Exposure to diesel exhaust particulates and desert sand dust generates microvesicle particles and platelet-activating factor agonists

The authors address the editor in their article, stating that the majority of the general population, particularly, servicemen and women deployed across the globe are exposed to various airborne hazards, including diesel exhaust particulate (DEP) and desert sand dust (DSD). Studies, including the author's study, have shown that exposure to ROS-generating pro-oxidative stressors ranging from environmental carcinogens to pollutants, including cigarette smoke, produces a class of potent phospholipid mediators, Platelet-activating factor (PAF) and PAF-like agonists via oxidative cleavage of lipid membrane glycerophosphocholines (GPCs)

Inhaled diesel exhaust particles result in microbiome‑related systemic inflammation and altered cardiovascular disease biomarkers in C57Bl/6 male mice

Article discusses the authors' investigation the hypothesis that exposure to inhaled diesel exhaust particles alters the gut microbiome and promotes microbial-related inflammation and cardiovascular disease biomarkers. To determine whether probiotics could prevent diet or DEP exposure mediated alterations in the gut microbiome or systemic outcomes, a subset of animals on the HF diet were treated orally with 0.3 g/day (~ 7.5 × 108 CFU/day) of Winclove Ecologic® Barrier probiotics throughout the study

Vascular and Cardiac Impairments in Rats Inhaling Ozone and Diesel Exhaust Particles

BackgroundMechanisms of cardiovascular injuries from exposure to gas and particulate air pollutants are unknown.ObjectiveWe sought to determine whether episodic exposure of rats to ozone or diesel exhaust particles (DEP) causes differential cardiovascular impairments that are exacerbated by ozone plus DEP.Methods and resultsMale Wistar Kyoto rats (10–12 weeks of age) were exposed to air, ozone (0.4 ppm), DEP (2.1 mg/m3), or ozone (0.38 ppm) + DEP (2.2 mg/m3) for 5 hr/day, 1 day/week for 16 weeks, or to air, ozone (0.51 or 1.0 ppm), or DEP (1.9 mg/m3) for 5 hr/day for 2 days. At the end of each exposure period, we examined pulmonary and cardiovascular biomarkers of injury. In the 16-week study, we observed mild pulmonary pathology in the ozone, DEP, and ozone + DEP exposure groups, a slight decrease in circulating lymphocytes in the ozone and DEP groups, and decreased platelets in the DEP group. After 16 weeks of exposure, mRNA biomarkers of oxidative stress (hemeoxygenase-1), thrombosis (tissue factor, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor), vasoconstriction (endothelin-1, endothelin receptors A and B, endothelial NO synthase) and proteolysis [matrix metalloprotease (MMP)-2, MMP-3, and tissue inhibitor of matrix metalloprotease-2] were increased by DEP and/or ozone in the aorta, but not in the heart. Aortic LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) mRNA and protein increased after ozone exposure, and LOX-1 protein increased after exposure to ozone + DEP. RAGE (receptor for advanced glycation end products) mRNA increased in the ozone + DEP group. Exposure to ozone or DEP depleted cardiac mitochondrial phospholipid fatty acids (DEP > ozone). The combined effect of ozone and DEP exposure was less pronounced than exposure to either pollutant alone. Exposure to ozone or DEP for 2 days (acute) caused mild changes in the aorta.ConclusionsIn animals exposed to ozone or DEP alone for 16 weeks, we observed elevated biomarkers of vascular impairments in the aorta, with the loss of phospholipid fatty acids in myocardial mitochondria. We conclude that there is a possible role of oxidized lipids and protein through LOX-1 and/or RAGE signaling

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Cardiac hypertrophy in aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin-1, and mean arterial blood pressure.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates toxicity of xenobiotics, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Genetic deletion of the AhR leads to cardiac hypertrophy, suggesting a role for the AhR in cardiovascular physiology and disease; however, the pathways involved in the development of cardiac hypertrophy have not been determined. Thus, we investigated the role of (1) pressure overload using indwelling catheters and (2) vasoactive peptides endothelin-1 (ET-1) and angiotensin II (Ang II), assessed by RIA, in the progression of cardiac hypertrophy in AhR-null mice. Histochemical analysis, expression of cardiac hypertrophy marker genes, and echocardiography were used to assess the degree of cardiac hypertrophy. AhR-null mice developed elevated mean arterial pressures (MAP) by 5 months, which was associated with a two- and ninefold increase in plasma ET-1 and Ang II, respectively, compared to wild-type. Captopril-treatment (4 mg/kg) of AhR-null mice from 2 to 5 months of age significantly decreased MAP and plasma Ang II, but did not affect ET-1. Further, captopril improved cardiac function and reduced cardiac hypertrophy as evidenced by reduction in left ventricle mass, left ventricle internal dimension, and molecular cardiac hypertrophy markers. Captopril also decreased fibrosis of the heart and kidney. These findings show that pressure overload is associated with elevated ET-1 and hypertrophic growth of the heart and that cardiac hypertrophy is mediated, in part, by Ang II

Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy and fibrosis, associated with elevated plasma angiotensin II (Ang II) and endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular homeostasis. In these studies, we tested the hypothesis that ET-1 mediates cardiovascular pathology in AhR null mice via ETA receptor activation. First, we determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1 expression in AhR wildtype and null mice. AhR null mice exhibited increases in heart-to-body weight ratio and age-related expression of cardiac hypertrophy markers, beta-myosin heavy chain (beta-MHC), and atrial natriuretic factor (ANF), which were significant at 2 months. Similarly, plasma and tissue ET-1 expression was significantly elevated at 2 months and increased further with age. Second, AhR null mice were treated with ETA receptor antagonist, BQ-123 (100 nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28 days significantly reduced the histological appearance of cardiac fibrosis. Treatment for 58 days significantly reduced cardiac mass, assessed by heart weight, echocardiography, and beta-MHC and ANF expression; and reduced cardiac fibrosis as determined by osteopontin and collagen I mRNA expression. These findings establish ET-1 and the ETA receptor as primary determinants of hypertension and cardiac pathology in AhR null mice

Probiotics Function as Immunomodulators in the Intestine in C57Bl/6 Male Mice Exposed to Inhaled Diesel Exhaust Particles on a High-Fat Diet

Epidemiological studies reveal a correlation between air pollution exposure and gastrointestinal (GI) diseases, yet few studies have investigated the role of inhaled particulate matter on intestinal integrity in conjunction with a high-fat (HF) diet. Additionally, there is currently limited information on probiotics in mitigating air-pollutant responses in the intestines. Thus, we investigated the hypothesis that exposure to inhaled diesel exhaust particles (DEP) and a HF diet can alter intestinal integrity and inflammation, which can be attenuated with probiotics. 4–6-w-old male C57Bl/6 mice on a HF diet (45% kcal fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg of DEP suspended in 35 µL of 0.9% sterile saline or sterile saline (CON) only twice a week for 4 w. A subset of mice was treated with 0.3 g/day of Winclove Ecologic® barrier probiotics (PRO) in drinking water throughout the duration of the study. Our results show that DEP exposure ± probiotics resulted in increased goblet cells and mucin (MUC)-2 expression, as determined by AB/PAS staining. Immunofluorescent quantification and/or RT-qPCR showed that DEP exposure increases claudin-3, occludin, zona occludens (ZO)-1, matrix metalloproteinase (MMP)-9, and toll-like receptor (TLR)-4, and decreases tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression compared to CON. DEP exposure + probiotics increases expression of claudin-3, occludin, ZO-1, TNF-α, and IL-10 and decreases MMP-9 and TLR-4 compared to CON + PRO in the small intestine. Collectively, these results show that DEP exposure alters intestinal integrity and inflammation in conjunction with a HF diet. Probiotics proved fundamental in understanding the role of the microbiome in protecting and altering inflammatory responses in the intestines following exposure to inhaled DEP

Histological features of non-alcoholic fatty liver disease revealed in response to mixed vehicle emission exposure and consumption of a high-fat diet in wildtype C57Bl/6 male mice

Non-alcoholic fatty liver disease (NAFLD) is currently plaguing the population at pandemic proportions and is expected to become more prevalent over the next decade. Recent epidemiological studies have demonstrated a correlation between the manifestation of NAFLD and ambient air pollution levels, which is exacerbated by other risk factors, such as diabetes, dyslipidemia, obesity, and hypertension. Exposure to airborne particulate matter has also been associated with inflammation, hepatic lipid accumulation, oxidative stress, fibrosis, and hepatocyte injury. While prolonged consumption of a high-fat (HF) diet is associated with NAFLD, little is known regarding the effects of inhaled traffic-generated air pollution, a ubiquitous environmental pollutant, on the pathogenesis of NAFLD. Therefore, we investigated the hypothesis that exposure to a mixture of gasoline and diesel engine emissions (MVE), coupled with the concurrent consumption of a HF diet, promotes the development of a NAFLD phenotype within the liver. Three-month-old male C57Bl/6 mice were placed on either a low-fat or HF diet and exposed via whole-body inhalation to either filtered (FA) air or MVE (30 µg PM/m3 gasoline engine emissions + 70 µg PM/m3 diesel engine emissions) 6 hr/day for 30 days. Histology revealed mild microvesicular steatosis and hepatocyte hypertrophy in response to MVE exposure alone, compared to FA controls, yielding a classification of ''borderline NASH'' under the criteria of the modified NAFLD active score (NAS) system. As anticipated, animals on a HF diet exhibited moderate steatosis; however, we also observed inflammatory infiltrates, hepatocyte hypertrophy, and increased lipid accumulation, with the combined effect of HF diet and MVE exposure. Our results indicate that inhalation exposure to traffic-generated air pollution initiates hepatocyte injury and further exacerbates lipid accumulation and hepatocyte injury induced by the consumption of a HF diet, thereby contributing to the progression of NAFLD-related pathologies