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Naringin, a natural occurring flavonoid compound, enriches in citrus fruits. We aimed to evaluate the inhibitory effect of naringin on colitis and chronic inflammation-driven carcinogenesis. Male C57BL/6 mice were exposed to AOM/DSS to induce colorectal inflammation and carcinogenesis. Naringin by oral administration prevented AOM/DSS-induced ulcerative colitis and carcinogenesis without significant side effects. Naringin attenuated the severity of colitis and colorectal adenomas through inhibiting myeloid-derived suppressor cells (MDSCs), pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-α and the NF-κB/IL-6/STAT3 cascades in colorectal tissues. Naringin-treated mice exhibited normalized structures of colorectal tissues. Electron microscopy analysis showed the suppression of robust endoplasmic reticulum (ER) stress-induced autophagy. Naringin inhibited the secretion of the ER-spanning transmembrane proteins, such as GRP78 ATF6, IRE1α and activated PERK phosphorylated eIF-2α and complex of autophagosomes ATG3, ATG5, ATG7, ATG12, ATG16 and ATG16L1 in the colorectal mucosal cells., Conclusion: Naringin prevented colitis and colorectal carcinogenesis through suppressing robust ER stress-induced autophagy in colorectal mucosal cells. Naringin could develop a promising therapeutic agent for the prevention of ulcerative colitis and colorectal tumor.

Unlabelled: A number of literatures have documented adverse health effects of exposure to fine particulate matter (PM2.5), and secondary sulfate aerosol and black carbon may contribute to health impacts of PM2.5 exposure. We designed an exposure system to generate sulfate and traffic soot particles, and assessed the feasibility of using it for human exposure assessment in a pilot human exposure study. In the designed exposure system, average mass concentrations of generated sulfate and soot particles were 74.19 μg/m3 and 11.54 μg/m3 in the chamber and did not vary significantly during two-hour human exposure sessions. The size ranges of generated sulfate were largely between 20 to 200 nm, whereas those of generated soot particles were in the size ranges of 50 to 200 nm. Following two-hour exposure to generated sulfate and soot particles, we observed significant increases in fractional exhaled NO (FeNO) in young and health subjects. Building on established human exposure system and health response follow-up methods, future full-scale studies focusing on the effects of mixed particulates and individual PM2.5 components would provide data in understanding the underpinning cardio-respiratory outcomes in relation to air pollution mixture exposure., Implications: Controlled exposure is a useful design to measure the biological responses repeatedly following particulate exposures of target components and set exposure at target levels of health concerns. Our study provides rational and establishes method for future full-scale studies to focus on examining the effects of mixed particulates and individual PM2.5 components.

Air pollution and premature death are important public health concerns. Analyses have repeatedly demonstrated that airborne particles are associated with increased mortality and estimates have been used to forecast the impact on life expectancy. In this analysis, we draw upon data from the American Cancer Society (ACS) cohort and literature on utility-based measures of quality of life in relation to health status to more fully quantify the effects of air pollution on mortality in terms of quality-adjusted life expectancy. The analysis was conducted within a decision analytic model using Monte Carlo simulation techniques. Outcomes were estimated based on projections of the Canadian population. A one-unit reduction in sulfate air pollution would yield a mean annual increase in Quality-Adjusted Life Years (QALYs) of 20,960, with gains being greater for individuals with lower educational status and for males compared to females. This suggests that the impact of reductions in sulfate air pollution on quality-adjusted life expectancy is substantial. Interpretation of the results is unclear. However, the potential gains in QALYs from reduced air pollutants can be contrasted to the costs of policies to bring about such reductions. Based on a tentative threshold for the value of health benefits, analysis suggests that an investment in Canada of over 1 billion dollars per annum would be an efficient use of resources if it could be demonstrated that this would reduce sulfate concentrations in ambient air by 1 microg/m(3). Further analysis can assess the efficiency of targeting such initiatives to communities that are most likely to benefit.

The American Cancer Society (ACS) Study and its reanalysis are built upon in order to examine the impact of scale on the observed relationship between sulfates and mortality. The limitations of the original ACS Study (Pope et al., 1995) and the reanalysis of this study (Krewski et al., 2000) are discussed; while the latter dealt with some issues in using ecological data, it did not address scale. Next, the article outlines the county-scale study, the methods used to aggregate data, and the two-stage analysis used to derive relative risk (RR). Finally, the results of working at the county scale are compared with those obtained by the reanalysis team using larger metropolitan areas. Less than half of the cohort used in the metropolitan study were used at the county scale because of the limited availability of sulfate monitors and because five-digit ZIP codes more accurately assigned individuals to geographical areas. Therefore, the county data should be considered as new and not as a reorganization of the original data set. The reanalysis and the county studies should be considered as two separate studies that took different scales as their basic organizing principle. The RR of all-cause mortality from sulfate exposure at the county scale was 1.50 (1.30, 1.73) compared with 1.25 (1.13, 1.37) at the metropolitan scale; for cardiopulmonary mortality, the RR was 1.75 (1.48, 2.08) at the county scale compared with 1.29 (1.15, 1.46) at the metropolitan scale. Because lung cancer mortality was low in some counties, the two-stage random effects model became unstable. At the county scale, the RR from sulfates was more robust to the inclusion of ecologic covariates. Other place-specific ecologic covariates were either insignificant or barely significant (with a lower 95% confidence limit near 0.99 or 1.00) when included in the two-stage regression model for all-cause mortality with sulfates. Moreover, no ecologic covariate changed the RR of all-cause mortality from sulfates by 25% or more. Both population change and unemployment rate affected the RR for cardiopulmonary mortality from sulfate exposure by 25% or more in the county-scale analysis. However, when these two variables were entered into a multiple covariate analysis, the RR from sulfates decreased but remained strongly significant. Sulfur dioxide was not an important covariate at the county scale. Thus, at the county scale, long-term exposure to sulfates appears to be more strongly associated with increased risk of all-cause and cardiopulmonary mortality than previously indicated by the ACS study and its reanalysis.

Cohort study designs are often used to assess the association between community-based ambient air pollution concentrations and health outcomes, such as mortality, development and prevalence of disease, and pulmonary function. Typically, a large number of subjects are enrolled in the study in each of a small number of communities. Fixed-site monitors are used to determine long-term exposure to ambient pollution. The association between community average pollution levels and health is determined after controlling for risk factors of the health outcome measured at the individual level (i.e., smoking). We present a new spatial regression model linking spatial variation in ambient air pollution to health. Health outcomes can be measured as continuous variables (pulmonary function), binary variables (prevalence of disease), or time-to-event data (survival or development of disease). The model incorporates risk factors measured at the individual level, such as smoking, and at the community level, such as air pollution. We demonstrate that the spatial autocorrelation in community health outcomes, an indication of not fully characterizing potentially confounding risk factors to the air pollution--health association, can be accounted for through the inclusion of location in the deterministic component of the model assessing the effects of air pollution on health or through a distance-decay spatial autocorrelation function in the stochastic component of the model, or both. We present a statistical approach that can be implemented for very large cohort studies. Our methods are illustrated with an analysis of the American Cancer Society cohort to determine whether the prevalence of heart disease is associated with concentrations of sulfate particles. From a statistical point of view, it appears that a location surface in the deterministic component of the model was preferred to a distance-decay autocorrelation structure in the model's stochastic component.

The estimation of health benefits from reductions in ambient air pollution requires information both about the relationship between concentrations and health effects and about the ultimate value of health outcomes. In this commentary, I discuss significant issues and uncertainties that must be addressed for both elements. Critical issues for concentration-response estimation include the shape of the concentration-response curve at current and projected ambient levels, the relevant exposure period, the existence of high-risk subpopulations, and the ability to generalize across study settings. Health outcomes can be valued using either health-based measures like quality-adjusted life years or economic measures like value of statistical life; the choice of measure has a significant effect on the magnitude and distribution of health benefits. Analysts estimating health benefits for ultimate benefit-cost applications should provide results using multiple valuation frameworks and multiple assumptions about health evidence to facilitate interpretation and to determine whether policy decisions depend on these assumptions.

Several inhaled atmospheres were tested for effects on the rat respiratory defense system. Materials studied included ozone and aerosols of ammonium sulfate, ferric sulfate, and sulfuric acid; relative humidity was also a controlled experimental variable. Each sulfate was studied alone as a submicrometer aerosol at a concentration of 3.5 mg/m3 in air and combined with ozone at 0.8 ppm. Results were compared with those for sham-exposed animals and for rats exposed to ozone alone. Air pollutant exposures, inside stainless steel chambers, were one time only for 4 h. The end points for evaluation of effects were measurements of early and late rates of clearance of radiolabeled insoluble tracer particles. Tracer particles were inhaled before air pollutant exposures and particle clearance was followed for about 2 wk. Ozone alone slowed the early (0-50 h after exposure) particle clearance and stimulated clearance during the later phase (2-17 d). High humidity usually amplified these effects of ozone as well as many of the other atmospheres studied. Sulfate aerosols alone tended to produce relatively small effects on early or late clearance. Combinations of ozone and aerosols resulted in effects that were similar to those of ozone alone. The data do not support the hypotheses that sulfate aerosols synergize with ozone in altering respiratory tract clearance, sulfuric acid being a probable exception. These data alone cannot be used to predict the overall health effects of the materials studied.