Fine Particulate Matter and Diabetes Prevalence in Okayama, Japan.

Many studies have shown an association between long-term exposure to particulate matter having an aerodynamic diameter of 2.5 µm or less (PM2.5) and diabetes mellitus (DM), but few studies have focused on Asian subjects. We thus examined the association between long-term exposure to PM2.5 and DM prevalence in Okayama City, Japan. We included 76,591 participants who had received basic health checkups in 2006 and 2007. We assigned the census-level modeled PM2.5 data from 2006 and 2007 to each participant and defined DM using treatment status and the blood testing. PM2.5 was associated with DM prevalence, and the prevalence ratio (95% confidence interval) was 1.10 (1.00-1.20) following each interquartile range increase (2.1 µg/m3) in PM2.5. This finding is consistent with previous results and suggests that long-term exposure to PM2.5 is associated with an increased prevalence of DM in Okayama City, Japan, where the PM2.5 level is lower than in other cities in Asian countries.

Long-term exposure to fine particulate matter and natural-cause and cause-specific mortality in Japan.

BACKGROUND: A number of studies have linked long-term exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) with mortality, but most of these studies were conducted in Europe and North America. Studies in Asian countries had been conducted at relatively high exposures. We evaluated the association of long-term exposure to PM2.5 and natural-cause and cause-specific mortality in Japan, where PM2.5 levels are relatively low compared with levels in other Asian countries. METHODS: A cohort of 75,531 participants underwent basic health checkups in Okayama City in 2006 or 2007. We followed the participants until the end of 2016. Average PM2.5 levels from 2006 to 2010 were obtained and assigned to the participants by geographical location. We used the Cox proportional hazard models to estimate hazard ratios for a 5-µg/m3 increase in PM2.5 levels for natural-cause or cause-specific mortality, adjusting for potential confounders. RESULTS: PM2.5 exposure was associated with increased risk of mortality; the hazard ratios were 1.29 (95% confidence interval = 1.18, 1.41) for mortality from natural causes, 1.16 (1.02, 1.32) for cardiorespiratory mortality, and 1.63 (1.13, 2.34) for lung cancer mortality. PM2.5 exposure was more strongly associated with cardiorespiratory mortality from hypertension, pneumonia and influenza, and chronic obstructive pulmonary disease than with ischemic heart disease or cerebrovascular disease. Elderly participants and smokers tended to have higher effect estimates. CONCLUSION: Long-term exposure to PM2.5 can increase the risk of natural-cause, cardiorespiratory, and lung cancer mortality in Japan.

Cyclin G2 promotes hypoxia-driven local invasion of glioblastoma by orchestrating cytoskeletal dynamics.

Microenvironmental conditions such as hypoxia potentiate the local invasion of malignant tumors including glioblastomas by modulating signal transduction and protein modification, yet the mechanism by which hypoxia controls cytoskeletal dynamics to promote the local invasion is not well defined. Here, we show that cyclin G2 plays pivotal roles in the cytoskeletal dynamics in hypoxia-driven invasion by glioblastoma cells. Cyclin G2 is a hypoxia-induced and cytoskeleton-associated protein and is required for glioblastoma expansion. Mechanistically, cyclin G2 recruits cortactin to the juxtamembrane through its SH3 domain-binding motif and consequently promotes the restricted tyrosine phosphorylation of cortactin in concert with src. Moreover, cyclin G2 interacts with filamentous actin to facilitate the formation of membrane ruffles. In primary glioblastoma, cyclin G2 is abundantly expressed in severely hypoxic regions such as pseudopalisades, which consist of actively migrating glioma cells. Furthermore, we show the effectiveness of dasatinib against hypoxia-driven, cyclin G2-involved invasion in vitro and in vivo. Our findings elucidate the mechanism of cytoskeletal regulation by which severe hypoxia promotes the local invasion and may provide a therapeutic target in glioblastoma.