Role of ROS-mediated PERK/ATF4 signaling activation in extracorporeal tube formation injury of human umbilical vein endothelial cells induced by cooking oil fume PM2.5 exposure.

Cooking oil fume-derived PM2.5 (COF-PM2.5) is a major source of indoor air contamination in China, which has been demonstrated to be a hazard factor of cardiovascular and cerebrovascular diseases. This study aimed to investigate the role of ROS-mediated PERK/ATF4 signaling activation in COF-PM2.5-inhibited extracorporeal tube formation in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 100 µg/mL COF-PM2.5 at different times, with or without 100 nM PERK activity inhibitor GSK2606414 (GSK) or 200 µM antioxidant N-acetylcysteine (NAC) pretreatment. Our results showed that COF-PM2.5 exposure can inhibit extracorporeal tube formation and down-regulate VEGFR2 expression in HUVECs. Furthermore, our data indicated that COF-PM2.5 exposure can activate the PERK/ATF4 signaling in HUVECs. Mechanistically, pretreatment with GSK interdicted PERK/ATF4 signaling, thereby reversing COF-PM2.5-downregulated VEGFR2 protein expression in HUVECs. Furthermore, NAC reversed VEGFR2 expression downregulated induced by COF-PM2.5 by inhibiting the upregulation of intracellular ROS levels and PERK/ATF4 signaling in HUVECs. As above, COF-PM2.5 exposure could induce ROS release from HUVECs, which in turn activate the endoplasmic reticulum PERK/ATF4 signaling and inhibit tube formation of HUVECs.

Vitamin D3 protects intrauterine growth restriction induced by cooking oil fume derived fine particulate matters.

BACKGROUND: Cooking oil fume (COF) is an important source of indoor air pollution which severely affects human health, and sufficient vitamin D3 (VitD3) is necessary for maternal and child health. However, the effects of cooking oil fume-derived PM2.5 (COF-PM2.5) on birth outcomes and whether VitD3 could protect from adverse effects caused by COFs-PM2.5 are still unclear. METHODS: Twenty-four pregnant rats were divided into 4 groups and treated with various treatments: normal feeding, COFs-PM2.5 intratracheal instillation, VitD3 intragastric administration, and COFs-PM2.5 and VitD3 co-treatment, respectively. The fetal rats were obtained in pregnant 21 days and the development of them was recorded. Morphological changes in umbilical cord were measured with HE staining, and the oxidative stress and inflammatory levels were also investigated. Western blotting and RT-PCR was used to detect the expression of angiogenesis related factors. RESULTS: We successfully established an intrauterine growth restriction model in rats induced by COFs-PM2.5 where fetus weight significantly decreased after COFs-PM2.5 exposure. As for the umbilical cord vasculature, the wall thickened and the lumen narrowed down, and the contractility of the umbilical cord vasculature enhanced after COFs-PM2.5 exposure. COFs-PM2.5 exposure also increased the oxidative stress and inflammation level and activated the HIF-1α/eNOS/NO and VEGF/VEGFR2/eNOS signaling pathway. Interestingly, VitD3 intervention significantly increased the fetus weight and attenuated the injury of umbilical cord vascular, and partly or completely reversed the changes in the ROS/eNOS/ET-1 axis caused by COF-PM2.5. CONCLUSIONS: The findings of this study suggested that COF-PM2.5 exposure could contribute to intrauterine growth restriction through disturbing the ROS/eNOS/ET-1 axis, while VitD3 supplementation could be an effective prophylactic measurement.

Uterine decidual stromal cell-derived exosomes mediate the indirect effects of 1-nitropyrene on trophoblast biological behaviors.

1-nitropyrene (1-NP) is representative nitropolycyclic aromatic hydrocarbon pollutant widely present in exhaust particles of internal combustion engine, which is known for its carcinogenicity and mutagenicity. Previous studies have demonstrated that 1-NP has reproductive toxicity, but the specific mechanism is unknown. In this study, Human decidual stromal cells (HDSCs) were treated by 1-NP, exosomes were extracted from the conditioned medium of HDSCs, which were then used to treat human chorionic trophoblast cells (HTR8/SVneo) for 24 h. The findings showed that human decidual stromal cell-derived exosomes (HDSC-EXOs) can promote the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT; Vimentin and N-cadherin) of HTR8/SVneo by about 64%, 17%, 23%, 81% and 13%. The process of regulating the biological behaviors of embryonic trophoblast cells by maternal decidual stromal cells during pregnancy was simulated. Further investigations showed that HDSC-EXOs treatment activated the Wnt/ß-catenin signaling pathway in HTR8/SVneo. Co-treatment by dickkopf-1 (DKK-1) significantly suppressed the activation of Wnt/ß-catenin signaling pathway in HTR8/SVneo, and inhibited the proliferation, migration, invasion and EMT (N-cadherin and E-cadherin) of HTR8/SVneo by about 60%, 22%, 42%, 25%, 55% and 21%. These findings indicated that 1-NP exposure could induce the secretion of HDSC-EXOs from HDSCs, which in turn activate the Wnt/ß-catenin signaling pathway and enhance the proliferation, migration, invasion and EMT of HTR8/SVneo.

Maternal air pollution exposure increases the risk of preterm birth: Evidence from the meta-analysis of cohort studies.

Preterm birth (PTB), a major public health impact, has been shown to be associated with prenatal air pollution exposure, but the results are still inconsistent. This meta-analysis was performed to quantitatively evaluate the correlation between maternal air pollutant exposure and PTB, and provide evidence of higher grade to help improving the pregnancy outcomes. Databases including Web of Science and PubMed were searched to retrieve eligible studies published up to October 2020. The quality of the articles was assessed by the Newcastle-Ottawa Quality Score (NOS), after which the pooled estimate of the effect was calculated. The robustness of the joint estimates was confirmed by sensitivity analysis of excluded studies one by one, and the sources of heterogeneity were discussed by stratification analysis. Egger's and Begg's tests were performed to examine publication bias. Sixty studies that met the eligible criteria were finally included in this study. The findings showed combined relative risks of 1.032-1.070 for PTB, 0.859-1.081 for moderate PTB, 1.119-1.194 for very PTB and 1.128-1.259 for extremely PTB when mothers were exposed to PM2.5, PM10, NO2, O3, SO2, CO and NOx during pregnancy, while the sensitive windows varied for different air pollutants. Notably, PM2.5 exposure in only the 2nd trimester, NO2 exposure in only the 3rd trimester, and O3 exposure in all three trimesters were positively associated with PTB, while NO2 exposure in the 1st trimester was negatively associated with PTB. In addition, exposure of PM2.5 and PM10 in the 2nd trimester was positively associated with moderate PTB, and in the 1st and 2nd trimesters were positively associated with very PTB. These findings demonstrated that PM2.5, PM10, O3, NO2 were associated with PTB (including moderate PTB, very PTB, and/or extremely PTB), while NOx was not, and the relationship between CO and SO2 and PTB was not stable.

Association between preconceptional air pollution exposure and medical purposes for selective termination of pregnancy.

BACKGROUND: Exposure to air pollutants is associated with adverse pregnancy outcomes. But evidence on the effects of preconceptional air pollution exposure on the risk of termination of pregnancy (TOP) caused by pregnancy losses and congenital malformations is lacking. METHODS: The distributed lag nonlinear model (DLNM) was used to evaluate the impact of short-term air pollutants exposure on the risk of TOP. Stratified analyses by age (<35 years old, ≥ 35 years old) and season (warm season, cold season) were further conducted. Relative risk (RR) and 95 % confidential interval (95 % CI) were calculated for per interquartile range (IQR) increment in air pollutants during the study period. RESULTS: PM2.5, PM10, and O3 exposure were significantly associated with elevated risk of TOP. The risk of TOP was associated with PM2.5 exposure from lag11 to lag15 in the single-pollutant model, and the strongest association was observed at lag13 (RR = 1.021, 95%CI:1.002-1.040). PM10 exposure from lag10 to lag15 was associated with increased TOP risk, with the corresponding peak association being at lag13 (RR = 1.020, 95%CI: 1.004-1.037). For O3, the single-day lag association appeared to be statistically significant from lag26 to lag27, with the highest RR of TOP cases being at lag27 (RR = 1.044, 95%CI: 1.005-1.084). Similar results were observed for pregnancy losses (PL). However, no significantly association between air pollution exposure and the risk of congenital malformations (CM) was found in this study. Stratified analyses showed that pregnant women with more advanced ages were more susceptible to PM2.5, PM10, and O3 exposure. The effect of PM2.5 exposure was statistically significant in cold season subgroups. CONCLUSION: The findings suggest that exposure to PM2.5, PM10, and O3 before pregnancy are associated with the risk of TOP in Lu'an, China, reflecting the significance of preconceptional environmental exposure in the development of adverse pregnancy outcomes.

Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation.

BACKGROUND: This study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms. METHODS: Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1ß and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content. RESULTS: Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1ß, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-κB (NF-κB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-κB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression. CONCLUSION: This study demonstrated that the ASM/Cer/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-κB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.

The short-term effect of PM2.5/O3 on daily mortality from 2013 to 2018 in Hefei, China.

This research intends to explore the short-term impacts of PM2.5/O3 on daily death in Hefei from 2013 to 2018. Data on daily death of Hefei residents, meteorological factors, and air pollutants were collected from Jan 1, 2013, to Dec 31, 2018. The correlation between PM2.5/O3 and daily death in Hefei during the research period was studied by time series analysis. From 2013 to 2018, there were 61,683 non-accidental deaths, including 27,431 cardiovascular deaths, 5587 respiratory deaths, 20,921 malignant tumor deaths, and 1674 diabetes deaths, in Hefei. Annual mean concentrations of PM2.5, PM10, NO2, SO2, CO, and O3 in Hefei were 66.18, 92.37, 39.75, 15.39, 930, and 79.08 µg m-3, respectively. An increase of 10 µg m-3 in PM2.5 was related with 0.53% (95% CI 0.31-0.75%), 0.93% (95% CI 0.60-1.26%), 0.90% and (95% CI 0.23-1.57%) increase in non-accidental, cardiovascular and respiratory diseases mortality, respectively. The association between ozone and mortality was not significant. In cold seasons, PM2.5 had a stronger effect on the deaths resulting from non-accidental, cardiovascular, and respiratory diseases. The effect of O3 on deaths was not significantly different between the cold season and the warm season. Women and the elders (over 65 years) were at high risk of being affected by PM2.5/O3. Short-term exposure to PM2.5 was positively correlated with increased deaths due to non-accidental, cardiovascular and respiratory diseases in Hefei. Females and elders were more vulnerable to PM2.5/O3 exposure. No significant associations were observed between ozone and deaths from non-accidental, cardiovascular, respiratory, malignant tumors, and diabetes diseases.

Acute associations between air pollution on premature rupture of membranes in Hefei, China.

Numerous studies had focused on the association between air pollution and health outcomes in recent years. However, little evidence is available on associations between air pollutants and premature rupture of membranes (PROM). Therefore, we performed time-series analysis to evaluate the association between PROM and air pollution. The daily average concentrations of PM2.5, SO2 and NO2 were 54.58 µg/m3, 13.06 µg/m3 and 46.09 µg/m3, respectively, and daily maximum 8-h average O3 concentration was 95.67 µg/m3. The strongest effects of SO2, NO2 and O3 were found in lag4, lag06 and lag09, and an increase of 10 µg/m3 in SO2, NO2 and O3 was corresponding to increase in incidence of PROM of 8.74% (95% CI 2.12-15.79%), 3.09% (95% CI 0.64-5.59%) and 1.68% (95% CI 0.28-3.09%), respectively. There were no significant effects of PM2.5 on PROM. Season-specific analyses found that the effects of PM2.5, SO2 and O3 on PROM were more obvious in cold season, but the statistically significant effect of NO2 was observed in warm season. We also found the modifying effects by maternal age on PROM, and we found that the effects of SO2 and NO2 on PROM were higher among younger mothers (< 35 years) than advanced age mothers (≥ 35 years); however, ≥ 35 years group were more vulnerable to O3 than < 35 years group. This study indicates that air pollution exposure is an important risk factor for PROM and we wish this study could provide evidence to local government to take rigid approaches to control emissions of air pollutants.

Associations between air pollution exposure and birth defects: a time series analysis.

Air pollution is a serious environmental problem in China. Birth defects are particularly vulnerable to outdoor air pollution. Our study was to evaluate the association between short-term exposure to air pollutants and the risk of birth defects. Daily data including the air pollutants, meteorological characteristics, and birth records were obtained in Hefei, China, during January 2013 to December 2016. The findings showed that PM2.5, PM10, SO2, NO2, and O3 exposures were positively correlated with the risk of birth defects. Maternal exposure to PM2.5 and SO2 during the 4th to 13th gestational weeks was observed to have a significant association with the risk of birth defects, with the maximum effect in the 7th or 8th week for PM2.5 and the maximum effect in the 7th week for SO2. The positively significant exposure windows were the 4th to 14th weeks for PM10, the 4th to 12th weeks for NO2, and the 26th to 35th weeks for O3, respectively. The strongest associations were observed in the 8th week for PM10, the 7th week for NO2, and in the 31st or 32nd week for O3. The findings of this study demonstrate that air pollutants increase the risk of birth defects among women during pregnancy in Hefei, China, which provide evidence for improving the health of pregnant women and neonates in developing countries, and uncovered potential opportunities to reduce or prevent birth defects by proactive measures during pregnancy.

Maternal exposure to air pollution and the risk of low birth weight: A meta-analysis of cohort studies.

Previous studies have evaluated the relationship between prenatal air pollution exposure and low birth weight, but the results are inconsistent. The purpose of this meta-analysis is to quantitatively analyze the relationship between maternal air pollutant exposure and low birth weight (LBW). PubMed and Web of Science databases were searched to obtain the studies on the relationship between the prenatal exposure of air pollutants and LBW that published as of June 2020. The pooled effects of air pollutant exposure and LBW were calculated using random-effect model (for studies with significant heterogeneity) or fixed-effect model (for studies without significant heterogeneity). Totally, 54 studies were included in this meta-analysis. The pooled effect of PM2.5, PM10, NO2, CO, SO2, and O3 exposure on LBW were 1.081 (95% CI: 1.043, 1.120), 1.053 (95% CI: 1.030, 1.076), 1.030 (95% CI: 1.008, 1.053), 1.007 (95% CI: 1.001, 1.014), 1.125 (95% CI: 1.017, 1.244), and 1.045 (95% CI: 1.005, 1.086), respectively. NO2 (per 10 ppb increase) and CO (per 100 ppb increase) exposure in the first trimester were positively correlated with LBW, of which the pooled effect was 1.022 (95% CI: 1.009, 1. 035) and 1.008 (95% CI: 1.004, 1.012), respectively. PM2.5 (per 10 µg/m3 increase) exposure in the third trimester significantly affected the LBW, of which the pooled effect was 1.053 (95% CI: 1.010, 1.097). In addition, PM10 (per 10 µg/m3 increase) exposure in the second trimester also significantly affected the LBW, with the pooled effect of 1.011 (95% CI: 1.005, 1.017). Prenatal exposure of the major air pollutants during the entire pregnancy could increase the risk of LBW, while the susceptible window of the pollutants varied.

Short-term effect of ambient temperature change on the risk of tuberculosis admissions: Assessments of two exposure metrics.

BACKGROUND: Although the effects of seasonal variations and ambient temperature on the incidence of tuberculosis (TB) have been well documented, it is still unknown whether ambient temperature change is an independent risk factor for TB. The aim of this study was to assess the association between ambient temperature change and the risk of TB admissions. METHOD: A distributed lag non-linear model (DLNM) combined with Poisson generalized linear regression model was performed to assess the association between ambient temperature change and the risk of TB admissions from 2014 to 2018 in Hefei, China. Two temperature change metrics including temperature change between neighboring days (TCN) and diurnal temperature range (DTR) were used to assess the effects of temperature change exposure. Subgroup analyses were performed by gender, age and season. Besides, the attributable risk was calculated to evaluated the public health significance. RESULTS: The overall exposure-response curves suggested that there were statistically significant associations between two temperature change metrics and the risk of TB admissions. The maximum lag-specific relative risk (RR) of TB admissions was 1.088 (95%CI: 1.012-1.171, lag 4 day) for exposing to large temperature drop (TCN= -4 °C) in winter. Besides, the overall cumulative risk of TB admissions increased continuously and peaked at a lag of 7 days (RR=1.350, 95%CI: 1.120-1.628). Subgroup analysis suggested that exposure to large temperature drop had an adverse effect on TB admissions among males, females and adults. Similarly, large level of DTR exposure (DTR=15 °C) in spring also increased the risk of TB admissions on lag 0 day (RR=1.039, 95%CI: 1.016-1.063), and the cumulative RRs peaked at a lag of 1 days (RR=1.029, 95%CI: 1.012-1.047). We also found that females and elderly people were more vulnerable to the large level of DTR exposure. Additionally, the assessment of attributable risk suggested that taking target measures for the upcoming large temperature drop (b-AF = 4.17%, 95% eCI: 1.24%, 7.22%, b-AN = 1195) may achieve great public health benefits for TB prevention. CONCLUSION: This study suggests that ambient temperature change is associated with the risk of TB admissions. Besides, TCN may be a better predictor for the TB prevention and public health.

Association between short-term exposure to ambient air pollutants and the risk of tuberculosis outpatient visits: A time-series study in Hefei, China.

BACKGROUND: The current evidence has presented mixed results between air pollutants exposure and the progression of tuberculosis (TB). The purpose of this study was to explore the association between short-term exposure to air pollutants and the risk of TB outpatient visits in Hefei, China. METHODS: Time-series analysis was used to assess the effect of short-term exposure to ambient air pollutants on the risk of TB outpatient visits. A Poisson generalized linear regression model combined with a distributed lag non-linear model (DLNM) was applied to explore the association. The effects of different gender (male, female), age (≤65 years old, >65 years old) and season (cold season, warm season) on the risk of TB were investigated by stratified analysis. Sensitivity analyses were conducted to test the robustness of our findings. RESULTS: A total of 22,749 active TB cases were identified from November 1, 2013 to December 31, 2018 in Hefei. The overall exposure-response curve showed that the concentration of particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) exposure were positively correlated with the risk of TB outpatient visits, while ozone (O3) and sulfur dioxide (SO2) exposure were negatively correlated with the risk of TB outpatient visits. The maximum lag-specific and cumulative relative risk (RR) of TB outpatient visits were 1.057 [95%CI: 1.002-1.115, lag 3 day] and 1.559 (95%CI: 1.057-2.300, lag 13 days) for each 10 µg/m³ increase in PM2.5; 1.026 (95% CI: 1.008-1.044, lag 0 day) and 1.559 (95%CI: 1.057-2.300, lag 07 days) for each 10 µg/m³ increase in NO2; 0.866 (95% CI: 0.801-0.935, lag 5 day) and 0.852 (95%CI: 1.01-1.11, lag 0-14 days) for each 10 µg/m³ increase in SO2 in the single-pollutant model. There was only a negative association between O3 exposure and the cumulative risk of TB outpatient visits (RR = 0.960, 95%CI: 0.936-0.984, lag 07 days). Stratified analyses showed that the effects of SO2 and O3 exposure were different between warm and cold seasons. The effect of NO2 exposure remained statistically significant in male, younger, and cold season subgroups. Besides, elderly people are more susceptible to PM2.5 exposure. CONCLUSION: This study suggests that exposure to PM2.5, NO2, SO2, and O3 are associated with the risk of TB outpatient visits. Seasonal variation may have a greater impact on the risk of TB outpatient visits compared with gender and age.

Toxicity of cooking oil fume derived particulate matter: Vitamin D3 protects tubule formation activation in human umbilical vein endothelial cells.

Cooking oil fumes-derived PM2.5 (COFs-derived PM2.5) is the main source of indoor pollution. Exposure to COFs-derived PM2.5 can cause oxidative stress and affect angiogenesis. Here we investigated the roles of vitamin D3 (VD3) in protecting tubule formation injury induced by COFs-derived PM2.5, and the roles of ROS/NLRP3/VEGF signaling pathway in the effects. Human umbilical vein endothelial cells (HUVECs) were exposed to 0 (1‰ DMSO), 1000 nmol/l VD3, 100 µg/ml PM2.5, and 1000 nmol/l VD3 + 100 µg/ml PM2.5, respectively. Cell viability and tube formation, as well as protein and mRNA levels were measured. The results showed that exposure of COFs-derived PM2.5 dose-and time-dependently reduced the viability of HUVECs, increased the levels of mitochondrial and intracellular ROS, and changed the mitochondrial membrane potential level. While co-incubation with VD3 rescued these adverse effects. Both Western blot and real-time PCR (RT-PCR) showed that the expressions of NLRP3, caspase-1, Interleukin (IL)-1ß, and IL-18 in COFs-derived PM2.5 exposure group increased significantly, which could be effectively decreased by co-incubation with VD3. COFs-derived PM2.5 exposure could also reduce the expression of VEGF, while co-incubating HUVECs with VD3 evidently up-regulated the protein level of VEGF in HUVECs. In addition, COFs-derived PM2.5 could also inhibit the tube formation of HUVECs in vitro, which could be effectively rescued by the co-incubation of VD3. Our study proved that COFs-derived PM2.5 could damage the tubule formation of HUVECs in vitro, which could be effectively rescue by co-incubation with VD3, in which processes the ROS/NLRP3/VEGF signaling pathway played a crucial role. It provides a new theoretical basis for further study on the toxicity of PM2.5 to umbilical cord blood vessels.

The effects of cooking oil fumes-derived PM2.5 on blood vessel formation through ROS-mediated NLRP3 inflammasome pathway in human umbilical vein endothelial cells.

BACKGROUND: Cooking oil fumes (COFs), a main pollutant in kitchen air, is a major risk to human health. In our previous research, exposure to COFs-derived PM2.5 could cause umbilical vascular endothelial dysfunction, leading to decreased fetal weight. Here, to test the role of ROS-mediated NLRP3 inflammasome pathway in blood vessel formation of human umbilical vein endothelial cells (HUVECs) caused by COFs-derived PM2.5, the cells were exposed to COFs-derived PM2.5 at different concentrations with and without N-acetyl-L-cysteine (NAC). METHODS: MTT assay was used to determine HUVECs viability. Intracellular ROS and mitochondrial ROS levels were assessed with DCFH-DA and MitoSOX™ assay. The levels of proteins and mRNA involved in NLRP3 inflammasome signaling pathway and VEGF were measured by western blot and real-time PCR (RT-PCR). Tube formation in HUVECs was detected by tube formation assay. RESULTS: The results revealed that COFs-derived PM2.5 exposure reduced HUVECs viability, increased the intracellular and mitochondrial ROS levels in cells, and up-regulated the levels of proteins and mRNA involved in NLRP3 inflammasome signaling pathway. However, the protein and mRNA expression of VEGF were reduced with the increasing exposure concentrations. In addition, COFs-derived PM2.5 also affected the tube formation. However, co-incubation with NAC effectively rescued the damages caused by COFs-derived PM2.5 exposure. CONCLUSIONS: This study proved that COFs-derived PM2.5 could significantly reduce HUVECs viability, induce the overproduction of ROS, lead to inflammation and inhibit VEGF expression, thus affect angiogenesis of HUVECs in vitro. It was revealed that the impact caused by COFs-derived PM2.5 on blood vessel formation through a ROS-mediated NLRP3 inflammasome pathway.

1,25-Vitamin D3 protects against cooking oil fumes-derived PM2.5-induced cell damage through its anti-inflammatory effects in cardiomyocytes.

The functional role of 1,25-vitamin D3 in cooking oil fumes (COFs)-derived PM2.5-induced cell damage is largely unexplored. The present study investigated the protective role of 1,25-vitamin D3 against cell injury by possible involvement of JAK/STAT and NF-κB signaling pathways in cardiomyocytes. Cell viability was measured using CCK-8 assay, and cell apoptosis was analyzed by flow cytometry, qRT-PCR and Western blot in cultured rat neonatal cardiomyocytes treated with 1,25-vitamin D3 and COFs-derived PM2.5. Expressions of JAK/STAT and NF-κB signaling pathway were measured by Western blot. The results suggested that treatment with COFs-derived PM2.5 significantly decreased cell viability and increased apoptosis and oxidative stress in cultured rat neonatal cardiomyocytes. 1,25-vitamin D3 pretreatment alleviated the cell injury by increasing cell viability and decreasing apoptosis in the cardiomyocytes. 1,25-vitamin D3 pretreatment also decreased the ROS level and inflammation in the cardiomyocytes. Furthermore, 1,25-vitamin D3 pretreatment alleviated COFs-derived PM2.5-evoked elevation of JAK/STAT and NF-κB signaling pathways. Our study showed that 1,25-vitamin D3 pretreatment protected cardiomyocytes from COFs-derived PM2.5-induced injury by decreasing ROS, apoptosis and inflammation level via activations of the JAK/STAT and NF-κB signaling pathways.

Associations of ambient PM2.5 and O3 with cardiovascular mortality: a time-series study in Hefei, China.

China is among the countries with the worst air quality throughout the world. As PM2.5 was not included in the national air quality monitoring network before January 2013 in China, no study has investigated the associations of ambient PM2.5 and O3 with cardiovascular mortality in Hefei, China. In this time-series analysis, Poisson regression in generalized additive model was adopted to assess the associations between the air pollutants and cardiovascular mortality during the 2013-2015 in Hefei, China. The findings showed that the daily average level of PM2.5 and O3 was 77.8 µg/m3 and 60.1 µg/m3 in the study period, respectively. PM2.5 and O3 exposure tended to increase cardiovascular mortality, but the associations were statistically insignificant. Further stratified analyses by seasons showed that with every 10 µg/m3 increase of PM2.5 in the cold season (October-March), the risk of cardiovascular death increased by 0.22% (95% CI 0.05%, 0.39%); while every 10 µg/m3 increase of O3 in the warm season (April-September), the risk of cardiovascular death increased by 1.29% (95% CI 0.26%, 2.33%) on Lag0. Interestingly, stratified analysis by gender showed that the associations of PM2.5, but not O3 exposure, could significantly increase cardiovascular mortality in females, but not males. The findings of this study especially underscored the adverse associations of PM2.5 and O3 exposure with females in specific seasons. More studies are needed to verify our findings and further investigate the underlying mechanisms. Graphical Abstract.

Impairment of learning and memory of mice offspring at puberty, young adulthood, and adulthood by low-dose Cd exposure during pregnancy and lactation via GABAAR α5 and δ subunits.

Cadmium (Cd) is a pervasive carcinogen and environmental endocrine disruptor. We studied the changes in learning and memory of offspring mice, whose mothers were exposed to 10 mg Cd/L via the drinking water during pregnancy and lactation period, as well as the changes of testosterone and estrogen levels, serum Cd levels, the histopathological changes and the changes in the mRNA and protein levels of different subunits of γ-aminobutyric acid receptor subtype A subunits (GABAARs) in the hippocampus at the prepuberty, puberty, young adult, and adult stages. At birth, Cd had no obvious effect on mice offspring as statistically accessed based on their body weight, body length, and tail length (all p > 0.05). After grouped, the serum Cd levels increased in the three exposed groups more than in the normal control group at stages (all p < 0.05). Only serum estradiol of female offspring at age 7 weeks was significantly decreased compared with other groups (all p < 0.05). Histopathological results showed that the arrangement of the cells in hippocampal CA1 area of mice offspring was significantly sparse in the exposed groups compared with the control group. At 5 and 7 weeks, two Cd-exposed groups showed prolonged escape latency and exploring time for the platform compared with the normal group in the Morris water maze (all p < 0.05). Only increased protein expression of GABAARα5 was found in the Cd group at these two ages. At age 12 weeks, similar impaired learning and memory of female mice, and decreased protein expression of GABAARδ was found in Cd-exposed groups. Collectively, low-dose Cd had no effect on the growth of mice offspring but affected their learning and memory, especially female offspring, at puberty, young adulthood, and adulthood through changed structure in the hippocampal CA1 area and protein expression of GABAARα5 and GABAARδ.

Association between ubiquitin carboxy-terminal hydrolase-L1 S18Y variant and risk of Parkinson's disease: the impact of ethnicity and onset age.

The Ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) is a candidate risk gene for Parkinson' disease (PD), and a function SNP (rs5030732) in the coding region of this gene has been studied for the association with the disease extensively among worldwide populations, but the results were inconsistent and controversial. Here, to estimate the association between UCHL1 S18Y polymorphism and risk of PD in general population, we conducted a systematic meta-analysis by combining all available case-control subjects in Asian, European, and American populations, with a total of 7742 PD cases and 8850 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for UCHL1 S18Y polymorphism and PD were calculated using the Mantel-Haenszel method with a fixed- or random-effects model. Subgroup analysis was also performed in different onset age-matched groups. Among high-quality studies, UCHL1 S18Y polymorphism was moderately associated with the risk of PD (allele contrasts, OR = 1.063, 95% CI 1.008-1.122; p = 0.024; regressive genetic model, OR = 1.078, 95% CI 1.005-1.157; p = 0.035). When stratifying for ethnicity, none association were observed in subgroups. Analysis of early-onset PD (EOPD) and late-onset PD (LOPD) revealed that the polymorphism was not associated with the risk of PD. In conclusion, our meta-analysis suggests that UCHL1 S18Y polymorphism is moderately associated with susceptibility to PD, and more studies are needed to confirm our conclusion.

[Effect of C8-ceramide on apoptosis of alveolar type II epithelial cells].

OBJECTIVE: To investigate the effects of exogenous C8-ceramide on primary alveolar type II epithelial cells (AECII). METHODS: AECII were isolated from 18 day gestational age ICR mice, and cultured in Dulbecco's Modified Eagle Medium with 95% air and 5% CO2at 37 °C. The cells were treated with different concentrations (0, 20, 40 and 80 µmol/L) of C8-ceramide for 24 h and treated with 80 µmol/L of C8-ceramide for different time (3, 6, 12, and 24 h) to observe the viability of cells by MTT assay. Then, the annexin V externalization assay and TUNEL assay were performed to determine apoptosis after the cells were treated with different concentrations (0, 20, 40, and 80 µmol/L) of C8-ceramide for different time (12 and 24 h). RESULTS: The results of MTT assay showed that cell viability decreased in a dose- and time- dependent manner. In Annexin V externalization assay, the cells showed a distribution of (20.63 ± 0.86)%, (22.67 ± 1.72)%, (42.03 ± 1.34)%, (50.40 ± 1.30)% and (20.93 ± 2.51)%, (28.93 ± 3.19)%, (47.00 ± 1.08)%, (57.77 ± 3.04)% cells in apoptosis after treated with 0, 20, 40, 80 µmol/L of C8-ceramide for 12 and 24 h (It is significant difference from untreated cells except for 20 µmol/L at 12 h point, all P<0.05). In TUNEL assay, the cells showed a distribution of (5.51 ± 1.41)%, (13.24 ± 2.62)%, (35.10 ± 4.59)%, (75.07 ± 4.37)% and (5.56 ± 1.36)%, (21.34 ± 2.09)%, (37.12 ± 2.11)%, (91.33 ± 0.72)% cells in apoptosis after treated with 0, 20, 40, 80 µmol/L of C8-ceramide for 12 and 24 h (It is significant difference from untreated cells at the same time point, all P<0.05). CONCLUSION: The results demonstrate that C8-ceramide can decrease the viability of AECII and induce apoptosis.

The apoptotic pathways effect of fine particulate from cooking oil fumes in primary fetal alveolar type II epithelial cells.

Apoptosis occurs along three major pathways: (i) an extrinsic pathway, mediated by death receptors; (ii) an intrinsic pathway centered on mitochondria; and (iii) an ER-stress pathway. We investigated the apoptotic pathway effects of cooking oil fumes (COF) in fetal lung type II-like epithelium cells (AEC II). Exposure to COF caused up-regulation of the pro-apoptotic protein Bax and down-regulation of the anti-apoptotic protein Bcl-2. COF induced the mitochondrial permeability transition, an early event in apoptosis; cytochrome c was translocated from the mitochondria to the cytoplasm and nucleus. Caspase-9 and caspase-3 were activated, as a consequence of the mitochondrial permeability transition. The death receptor apoptotic pathway was triggered by COF, as indicated by a change in Fas expression, resulting in increased caspase-8 content. COF exposure arrested the cell cycle the at G0-G1 phase. In summary, COF can lead to apoptosis via mitochondrial and death receptor pathways in AEC II cells.