Institute of Environmental and Occupational Health science

Anderson, United States

Institute of Environmental and Occupational Health science

Anderson, United States
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Pan W.-C.,National Cheng Kung University | Pan W.-C.,Institute of Environmental and Occupational Health science | Wu C.-D.,National Chiayi University | Wu C.-D.,Harvard University | And 8 more authors.
Journal of the National Cancer Institute | Year: 2016

Background: Exposure to fine particulate matter (PM2.5) may promote hepatic tumorgenesis through low-grade inflammation. Therefore, we assessed the association of long-term exposure levels of PM2.5 and subsequent risk of hepatocellular carcinoma (HCC) and investigated the mediation effect of inflammation as represented by alanine aminotransferase (ALT) on this association. Methods: Between 1991 and 1992, we recruited 23 820 participants in Taiwan with no history of HCC. Case patients of HCC were ascertained through computerized data linkage with the National Cancer Registry and death certification systems. Participants' exposures to PM2.5 were based on a four-year average retrieved from stationary monitoring sites. Cox proportional hazards models were used to assess the association between PM2.5 exposure and HCC incidence. Mediation effects of ALT on PM2.5-associated HCC incidence were estimated. Results: A total of 464 HCC cases were newly diagnosed with a median follow-up of 16.9 years. Statistically significantly increasing trends between PM2.5 exposures and ALT were observed on the Main Island and Penghu Islets. The adjusted hazard ratio (HR) for HCC on the Penghu Islets was 1.22 (95% confidence interval [CI] = 1.02 to 1.47) per PM2.5 interquartile range (IQR) increment (0.73 μg/m3) exposure. We also found a positive association between PM2.5 exposure (per IQR increment, 13.1 μg/m3) and HCC incidence on the Main Island. Furthermore, ALT had a statistically significant mediation effect on PM2.5-associated HCC incidence (HR = 1.17, 95% CI = 1.02 to1.52 on the Main Island; HR = 1.04, 95% CI = 1.03 to 1.07 on the Penghu Islets) per PM2.5 IQR increment. Conclusions: Long-term PM2.5 exposure increased the risk for liver cancer, and chronic inflammation of the liver may underlie the pathogenesis. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved.


How C.-K.,Institute of Clinical Medicine | How C.-K.,National Yang Ming University | How C.-K.,Taipei Veterans General Hospital | Hou S.-K.,Institute of Environmental and Occupational Health science | And 14 more authors.
Shock | Year: 2015

Bacterial lipopolysaccharide (LPS) is an effective trigger of the inflammatory response during infection with gram-negative bacilli (GNB), which implicates the pathogenesis of sepsis and septic shock. MicroRNAs (miRNAs) are shown to have a significant role in the fine-tuning of toll-like receptor (TLR)-mediated inflammatory response. We profiled miRNA expression levels in peripheral leukocytes of GNB urosepsis patients and compared them with those of healthy controls. We further explored the regulatory mechanism of endotoxin-responsive miRNAs in TLR and cytokine signaling by using human monocytic cell line (THP-1 cells) treated with LPS antigen stimulation. The expression of two miRNAs, that is, let-7a (P < 0.001) and miR-150 (P < 0.001), were confirmed to be significantly downregulated in GNB urosepsis patients compared with healthy controls. The expression of let-7a is first to be identified as a biomarker of GNB sepsis. By using an in vitro model with the human monocytic cell line, we demonstrated that LPS stimulation downregulated the THP-1 cell expression of let-7a. The downregulation of let-7a is correlated with the induced expression of cytokine-inducible Src homology 2-containing protein without change in cytokine-inducible Src homology 2-containing protein mRNA levels in THP-1 cells via TLR signaling pathway activation. Moreover, gain of function by overexpression of let-7a revealed that let-7a significantly decreased tumor necrosis factor-α and interleukin-1β production in response to LPS. Reduced let-7a and miR-150 levels in peripheral leukocytes correlate with GNB urosepsis patients. Furthermore, let-7a is relevant to the regulation of TLR-mediated innate immune response. © 2014 by the Shock Society.

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