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Weng S.,Huazhong University of Science and Technology | Weng S.,Shenzhen Prevention and Treatment Center for Occupational Disease | Wang L.,Huazhong University of Science and Technology | Wang L.,U.S. Center for Disease Control and Prevention | And 5 more authors.
PLoS ONE | Year: 2015

Objectives To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL)-1β genes and occupational dust exposure on the risk of silicosis. Methods We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE) for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1β genes. We estimated odds ratios(ORs), 95% confidence intervals(95%CIs), and p-values using logistic regression models adjusted for selected confounders. Results After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12-5.12] and 3.62 [1.63-8.02], respectively). Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C inNalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24 [0.06-0.88]). Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04-6.12] and 5.19[1.88-14.35], respectively). Among subjects with CDE greater than 120 mg/m3×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35-207.39] and 3.47[1.40-8.64], respectively). Conclusions Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status. © 2015 Weng et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Linqing Y.,U.S. Center for Disease Control and Prevention | Bo X.,U.S. Center for Disease Control and Prevention | Xueqin Y.,Shenzhen Prevention and Treatment Center for Occupational Disease | Hong D.,Shenzhen Longgang District Center for Disease Control and Prevention | And 5 more authors.
Toxicology Letters | Year: 2016

A matched case-control study was conducted to examine the relationship between chromium (Cr) exposure and variation in mitochondrial (mt) DNA methylation. We enrolled 29 pairs of subjects in this study; Cr exposure was confirmed in the cases by detecting blood Cr and other metal ion concentrations. DNA damage caused by Cr exposure was determined in terms of binucleated micronucleus frequency (BNMN) and mtDNA copy number. Finally, a Sequenom MassARRAY platform was applied to inspect the DNA methylation levels of mitochondrially encoded tRNA phenylalanine (MT-TF), mitochondrially encoded 12S RNA (MT-RNR1), and long interspersed nucleotide element-1 (LINE-1) genes. The blood Cr ion concentration and micronucleus frequency of the Cr-exposed group were higher than those of the control group, whereas the mtDNA copy number remained unchanged. The methylation levels of MT-TF and MT-RNR1 but not LINE-1 were significantly lower in Cr-exposed workers. Pearson correlation analysis showed that workers with higher blood Cr ion concentrations exhibited lower MT-TF and MT-RNR1 gene methylation, and multiple linear regression analysis indicated that CpG sites 1 and 2 in MT-TF and CpG site 6 in MT-RNR1 were affected. These results suggested that methylation level of mtDNA has the possibility of acting as an alternative effect biomarker for Cr exposure. © 2015.

Hui C.-Y.,Shenzhen Prevention and Treatment Center for Occupational Disease | Xie X.-B.,Hunan University | Cao H.,Southern Medical University | Huang S.-H.,Saban Research Institute
Anti-Infective Agents | Year: 2013

Continual genetic variation supports hepatitis C virus (HCV) persistent infection, a leading cause of cirrhosis and hepatocellular carcinoma. The current standard of care has limited efficacy and is associated with severe adverse effects. Efforts to improve patients' outcomes have focused on the design and development of small molecule compounds targeted towards essential viral proteins. Following the clinical success of HIV protease inhibitors, the HCV NS3-4A protease domain emerged as one of the most successful antiviral drug targets. This mini-review describes several HCV protease inhibitors in the various stages of clinical trials, and discusses their antiviral activities, pharmacokinetic properties, side effects and resistance profiles. © 2013 Bentham Science Publishers.

He X.L.,Southern Medical University | Wang Q.,Southern Medical University | Peng L.,Guangzhou University | Qu Y.-R.,Southern Medical University | And 6 more authors.
Pathogens and disease | Year: 2015

OmpT is one of the members of the outer membrane protein family that has been identified as a virulence factor in most of the uropathogenic Escherichia coli (UPEC). However, the exact role of OmpT in the urinary tract infections (UTIs) remains unclear. To determine the role of OmpT in the pathogenesis of UPEC, an isogenic deletion mutant of ompT (COTD) was constructed by the λ Red recombination. Human bladder epithelial cell line 5637(HBEC 5637) was used to evaluate the ability of bacterial adhesion/invasion. A murine model of UTI was established to study the formation of intracellular bacterial communities (IBCs) in the process of UTIs. The cytokines were also examined during the pathogenesis. The results showed that the COTD strain was deficient in bacterial adhesion and invasion as well as in IBC formation compare to the parent strain. ELISA quantification analysis of cytokines showed that the levels of TNF-α, IL-6 and IL-8 in the serum, bladder and kidney tissues of the mice infected with COTD were lower than that of the CFT073 group. In summary, these results suggest that OmpT plays a multifaceted role in pathogenesis of UTI, including increased bacterial adhesiveness/invasiveness, formation of IBCs and upregulated proinflammatory cytokines. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Li S.F.,Shenzhen Prevention and Treatment Center for Occupational Disease
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases | Year: 2011

To develop a method to determine phosphoric acid in the air of workplace by ion chromatography. Phosphoric acid was collected by millipore filter and washed by deionized water then detected by ion chromatography. Linearity range of test was 0 ∼ 20 μg/ml, relative standard deviation (RSD) was 1.95% ∼ 3.31%, the elution efficiency was 103.0% ∼ 109.6%, determination limit was 0.1 μg/ml (when sample size was 20.01) concentration limit was 0.01 mg/m(3) (when the collected air was 75 L). This method is convenient for air collection, simple, with high sensitivity and good precision, is a good method for determination of phosphoric acid in the air of workplace.

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