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Epidemiological studies have associated high levels of airborne particulate matter (PM) with increased respiratory diseases. In order to investigate the mechanisms of air pollution-induced lung toxicity in humans, human bronchial epithelial cells (16HBE) were exposed to various concentrations of particles smaller than 2.5 μm (PM2.5) collected from Beijing, China. After observing that PM2.5 decreased cell viability in a dose-dependent manner, we first used Illumina RNA-seq to identify genes and pathways that may contribute to PM2.5-induced toxicity to 16HBE cells. A total of 539 genes, 283 up-regulated and 256 down-regulated, were identified to be significantly differentially expressed after exposure to 25 μg/cm2 PM2.5. PM2.5 induced a large number of genes involved in responses to xenobtiotic stimuli, metabolic response, and inflammatory and immune response pathways such as MAPK signaling and cytokine-cytokine receptor interaction, which might contribute to PM2.5-related pulmonary diseases. We then confirmed our RNA-seq results by qPCR and by analysis of IL-6, CYP1A1, and IL-8 protein expression. Finally, ELISA assay demonstrated a significant association between exposure to PM2.5 and secretion of IL-6. This research provides a new insight into the mechanisms underlying PM2.5-induced respiratory diseases in Beijing.

(2015) Enhanced oral bioavailability of piperine by selfemulsifying drug delivery systems: invitro,invivo and insitu intestinal permeability studies, Drug Delivery, 22:6, 740-747, DOI: 10.3109/10717544.2014 AbstractThe main purpose of this work was to develop and evaluate a self-emulsifying drug delivery system (SEDDS) of piperine to enhance its solubility and bioavailability. The formulation was optimized by solubility test and ternary phase diagrams. Then physiochemical properties and in vitro release of SEDDS were characterized. In vivo pharmacokinetics study and in situ singlepass intestinal perfusion were performed to investigate the effects of SEDDS on the bioavailability and intestinal absorption of piperine. The optimized formulation was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of piperine SEDDS were significantly higher than the self-prepared capsules. In vivo pharmacokinetic study showed C max1 , C max2 and area under the curve of piperine after oral administration of SEDDS in rats were 3.8-, 7.2-and 5.2-fold higher than the self-prepared capsules, respectively, and the relative bioavailability of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the effective permeability and the effective absorption rate values of piperine for SEDDS were significantly improved comparing to solutions (p50.01). So SEDDS formulation could improve the oral bioavailability and intestinal absorption of piperine effectively.

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