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Particulate matter (PM) is associated with the incidence, exacerbation, and mortality of variable respiratory diseases. However, the molecular mechanisms of PM

Recent studies demonstrate that the autophagy-dependent turnover of mitochondria (mitophagy) mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure, and contributes to emphysema development in vivo during chronic cigarette smoke (CS)-exposure, although the underlying mechanisms remain unclear. Here, we investigated the role of mitophagy in regulating apoptosis in CSE-exposed human lung bronchial epithelial cells. Furthermore, we investigated the potential of the polymethoxylated flavone antioxidant quercetogetin (QUE) to inhibit CSE-induced mitophagy-dependent apoptosis. Our results demonstrate that CSE induces mitophagy in epithelial cells via mitochondrial dysfunction, and causes increased expression levels of the mitophagy-regulator protein PTEN-induced putative kinase-1 (PINK1) and the mitochondrial fission protein dynamin-1-like protein (DRP-1). CSE induced epithelial cell death and increased the expression of the apoptosis-related proteins cleaved caspase-3, -8 and -9. Caspase-3 activity was significantly increased in Beas-2B cells exposed to CSE, and decreased by siRNA-dependent knockdown of DRP-1. Treatment of epithelial cells with QUE inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting phospho (p)-DRP-1 and PINK1 expression. QUE suppressed mitophagy-dependent apoptosis by inhibiting the expression of cleaved caspase-3, -8 and -9 and downregulating caspase activity in human bronchial epithelial cells. These findings suggest that QUE may serve as a potential therapeutic in CS-induced pulmonary diseases.

Primer-probe sets to detect Bacillus cereus and/or B. subtilis in food products were developed based on panX (a pan-genome analysis tool). Data for 60 B. cereus strains and 131 B. subtilis strains retrieved from the NCBI RefSeq database were analyzed by panX. Primer-probe sets for B. cereus (ccpA) and B. subtilis (cotQ) were developed by comparing the core genomes of the two bacteria. The developed primer-probe sets’ sensitivity and selectivity were identified using 45 strains, including ten B. cereus, five B. subtilis, 13 non-B. cereus and non-B. subtilis strains, and 17 non-Bacillus strains using real-time polymerase chain reaction (PCR). The developed primer-probe sets displayed high sensitivity and selectivity for B. cereus and B. subtilis, validated with two different real-time PCR instruments. PCR analysis using the developed primer-probe showed high efficiency in buffer and milk samples. These results indicate that the primer-probe sets developed based on the panX analysis can be used effectively for detecting B. cereus and/or B. subtilis in food products.

This study was conducted to investigate the antimicrobial effect of thiamine dilaurylsulfate (TDS), known as a vitamin B 1 derivative, on custard cream. The inactivation of Escherichia coli O157:H7, Salmonella Typhimurium, Listeria monocytogenes , and Bacillus cereus spores in custard cream over a 5 day storage period and the influence of storage temperature at 4 and 25 °C were investigated. Samples were inoculated with a cocktail of these pathogens and subjected to addition of TDS at concentrations ranging from 0 to 2%. As the concentration of TDS and storage time increased, the inactivation effect increased among all tested pathogens except for B . cereus . The addition of 2% TDS achieved 2.43-, 2.37-, and 0.93-log reductions in inoculated E. coli O157:H7, S . Typhimurium, and L. monocytogenes , respectively, during 5 day storage at 25 °C. Gram-negative bacteria were more susceptible to TDS than Gram-positive bacteria, and TDS was more effective at 25 °C than 4 °C. However, regardless of TDS concentration during storage at 4 and 25 °C, there were no significant ( P > 0.05) differences in populations of B. cereus spores between untreated control and TDS-treated samples. These results suggest that TDS has potential for preventing spoilage of dairy products by improving microbiological safety.

Cigarette smoke, a major causative agent of chronic obstructive pulmonary disease (COPD), induces lung cell death by incompletely understood mechanisms. The induction of apoptosis in lung structural cells by cigarette smoke may contribute to the pathogenesis of emphysema. Phosphodiesterase-4 (PDE4) inhibitors are anti-inflammatory agents used in COPD therapy that can prevent cigarette smoke-induced emphysema in mice. We investigated the effect of rolipram, a first generation PDE4 inhibitor, on the regulation of cigarette smoke-induced apoptosis. Human lung fibroblast (MRC-5) cells were exposed to cigarette smoke extract (CSE). Cell viability and apoptosis were determined by MTT assay and Annexin-V staining, respectively. Caspase activation was determined by Western immunoblot analysis. Rolipram protected against cell death and increased viability in MRC-5 fibroblasts after CSE exposure. Furthermore, rolipram protected against apoptosis, decreased caspase-3 and -8 cleavage in MRC-5 cells exposed to CSE. Pre-treatment with rolipram enhanced Akt phosphorylation and associated cytoprotection in CSE-treated cells, which could be reversed by the PI3K inhibitor LY294002 partly. In conclusion, rolipram protects against apoptosis of MRC-5 cells through inhibition of caspase-3 and caspase-8. Rolipram may represent an effective therapeutic agent to reduce cigarette smoke-induced apoptosis of lung fibroblasts.

Thoroughbred is the main horse breed in the horse racing industry. The horses which record excellent performance are valuable in the aspects of economics and industry. Because of the limitation of the conventional breeding methods, it is needed to develop a reliable system for the selection of stallion stud based on molecular breeding. Therefore we conducted high throughput analysis to discover exercise-related single nucleotide variations (SNVs) and differentially expressed genes (DEGs). We sequenced the whole mRNA from the blood and muscle tissues of six thoroughbred horses before and after exercise. By comparing current horse genome annotation, we identified 32,361 unigene clusters and 189,973 SNVs from the sequence aligned against the horse reference genome. We also identified genes regulated by exercise: 62 up-regulated and 80 down-regulated genes in the blood, and 878 up-regulated and 285 down-regulated genes in the muscle, respectively. In addition to DEGs, we also found differentially expressed alternative splicing forms of AXL, DYNC1, PLEKHG1, and COBLL1 before and after exercise. Overall, our results indicated that exercise stress induces massive gene expression change. Further studies should be focused on the mechanism of exercise-induced change and their relation in excellent performance in racing horses. Our data would be valuable information to develop exercise-related markers in horses and ultimately applied to establish a reliable selection system for producing a better stallion.

Docetaxel and gemcitabine combination chemotherapy has been reported to be active against non-small cell lung cancer (NSCLC) and myelosuppression is the most common dose-limiting toxicity. This prospective phase II study was designed to test the hypothesis that better tolerance and increased dose intensity might be achieved if patients are treated with weekly administration schedule. Thirty-five patients with stage IIIB/IV NSCLC and a performance status 0-2 received first-line chemotherapy with docetaxel 35mg/m2 and gemcitabine 600mg/m2 on days 1, 8 and 15. Treatment was repeated every 4 weeks, for up to 4 cycles. In total, 85 chemotherapy cycles were given (median, 2; range, 1-4). Other than the completion of all 4 planned cycles (n=6), the main reasons for treatment discontinuation were toxicity (n=15) and progressive disease (n=14). The most frequently encountered toxic effects were anemia (52% of patients), nausea and vomiting (60%), fatigue (71%) and anorexia (57%). One patient died of bilateral pneumonitis, which developed shortly after the administration of second cycle. Disease control (objective response and stable disease) in the intent-to-treat (ITT) population was achieved in 60% of patients and the overall response rate was 29% (95% CI, 14-44%). With a median follow-up duration of 13 months, the median progression-free survival and overall survival were 2.8 (95% CI, 0.7-4.8) months and 10.6 (95% CI, 7.0-14.3) months, respectively. In conclusion, weekly schedule of docetaxel and gemcitabine has modest activity with acceptable toxicity profile in advanced NSCLC, but as high frequency of early discontinuation occurred does not merit further study with the present regimen.

(LCX) coronary artery communicated with a branch of the bronchial artery (Fig. 1). The left ventricular ejection fraction was 60% based on echocardiography. We suspected that the stenosis of the LAD coronary artery contributed to the chest pain, and decided to treat with an anti-angina drug for this lesion. We reasoned that the coronary-to-bronchial artery fistula might be secondary to coronary artery stenosis inducing a steal phenomenon in patient with bronchiectasis. If the hemoptysis recurs at the coronary-to-left bronchial artery fistula, it may be accompanied by complications, such as myocardial infarction, and increase the risk of mortality during embolization. Therefore, we advised the patient to undergo prophylactic cardiac catheterization with embolization to close the