Potential of NRF2 Pathway in Preventing Developmental and Reproductive Toxicity of Fine Particles.

Air pollution is associated with significant adverse health effects. Recent studies support the idea that inhalation of fine particles can instigate extrapulmonary effects on the cardiovascular system through several pathways. The systemic transfer of ultrafine particles (UFPs) or soluble particle components (organic compounds and metals) is of particular concern.

Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice.

In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J and mice were exposed to DE or clean air for 8 h/day and 6 days/week for 4 weeks. After DE exposure, the number of neutrophils and macrophage inflammatory protein (MIP)-2 level in bronchoalveolar lavage fluid (BALF) and interleukin (IL)-17 level in the lung tissue increased in mice compared with mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in mice and mild suppression of the level of TNF-α in mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in mice than in mice; the number of DE particle-laden alveolar macrophages in BALF were larger in mice than in mice.

Nrf2 Regulates the Risk of a Diesel Exhaust Inhalation-Induced Immune Response during Bleomycin Lung Injury and Fibrosis in Mice.

The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to both and C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection.

Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E2 (PGE2) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells.

Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes.

This study assessed the effect of extended exposure to cigarette smoke extract (CSE) on tissue repair functions in lung fibroblasts. Human fetal (HFL-1) and adult lung fibroblasts were exposed to CSE for 14 days. Senescence-associated β-galactosidase (SA β-gal) expression, cell proliferation, and tissue repair functions including chemotaxis and gel contraction were assessed.

Nrf2 is a protective factor against oxidative stresses induced by diesel exhaust particle in allergic asthma.

Epidemiological studies have shown that air pollutants, such as diesel exhaust particle (DEP), are implicated in the increased incidence of allergic airway disorders. In vitro studies of molecular mechanisms have focused on the role of reactive oxygen species generated directly and indirectly by the exposure to DEP. Antioxidants effectively reduce the allergic inflammatory effects induced by DEP both in vitro and in vivo.

EM, EM703 inhibit NF-kB activation induced by oxidative stress from diesel exhaust particle in human bronchial epithelial cells: importance in IL-8 transcription.

Diesel exhaust particle (DEP) is the major components of PM2.5, and much attention has focused on PM2.5 in relation to adverse health effects, and many pulmonary diseases.

The p38 mitogen-activated protein kinases modulate endothelial cell survival and tissue repair.

Objective And Design: This study is designed to investigate the role of p38 MAPK in modulating human pulmonary artery endothelial cells (HPAECs) survival and tissue repair functions.

Methods: HPAECs (passage 8-12) were used for all experiments. Cells were treated with IL-1β (0.

Serum insulin is significantly related to components of the metabolic syndrome in Japanese working women.

Background: The aim of this study was to examine the association between serum insulin levels and components of the metabolic syndrome (MetS) in working women.

Methods: The target subjects were 141 working women. Serum triglyceride, HDL cholesterol, uric acid, plasma insulin and plasma glucose were measured in addition to waist circumference and blood pressure.

Acute effects of walking in forest environments on cardiovascular and metabolic parameters.

We previously found that forest environments reduced stress hormones such as adrenaline and noradrenaline and showed the relaxing effect both in male and female subjects. In the present study, we investigated the effects of walking under forest environments on cardiovascular and metabolic parameters. Sixteen healthy male subjects (mean age 57.

Depressive state and subsequent weight gain in workers: A 4-year follow-up study.

Objective: It has been suggested that the presence of a depressive state is a predictor of increase of the body weight. However, to precisely understand the nature of this relationship, the data should be controlled for other factors that can also be associated with weight gain.

Methods And Participants: To test the hypothesis that the presence of a depressive state is associated with future weight gain, a 4-year prospective occupation-based cohort study was conducted in male adult workers (N=1730) at a railway company.

Optimal cut-off levels of body mass index and waist circumference in relation to each component of metabolic syndrome (MetS) and the number of MetS component.

Aims: There is an ethnic difference of obesity index to diagnose metabolic syndrome. The authors explored the optimal cut-off levels for body mass index (BMI) and waist circumference (WC) in relation to each component of metabolic syndrome.

Materials And Methods: Receiver operating characteristics (ROC) analysis was used to determine the optimal cut-off levels for each component of metabolic syndrome.

Role of oxidative stresses induced by diesel exhaust particles in airway inflammation, allergy and asthma: their potential as a target of chemoprevention.

Epidemiological studies have shown that particulate air pollutants, such as diesel exhaust particles (DEPs) are implicated in the increased incidence of allergic airway disorders. DEPs induce and exaggerate allergic airway inflammation in vitro and in vivo. Studies of molecular mechanisms have focused on the role of reactive oxygen species (ROS) generated directly and indirectly by exposure to DEPs.

Relationship among lifestyles, aging and psychological wellbeing using the General Health Questionnaire 12-items in Japanese working men.

INTRODUCTION. The relationship among lifestyle, aging and psychological wellbeing was evaluated in Japanese working men. METHODS.

Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice.

We have recently reported that disruption of nuclear erythroid 2 P45-related factor 2 (Nrf2) enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles (DEP) in mice. C57BL/6 Nrf2 knockout (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) mice were further exposed to low-dose DEP for 7h/day, 5 days/week, for a maximum of 8 weeks. After exposure to DEP for 5 weeks, allergic airway inflammation was generated in the mice by intraperitoneal sensitization with OVA followed by intranasal challenge.

Association of smoking status, insulin resistance, body mass index, and metabolic syndrome in workers: A 1-year follow-up study.

Objective: We performed a 1-year follow-up study to determine the effects of smoking status and insulin resistance on the prevalence of metabolic syndrome.

Methods: This study included 2136 workers without metabolic syndrome at baseline who were followed for 1 year. The subjects were divided into four categories of smoking and work history, respectively.

Prostaglandin E₂ inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors.

The migration of fibroblasts is believed to play a key role in both normal wound repair and abnormal tissue remodeling. Prostaglandin E (PGE)(2), a mediator that can inhibit many fibroblast functions including chemotaxis, was reported to be mediated by the E-prostanoid (EP) receptor EP2. PGE(2), however, can act on four receptors.

Increase in the prevalence of metabolic syndrome among workers according to age.

Introduction: Statistical information regarding the prevalence of metabolic syndrome among a wide age range of workers is insufficient.

Methods: A total of 4278 men between the ages of 20 and 59 years participated in the study. Metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) and the National Cholesterol Education Program (NCEP) III criteria.

A cross-sectional study on the shift work and metabolic syndrome in Japanese male workers.

Introduction: Shift work has been reported to be associated with an increase in the metabolic syndrome (MetS). To clarify the association between the type of shift work and the risk of MetS, a cross-sectional field survey was conducted after adjusting for age and lifestyle factors.

Methods: The subjects were 3007 Japanese males, aged 34-64 years old, who were employees (1700 day and 1307 shift workers) of a car-manufacturing company.

Insulin resistance, as expressed by HOMA-R, is strongly determined by waist circumference or body mass index among Japanese working men.

Objective: This study was intended to identify significant determinant factors of insulin resistance.

Methods: Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R) and was calculated as "Fasting plasma glucose × Fasting serum insulin)/405". The target subjects were 3008 working men.

Patterns in self-rated health according to age and sex in a Japanese national survey, 1989-2004.

Background: Perceived good health or good self-rated health is considered to be a predictor of longer survival and maintenance of good quality of life, which is a public health goal.

Objective: This study assessed trends in the percentage of self-rated poor health among Japanese residents, based on data from the National Comprehensive Survey of the Living Conditions of People on Health and Welfare.

Methods: Results of the survey (which is conducted in Japan every 3 years to determine the living conditions of people receiving health and welfare services) were analyzed using multistage and stratified cluster sampling of households.

MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis.

MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-beta1 plus cytomix (a mixture of IL-1beta, IFN-gamma and TNF-alpha). TGF-beta1 plus cytomix (TCM) induced apoptosis in HBECs (3.

The effects of oxidative stress induced by prolonged low-dose diesel exhaust particle exposure on the generation of allergic airway inflammation differ between BALB/c and C57BL/6 mice.

We have recently reported that airway inflammatory responses to the oxidative stress induced by prolonged low-dose diesel exhaust particle (DEP) exposure differ markedly between BALB/c and C57BL/6 mice. In the present study, the effects of genetic differences in the response to prolonged low-dose DEP exposure on the generation of ovalbumin-induced allergic airway inflammation were further explored using the same mouse strains. In BALB/c mice, eosinophils and mucous goblet cells in histopathological pulmonary specimens increased significantly after DEP exposure, and were more marked than in C57BL/6 mice.

Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice.

To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative stress and host antioxidant responses play a key role in the development of DEP-induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose DEP for 7 h/day, 5 days/week, for 8 weeks. Nrf2(-/-) mice exposed to low-dose DEP showed significantly increased airway hyperresponsiveness and counts of lymphocytes and eosinophils, together with increased concentrations of IL-12 and IL-13, and thymus and activation-regulated chemokine (TARC), in BAL fluid than wild-type mice. In contrast, expression of antioxidant enzyme genes was significantly higher in wild-type mice than in Nrf2(-/-) mice.

EM703, a new derivative of erythromycin, inhibits transforming growth factor-beta signaling in human lung fibroblasts.

Long-term, low-dose macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis and cystic fibrosis, although the mechanisms by which it does so remain unknown. To elucidate the molecular mechanisms of the anti-inflammatory effects of macrolides, the authors examined the effects of erythromycin (EM-A) and new derivative EM703 on transforming growth factor (TGF)-beta /Smad signaling fibroblasts. EM-A and EM703 each inhibited fibroblast proliferation and the collagen production in human lung fibroblasts induced by TGF-beta.