Whole genome expression in peripheral-blood samples of workers professionally exposed to polycyclic aromatic hydrocarbons.

This study aims to examine global gene expression profiles before and after the work-shift among coke-oven workers (COWs). COWs work six consecutive days and then take two days off. Two blood and urine samples in each worker were collected before starting to work after two days off and end-of-shift in the sixth day of work in 2009. Altered gene expressions (ratio of gene expression levels between end-of-shift and preshift work) were performed by a Human OneArray expression system which probes ~30,000-transcription expression profiling of human genes. Sixteen workers, all men, were enrolled in this study. Median urinary 1-hydroxypyrene (1OHP) levels (µmol/mol creatinine) in end-of-shift work were significantly higher than those in preshift work (2.58 vs 0.29, p = 0.0002). Among the 20,341 genes which passed experimental quality control, 26 gene expression changes, 7 positive and 19 negative, were highly correlated with across-the-shift urinary 1OHP levels (end-of-shift-preshift 1OHP) (p-value <0.001). The high and low exposure groups of across-the-shift urinary 1OHP levels dichotomized in ~2.00 µmol/mol creatinine were able to be distinguished by these 26 genes. Some of them are known to be involved in apoptosis, chromosome stability/DNA repair, cell cycle control/tumor suppressor, cell adhesion, development/spermatogenesis, immune function, and neuronal cell function. These findings in COWs will be an ideal model to study the relationship of PAH exposure with acute changes of gene expressions.

Baculovirus transduction of mesenchymal stem cells triggers the toll-like receptor 3 pathway.

Human mesenchymal stem cells (hMSCs) can be genetically modified with viral vectors and hold promise as a cell source for regenerative medicine, yet how hMSCs respond to viral vector transduction remains poorly understood, leaving the safety concerns unaddressed. Here, we explored the responses of hMSCs against an emerging DNA viral vector, baculovirus (BV), and discovered that BV transduction perturbed the transcription of 816 genes associated with five signaling pathways. Surprisingly, Toll-like receptor-3 (TLR3), a receptor that generally recognizes double-stranded RNA, was apparently upregulated by BV transduction, as confirmed by microarray, PCR array, flow cytometry, and confocal microscopy. Cytokine array data showed that BV transduction triggered robust secretion of interleukin-6 (IL-6) and IL-8 but not of other inflammatory cytokines and beta interferon (IFN-beta). BV transduction activated the signaling molecules (e.g., Toll/interleukin-1 receptor domain-containing adaptor-inducing IFN-beta, NF-kappaB, and IFN regulatory factor 3) downstream of TLR3, while silencing the TLR3 gene with small interfering RNA considerably abolished cytokine expression and promoted cell migration. These data demonstrate, for the first time, that a DNA viral vector can activate the TLR3 pathway in hMSCs and lead to a cytokine expression profile distinct from that in immune cells. These findings underscore the importance of evaluating whether the TLR3 signaling cascade plays roles in the immune response provoked by other DNA vectors (e.g., adenovirus). Nonetheless, BV transduction barely disturbed surface marker expression and induced only transient and mild cytokine responses, thereby easing the safety concerns of using BV for hMSCs engineering.

l-Arginine Grafted Poly(Glycerol Sebacate) Materials: An Antimicrobial Material for Wound Dressing.

This study focuses on the development and evaluation of a novel wound dressing material. l-arginine grafted poly(glycerol sebacate) materials (PGS-g-Arg) are developed by chemical conjugation of l-arginine on poly(glycerol sebacate) chains and the mechanical property, water vapor transmission rate, antimicrobial functions and biocompatibility are investigated. At various l-arginine grafting ratio, the mechanical properties are tunable. It was found that between 7-13% l-arginine grafting ratios, the tensile strengths of PGS-g-Arg were similar to that of natural skin. These materials are shown with a low water vapor transmission rate, 6.1 to 10.3 g/m2/h, which may form a barrier and assist in the closure of wounds. Inhibition in the growth of Pseudomonas aeruginosa and Staphylococcus aureus was observed on PGS-g-Arg, and a series of experiments were conducted to confirm its biocompatibility. In summary, l -arginine grafted poly(glycerol sebacate) may offer a novel option for wound dressing.

Comparison of genomic signatures of non-small cell lung cancer recurrence between two microarray platforms.

BACKGROUND: Cancer genomic signatures may vary using different platforms. We compared the differential gene expression in non-small cell lung cancer (NSCLC) between two platforms in order to find the most relevant genomic signatures of tumor recurrence. MATERIALS AND METHODS: We analyzed gene expression in frozen lung cancer tissue from 59 selected patients who had undergone surgical resection of NSCLC. These patients were divided into two groups: group R, patients who had a tumor recurrence within four years, n=37; group NR, patients who remained disease-free four years following initial surgery, n=22. Each RNA sample was assayed twice using both Affymetrix and Illumina GeneChip. Data were analyzed by principal component analysis and leave-one-out cross-validation. RESULTS: Using the same filtering criteria, 13 genes that were differentially expressed between R and NR were identified by Affymetrix, while 21 genes were identified by Illumina GeneChip. In common, a total of six genes were detected by both systems. Using univariate analysis, four (lipocalin 2, LCN2; parathyroid hormone-like hormone, PTHLH; ras-related protein Rab-38, RAB38; and four jointed box 1, FJX1) of these six genes were associated with survival. A risk score of survival was calculated according to the four-gene expression. There was a significant difference in overall survival between low- and high-risk groups. CONCLUSION: A four-gene signature is associated with survival among patients with early-stage NSCLC. Further validation of these findings is warranted.

Effect of co-axially hybridized gene targets on hybridization efficiency of microarrayed DNA probes.

The effect of relative size of two co-axially hybridized gene targets on the hybridization efficiency was studied for two DNA probe configurations and various probe concentrations. Each of two sets of microarrayed probes contained a pair of DNA probes and a pair of their complementary samples labeled with two distinct fluorescent dyes. The sequence of each probe is especially designed so that two targets are simultaneously complementary to two adjacent sections of the probe. The molecular steric effect on the hybridization efficiency is investigated by comparing the dye signals between configurations of one-target and two-target hybridization scenarios. The results show that a low probe concentration gives better hybridization efficiency and the first-hybridization conducted by a shorter-size DNA target improves the hybridization efficiency of the second target coupling onto the same probe.

Cigarette smoking and alcohol drinking and esophageal cancer risk in Taiwanese women.

AIM: To investigate the etiology of esophageal cancer among Taiwanese women. METHODS: This is a multi-center, hospital-based, case-control study. Case patients consisted of women who were newly diagnosed and pathology-proven to have esophageal squamous cell carcinoma (ESCC) from three large medical centers (one from Northern and two from Southern Taiwan, respectively) between August 2000 and December 2008. Each ESCC patient was matched with 4 healthy women based on age (within 3 years) and hospital of origin, from the Department of Preventive Medicine in each hospital. A total of 51 case patients and 204 controls, all women, were studied. RESULTS: Frequencies of smokers and drinkers among ESCC patients were 19.6% and 21.6%, respectively, which were significantly higher than smokers (4.4%) and drinkers (4.4%) among controls (OR = 4.07, 95% CI: 1.36-12.16, P = 0.01; OR = 3.55, 95% CI: 1.03-12.27, P = 0.04). Women who drank an amount of alcohol more than 158 g per week had a 20.58-fold greater risk (95% CI: 1.72-245.62, P = 0.02) of ESCC than those who never drank alcohol after adjusting for other covariates, although the sample size was small. CONCLUSION: Cigarette smoking and alcohol drinking, especially heavy drinking, are the major risks for developing ESCC in Taiwanese women.