Integrated hepatic transcriptomics and metabolomics identify Pck1 as a key factor in the broad dysregulation induced by vehicle pollutants.

Background: Exposure to air pollution is associated with worldwide morbidity and mortality. Diesel exhaust (DE) emissions are important contributors which induce vascular inflammation and metabolic disturbances by unknown mechanisms. We aimed to determine molecular pathways activated by DE in the liver that could be responsible for its cardiometabolic toxicity.

Diesel exhaust particle extract elicits an oxPAPC-like transcriptomic profile in macrophages across multiple mouse strains.

Air pollution is a prominent cause of cardiopulmonary illness, but uncertainties remain regarding the mechanisms mediating those effects as well as individual susceptibility. Macrophages are highly responsive to particles, and we hypothesized that their responses would be dependent on their genetic backgrounds. We conducted a genome-wide analysis of peritoneal macrophages harvested from 24 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP).

Subchronic inhalation exposure to ultrafine particulate matter alters the intestinal microbiome in various mouse models.

Exposure to ultrafine particles (UFPs) has been associated with multiple adverse health effects. Inhaled UFPs could reach the gastrointestinal tract and influence the composition of the gut microbiome. We have previously shown that oral ingestion of UFPs alters the gut microbiome and promotes intestinal inflammation in hyperlipidemic Ldlr mice.

Ectodomain shedding of proteins important for SARS-CoV-2 pathogenesis in plasma of tobacco cigarette smokers compared to electronic cigarette vapers: a cross-sectional study.

The impact of tobacco cigarette (TCIG) smoking and electronic cigarette (ECIG) vaping on the risk of development of severe COVID-19 is controversial. The present study investigated levels of proteins important for SARS-CoV-2 pathogenesis present in plasma because of ectodomain shedding in smokers, ECIG vapers, and non-smokers (NSs). Protein levels of soluble angiotensin-converting enzyme 2 (ACE2), angiotensin (Ang) II (the ligand of ACE2), Ang 1-7 (the main peptide generated from Ang II by ACE2 activity), furin (a protease that increases the affinity of the SARS-CoV-2 spike protein for ACE2), and products of ADAM17 shedding activity that predict morbidity in COVID-19 (IL-6/IL-6R alpha (IL-6/IL-6Rα) complex, soluble CD163 (sCD163), L-selectin) were determined in plasma from 45 NSs, 30 ECIG vapers, and 29 TCIG smokers using ELISA.

Arachidonic acid metabolism and inflammatory biomarkers associated with exposure to polycyclic aromatic hydrocarbons.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with systemic inflammation, yet what mechanisms regulate PAHs' inflammatory effects are less understood. This study evaluated the change of arachidonic acid (ARA) metabolites and inflammatory biomarkers in response to increased exposure to PAHs among 26 non-smoking healthy travelers from Los Angeles to Beijing. Traveling from Los Angeles to Beijing significantly increased urinary metabolites of dibenzofuran (800%), fluorene (568%), phenanthrene (277%), and pyrene (176%), accompanied with increased C-reactive protein, fibrinogen, IL-8, and IL-10, and decreased MCP-1, sCD40L, and sCD62P levels in the blood.

Triglyceride profiles are associated with subacute exposure to bisphenol A in healthy young adults.

Conflicted results from previous epidemiological studies call for mechanistic evidence to associate exposure to bisphenol A (BPA) with cardiometabolic diseases. In this natural experiment among healthy travelers from Los Angeles (LA) to Beijing, we collected paired urine and blood samples before their departure, 6-8 weeks after their arrival to Beijing, and 4-7 weeks after their return to LA for the assessment of urinary BPA and lipidome in the serum fraction of blood, to study the effects of drastically changed BPA exposure on the lipid metabolism in relation to the development of cardiometabolic disorders. We used linear mixed-effects models with random intercepts for participant and phase to examine the associations between urinary BPA and serum lipidome.

Key Characteristics of Cardiovascular Toxicants.

Background: The concept of chemical agents having properties that confer potential hazard called key characteristics (KCs) was first developed to identify carcinogenic hazards. Identification of KCs of cardiovascular (CV) toxicants could facilitate the systematic assessment of CV hazards and understanding of assay and data gaps associated with current approaches.

Objectives: We sought to develop a consensus-based synthesis of scientific evidence on the KCs of chemical and nonchemical agents known to cause CV toxicity along with methods to measure them.

Differential Effects of Electronic Hookah Vaping and Traditional Combustible Hookah Smoking on Oxidation, Inflammation, and Arterial Stiffness.

Background: Traditional hookah smoking has grown quickly to become a global tobacco epidemic. More recently, electronic hookahs (e-hookahs)-vaped through traditional water pipes-were introduced as healthier alternatives to combustible hookah. With combustible tobacco smoking, oxidative stress, inflammation, and vascular stiffness are key components in the development and progression of atherosclerosis.

Electronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers.

[Figure: see text].

Metabolomic Changes after Subacute Exposure to Polycyclic Aromatic Hydrocarbons: A Natural Experiment among Healthy Travelers from Los Angeles to Beijing.

Emerging epidemiological evidence has associated exposure to polycyclic aromatic hydrocarbons (PAHs) with chronic diseases including cardiometabolic diseases and neurodegeneration. However, little information is available about their subacute effects, which may accumulate over years and contribute to chronic disease development. To fill this knowledge gap, we designed a natural experiment among 26 healthy young adults who were exposed to elevated PAHs for 10 weeks after traveling from Los Angeles to Beijing in 2014 and 2015.

Urinary carboxylic acid metabolites as possible novel biomarkers of exposures to alkylated polycyclic aromatic hydrocarbons.

Previous studies have found that alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) were more abundant in petrogenic sources (e.g., crude oil and its refined products) than pyrogenic sources of incomplete combustion.

Changes in lipid composition associated with electronic cigarette use.

Background: Electronic cigarette use is on the rise despite a number of reports linking electronic cigarettes with adverse health outcomes. Recent studies have suggested that alterations in lipid signaling may be one mechanism by which electronic cigarettes contribute to lung pulmonary function. Vitamin E acetate, for example, is synthetic form of Vitamin E transported via lipids, found to be associated with electronic cigarette associated lung injury.

Different temporal trends of exposure to Bisphenol A among international travelers between Los Angeles and Beijing.

Recent studies suggested a significant downward trend in population's exposure to bisphenol A (BPA) in the United States. However, the temporal trend of BPA exposure remains unclear in China - a populous country with substantial industrial activities but less efforts made to phase out BPA in consumer products. In addition, it is unclear to what extent a visit from the United States to China could affect human exposure to BPA.

Diesel Exhaust Extract Exposure Induces Neuronal Toxicity by Disrupting Autophagy.

The vast majority of neurodegenerative disease cannot be attributed to genetic causes alone and as a result, there is significant interest in identifying environmental modifiers of disease risk. Epidemiological studies have supported an association between long-term exposure to air pollutants and disease risk. Here, we investigate the mechanisms by which diesel exhaust, a major component of air pollution, induces neurotoxicity.

Pro-Oxidative and Proinflammatory Effects After Traveling From Los Angeles to Beijing: A Biomarker-Based Natural Experiment.

Background: Exposure to air pollution increases cardiovascular morbidity and mortality. Preventing chronic cardiovascular diseases caused by air pollution relies on detecting the early effects of pollutants on the risk of cardiovascular disease development, which is limited by the lack of sensitive biomarkers. We have previously identified promising biomarkers in experimental animals but comparable evidence in humans is lacking.

Diesel exhaust particles dysregulate multiple immunological pathways in murine macrophages: Lessons from microarray and scRNA-seq technologies.

Exposure to ambient particulate matter has been shown to promote a variety of disorders, including cardiovascular diseases predominantly of ischemic etiology. However, the mechanisms linking inhaled particulates with systemic vascular effects, resulting in worsened atherosclerosis, are not well defined. We assessed the potential role of macrophages in translating these effects by analyzing gene expression patterns in response to diesel exhaust particles (DEP) at the average cell level, using Affymetrix microarrays in peritoneal macrophages in culture (in vitro), and at the individual cell level, using single-cell RNA sequencing (scRNA-seq) in alveolar macrophages collected from exposed mice (in vivo).

Diesel Exhaust Induces Mitochondrial Dysfunction, Hyperlipidemia, and Liver Steatosis.

Objective: Air pollution is associated with increased cardiovascular morbidity and mortality, as well as dyslipidemia and metabolic syndrome. Our goal was to dissect the mechanisms involved. Approach and Results: We assessed the effects of exposure to air pollution on lipid metabolism in mice through assessment of plasma lipids and lipoproteins, oxidized fatty acids 9-HODE (9-hydroxyoctadecadienoic) and 13-HODE (13-hydroxyoctadecadienoic), lipid, and carbohydrate metabolism.

Exposure to Nanoscale Particulate Matter from Gestation to Adulthood Impairs Metabolic Homeostasis in Mice.

Emerging evidence from epidemiological and animal studies suggests that exposure to traffic-related air pollutants and particulate matter less than 2.5 µm in diameter (PM) contributes to development of obesity and related metabolic abnormalities. However, it is not known whether nanoscale particulate matter (nPM) with aerodynamic diameter ≤200 nm have similar adverse metabolic effects.

Myeloid HO-1 modulates macrophage polarization and protects against ischemia-reperfusion injury.

Macrophages polarize into heterogeneous proinflammatory M1 and antiinflammatory M2 subtypes. Heme oxygenase 1 (HO-1) protects against inflammatory processes such as ischemia-reperfusion injury (IRI), organ transplantation, and atherosclerosis. To test our hypothesis that HO-1 regulates macrophage polarization and protects against IRI, we generated myeloid-specific HO-1-knockout (mHO-1-KO) and -transgenic (mHO-1-Tg) mice, with deletion or overexpression of HO-1, in various macrophage populations.

Recipient HO-1 inducibility is essential for posttransplant hepatic HO-1 expression and graft protection: From bench-to-bedside.

By documenting potent antioxidative and anti-inflammatory functions, preclinical studies encourage heme oxygenase-1 (HO-1)-inducing regimens in clinical orthotopic liver transplantation (OLT). We aimed to determine the importance of recipient-derived HO-1 in murine and human OLTs. Hepatic biopsies from 51 OLT patients were screened for HO-1 expression (Western blots) prior to put-in (basal) and post reperfusion (stressed) and correlated with the hepatocellular function.