Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.
Multicenter, longitudinal studies on nontuberculous mycobacteria (NTM) pulmonary infection (PI) are lacking. This study provides a 5-year epidemiological overview of NTM-PI in Taiwan and investigated its predictors. The clinical relevance of each respiratory NTM isolate in six hospitals between 2008 and 2014 was determined according to current guidelines. Recurrent episodes were judged by serial bacteriological results. New episodes of NTM-PI and pulmonary colonization (PC) occurring since 2010 were analyzed. Logistic regression analysis was performed to identify the predictors of NTM-PI. Between 2010 and 2014, the incidence rate of NTM-PI was 46.0 episodes per 100,000 hospital-based patient-years. Mycobacterium avium intracellulare complex (MAC) was predominant in Northern Taiwan, whereas MAC and M. abscessus were copredominant in Southern Taiwan. Multiple episodes occurred in 9.5% of NTM-PI patients. No female predominance was observed, except for MAC-PI. Previous pulmonary tuberculosis and chronic obstructive pulmonary disease (COPD) were the most common pulmonary comorbidities and independent risk factors for NTM-PI. Other risk factors included M. kansasii, M. abscessus, and southern Taiwan. Geographical variation of NTM-PI exists in Taiwan. Clinicians should keep a high suspicion on NTM-PI in the risk population. In endemic area of tuberculosis and COPD, there may be no female predominance in NTM-PI.
This study was undertaken to determine whether there was an association between coarse particles (PM2.5–10) levels and frequency of hospital admissions for respiratory diseases (RD) in Kaohsiung, Taiwan. Hospital admissions for RD including chronic obstructive pulmonary disease (COPD), asthma, and pneumonia, and ambient air pollution data levels for Kaohsiung were obtained for the period from 2006 to 2010. The relative risk of hospital admissions for RD was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single pollutant model (without adjustment for other pollutants), increased rate of admissions for RD were significantly associated with higher coarse PM levels only on cool days (<25 °C), with a 10 µg/m3 elevation in PM2.5–10 concentrations associated with a 3% (95% CI = 1%–5%) rise in COPD admissions, 4% (95% CI = 1%–7%) increase in asthma admissions, and 3% (95% CI = 2%–4%) rise in pneumonia admissions. No significant associations were found between coarse particle levels and the number of hospital admissions for RD on warm days. In the two-pollutant models, PM2.5–10 levels remained significantly correlated with higher rate of RD admissions even controlling for sulfur dioxide, nitrogen dioxide, carbon monoxide, or ozone on cool days. This study provides evidence that higher levels of PM2.5–10 enhance the risk of hospital admissions for RD on cool days.
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