[Personal nitrogen oxides exposure levels and related influencing factors in adults over 35 years old in Tianjin and Shanghai].

OBJECTIVE: To investigate personal exposures to nitrogen oxides (NOX) and nitrogen di-oxide (NO2) and the influence of baseline personal characteristics, living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai. METHODS: In this panel study, 91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study. The study was conducted in summer and winter. The participants were followed for three times with an interval of at least two weeks. Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic. Twenty-seven participants completed follow-up visits in both seasons. We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity information through questionnaire/diary. The linear mixed model was used to analyze the associations between potential influencing factors and personal NOX and NO2 exposure levels. RESULTS: There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities. The ave-rage 24 h personal exposures to NO2 and NOX (volume fraction) in Tianjin participants were 18.0×10-9 and 26.2×10-9 in summer, and 31.0×10-9 and 54.9×10-9 in winter, respectively; and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7×10-9 and 100.0×10-9 in summer, and 45.5×10-9 and 139.2×10-9 in winter, respectively. The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city, season, gender, average daily cooking times, and ambient NO2 concentrations measured at fixed-site monitoring stations. In addition to the above factors, the personal NOX exposure levels were also significantly associated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking, average daily home time, cooking energy type, residential distance from main traffic road, and use of kitchen ventilators. Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai, were significantly lower in summer than that in winter, and were significantly and positively associated with ambient NO2 concentrations measured at fixed-site monitoring stations. In addition, personal NOX exposure levels were significantly lower in females than in males, and personal NO2 exposure levels were significantly positively associated with average daily cooking times and significantly inversely associated with average daily home time. For every interquartile range (IQR) increase (12.7×10-9) in ambient NO2, the personal NO2 exposure levels increased by 27.5% (95%CI: 17.0%-38.9%), and personal NOX exposure levels increased by 16.1% (95%CI: 7.1%-25.8%). CONCLUSION: Season, city and ambient NO2 concentrations are significant influencing factors of personal exposure levels of NO2and NOX. At the same time, the personal exposures levels of NO2are also affected by lifestyle factors. Our study provides scientific evidence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.

Ambient ultrafine particles exacerbate oxygen desaturation during sleep in patients with chronic obstructive pulmonary disease: New insights into the effect spectrum of ultrafine particles on susceptible populations.

The health effects of ultrafine particles (UFPs) are of growing global concern, but the epidemiological evidence remains limited. Sleep-disordered breathing (SDB) characterized by hypoxemia is a prevalent condition linked to many debilitating chronic diseases. However, the role of UFPs in the development of SDB is lacking. Therefore, this prospective panel study was performed to specifically investigate the association of short-term exposure to UFPs with SDB parameters in patients with chronic obstructive pulmonary disease (COPD). Ninety-one COPD patients completed 226 clinical visits in Beijing, China. Personal exposure to ambient UFPs of 0-7 days was estimated based on infiltration factor and time-activity pattern. Real-time monitoring of sleep oxygen saturation, spirometry, respiratory questionnaires and airway inflammation detection were performed at each clinical visit. Generalized estimating equation was used to estimate the effects of UFPs. Exposure to UFPs was significantly associated with increased oxygen desaturation index (ODI) and percent of the time with oxygen saturation below 90 % (T90), with estimates of 21.50 % (95%CI: 6.38 %, 38.76 %) and 18.75 % (95%CI: 2.83 %, 37.14 %), respectively, per 3442 particles/cm3 increment of UFPs at lag 0-3 h. Particularly, UFPs' exposure within 0-7 days was positively associated with the concentration of alveolar nitric oxide (CaNO), and alveolar eosinophilic inflammation measured by CaNO exceeding 5 ppb was associated with 29.63 % and 33.48 % increases in ODI and T90, respectively. In addition, amplified effects on oxygen desaturation were observed in current smokers. Notably, individuals with better lung function and activity tolerance were more affected by ambient UFPs due to longer time spent outdoors. To our knowledge, this is the first study to link UFPs to hypoxemia during sleep and uncover the key role of alveolar eosinophilic inflammation. Our findings provide new insights into the effect spectrum of UFPs and potential environmental and behavioral intervention strategies to protect susceptible populations.

Associations of multiple air pollutants with kidney function in normal-weight and obese adults and effect modification by free fatty acids.

Increasing studies have linked air pollution to kidney dysfunction, however, the associations between the mixture of air pollutants and kidney function and potential effect modifiers remain unclear. We aimed to investigate whether obese adults were more susceptible than normal-weight ones to the joint effects of multiple air pollutants on kidney function and further to explore effect modification by free fatty acids (FFAs). Forty obese and 49 normal-weight adults were recruited from a panel study (252 follow-up visits). Individual exposure levels of air pollutants (PM2.5, PM10, O3, NO2, SO2 and CO) were estimated. Glomerular function (cystatin C (CysC) and estimated glomerular filtration rate (eGFR)) and tubular function (neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1) were evaluated. Plasma levels of FFAs including trans fatty acids (TFAs) and essential fatty acids (EFAs) were quantified using targeted metabolomics. Bayesian kernel machine regression model was applied to estimate the associations between the mixture of air pollutants and kidney function. The results showed significant joint effects of air pollutants on kidney function indicators. In the normal-weight group, the mixture of air pollutants was significantly associated with CysC and eGFRcr-cys when the mixture was at or above its 70 percentile compared with the median, where O3 was identified as the key pollutant. In the obese group, a significantly positive association between the pollutant mixture and NGAL was observed in addition to trends in CysC and eGFRcr-cys, mainly driven by SO2. Interaction analysis suggested that the associations of air pollutants with kidney function were augmented by TFAs in both groups and weakened by EFAs in the normal-weight group. This study highlighted the renal adverse effects of air pollutants and modification of FFAs, which has implications for target prevention for kidney dysfunction associated with air pollution, especially among vulnerable populations.

Association of multiple air pollutants with oxygen saturation during sleep in COPD patients: Effect modification by smoking status and airway inflammatory phenotypes.

Air pollution contributes substantially to the development of chronic obstructive pulmonary disease (COPD). To date, the effect of air pollution on oxygen saturation (SpO2) during sleep and potential susceptibility factors remain unknown. In this longitudinal panel study, real-time SpO2 was monitored in 132 COPD patients, with 270 nights (1615 h) of sleep SpO2 recorded. Exhaled nitric oxide (NO), hydrogen sulfide (H2S) and carbon monoxide (CO) were measured to assess airway inflammatory characteristics. Exposure levels of air pollutants were estimated by infiltration factor method. Generalized estimating equation was used to investigate the effect of air pollutants on sleep SpO2. Ozone, even at low levels (<60 µg/m3), was significantly associated with decreased SpO2 and extended time of oxygen desaturation (SpO2 < 90%), especially in the warm season. The associations of other pollutants with SpO2 were weak, but significant adverse effects of PM10 and SO2 were observed in the cold season. Notably, stronger effects of ozone were observed in current smokers. Consistently, smoking-related airway inflammation, characterized by higher levels of exhaled CO and H2S but lower NO, significantly augmented the effect of ozone on SpO2 during sleep. This study highlights the importance of ozone control in protecting sleep health in COPD patients.

Connexin hemichannels and pannexin channels in toxicity: Recent advances and mechanistic insights.

Connexin hemichannels and pannexin channels are two types of transmembrane channels that allow autocrine/paracrine signalling through the exchange of ions and molecules between the intra- and extracellular compartments. However, owing to the poor selectivity of permeable ions and metabolites, the massive opening of these plasma membrane channels can lead to an excessive influx of toxic substances and an outflux of essential metabolites, such as adenosine triphosphate, glutathione, glutamate and ions, resulting in unbalanced cell homeostasis and impaired cell function. It is becoming increasingly clear that these channels can be activated in response to external stimuli and are involved in toxicity, yet their concrete mechanistic roles in the toxic effects induced by stress and various environmental changes remain poorly defined. This review provides an updated understanding of connexin hemichannels and pannexin channels in response to multiple extrinsic stressors and how these activated channels and their permeable messengers participate in toxicological pathways and processes, including inflammation, oxidative damage, intracellular calcium imbalance, bystander DNA damage and excitotoxicity.

Joint effect of indoor size-fractioned particulate matters and black carbon on cardiopulmonary function and relevant metabolic mechanism: A panel study among school children.

Indoor particulate matter (PM) and black carbon (BC) are associated with adverse cardiopulmonary effect. However, the cumulative and interactive effects of the mixture of size-fractioned PMs and BC on cardiopulmonary function are not well understood, and the underlying biological mechanisms remain unclear. This repeated-measure study was conducted to assess the joint cardiopulmonary effect and metabolic mechanisms of multiple-size particles and BC among 46 children. PM0.5, PM1, PM2.5, PM5, PM10 and BC were monitored for 5 weekdays. Cardiorespiratory function measurements and urine samples collection were conducted three times. Untargeted-metabolomics and meet-in-metabolite approach were applied to mechanism investigation. Bayesian machine kernel regression was adopted to analyze associations among PMs, cardiopulmonary function and metabolites. Lung function and heart rate variability significantly decreased with the increased PMs and BC co-exposure (p < 0.05). The effective particles were BC, PM1-2.5 and PM0.5 in turn. No interaction effects of different particles on cardiopulmonary function were observed at different lag days. BC-related glucose and fatty acid increase, and PM1-2.5-related branched-chain amino acid degradation were primarily observed. Other metabolisms were successively disturbed. The greatest joint effects of PMs and BC on metabolism were mainly at lag0 and lag01 day. They occurred earlier than the strongest effects on cardiopulmonary function, which were at lag01 and lag02 day. BC, PM1-2.5 and PM0.5 were mainly associated with cardiorespiratory indices by disturbing amino acids, glucose, lipid, isoflavone and purine metabolism. Mitochondrial productivity and antioxidation reduction are pivotal to the relevant metabolic alterations. More attention should be paid to BC and smaller-size PMs to control indoor PM pollution and its adverse effect on children.

Association between gaseous air pollutants and biomarkers of systemic inflammation: A systematic review and meta-analysis.

BACKGROUND: Studies have linked gaseous air pollutants to multiple health effects via inflammatory pathways. Several major inflammatory biomarkers, including C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have also been considered as predictors of cardiovascular disease. However, there has been no meta-analysis to evaluate the associations between gaseous air pollutants and these typical biomarkers of inflammation to date. OBJECTIVES: To evaluate the overall associations between short-term and long-term exposures to ambient ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon dioxide (CO) and major inflammatory biomarkers including CRP, fibrinogen, IL-6 and TNF-α. METHODS: A meta-analysis was conducted for publications from PubMed, Web of Science, Scopus and EMBASE databases up to Feb 1st, 2021. RESULTS: The meta-analysis included 38 studies conducted among 210,438 participants. Generally, we only observed significant positive associations between short-term exposures to gaseous air pollutants and inflammatory biomarkers. For a 10 µg/m3 increase in short-term exposure to O3, NO2, and SO2, there were significant increases of 1.05% (95%CI: 0.09%, 2.02%), 1.60% (95%CI: 0.49%, 2.72%), and 10.44% (95%CI: 4.20%, 17.05%) in CRP, respectively. Meanwhile, a 10 µg/m3 increase in NO2 was also associated with a 4.85% (95%CI: 1.10%, 8.73%) increase in TNF-α. Long-term exposures to gaseous air pollutants were not statistically associated with these biomarkers, but the study numbers were relatively small. Subgroup analyses found more apparent associations in studies with better study design, higher quality, and smaller sample size. Meanwhile, the associations also varied across studies conducted in different geographical regions. CONCLUSION: Short-term exposure to gaseous air pollutants is associated with increased levels of circulating inflammatory biomarkers, suggesting that a systemic inflammatory state is activated upon exposure. More studies on long-term exposure to gaseous air pollutants and inflammatory biomarkers are warranted to verify the associations.

Health Knowledge about Smoking, Role of Doctors, and Self-Perceived Health: A Cross-Sectional Study on Smokers' Intentions to Quit.

Limited empirical work has been done to compare the effects that health knowledge and advice from doctors have on smokers' intentions to quit. This paper examines the association of smokers' intentions to quit with health knowledge, advice from doctors, and self-perceived health. A sample of 2509 smokers aged 15-69 years old in Ningbo was used from China's National Health Literacy Surveillance survey, conducted in 2018 and 2019. Respondents were asked whether they agree smoking causes stroke, heart attack, lung cancer; and heart diseases in adults, lung illnesses in children, and lung cancer in adults, by secondhand smoke, respectively. Using the logistic model, we found that knowing that smoking causes stroke and lung cancer more than doubles the odds of one's intention to quit (OR = 2.705, p < 0.01), the effect of which is much greater than knowing that smoking causes lung cancer only (OR = 1.795, p < 0.01). Doctors' advice to quit is more important than health knowledge, in terms of predicting smokers' past cessation behaviours. In addition, smokers' self-perceived health is negatively associated with their decisions to quit. This paper highlights that more resources should be directed towards training health care providers to advise smokers to quit, which might be more effective than health education alone.

Multi-walled carbon nanotubes induce IL-1ß secretion by activating hemichannels-mediated ATP release in THP-1 macrophages.

Multi-walled carbon nanotubes (MWCNTs) are known to induce pulmonary inflammatory effects through stimulating pro-inflammatory cytokine secretion from alveolar macrophages. Despite extensive studies on MWCNTs' pro-inflammatory reactivity, the understanding of molecular mechanisms involved is still incomplete. In this study, we investigated hemichannel's involvement in MWCNTs-induced macrophage IL-1ß release. Our results showed that the unmodified and COOH MWCNTs could induce ATP release and ATP-P2X7R axis-dependent IL-1ß secretion from THP-1 macrophages. By using various inhibitors, we confirmed that the MWCNTs-induced ATP release was primarily through hemichannels. EtBr dye uptake assay detected significant hemichannels opening in MWCNTs exposed THP-1 macrophages. Inhibition of hemichannels by CBX, 43Gap27, or 10Panx1 pretreatment results in decreased ATP and IL-1ß release. The addition of ATP restored the reduced IL-1ß secretion level from hemichannel inhibition. We also confirmed with five other types of MWCNTs that the induction of hemichannels by MWCNTs strongly correlates with their capacity to induce IL-1ß secretion. Taken together, we conclude that hemichannels-mediated ATP release and subsequent NLRP3 inflammasome activation through P2X7R may be one mechanism by which MWCNTs induce macrophage IL-1ß secretion. Our findings may provide a novel molecular mechanism for MWCNTs induced IL-1ß secretion.

Paracellular permeability changes induced by multi-walled carbon nanotubes in brain endothelial cells and associated roles of hemichannels.

Multi-walled carbon nanotubes (MWCNTs) have promising applications in neurology depending on their unique physicochemical properties. However, there is limited understanding of their impacts on brain microvascular endothelial cells, the cells lining the vessels and maintaining the low and selective permeability of the blood-brain barrier. In this study, we examined the influence of pristine MWCNT (p-MWCNT) and carboxylated MWCNT (c-MWCNT) on permeability and tight junction tightness of murine brain microvascular endothelial cells, and investigated the potential mechanisms in the sight of hemichannel activity. Treatment with p-MWCNT for 24 h at subtoxic concentration (20 µg/mL) decreased the protein expression of occludin, disrupted zonula occludens-1 continuity, and elevated monolayer permeability as quantified by transendothelial electrical resistance and paracellular flux of 4000 Da fluorescein isothiocyanate-dextran conjugates. Moreover, p-MWCNT exposure also increased hemichannel activity with upregulated protein expression and altered subcellular localization of connexin (Cx)43 and pannexin (Panx)1. p-MWCNT-induced elevation in endothelial permeability could be prevented by hemichannel inhibitor carbenoxolone and peptide blocker of Cx43 and Panx1, indicating the crucial role of activated Cx43 and Panx1 hemichannels. Furthermore, Cx43 and Panx1 hemichannel-mediated ATP release might be involved in p-MWCNT-induced rise in endothelial permeability. In contrast, the above effects caused by p-MWCNT were not observed in cells treated with c-MWCNT, the functionalized form with more stable dispersion and a lower tendency to aggregate. Our study contributes further understanding of the impact of MWCNTs on brain endothelial tightness and permeability, which may have important implications for the safety application of MWCNTs in nanomedicine.

Different cardiorespiratory effects of indoor air pollution intervention with ionization air purifier: Findings from a randomized, double-blind crossover study among school children in Beijing.

Indoor air pollution is associated with numerous adverse health outcomes. Air purifiers are widely used to reduce indoor air pollutants. Ionization air purifiers are becoming increasingly popular for their low power consumption and noise, yet its health effects remain unclear. This randomized, double-blind crossover study is conducted to explore the cardiorespiratory effects of ionization air purification among 44 children in Beijing. Real or sham purification was performed in classrooms for 5 weekdays. Size-fractionated particulate matter (PM), black carbon (BC), ozone (O3), and negative air ions (NAI) were monitored, and cardiorespiratory functions were measured. Mixed-effect models were used to establish associations between exposures and health parameters. Real purification significantly decreased PM and BC, e.g. PM0.5, PM2.5, PM10 and BC were decreased by 48%, 44%, 34% and 50%, respectively. O3 levels were unchanged, while NAI was increased from 12 cm-3 to 12,997 cm-3. Real purification was associated with a 4.4% increase in forced exhaled volume in 1 s (FEV1) and a 14.7% decrease in fractional exhaled nitrogen oxide (FeNO). However, heart rate variability (HRV) was altered negatively. Interaction effects of NAI and PM were observed only on HRV, and alterations in HRV were greater with high NAI. Ionization air purifier could bring substantial respiratory benefits, however, the potential negative effects on HRV need further investigation.

Cardiorespiratory responses to low-level ozone exposure: The inDoor Ozone Study in childrEn (DOSE).

BACKGROUND: Indoor air pollution has emerged as a significant environmental and public health concern in recent years. However, evidence regarding the cardiorespiratory effects of indoor ozone is limited, and the underlying biological mechanisms are unclear, especially in children. Our study aimed to assess the cardiorespiratory responses to indoor ozone exposure in children. METHODS: A repeated-measure study was conducted in 46 middle-school children in Beijing, China. Real-time concentrations of ozone, along with co-pollutants including particulate matter (PM) and black carbon (BC), were monitored in classrooms from Monday to Friday. Three repeated health measurements of cardiorespiratory functions, including ambulatory electrocardiogram (ECG), blood pressure, fractional exhaled nitric oxide (FeNO) and lung function, were performed on each participant. Mixed-effect models were used to evaluate the effects of indoor ozone exposure. RESULTS: The mean (SD) indoor ozone concentration was 8.7 (6.6) ppb during the study period, which was largely below the current guideline and standards. However, even this low-level ozone exposure was associated with reduced cardiac autonomic function and increased heart rate (HR) in children. For instance, per interquartile range (IQR) increase in ozone at 2-hour moving average was associated with -7.8% (95% CI: -9.9%, -5.6%) reduction in standard deviation of all normal-to-normal intervals (SDNN), and 2.6% (95% CI: 1.6%, 3.6%) increment in HR. In addition, the associations were stronger at high BC levels (BC ≥ 3.7 µg/m3). No significant associations were found for airway inflammation and pulmonary function. CONCLUSIONS: Exposure to low-level indoor ozone that is not associated with respiratory effects was significantly related to disturbed cardiac autonomic function and increased HR in children, which suggested a possible mechanism through which ozone may affect cardiovascular health in children, and indicated more protective measures should be taken to alleviate the acute adverse effects of indoor ozone in this susceptible population.

The short-term effects of indoor size-fractioned particulate matter and black carbon on cardiac autonomic function in COPD patients.

BACKGROUND: Previous studies have reported adverse health effects of indoor air pollutants especially particulate matter (PM) and black carbon (BC). Patients with chronic obstructive pulmonary disease (COPD) have been shown to be more likely with cardiovascular comorbidities in which cardiac autonomic dysfunction plays an important role. However, there is little evidence for the effect of indoor PM and BC exposures on cardiac autonomic function in COPD patients. OBJECTIVES: To evaluate the association between exposure to indoor size-fractioned PM and BC and changes in HRV and HR in COPD patients. METHODS: Forty-three doctor diagnosed, stable COPD patients were recruited and measured for 24-h HRV and HR. Real-time indoor size-fractioned PM and BC were monitored on the day before and the day of performing health measurements. Mixed-effects models were used to estimate the associations between indoor PM and BC and HRV indices and HR after controlling for potential confounders. RESULTS: Increasing levels of size-fractioned PM and BC were associated with decreased HRV indices and increased HR. An IQR (3.14µg/m3) increase in 8-h BC moving average and an IQR (20.72µg/m3) increase in 5-min PM0.5 moving average concentrations were associated with declines of 7.45% (95% CI: -10.89%, -3.88%) and 16.40% (95% CI: -21.06%, -11.41%) in LF, respectively. The smaller the particles size, the greater effects on HRV indices and HR. Patients' BMI modified the associations between size-fractioned PM and BC and their HRV and HR. For an IQR increase in PM0.5, there was decline in HF of 34.85% (95% CI: -39.08%, -30.33%) in overweight patients, compared to a 2.01% (95% CI: -6.44%, 11.19%) increase in normal-weight patients. CONCLUSIONS: Exposures to indoor PM and BC were associated with altered cardiac autonomic function in COPD patients, and the associations for HRV measures of parasympathetic activity (e.g., HF) were more apparent in overweight patients.

Human bronchial epithelial cell injuries induced by fine particulate matter from sandstorm and non-sandstorm periods: Association with particle constituents.

Epidemiological studies have demonstrated the exacerbation of respiratory diseases following sandstorm-derived particulate matter (PM) exposure. The presence of anthropogenic and biological agents on the sandstorm PM and the escalation of PM<2.5µm (PM2.5) pollution in China have led to serious concerns regarding the health effects of PM2.5 during Asian sandstorms. We investigated how changes in PM2.5 composition, as the weather transitioned towards a sandstorm, affected human airway epithelial cells. Six PM2.5 samples covering two sandstorm events and their respective background and transition periods were collected in Baotou, an industrial city near the Gobi Desert in China. PM samples from all three periods had mild cytotoxicity in human bronchial epithelial cell line BEAS-2B, which was positively correlated with the contents of polycyclic aromatic hydrocarbons and several metals. All PM samples potently increased the release of interleukin-6 (IL-6) and interleukin-8 (IL-8). Endotoxin in all samples contributed significantly to the IL-6 response, with only a minor effect on IL-8. Cr was positively correlated with both IL-6 and IL-8 release, while Si was only associated with the increase of IL-6. Our study suggests that local agricultural and industrial surroundings in addition to the sandstorm play important roles in the respiratory effects of sandstorm-derived PM.

Ultrafine carbon black attenuates the antihypertensive effect of captopril in spontaneously hypertensive rats.

Particulate matter (PM) has been associated with increased blood pressure (BP) by affecting renin-angiotensin system (RAS) on a systemic level in spontaneously hypertensive rats (SHR). RAS in SHR is also an important target for the angiotensin converting enzyme (ACE) inhibitors such as captopril. We aimed to determine if ultrafine carbon black (UCB) could affect antihypertensive effect of captopril in SHR. The rats were randomly divided into six groups. Group 1 did not receive intratracheal instillation; group 2 received saline instillation plus captopril administration; groups 3, 4 and 5 received 0.15 mg/kg, 0.45 mg/kg and 1.35 mg/kg UCB per instillation plus captopril administration, respectively; group 6 received 1.35 mg/kg UCB instillation only. Rats in the above groups were intratracheally instilled with saline or UCB once every two days for three times and captopril was administered to group 2-5 after the final UCB treatment, once a day for one week. The BP was measured 24 h after each intratracheal instillation. During captopril administration and 24 h after last captopril administration, we measured BP every two days for four times. Our results showed that UCB at the dose of 1.35 mg/kg induced pulmonary and systemic inflammation in SHR. Captopril reduced BP in rats exposed to 0, 0.15 and 0.45 mg/kg UCB seven and eleven days after the first UCB instillation, and had no effect on BP in rats exposed to 1.35 mg/kg UCB. Captopril also reduced angiotensin II (AngII) in rats exposed to saline. The reduction, however, was attenuated with increasing doses of UCB. We conclude that UCB attenuated the antihypertensive effect of captopril in SHR, and the effect was accompanied by a systemic increase in the concentration of AngII.

[Bibliometric analysis of associations between ambient pollution and reproductive and developmental health].

OBJECTIVE: This study aims to evaluate the characteristics and the popular themes in the field of air pollution and reproductive and developmental health with the bibliometric approach. METHOD: The articles from the year 1955 to 2013 in this field were retrieved by searching PubMed/MEDLINE using MeSH terms. The bibliographic information was analyzed to summarize the overall research characteristics. MeSH terms were sorted by their normalized frequency (NF) and classified into categories (air pollutants/components, reproductive and developmental outcomes and biological mechanisms) and then analyzed by regressive analysis to investigate the popular themes and their tendency. RESULTS: All 2 315 papers are retrieved in this field, and 52.9% of the papers are published from the year 2004 to 2013. The 84.1% of the studies are conducted on the population, in which 10.9% are cohort studies. The researchers from USA conduct 28.0% of the studies. Only 2.3% of the studies are conducted by researchers from China. In the category of air pollutants/components, the high NF of MeSH terms, tobacco smoke pollutants, dust, carbon monoxide and heavy metals are 46.96%, 15.92%, 5.03% and 7.84% respectively. In the category of reproductive and developmental outcomes, the high NF of abortion, prenatal exposure delayed effects and pregnancy complications are 4.36%, 12.17% and 6.01%. In the category of biological mechanisms, the high NF of maternal-fetal exchange and DNA damage are 6.58% and 1.31%. CONCLUSION: Tobacco smoke pollutants, dust, carbon monoxide and heavy metals are the major concerns of air pollutants/components. Reproductive and developmental outcomes mainly focus on the abortion, prenatal exposure delayed effects and pregnancy complications. Maternal-fetal exchange and DNA damage are mostly concerned as the biological mechanisms.

Ultrafine carbon black induces glutamate and ATP release by activating connexin and pannexin hemichannels in cultured astrocytes.

Ultrafine particles could enter central nervous system and were associated with brain damage. The underlying mechanisms have not been fully elucidated. Glutamate and ATP are important signaling molecules in brain physiology and pathology. We investigated whether ultrafine carbon black (ufCB) could regulate the release of glutamate and ATP from cultured cortical astrocytes and the involvement of hemichannels in the release mechanism. Our results showed that ufCB dose-dependently increased glutamate and ATP release and activated hemichannels in astrocytes. ufCB-activated hemichannels were attributed to the activation of both connexin 43 (Cx43) and pannexin1 (Panx1) hemichannels, which was based on the finding of increased protein expression and distribution on cell surface of Cx43 and Panx1, and the inhibiting effects of hemichannel inhibitor carbenoxolone, Cx43 hemichannel inhibitor (43)Gap27 and Panx1 hemichannel inhibitor (10)Panx1 on hemichannel activation. Furthermore, ufCB-induced glutamate and ATP release were dependent on Cx43 and Panx1 hemichannels, because carbenoxolone and (43)Gap27 inhibited ufCB-induced glutamate and ATP release, and (10)Panx1 inhibited ufCB-induced ATP release. Taken together, we demonstrated, for the first time, that ufCB could induce glutamate and ATP release by activating Cx43 and Panx1 hemchannels in astrocytes. Our findings suggest a novel mechanism for neurotoxicity caused by ultrafine particles.

Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers.

Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated with benzene-induced alterations in DNA methylation and hematotoxicity, we genotyped four commonly studied SNPs in three metabolic enzymes genes CYP1A1, EPHX1 and NQO1; and analyzed promoter DNA methylation status in 11 genes which have been reported to be associated with benzene-induced hematotoxicity (BLM, CYP1A1, EPHX1, ERCC3, NQO1, NUDT1, p15, p16, RAD51, TP53 and WRAP53) in 77 benzene-exposed workers and 25 unexposed controls in China. ERCC3, a DNA repair gene, showed a small but statistically significant increase of promoter DNA methylation in the exposed group compared with the unexposed group (mean ± SD: 4.73 ± 3.46% vs. 3.63 ± 1.96%, P = 0.048). We also observed that an increased number of C allele for rs1051740 in EPHX1 was associated with decreased ERCC3 methylation levels in benzene-exposed workers (P(trend) = 0.001), but not in unexposed controls (P(trend) = 0.379). Interestingly, another EPHX1 SNP (rs2234922) was associated with lower white blood cell (WBC) counts (P(trend) = 0.044) in benzene-exposed workers. These associations remained the same when ERCC3 promoter methylation and WBCs were dichotomized according to the 90th percentile (≥6%) of methylation levels in controls and a leucopenia cutoff (<4 × 10(9) /L), respectively. Our findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene-exposed workers.

The role of metal components in the cardiovascular effects of PM2.5.

Exposure to ambient fine particulate matter (PM2.5) increases risks for cardiovascular disorders (CVD). However, the mechanisms and components responsible for the effects are poorly understood. Based on our previous murine exposure studies, a translational pilot study was conducted in female residents of Jinchang and Zhangye, China, to test the hypothesis that specific chemical component of PM2.5 is responsible for PM2.5 associated CVD. Daily ambient and personal exposures to PM2.5 and 35 elements were measured in the two cities. A total of 60 healthy nonsmoking adult women residents were recruited for measurements of inflammation biomarkers. In addition, circulating endothelial progenitor cells (CEPCs) were also measured in 20 subjects. The ambient levels of PM2.5 were comparable between Jinchang and Zhangye (47.4 and 54.5 µg/m(3), respectively). However, the levels of nickel, copper, arsenic, and selenium in Jinchang were 82, 26, 12, and 6 fold higher than Zhangye, respectively. The levels of C-reactive protein (3.44 ± 3.46 vs. 1.55 ± 1.13), interleukin-6 (1.65 ± 1.17 vs. 1.09 ± 0.60), and vascular endothelial growth factor (117.6 ± 217.0 vs. 22.7 ± 21.3) were significantly higher in Jinchang. Furthermore, all phenotypes of CEPCs were significantly lower in subjects recruited from Jinchang than those from Zhangye. These results suggest that specific metals may be important components responsible for PM2.5-induced cardiovascular effects and that the reduced capacity of endothelial repair may play a critical role.

Chemical constituents of ambient particulate air pollution and biomarkers of inflammation, coagulation and homocysteine in healthy adults: a prospective panel study.

BACKGROUND: Ambient air pollution has been associated with activation of systemic inflammation and hypercoagulability and increased plasma homocysteine, but the chemical constituents behind the association are not well understood. We examined the relations of various chemical constituents of fine particles (PM(2.5)) and biomarkers of inflammation, coagulation and homocysteine in the context of traffic-related air pollution. METHODS: A panel of 40 healthy college students underwent biweekly blood collection for 12 times before and after their relocation from a suburban campus to an urban campus with changing air pollution contents in Beijing. Blood samples were measured for circulatory biomarkers of high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), fibrinogen, plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), von Willebrand factor (vWF), soluble platelet selectin (sP-selectin), and total homocysteine (tHcy). Various air pollutants were measured in a central air-monitoring station in each campus and 32 PM(2.5) chemical constituents were determined in the laboratory. We used three different mixed-effects models (single-constituent model, constituent-PM(2.5) joint model and constituent residual model) controlling for potential confounders to estimate the effects of PM(2.5) chemical constituents on circulatory biomarkers. RESULTS: We found consistent positive associations between the following biomarkers and PM(2.5) chemical constituents across different models: TNF-α with secondary organic carbon, chloride, zinc, molybdenum and stannum; fibrinogen with magnesium, iron, titanium, cobalt and cadmium; PAI-1 with titanium, cobalt and manganese; t-PA with cadmium and selenium; vWF with aluminum. We also found consistent inverse associations of vWF with nitrate, chloride and sodium, and sP-selectin with manganese. Two positive associations of zinc with TNF-α and of cobalt with fibrinogen, and two inverse associations of nitrate with vWF, and of manganese with sP-selectin, were independent of the other constituents in two-constituent models using constituent residual data. We only found weak air pollution effects on hs-CRP and tHcy. CONCLUSIONS: Our results provide clues for the potential roles that PM(2.5) chemical constituents may play in the biological mechanisms through which air pollution may influence the cardiovascular system.