***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : MicroRNAs ( miRNAs ) are a key factor in epigenetic regulation of gene expression , but miRNA responses to fine particulate matter ( PM2.5 ) air pollution and their potential contribution to cardiovascular effects of PM2.5 are unknown . Objective : We explored the potential influence of PM2.5 on the expression of selected cytokines relevant to systemic inflammation , coagulation , and vasoconstriction , and on miRNAs that may regulate their expression . Methods : We design ed a double-blind , r and omized crossover study in which true and sham air purifiers were used to expose 55 healthy young adult students in Shanghai , China ,  to reduced or ambient levels of indoor PM2.5  during two-week periods , and we measured the expression ( mRNA and protein ) of 10 serum cytokines , and miRNAs that target them , after each intervention period . We used linear mixed-effect models to estimate associations of the intervention , and time-weighted personal PM2.5 exposures , with the cytokines , mRNA , and miRNAs ; we also explored potential mediation by miRNAs . Results : The findings were generally consistent for associations with the intervention and for associations with an interquartile range increase in time-weighted PM2.5 . Specifically , higher PM2.5 exposure was positively associated with the expression ( mRNA , protein , or both ) of interleukin-1 ( encoded by IL1 ) , IL6 , tumor necrosis factor ( encoded by TNF ) , toll-like receptor 2 ( encoded by TLR2 ) , coagulation factor 3 ( encoded by F3 ) , and endothelin 1 ( encoded by EDN1 ) , and was negatively associated with miRNAs ( miR-21 - 5p , miR-187 - 3p , miR-146a-5p , miR-1 - 3p , and miR-199a-5p ) predicted to target mRNAs of IL1 , TNF , TLR2 , and EDN1 . Conclusions : Our findings require confirmation but suggest that effects of PM2.5 on cardiovascular diseases may be related to acute effects on cytokine expression , which may be partly mediated through effects of PM2.5 on miRNAs that regulate cytokine expression . BACKGROUND Short-term exposure to fine particulate matter ( PM2.5 ) air pollution has been associated with altered DNA methylation in observational studies , but it remains unclear whether this change mediates the effects on cardiovascular biomarkers . OBJECTIVE To examine the impact of ambient PM2.5 on gene-specific DNA methylation and its potential mediation in the acute effects of PM2.5 on cardiovascular biomarkers . METHODS We design ed a r and omized , double-blind crossover trial using true or sham air purifiers for 48h among 35 healthy college students in Shanghai , China , in 2014 . We measured blood global methylation estimated in long interspersed nucleotide element-1 ( LINE‑1 ) and Alu repetitive elements , methylation in ten specific genes , and ten cardiovascular biomarkers . We used linear mixed-effect models to examine the associations between PM2.5 and methylation . We also performed causal mediation analyses to evaluate the potential mediation of methylation in the associations between PM2.5 and biomarkers . RESULTS Air purification increased DNA methylation in repetitive elements and all c and i date genes . An IQR increase ( 64μg/m(3 ) ) in PM2.5 was significantly associated with reduction of methylation in LINE-1 ( 1.44 % ) , one pro-inflammatory gene ( CD40LG , 9.13 % ) , two pro-coagulant genes ( F3 , 15.20 % ; SERPINE1 , 3.69 % ) , and two pro-vasoconstriction genes ( ACE , 4.64 % ; EDN1 , 9.74 % ) . There was a significant mediated effect ( 17.82 % , P=0.03 ) of PM2.5 on sCD40L protein through CD40LG hypomethylation . Hypomethylation in other c and i date genes generally showed positive but non-significant mediation . CONCLUSIONS This intervention study provided robust human evidence that ambient PM2.5 could induce rapid decreases in DNA methylation and consequently partly mediate its effects on cardiovascular biomarkers Objective The objective of the study was to analyze the effect of environmental factors on the differential expression of microRNAs in the peripheral blood of migratory and local patients in northern People ’s Republic of China and on clinical symptoms of local patients in northern People ’s Republic of China with COPD . Methods A total of 118 patients in the northern region and 8 migratory patients were enrolled in this prospect i ve study . We collected general information . Blood sample s were collected from 9 patients in the Beijing group , from 8 patients in the migratory group and from 9 healthy control subjects . After extracting the total RNA from these 3 groups , serum miRNA was identified by Solexa sequencing . We collected  COPD assessment test ( CAT ) and Modified British Medical Research Council ( mMRC ) scores at different levels of air pollution and also collected the  number of exacerbations  over the year prior to the baseline and in the year preceding the follow-up . Results In total 9 miRNAs were differentially expressed . When air quality index ( AQI ) > 100 , the CAT and mMRC scores at baseline were significantly higher than those when the AQI ≤100 ( P<0.001 ) . When AQI > 100 , the follow-up CAT and mMRC scores were significantly higher than those when AQI ≤100 ( P<0.001 ) . Follow-up mMRC scores were significantly higher than baseline scores ( P=0.04 ) . When AQI ≤100 , the baseline CAT score of the group with fewer symptoms was 6.50 ( 4.00–8.75 ) . However , when AQI > 100 , the baseline CAT score of this fewer symptoms group was 10.00 ( 6.25–12.00 ) . The median CAT score was close to 10 . When AQI ≤100 , the follow-up CAT score of the fewer symptoms group was 8.00 ( 4.25–12.00 ) . However , when AQI > 100 , the follow-up CAT score of the fewer symptoms group was 9.50 ( 6.00–16.75 ) . The median CAT score was close to 10 . Conclusion Environmental factors may cause differential expression of miRNAs in the peripheral blood of migratory and local patients in northern People ’s Republic of China . Air pollution may aggravate clinical symptoms of patients with COPD Background : Epidemiological studies have reported associations between particulate matter ( PM ) concentrations and  cancer and respiratory and cardiovascular diseases .  DNA methylation has been identified as a possible link but so far it has only been analyzed in c and i date sites . Objectives : We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation . Methods : We collected  whole blood sample s from three independent studies —KORA F3 ( 2004–2005 ) and F4 ( 2006–2008 ) in Germany , and the Normative Aging Study ( 1999–2007 ) in the United States— and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip .  PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation : 2-day , 7-day and 28-day . Meta- analysis was performed to pool the study -specific results . Results : R and om-effect meta- analysis revealed 12 CpG ( cytosine-guanine dinucleotide ) sites as associated with PM concentration ( 1 for 2-day average , 1 for 7-day , and 10 for 28-day ) at a genome-wide Bonferroni significance level ( p ≤ 7.5E-8 ) ; 9 out of these 12 sites expressed increased methylation . Through estimation of I2 for homogeneity assessment across the studies , 4 of these sites ( annotated in NSMAF , C1orf212 , MSGN1 , NXN ) showed p > 0.05 and I2 < 0.5 : the site from the 7-day average results and 3 for the 28-day average . Applying false discovery rate , p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively . Conclusion : The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation . Citation : Panni T , Mehta AJ , Schwartz JD , Baccarelli AA , Just AC , Wolf K , Wahl S , Cyrys J , Kunze S , Strauch K , Waldenberger M , Peters A. 2016 . A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study population s : KORA F3 , KORA F4 , and the Normative Aging Study . Environ Health Perspect 124:983–990 ; Background Air pollution from particulate matter ( PM ) has been linked to cardiovascular morbidity and mortality ; however the underlying biological mechanisms remain to be uncovered . Gene regulation by microRNAs ( miRNAs ) that are transferred between cells by extracellular vesicles ( EVs ) may play an important role in PM-induced cardiovascular risk . This study sought to determine if ambient PM2.5 levels are associated with expression of EV-encapsulated miRNAs ( evmiRNAs ) , and to investigate the participation of such evmiRNAs in pathways related to cardiovascular disease ( CVD ) . Methods We estimated the short- ( 1-day ) , intermediate- ( 1-week and 1-month ) and long-term ( 3-month , 6-month , and 1-year ) moving averages of ambient PM2.5 levels at participants ’ addresses using a vali date d hybrid spatio-temporal l and -use regression model . We collected 42 serum sample s from 22 r and omly selected participants in the Normative Aging Study cohort and screened for 800 miRNAs using the NanoString nCounter ® platform  . Mixed effects regression models , adjusted for potential confounders were used to assess the association between ambient PM2.5 levels and evmiRNAs . All p-values were adjusted for multiple comparisons . In-silico Ingenuity Pathway Analysis ( IPA ) was performed to identify biological pathways that are regulated by PM-associated evmiRNAs . Results We found a significant association between long-term ambient PM2.5 exposures and levels of multiple evmiRNAs circulating in serum . In the 6-month window , ambient PM2.5 exposures were associated with increased levels of miR-126 - 3p ( 0.74 ± 0.21 ; p = 0.02 ) , miR-19b-3p ( 0.52 ± 0.15 ; p = 0.02 ) , miR-93 - 5p ( 0.78 ± 0.22 ; p = 0.02 ) , miR-223 - 3p ( 0.74 ± 0.22 ; p = 0.02 ) , and miR-142 - 3p ( 0.81 ± 0.21 ; p = 0.03 ) . Similarly , in the 1-year window , ambient PM2.5 levels were associated with increased levels of miR-23a-3p ( 0.83 ± 0.23 ; p = 0.02 ) , miR-150 - 5p ( 0.90 ± 0.24 ; p = 0.02 ) , miR-15a-5p ( 0.70 ± 0.21 ; p = 0.02 ) , miR-191 - 5p ( 1.20 ± 0.35 ; p = 0.02 ) , and let-7a-5p ( 1.42 ± 0.39 ; p = 0.02 ) . In silico pathway analysis on PM2.5-associated evmiRNAs identified several key CVD-related pathways including oxidative stress , inflammation , and atherosclerosis . Conclusions We found an association between long-term ambient PM2.5 levels and increased levels of evmiRNAs circulating in serum . Further observational studies are warranted to confirm and extend these important findings in larger and more diverse population s , and experimental studies are needed to eluci date the exact roles of evmiRNAs in PM-induced CVD Air pollution is associated with a broad range of adverse health effects , including mortality and morbidity due to cardio‐ and cerebrovascular diseases ( CCVD ) , but the molecular mechanisms involved are not entirely understood . This study aims to investigate the involvement of oxidative stress and inflammation in the causal chain , and to identify intermediate biomarkers that are associated retrospectively with the exposure and prospect ively with the disease . We design ed a case‐control study on CCVD nested in a cohort of 18,982 individuals from the EPIC‐Italy study . We measured air pollution , inflammatory biomarkers , and whole‐genome DNA methylation in blood  collected up to 17 years before the diagnosis . The study sample includes 
    Output:
    
Panel and experimental studies revealed a relatively large number of significant methylome alterations , though based on smaller sample sizes .
Particulate matter levels were positively associated in several studies with global or LINE-1 hypomethylation , a hallmark of several diseases , and with decondensed chromatin structure .
Several air pollution species altered the DNA methylation clock , inducing accelerated biological aging .
The causal nature of identified associations is not clear , however , especially that most originate from countries with low air pollution levels .