Fine particulate matter exposure and systemic inflammation: A potential mediating role of bioactive lipids.

Inflammation is a key mechanism underlying the adverse health effects of exposure to fine particulate matter (PM2.5). Bioactive lipids in the arachidonic acid (ARA) pathway are important in the regulation of inflammation and are reportedly altered by PM2.5 exposure. Ceramide-1-phosphate (C1P), a class of sphingolipids, is required to initiate ARA metabolism. We examined the role of C1P in the alteration of ARA metabolism after PM2.5 exposure and explored whether changes in the ARA pathway promoted systemic inflammation based on a panel study involving 112 older adults in Beijing, China. Ambient PM2.5 levels were continuously monitored at a fixed station from 2013 to 2015. Serum cytokine levels were measured to assess systemic inflammation. Multiple bioactive lipids in the ARA pathway and three subtypes of C1P were quantified in blood samples. Mediation analyses were performed to test the hypotheses. We observed that PM2.5 exposure was positively associated with inflammatory cytokines and the three subtypes of C1P. Mediation analyses showed that C1P significantly mediated the associations of ARA and 5, 6-dihydroxyeicosatrienoic acid (5, 6-DHET), an ARA metabolite, with PM2.5 exposure. ARA, 5, 6-DHET, and leukotriene B4 mediated systemic inflammatory response to PM2.5 exposure. For example, C1P C16:0 (a subtype of C1P) mediated a 12.9 % (95 % confidence interval: 3.7 %, 32.5 %) increase in ARA associated with 3-day moving average PM2.5 exposure, and ARA mediated a 27.1 % (7.8 %, 61.2 %) change in interleukin-8 associated with 7-day moving average PM2.5 exposure. Our study indicates that bioactive lipids in the ARA and sphingolipid metabolic pathways may mediate systemic inflammation after PM2.5 exposure.

Assessing the impact of incentive coordination effect on the equilibrium of agricultural water usage by China's South-to-North Water Diversion Middle Route Project.

In recent years, the sustainable development of agricultural water resources has received much attention. The mismatch between agricultural water distribution patterns, land resources, and socioeconomics threatens food production, especially in vast water-scarce plains. Therefore, monitoring agricultural water spatial equilibrium (AWRSE) is necessary. Based on equilibrium theory and information entropy, in this study, the AWRSE evaluation model is constructed from three aspects: agricultural water resources, land resources, and socioeconomics. In addition, the relationship between social factors with cropping pattern as the primary explanatory variable and AWRSE was examined in conjunction with the extended STIRPAT model and applied to the water-receiving area of the Middle Route of South-to-North Water Diversion Project (MR-SNWDP). The results show that compared with the pre-diversion period, the AWRSE of 75% of the water-receiving cities has been significantly improved by the MR-SNWTP water supply. The MK test z value of the overall regional AWRSE has changed from - 0.328 to - 2.65, and the AWRSE development has shifted from not significantly better to significantly better. The cropping pattern shows a positive response to this development, and this effect can be mitigated in the late stage of water transfer; when the proportion of food crop cultivation increases by 1%, the sub-regional AWRSE value will increase by 0.347%. The evaluation model demonstrates a broad range of inclusiveness and application potential; it provides novel insights for examining agroecological, social, and economic stability.

Uterine Immunoprivileged Cells Restore Cardiac Function of Male Recipients After Myocardial Infarction.

It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction, being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, we aimed to fill in this gap in knowledge by examining the effects of transplanted uterine cells on infarcted male hearts. We identified, based on major histocompatibility complex class I (MHC-I) expression levels, 3 uterine reparative cell populations: MHC-I(neg), MHC-I(mix), and MHC-I(pos). In vitro, MHC-I(neg) cells showed higher levels of pro-angiogenic, pro-survival, and anti-inflammatory factors, compared to MHC-I(mix) and MHC-I(pos). Furthermore, when cocultured with allogeneic mixed leukocytes, MHC-I(neg) had lower cytotoxicity and leukocyte proliferation. In particular, CD8+ cytotoxic T cells significantly decreased, while CD4+CD25+ Tregs and CD4-CD8- double-negative T cells significantly increased when cocultured with MHC-I(neg), compared to MHC-I(mix) and MHC-I(pos) cocultures. In vivo, MHC-I(neg) as well as MHC-I(mix) were found under both syngeneic and allogeneic transplantation in infarcted male hearts, to significantly improve cardiac function and reduce the scar size, via promoting angiogenesis in the infarcted area. All of these findings thus support the view that males could also benefit from the cardio-protective effects observed among females, via cell therapy approaches involving the transplantation of immuno-privileged uterine reparative cells in infarcted hearts.

Multiple temporal reference frames revealed by a reproduction task.

The study investigates whether participants can establish multiple temporal references in a temporal reproduction task. The results show that participants can learn and maintain two references for the overlapping intervals with the short distribution being overestimated towards the long one.

Effect of the Lipoxin Receptor Agonist BML-111 on Cigarette Smoke Extract-Induced Macrophage Polarization and Inflammation in RAW264.7 Cells.

Background: Macrophages are known to play a crucial role in the chronic inflammation associated with Chronic Obstructive Pulmonary Disease (COPD). BML-111, acting as a lipoxin A4 (LXA4) receptor agonist, has shown to be effective in protecting against COPD. However, the precise mechanism by which BML-111 exerts its protective effect remains unclear. Methods: In order to establish a cell model of inflammation, cigarette smoke extract (CSE) was used on the RAW264.7 cell line. Afterwards, an Enzyme-linked immunosorbent assay (ELISA) kit was employed to measure concentrations of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1ß), interleukin-18 (IL-18), and interleukin-10 (IL-10) in the cell supernatants of the RAW264.7 cells.In this study, we examined the markers of macrophage polarization using two methods: quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Additionally, we detected the expression of Notch-1 and Hes-1 through Western blotting. Results: BML-111 effectively suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-18, as well as inflammasome factors NLRP3 and Caspase-1, while simultaneously up-regulating the expression of the anti-inflammatory cytokine IL-10 induced by CSE. Moreover, BML-111 reduced the expression of iNOS, which is associated with M1 macrophage polarization, and increased the expression of Arg-1, which is associated with M2 phenotype. Additionally, BML-111 downregulated the expression of Hes-1 and the ratio of activated Notch-1 to Notch-1 induced by CSE. The effect of BML-111 on inflammation and macrophage polarization was reversed upon administration of the Notch-1 signaling pathway agonist Jagged1. Conclusion: BML-111 has the potential to suppress inflammation and modulate M1/M2 macrophage polarization in RAW264.7 cells. The underlying mechanism may involve the Notch-1 signaling pathway.

ELANE Promotes M2 Macrophage Polarization by Down-Regulating PTEN and Participates in the Lung Cancer Progression.

BACKGROUND: Macrophages are one of the most important immunoinflammatory cell populations in the tumor microenvironment (TME). In this study, we preliminarily investigated the upstream pathway of M2 macrophage polarization affecting lung cancer progression. METHODS: Bioinformatics analysis was used to evaluate genes closely associated with lung adenocarcinoma and their relationship with immune cells. THP-1 monocytes were induced into M2 macrophages. The expression of markers in M2 macrophages was detected by quantitative reverse transcription-PCR (qRT-PCR), enzyme linked immunosorbent assay (ELISA), and flow cytometry. The effects of neutrophil elastase (ELANE)-mediated M2 macrophages on lung cancer cell proliferation, migration and invasion and tumor growth were investigated by in vitro and in vivo experiments after co-culture of macrophage conditioned medium (CM) and lung cancer cell lines A549 and H1299. The PTEN protein expression was detected by Western blotting. RESULTS: ELANE was significantly positively correlated with M2 macrophages. ELANE up-regulated the expression of the M2 macrophage markers CD206, CCL22, IL-10 and CCL18 and increased the proportion of CD206+ macrophages. Compared with M0-CM, M2-CM promoted cell proliferation, migration, and invasion, and (M2+ELANE)-CM further enhanced this effect. In vivo, ELANE promoted M2 macrophage-induced tumor growth in lung cancer mice model. In vitro experiments showed that ELANE can down-regulate the expression of PTEN and promote the polarization of M2 macrophages. CONCLUSION: ELANE promotes the polarization of M2 macrophages by down-regulating PTEN, thus promoting cell proliferation, migration, and invasion in vitro and growth of lung cancer cells in vivo.

Epicardial delivery of a conductive membrane synchronizes conduction to reduce atrial fibrillation.

Conductive polymers have been investigated as a medium for the transmission of electrical signals in biological tissues, but their capacity to rewire cardiac tissue has not been evaluated. Myocardial tissue is unique in being able to generate an electrical potential at a fixed rate; this potential spreads rapidly among cells to trigger muscle contractions. Tissue injuries result in myocardial fibrosis and subsequent non-uniform conductivity, leading to arrhythmia. Atrial fibrillation (AF) is the most common sustained arrhythmia, associated with disruption of atrial electrical signaling, which can potentially be restored by the epicardial delivery of conductive polymers. In this work, poly-3-amino-4-methoxybenzoic acid, conjugated to gelatin, is fabricated as a membrane (PAMB-G) to support conductive velocities that are close to that of the myocardium. A cross-linked gelatin membrane (Gelatin) is used as a control. The as-fabricated PAMB-G has similar tensile elasticities, determined using the Young's modulus, as contracting myocardium; it can also transmit electrical signals to initiate cardiac cell and tissue excitation. Delivering PAMB-G onto the atrium of a rat AF model shortens AF duration and improves post-AF recovery for the duration of a 28-day-long study. Atrial tissue in the PAMB-G-implanted group has lower impedance, higher conduction velocity, and higher field potential amplitude than that in the Gelatin-implanted group. Therefore, the as-proposed PAMB-G is a suitable medium for restoring proper cardiac electrical signaling in AF hearts.

Partitioning indoor-generated and outdoor-generated PM2.5 from real-time residential measurements in urban and peri-urban Beijing.

Limited number of projects have attempted to partition and quantify indoor- and outdoor-generated PM2.5 (PM2.5ig and PM2.5og) where strong indoor sources (e.g., solid fuel, tobacco smoke, or kerosene) exist. This study aimed to apply and refine a previous recursive model used to derive infiltration efficiency (Finf) to additionally partition pollution concentrations into indoor and outdoor origins within residences challenged by elevated ambient and indoor combustion-related sources. During the winter of 2016 and summer of 2017 we collected residential measurements in 72 homes in urban and peri-urban Beijing, 12 of which had additional paired residential outdoor measurements during the summer season. Local ambient measurements were collected throughout. We then compared the calculated PM2.5ig and using (i) outdoor and (ii) ambient measurements as model inputs. The results from outdoor and ambient measurements were not significantly different, which suggests that ambient measurements can be used as a model input for pollution origin partitioning when paired outdoor measurements are not available. From the results calculated using ambient measurements, the mean percentage contribution of indoor-generated PM2.5 was 19 % (σ = 22 %), and 7 % (11 %) of the total indoor PM2.5 for peri-urban and urban homes respectively during the winter; and 18 % (18 %) and 6 % (10 %) of the total indoor PM2.5 during the summer. Partitioning pollution into PM2.5ig and PM2.5og is important to allow investigation of distinct associations between health outcomes and particulate mixes, often with different physiochemical composition and toxicity. It will also inform targeted interventions that impact indoor and outdoor sources of pollution (e.g., domestic fuel switching vs. power generation), which are typically radically different in design and implementation.

Associations of pregnancy complications with ambient air pollution in China.

BACKGROUND: Gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM) are common pregnancy complications and can result in maternal and prenatal morbidity and mortality. Air pollution exposure could adversely impact pregnancy complications; however, evidence remains limited in China, where ambient air pollution is relatively severe. OBJECTIVE: This study aims to examine the associations of GH, PE, and GDM with exposure to six air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) during pregnancy. METHODS: Leveraging a multicenter birth cohort study among pregnant women in 24 hospitals from 15 provinces in China, we obtained data for maternal characteristics and pregnancy outcomes. We generated ambient concentrations of the six air pollutants using a combination of chemical transport model simulations with monitoring data. We used multivariable logistic regression models to estimate the effects on pregnancy complications from exposure to six air pollutants in each trimester and the entire pregnancy. RESULTS: Among the total 3754 pregnant women in this study, the prevalences of GH, GDM, and PE were 2.6 %, 11.2 %, and 0.7 %, respectively. GH risk increased 11.9 % (95 % CI, -8.5 %, 36.8 %) and 13.8 % (1.4 %, 27.8 %) per 10 µg/m3 increases in PM2.5 and PM10 in the entire pregnancy, respectively. PM2.5 and PM10 exposures in the first trimester were significantly associated with an increased risk of GDM. Exposure to O3, SO2, NO2, and CO in early pregnancy could be associated with GDM risk. Geographic region and season of conception may influence the associations of GH and PE with air pollution. CONCLUSIONS: Ambient particulate matter pollution adversely affects GH, GDM, and PE among Chinese pregnant women. Since most regions of China still suffer from hazardous levels of air pollution, our findings indicate importance of better protecting pregnant women from the risk of air pollution.

Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids.

BACKGROUND: The pathophysiological mechanisms of air pollution-induced atherosclerosis are incompletely understood. Sphingolipids serve as biological intermediates during atherosclerosis development by facilitating production of proatherogenic apoB (apolipoprotein B)-containing lipoproteins. We explored whether sphingolipids mediate the proatherogenic effects of air pollution. METHODS: This was a prospective panel study of 110 participants (mean age 56.5 years) followed from 2013 to 2015 in Beijing, China. Targeted lipidomic analyses were used to quantify 24 sphingolipids in 579 plasma samples. The mass concentrations of ambient particulate matter ≤2.5 µm in diameter (PM2.5) were continuously monitored by a fixed station. We evaluated the associations between sphingolipid levels and average PM2.5 concentrations 1-30 days before clinic visits using linear mixed-effects models and explored whether sphingolipids mediate PM2.5-associated changes in the levels of proatherogenic apoB-containing lipoproteins (LDL-C [low-density lipoprotein cholesterol] and non-HDL-C [nonhigh-density lipoprotein cholesterol]) using mediation analyses. RESULTS: We observed significant increases in the levels of non-HDL-C and fourteen sphingolipids associated with PM2.5 exposure, from short- (14 days) to medium-term (30 days) exposure time windows. The associations exhibited near-monotonic increases and peaked in 30-day time window. Increased levels of the sphingolipids, namely, sphinganine, ceramide C24:0, sphingomyelins C16:0/C18:0/C18:1/C20:0/C22:0/C24:0, and hexosylceramides C16:0/C18:0/C20:0/C22:0/C24:0/C24:1 significantly mediated 32%, 58%, 35% to 93%, and 23% to 86%, respectively, of the positive association between 14-day PM2.5 average and the non-HDL-C level, but not the LDL-C level. Similar mediation effects (19%-91%) of the sphingolipids were also observed in 30-day time window. CONCLUSIONS: Our results suggest that sphingolipids may mediate the proatherogenic effects of short- and medium-term PM2.5 exposure.

Ceramide metabolism mediates the impaired glucose homeostasis following short-term black carbon exposure: A targeted lipidomic analysis.

BACKGROUND: Ambient particulate matter (PM), especially its carbonaceous composition black carbon (BC) increases cardiometabolic risks, yet the underlying mechanisms are incompletely understood. Ceramides (Cer; a class of sphingolipids) are biological intermediates in glucose metabolism. OBJECTIVES: To explore whether Cer metabolism mediates impaired glucose homeostasis following short-term PM exposure. METHODS: In a panel study in Beijing, China, 112 participants were followed-up between 2016 and 2017. Targeted lipidomic analyses quantified 26 sphingolipids in 387 plasma samples. Ambient BC and PM with aerodynamic diameter ≤ 2.5 µm (PM2.5) were continuously monitored in a station. We examined the associations of sphingolipid levels with average BC and PM2.5 concentrations 1-14 days before clinical visits using linear mixed-effects models, and explored the mediation effects of sphingolipids on PM-associated fasting blood glucose (FBG) difference using mediation analyses. RESULTS: Increased levels of FBG and multiple sphingolipids in Cer metabolic pathways were associated with BC exposure in 1-14-day time window, but not with PM2.5 exposure. For each 10 µg/m3 increase in the average BC concentration 1-14 days before the clinical visits, species in the Cer C24:1 pathway (Cer, dihydroceramide, hexosylceramide, lactosylceramide, and sphingomyelin C24:1) increased in levels ranging from 11.8% (95% confidence interval [CI]: -6.2-33.2) to 48.7% (95% CI: 8.8-103.4), as did the Cer C16:0, C18:0, and C20:0 metabolic pathway species, ranging from 3.2% (95% CI: -5.6-12.9) to 32.4% (95% CI: 7.0-63.8), respectively. The Cer C24:1 metabolic pathway species mediated 6.5-25.5% of the FBG increase associated with BC exposure in 9-day time window. The Cer C16:0, C18:0, and C20:0 metabolic pathway species mediated 5.4-26.2% of the BC-associated FBG difference. CONCLUSIONS: In conclusion, Cer metabolism may mediate impaired glucose homeostasis following short-term BC exposure. The current findings are preliminary, which need to be corroborated by further studies.

Personal exposure to electrophilic compounds of fine particulate matter and the inflammatory response: The role of atmospheric transformation.

Atmospheric oxidation can produce electrophilic compounds, altering the health effects induced by fine particulate matter (PM2.5); however, little is known about these electrophilic compounds or their health effects. Using electron capture negative ionization, we systematically detected 301 electrophilic compounds from personal PM2.5 samples in a panel study in urban Beijing. Most were oxygen-containing compounds with 3-17 double bond equivalents (DBE), suggesting the dominance of oxidized aromatic structures. Over 64% of the species, mostly outdoor-originated, were associated with inflammatory cytokines in both exhaled breath condensate and serum. Primary components of polycyclic aromatic hydrocarbons (PAHs) and high-DBE oxygenated PAHs, mainly from fossil fuel combustion, were positively associated with interleukin (IL)- 6, a cytokine related to oxidative homeostasis. Oxidized secondary species, particularly maleic and phthalic anhydrides, were negatively associated with IL-2/IL-8, which changed by - 3.8% to - 16.4% per one-fold increase in the abundance of the secondary source, indicating the immune disorders in response to the oxidized aerosols. Mediation analysis demonstrated the necessity of transformation products between atmospheric oxidation capacity and IL-2/IL-8 inhibition. This study provides new information on particulate electrophilic compounds and highlights the role of atmospheric chemistry in specific immune disorders.

Bio-Conductive Polymers for Treating Myocardial Conductive Defects: Long-Term Efficacy Study.

Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), is able to resynchronize myocardial contractions in vivo. Intravenous PAMB-G injections into mice show that it does not cause any acute toxicity, up to the maximum tolerated dose (1.6 mL kg-1 ), which includes the determined therapeutic dose (0.4 mL kg-1 ). There is also no short- or long-term toxicity when PAMB-G is injected into the myocardium of MI rats, with no significant changes in body weight, organ-brain ratio, hematologic, and histological parameters for up to 12 months post-injection. At the therapeutic dose, PAMB-G restores electrical conduction in infarcted rat hearts, resulting in lowered arrhythmia susceptibility and improved cardiac function. PAMB-G is also durable, as mass spectrometry detected the biopolymer for up to 12 months post-injection. PAMB-G did not impact reproductive organ function or offspring characteristics when given intravenously into healthy adult rats. Thus, PAMB-G is a nontoxic, durable, and conductive biomaterial that is able to improve cardiac function for up to 1 year post-implantation.

Organic Components of Personal PM2.5 Exposure Associated with Inflammation: Evidence from an Untargeted Exposomic Approach.

Fine particulate matter (PM2.5) can promote chronic diseases through the fundamental mechanism of inflammation; however, systemic information is lacking on the inflammatory PM2.5 components. To decipher organic components from personal PM2.5 exposure that were associated with respiratory and circulatory inflammatory responses in older adults, we developed an exposomic approach using trace amounts of particles and applied it on 424 personal PM2.5 samples collected in a panel study in Beijing. Applying an integrated multivariate and univariate untargeted strategy, a total of 267 organic compounds were filtered and then chemically identified according to their association with exhaled nitric oxide (eNO)/interleukin (IL)-6 or serum IL-1ß/IL-6, with monocyclic and polycyclic aromatic compounds (i.e., MACs and PACs) as the representatives. Indoor-derived species with medium volatility including MACs were mainly associated with systemic inflammation, while low-volatile ambient components that originate from combustion sources, such as PACs, were mostly associated with airway inflammation. Following ambient component exposure, we found an inverted U-shaped relationship on change of eNO with insulin resistance, suggesting a higher risk of cardiopulmonary dysfunction for individuals with homeostatic model assessment for insulin resistance (HOMA-IR) levels > 2.3. Overall, this study provided a practical untargeted strategy for the systemic investigation of PM2.5 components and proposed source-specific inflammatory effects.

SARS pandemic exposure impaired early childhood development in China.

Social and mental stressors associated with the pandemic of a novel infectious disease, e.g., COVID-19 or SARS may promote long-term effects on child development. However, reports aimed at identifying the relationship between pandemics and child health are limited. A retrospective study was conducted to associate the SARS pandemic in 2003 with development milestones or physical examinations among longitudinal measurements of 14,647 children. Experiencing SARS during childhood was associated with delayed milestones, with hazard ratios of 3.17 (95% confidence intervals CI: 2.71, 3.70), 3.98 (3.50, 4.53), 4.96 (4.48, 5.49), or 5.57 (5.00, 6.20) for walking independently, saying a complete sentence, counting 0-10, and undressing him/herself for urination, respectively. These results suggest relevant impacts from COVID-19 on child development should be investigated.

Changes in bioactive lipid mediators in response to short-term exposure to ambient air particulate matter: A targeted lipidomic analysis of oxylipin signaling pathways.

BACKGROUND: Exposure to ambient air particulate matter (PM) is a risk factor for cardiometabolic diseases. The knowledge of the underlying mechanisms is still evolving, but systemic inflammation and oxidative stress are central to the ability of PM to induce cardiometabolic effects. Oxylipins derived from polyunsaturated fatty acids (PUFAs) are bioactive lipid mediators that have fundamental roles in the signaling of inflammatory events. However, the associations between oxylipins and short-term exposure to PM in humans are unknown. METHODS: Using targeted lipidomic analyses, we measured 16 oxylipins derived from lipoxygenase (LOX), cytochrome P450 (CYP), and cyclooxygenase (COX) pathways and their parent PUFAs in serum samples of 110 adults enrolled in a panel study in Beijing, China. Each participant completed 2-7 clinical visits from 2013 to 2015. PM with aerodynamic diameter ≤ 2.5 µm (PM2.5) and ≤ 0.1 µm (ultrafine particles, UFPs) were continuously monitored at a station. Linear mixed-effects models were applied to examine the associations between changes in lipid mediators and exposure to ambient PM during the preceding 1 to 3 days before the clinical visit. RESULTS: Serum concentrations of PUFAs, including omega-6 arachidonic acid (ARA) and omega-3 eicosapentaenoic acid (EPA), were significantly increased in association with interquartile range (IQR) increases in PM with different exposure windows (i.e., 1-3 days). Regarding oxylipins, significant PM-associated changes included increases in LOX-derived leukotriene B4 (LTB4), 12(S)-, 15(S)-hydroxyeicosatetraenoic acid (HETE), 12-hydroxyeicosapentaenoic acid (HEPE), and 17-hydroxydocosahexaenoic acid (HDHA); an increase in CYP-derived 5,6-dihydroxyeicosatrienoic acid (DHET); and a decrease in COX-derived prostaglandin E2. CONCLUSIONS: Short-term exposure to PM was associated with PUFAs and oxylipins derived from LOX, CYP, and COX pathways in humans. Our findings provide mechanistic insight suggesting bioactive oxylipins might be used as biomarkers and have important implications as mediators of PM-associated systemic cardiometabolic effects.

Susceptibility of individuals with chronic obstructive pulmonary disease to respiratory inflammation associated with short-term exposure to ambient air pollution: A panel study in Beijing.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. There is no clear evidence of whether COPD patients are more susceptible to respiratory inflammation associated with short-term exposure to air pollutants than those without COPD. OBJECTIVES: This study directly compared air pollutant-associated respiratory inflammation between COPD patients and healthy controls. METHODS: This study is based on the COPDB panel study (COPD in Beijing). Fractional exhaled nitric oxide (FeNO) was repeatedly measured in 53 COPD patients and 82 healthy controls at up to four clinical visits. Concentrations of carbon monoxide (CO), nitrogen monoxide, nitrogen dioxide (NO2), sulfur dioxide (SO2), fine particulate matter (PM2.5), black carbon (BC), ultrafine particles (UFPs), and accumulated-mode particles (Acc) were monitored continuously at a fixed-site monitoring station. Linear mixed-effects models were used to compare the associations between ln-transformed FeNO and average 1-23 h concentrations of air pollutants before the clinical visits. RESULTS: FeNO was positively associated with interquartile range (IQR) increases in average concentrations of CO, NO2, SO2, BC, UFPs, and Acc in all participants, with the strongest associations in different time-windows (range from 6.6% for average 1 h NO2 exposure to 32.1% for average 7 h SO2 exposure). Associations between FeNO and average 13-23 h PM2.5 exposure differed significantly according to COPD status. Increases in FeNO associated with average 1-2 h NO exposure were significant in COPD patients (range 8.9-10.2%), while the associations were nonsignificant in healthy controls. Associations between FeNO and average 1-23 h CO and SO2 exposure tended to be higher in COPD patients than in healthy controls, although the differences were not significant. UFPs-associated respiratory inflammation was robust in both subgroups. CONCLUSIONS: COPD patients are more susceptible to respiratory inflammation following PM2.5, NO, CO, and SO2 exposure than individuals without COPD.

Association between a Rapid Reduction in Air Particle Pollution and Improved Lung Function in Adults.

Rationale: Lung function impairment is reportedly associated with elevated exposure to ambient fine particles (particulate matter ≤2.5 µm in aerodynamic diameter [PM2.5]). However, whether improvement of air quality prevents respiratory diseases is unclear.Objectives: To examine whether the policy-driven reduction in PM2.5 concentration after 2013 was associated with improved lung function among Chinese adults.Methods: We compared the longitudinal measurements of peak expiratory flow (PEF) before (2011) and after (2013 and 2015) China's clean air actions. Long-term exposure to ambient pollution was assessed using a state-of-the-art estimator of historical PM2.5 concentration, and its association with PEF was examined using a linear mixed-effects model. The robustness and homogeneity of the association were examined via sensitivity analyses.Results: We analyzed 35,055 repeated measurements from 13,959 adults. Mean of age at survey was 60.5 years (standard deviation = 9.7 yr). Compared with the reference in 2011, after the policy was implemented, the mean PEF was elevated by 9.19 (6.79-11.59) L/min and 36.64 (33.53-39.75) L/min in 2013 and 2015, respectively. According to the regression results, each 10-µg/m3 reduction of PM2.5 was associated with a 14.95 (12.62-17.28) L/min improvement of PEF. The significance of the association was not affected by adjustments for covariates, inclusion criteria, or the approach to control for the effects of age. Adults of lower socioeconomic status (e.g., those with an educational level of below middle school or rural residents) were more susceptible to the adverse effects of PM2.5 on PEF.Conclusions: We found a robust association between a reduction in PM2.5 and an increase in PEF among Chinese adults. The findings suggest that mitigation of air pollution can promote respiratory health.

MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA.

Kidney stone disease is a crystal concretion formed in the kidneys that has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis, and caused lipid accumulation in an immortalized renal tubular cell line (HK-2). Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation, and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed the peroxisome proliferator-activated receptor (PPAR)-α gene (PPARA) a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPAR-α by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients with calcium oxalate renal stones compared with healthy volunteers. In situ hybridization of biopsy samples from patients with nephrocalcinosis revealed that miR-21 was also significantly upregulated compared with normal kidney tissues from patients with renal cell carcinoma who underwent radical nephrectomy. These results suggested that miR-21 promoted calcium oxalate-induced renal tubular cell injury by targeting PPARA, indicating that miR-21 could be a potential therapeutic target and biomarker for nephrolithiasis.

Association of internal exposure to polycyclic aromatic hydrocarbons with inflammation and oxidative stress in prediabetic and healthy individuals.

Polycyclic aromatic hydrocarbons (PAHs) are key air pollutants that may contribute to the risk of numerous diseases by inducing inflammation and oxidative stress. Individuals with metabolic disorders may be more susceptible to PAH-induced inflammation and oxidative stress. To test this hypothesis, we designed a panel study involving 60 patients with pre-type 2 diabetes (pre-T2D) and 60 reference participants, and conducted up to seven repeated clinical examinations. Urinary metabolites of PAHs (i.e., OH-PAHs), measured as indicators of total PAH exposure, showed significant associations with markers of respiratory and systemic inflammation, including exhaled nitric oxide, interleukin (IL)-6 in exhaled breath condensate, and blood IL-2 and IL-8 levels and leucocyte count. The most significant effect was on urinary malondiadehyde (MDA), a marker of lipid peroxidation; a onefold increase of OH-PAHs was associated with 9.2-46.0% elevation in MDA in pre-T2D participants and 9.8-31.2% increase in healthy references. Pre-T2D participants showed greater increase in MDA, suggesting that metabolic disorder enhanced the oxidative damage induced by PAH exposure. This study revealed the association between PAH exposure and markers of inflammation and oxidative stress, and the enhanced responses of pre-T2D patients suggested that individuals with metabolic disorders were more susceptible to the adverse health effects of PAH exposure.