the associations of household environmental factors (primary cooking fuel, housing renovation, and home ventilation) with four adverse birth outcomes (preterm birth (PTB), small for gestational age (SGA), low birth weight (LBW), and term low birth weight (T-LBW)). We conducted a cohort study involving 10,324 pregnancies in women who delivered a live-born infant from 2015 to 2018 in Guangxi, China. Risk ratios and 95% confidence intervals (CI) were estimated with control for reproductive history, lifestyle, home environmental confounders, and other potential confounders. A total of 5.4% of the infants were PTB, 10.7% were SGA, 5.5% had LBW, and 3.0% had T-LBW. Household-use induction cookers as the primary cooking fuel during pregnancy was associated with SGA (RR = 1.31, 95% CI: 1.07-1.60), LBW (1.41, 1.09-1.82), and T-LBW(1.62, 1.16-2.26), as compared with household-use gas as the primary cooking fuel. Housing renovation within one year before pregnancy was associated with PTB (1.45, 1.06-1.98) and LBW (1.56, 1.17-2.09), while housing renovation during pregnancy was associated with a higher risk of SGA only in moderate home ventilation conditions (3.74, 1.69-8.28). Our findings suggested that household-use induction cookers as the primary cooking fuel increased the risks of SGA, LBW, and T-LBW. In addition, housing renovation within one year before pregnancy increased the risks of PTB and LBW. Proper home ventilation may reduce the effect on the association between housing renovation during pregnancy and SGA.

The toxicity mechanism of different sized iron nanoparticles on human breast cancer (MCF7) cells.

The toxicity mechanism of superparamagnetic iron oxide nanoparticles (SPIONs) were examined multidimensionally to reduce the toxicity risks. A higher dosage and more suitable size of SPIONs enhanced the uptake amount into MCF7 cells, leading to a higher specific uptake rate of SPIONs with the formation of more reactive oxygen species (ROS). ROS was an intrinsic factor of cell death. Interestingly, the smaller SPIONs (S1) liked to produce more ROS in mitochondria to damage mitochondria, while the larger SPIONs (S2 and S3) promoted ROS yield in plasma to destroy cytomembrane. Furthermore, ROS synthesis pathways were the partial of cell death pathways, and ferroptosis pathway was the main contributor to mitochondrial and cytomembrane damage. Meanwhile, ROS amount was well coincided to gene expression level of these cell death pathways, which inferred RNA-seq might be a new method to evaluate the oxidative stress and potential toxicity of nanomaterials.

Mechanism and intervention measures of iron side effects on the intestine.

Excess oral iron in the intestinal tract usually produces reactive oxygen species via Fenton and Haber-Weiss reaction, so oxidative stress is triggered. Lipid peroxidation procedurally appears, ferroptosis, apoptosis and necrosis are often induced, subsequently, mitochondrial damage, endoplasmic reticulum dysfunction and even cell death occur. As a result, the intestinal epithelial cells are destroyed, leading to the incompleteness of intestinal mechanical barrier. Simultaneously, iron supplement can change the compositions and metabolic processes of intestinal microbes, and the intestinal inflammatory may be worsened. In principle, the easier dissociation of Fe2+ from oral iron supplements is, the more serious intestinal inflammation will occur. Fortunately, some interventions have been developed to alleviate these side effects. For instance, some antioxidants e.g. VE and ferulic acid have been used to prevent the formation of free radicals or to neutralize the formed free radicals. Furthermore, some new iron supplements with the ability of slow-releasing Fe2+, e.g. ferrous citrate liposome and EDTA iron sodium, have been successfully prepared. In order to recover the intestinal micro-ecological balance, probiotics and prebiotics, bacterial consortium transplantation, and fecal microbiota transplantation have been developed. This study is meaningful for us to develop safer oral iron supplements and to maintain intestinal micro-ecological health.

LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF-1α/VEGF signaling in ischemic stroke.

Studies have shown that long noncoding ribonucleic acids (lncRNAs) play critical roles in multiple biologic processes. However, the Small Nucleolar RNA Host Gene 1 (SNHG1) function and underlying molecular mechanisms in ischemic stroke have not yet been reported. In the present study, we found that SNHG1 expression was remarkably increased both in isolated cerebral micro-vessels of a middle cerebral artery occlusion (MCAO) mice model, and in oxygen-glucose deprivation (OGD)-cultured mice brain micro-vascular endothelial cells (BMECs), meanwhile, the SNHG1 level was negatively correlated with miR-18a in MCAO mice. Mechanistically, SNHG1 inhibition presents larger brain infarct size and worsens neurological scores in MCAO mice. Consistent with the in vivo findings, SNHG1 inhibition also significantly increased caspase-3 activity and cell apoptosis in OGD-cultured BMECs. Furthermore, we found that SNHG1 functions as a competing endogenous RNA (ceRNA) for miR-18a, thereby regulating the de-repression of its endogenous target HIF-1α and promoting BMEC survival through HIF-1α/VEGF signaling. This study found a neuroprotective effect of SNHG1 mediated by HIF-1α/VEGF signaling through acting as a ceRNA for miR-18a. These findings reveal a novel function of SNHG1, which contributes to an extensive understanding of ischemic stroke and provides novel therapeutic options for this disease.

MicroRNA-433 Inhibits the Proliferation and Migration of HUVECs and Neurons by Targeting Hypoxia-Inducible Factor 1 Alpha.

Emerging evidence has demonstrated an important role of microRNAs (miRNAs) in the pathogenesis of cerebral infarction. In the present study, a down-regulation of microRNA-433 (miR-433) is identified in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs) as well as in rat neurons, and is found to be negatively regulated cell proliferation and migration. Moreover, the expression of miR-433 is inversely correlated with the expression of hypoxia-inducible factor 1 alpha (HIF-1α), which has been shown to play critical role in responding to hypoxia conditions. Overexpression or knockdown of miR-433 responsively alters both mRNA and protein levels of HIF-1α and its downstream genes, vascular endothelial growth factor, Glut-1, and Angpt2. In a luciferase reporter system, miR-433 down-regulates the luciferase activity of HIF-1α 3'-UTR, and these effects are abolished by a mutation in the putative miR-433-binding site. Further investigation confirms that knockdown of HIF-1α blocked the stimulatory effect of anti-miR-433, while overexpression of HIF-1α reversed the inhibitory effects of pre-miR-433 on proliferation and migration of HUVEC and neurons. Taken together, our findings indicate that miR-433 plays an important role in response to hypoxia, inhibiting HUVEC and neuron proliferation and migration by down-regulating HIF-1α.

Degradation of methylene blue with H2O2 activated by peroxidase-like Fe3O4 magnetic nanoparticles.

Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) were successfully prepared through an advanced reverse co-precipitation method under the assistance of ultrasound irradiation. The structure and size distribution were characterized by X-ray powder diffraction (XRD), laser particle size analyzer (LPSA), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. The magnetic properties of Fe3O4 nanoparticles were measured by the vibrating sample magnetometer (VSM). Such Fe3O4 MNPs were used as a peroxidase mimetic to remove the dye pollutant methylene blue (MB) in the presence of H2O2. Some important reaction parameters were optimized to improve the degradation of MB. It was observed that the degradation efficiency of 10 mg L(-1) MB was above 96% over 0.62 g L(-1) Fe3O4 MNPs within 0.30 mmol L(-1) H2O2 at pH 4.85 and temperature 25 degrees C in 15 min, being superior to the previous reports.