Lili Xiao

Blocking TGF-β expression inhibits silica particle-induced epithelial-mesenchymal transition in human lung epithelial cells.

The main characteristic of silicosis is irreversible fibrosis. Certain studies have shown that epithelial-mesenchymal transition (EMT) regulated by transforming growth factor-β (TGF-β) is involved in fibrosis. Thus, we suggest that TGF-β regulated EMT may play an important role in silicosis. In this study, we determined the expression of TGF-β-Smad2/3, EMT- and ECM-related markers in lung epithelial cells treated with silica particle by RT-PCR, western-blot and ELISA. In order to explore the role of TGF-β, we used TGF-β inhibitor in the cell model. We found that the cells lost the expression of epithelial phenotypic markers and acquired increased expression of mesenchymal cells markers with ECM deposition after treatment with silica particle. Moreover, the changes of EMT-related event was restricted in response to TGF-β inhibitor. These findings suggest that EMT is essentially involved in the pathogenesis of fibrosis induced by silica particles and down-regulating the TGF-β expression can inhibit the process of EMT.

Sleep duration and risk of coronary heart disease: A systematic review and meta-analysis of prospective cohort studies

BACKGROUND Epidemiological studies suggest an association between sleep duration and risk of coronary heart disease, however, the results are controversial. We conducted this systematic review and meta-analysis to summarize the potential dose-response relationship between sleep duration and risk of coronary heart disease. METHODS The electronic reference databases (PubMed and Embase) were searched through January 2016 with selection criteria for relevant studies. Both semiparametric and parametric methods were used to calculate the pooled risk estimates. RESULTS Seventeen articles with 22 independent reports involving 17,841 incident cases of coronary heart disease among 517,440 participants were included in our meta-analysis. A U-shaped relationship was detected between sleep duration and risk of coronary heart disease, with the lowest risk at 7-8h per day. Compared with 7h sleep duration per day, the combined relative risk of coronary heart disease were 1.11 (95% CI=1.05-1.16) for an reduction of 1h and 1.07 (95% CI=1.00-1.15) for an increment of 1h. And the results almost did not change in the subgroup analysis of gender and fatal cases. Exclusion of any single study did not alter the combined relative risk. In addition, visual inspection of funnel plots, Beggs and Eggers tests failed to identify publication bias. CONCLUSIONS Both short and long sleep durations are significantly associated with increased risk of coronary heart disease. Compared with 7h sleep duration per day, the risk of coronary heart disease increases 11% for an hour decrease and increases 7% for an hour increase.

Associations between Th17-related inflammatory cytokines and asthma in adults: A Case-Control Study.

Chronic airway inflammation is recognized as an essential process in the pathogenesis of asthma. Cytokine profiles derived from immune and inflammation cells such as T-helper (Th) cells, eosinophilia and neutrophilia are not limited to the Th2 type in asthma. However, little is understood about associations between Th2-low inflammatory cytokine profiles and risk of asthma in adults. A case-control study of 910 adult asthma and 881 healthy controls was conducted. Inflammatory cytokines screening was undertaken by high-throughput protein microarray technology, and Th17-related inflammatory cytokines (IL17A, IL-9, adipsin and CCL11) were finally selected. Associations between these four cytokines and adult asthma risk were analyzed by multivariate logistic regression models. We observed that plasma IL-17A and IL-9 levels were significantly increased in asthmatics when compared with controls. However, the plasma expressions of adipsin and CCL11 in asthmatics were significantly lower than that in health controls. The adjusted ORs (95%CI) of association between IL-17A, IL-9, adipsin and CCL11 expressions and adult asthma were 3.08 (1.91, 4.97), 1.93 (1.41, 2.64), 10.02 (6.99, 14.37) and 3.29 (2.36, 4.59), respectively (all Ptrend < 0.0001). Our results suggested that elevated IL-17A and IL-9 expressions and decreased levels of adipsin and CCL11 were positively associated with adult asthma.

Plasma LncRNA-ATB, a Potential Biomarker for Diagnosis of Patients with Coal Workers' Pneumoconiosis: A Case-Control Study.

LncRNA-ATB (lncRNA was activated by transforming growth factor-β) has been reported to be involved in specific physiological and pathological processes in human diseases, and could serve as biomarkers for cancers. However, the role of lncRNA-ATB in coal workers’ pneumoconiosis (CWP) is still unknown. This study aimed to investigate the association between lncRNA-ATB and CWP. Quantitative real-time polymerase chain reaction was performed to detect plasma lncRNA-ATB expression in 137 CWP patients, 72 healthy coal miners and 168 healthy controls. LncRNA-ATB was significantly upregulated in CWP (p < 0.05). Compared with the healthy controls and healthy coal miners, the odds ratios (ORs) (95% confidence interval (CI)) for CWP were 2.57 (1.52–4.33) and 2.17 (1.04–4.53), respectively. LncRNA-ATB was positively associated with transforming growth factor-β1 (TGF-β1) (r = 0.30, p = 0.003) and negative correlated with vital capacity (VC) (r = −0.18, p = 0.033) and forced vital capacity (FVC) (r = −0.18, p = 0.046) in CWP patients. Compared with healthy controls, the area under the curve (AUC) was 0.84, resulting in a 71.17% sensitivity and 88.14% specificity. When compared with healthy coal miners, the AUC was 0.83, the sensitivity and specificity were 70.07% and 86.36%, respectively. LncRNA-ATB expression is commonly increased in CWP and significantly correlates with the TGF-β1 in CWP patients. Furthermore, elevated lncRNA-ATB was associated with CWP risk and may serve as a potential biomarker for CWP.

Associations of urinary polycyclic aromatic hydrocarbon metabolites with fractional exhaled nitric oxide and exhaled carbon monoxide: A cross-sectional study

Exposure to Polycyclic aromatic hydrocarbons (PAHs) has been associated with inflammatory responses. Fractional exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) are both important inflammatory mediators especially in airways. However, few studies have investigated associations of PAH exposures with FeNO or eCO. Therefore, we aimed to quantify the associations of urinary PAH metabolites with FeNO and eCO levels, and investigate their potential effect modifiers by linear mixed models among 4133 participants from the Wuhan-Zhuhai cohort in China. We further performed stratified analyses to estimate effect modification. We found significant associations of increased urinary PAH metabolites with elevated eCO and FeNO. Among all participants, each 1% increase of 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 3-hydroxyphenanthrene, and total PAH metabolites was significantly associated with a 12.6% (95% confidence interval: 9.3%, 15.9%), 9.7% (6.5%, 12.9%), 7.5% (4.1%, 10.9%), 3.2% (0.2%, 6.2%), 2.7% (0.1%, 5.3%), and 6.5% (2.7%, 10.4%) increased eCO level, respectively; while each 1% increase of urinary 1-hydroxynaphthalene, 9-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 2-hydroxyphenanthrene was associated with a -3.0% (-5.8%, -0.2%), 2.9% (0.3%, 5.6%), 3.2% (1.0%, 5.4%), and 4.5% (2.2%, 6.9%) change of FeNO level, respectively. Positive associations between certain urinary PAH metabolites and eCO were observed among both ever-smokers and non-smokers, and the associations were stronger among ever-smokers than that among non-smokers. Increased urinary PAH metabolites were associated with decreased FeNO among ever-smokers and elevated FeNO levels among non-smokers. Our findings suggest that PAH exposures may impair airway through inducing inflammatory response, especially among ever-smokers.

Exogenous Gas6 attenuates silica-induced inflammation on differentiated THP-1 macrophages

Growth arrest specific 6 (Gas6) has been reported to be related to the modulation of innate immunity. To investigate the potential effect of Gas6 on the regulation of inflammations induced by silica, differentiated THP-1 macrophages were exposed to different concentrations of silica for 6h and 24h. Additionally, silica-activated macrophages were treated with Gas6 antibody and Gas6 respectively. Expression levels of Gas6 and inflammatory cytokines (TNF-α, IL-1β and IL-6) were measured. Our results showed that both cell viability and Gas6 expression were suppressed by silica in dose-dependent manners. After pretreatment with Gas6 antibody, silica induced a significant decrease in cell viability and a significant increase in inflammatory cytokines at two time points. Moreover, addition of Gas6 significantly suppressed silica induced TNF-α, IL-1β and IL-6 levels in negative dose-dependent manners, not only in mRNA levels but also in protein levels. Our results suggested that exogenous Gas6 might attenuate inflammations induced by silica on macrophages.

The cross-sectional and longitudinal associations of chromium with dyslipidemia: A prospective cohort study of urban adults in China

Chromium exposure can induce altered lipoprotein metabolism in animals, but the health effects of chromium on dyslipidemia in humans have not been fully evaluated. In this study, we aimed to investigate the cross-sectional and longitudinal effects of urinary chromium on lipid levels and dyslipidemia risk among urban adults from two cities in China. A total of 3762 urban adults from the Wuhan-Zhuhai cohort were included in the initial investigation, and followed up three years later. Urinary chromium concentration was measured at baseline and repeated at follow-up. Associations of urinary chromium concentration with lipid levels and risk of dyslipidemia were analyzed by generalized linear and binary logistic regression models, respectively. We found significant relationships between increased urinary chromium concentration and both reduced triglyceride (TG) level and elevated high-density lipoprotein cholesterol (HDL-C) level at baseline and follow-up. In the cross-sectional analysis, each 1-unit increase in log-transformed urinary chromium was associated with a 0.25 mmol/L decrease in TG and a 0.05 mmol/L increase in HDL-C (P < 0.05); also, downward trends for odds ratios of hyperTG (TG level ≥ 1.7 mmol/L) and hypoHDL-C (HDL-C level < 1.0 mmol/L) were significantly associated with increasing quartiles of urinary chromium (P trend < 0.05). In the longitudinal analysis, each 1-unit increase in log-transformed urinary chromium concentration was associated with a 3% and 6% decrease in the risk of developing hyperTG and hypoHDL-C, respectively (P > 0.05). Our study indicated that significant dose-response relationships between urinary chromium concentration and lipid levels were observed at baseline and at follow-up.

Cardiometabolic traits mediated the relationship from urinary polycyclic aromatic hydrocarbons metabolites to heart rate variability reduction: A community-based study

Polycyclic Aromatic Hydrocarbons (PAHs) exposure was related with metabolic syndrome (MetS) and heart rate variability (HRV) reduction, and HRV was also affected by cardiometabolic traits. However, the role of cardiometabolic traits in the associations from PAHs exposures to HRV was largely unknown. We conducted this study to investigate whether the relationship between PAHs exposure and HRV reduction was mediated by cardiometabolic traits. Levels of urinary polycyclic aromatic hydrocarbons metabolites (OH-PAHs), 10min-HRV, and metabolic traits were accurately measured for 2476 participants from Wuhan-Zhuhai (WHZH) cohort. Single mediator and multiple mediator models were used to evaluate the mediation effects of cadiometabolic traits. The concentrations of ΣOH-PAHs ranged from 4.20 to 8.63 mg/mmol Cr. When compared with the lowest tertile, ΣOH-PAHs in the highest tertile were significantly related with 20% (95% confidence interval [95%CI]:1%, 40%), 35% (95%CI: 14%, 56%), 22% (95%CI: 1%, 44%), and 38% (95%CI: 9%, 68%) decreases in very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) for participants with MetS, respectively. No statistically significant associations between ΣOH-PAHs and HRV indices were observed for participants without MetS. Similar results were found when we investigated the relationships between OH-PAHs and HRV indices by three groups of OH-PAHs (including total hydroxynaphthalene [ΣOHNa], total hydroxy fluorene [ΣOHFlu], and total hydroxyphenanthrene [ΣOHPh] metabolites). Further, mediation analysis suggested that cardiometabolic traits, including fasting glucose (GLU), high density lipoprotein (HDL), and blood pressure partially mediated the relationship from ΣOH-PAHs to HRV reduction. GLU was the strongest mediator, with mediation percentages of 15.70% for VLF, 14.70% for LF, 43.03% for HF, and 5.61% for TP. Our study found that the relationships between OH-PAHs and HRV reduction differed among participants with and without MetS, and these relationships were found to be partially mediated by cardiometabolic traits, especially fasting glucose. Further studies are encouraged to validate our findings and investigate potential mechanisms.

Urinary polycyclic aromatic hydrocarbon metabolites, Club cell secretory protein and lung function

BACKGROUND Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with lung function decline. However, the underlying mechanisms for the association remain unclear. OBJECTIVES To explore potential role of a lung epithelial biomarker, Club cell secretory protein (CC16), in associations between PAH exposures and lung function decline. METHODS We investigated 3384 adults from the Wuhan-Zhuhai cohort, and followed up at three years after first examination. Linear mixed models was used to quantify dose-response relationships between urinary monohydroxylated PAH metabolites (OH-PAHs) and lung function, as well as OH-PAHs and plasma CC16. Mediation analysis was conducted to investigate role of CC16 in the association between OH-PAHs and lung function. We also estimated the relationships between OH-PAHs and lung function change in three years among participants with different levels of CC16. RESULTS Each 1-unit increase of log-transformed total urinary high and low molecular weight OH-PAHs (∑HMW OH-PAH and ∑LMW OH-PAHs) were associated with a 22.59 and 25.25ml reduction of FEV1 respectively, while∑HMW OH-PAH was associated with a 30.38ml reduction of FVC. Moreover, these negative associations between OH-PAHs and lung function levels were significant only among low CC16 group (<15.83ng/ml). CC16 concentration decreased monotonically with increased high molecular weight OH-PAHs (∑HMW OH-PAHs) when ∑HMW OH-PAH concentration was over 0.67μg/mmol Cr. CC16 mediated 22.13% of the association between ∑HMW OH-PAH and FVC among individuals with higher ∑HMW OH-PAH. After three years of follow-up, subjects with low level of plasma CC16 had a significant decline of FVC when exposed to high level of ∑HMW OH-PAH. CONCLUSIONS CC16 play an important role in the association between high molecular weight PAHs and FVC. Individuals with low plasma CC16 level might suffer a decline in lung function when exposed to high level of high molecular weight PAHs.

Impacts of low socioeconomic status and polycyclic aromatic hydrocarbons exposure on lung function among a community-based Chinese population

Lung function is related to socioeconomic status (SES) and exposure to polycyclic aromatic hydrocarbons (PAHs). However, joint effect of SES and exposure to PAHs on lung function has been largely unknown. We aimed to investigate joint effects of SES and urinary OH-PAHs levels on lung function parameters. This study included 2739 Wuhan participants from the baseline survey of the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). They completed the questionnaire, physical examination and provided blood and urine samples. Twelve urinary monohydroxy-PAHs metabolites (OH-PAHs) and lung function were measured by gas chromatography-mass spectrometry and digital spirometers, respectively. Individuals with low educational levels and low or high levels of urinary ΣOH-PAHs had a 3.5% (95% CI: -5.4, -1.6%) or 4.2% (95% CI: -6.1, -2.3%) reduction in the ratio of forced expiratory volume in 1s to forced vital capacity (FEV1/FVC), respectively, and those with middle levels of education and high levels of urinary ΣOH-PAHs had a 2.1% (95% CI: -5.4, -1.6%) reduction in the FEV1/FVC ratio, rather than those with high levels of education and low levels of urinary ΣOH-PAHs. Individuals with low levels of education had a -3.0% (95% CI: -4.4, -1.6%) reduction in FEV1/FVC compared with individuals with high levels of education. Urinary OH-PAHs levels were marginally negatively related to FEV1 in all participants (p=0.073). The results indicated that there was a prominent effect of low levels of education and higher exposure to PAHs on lung function decline, indicating that it is a necessary to take measures to promote the education level and reduce exposure to environmental PAHs.