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Chen H.-F.,Sun Yat Sen University | Chen H.-F.,Guangdong Prevention and Treatment Center for Occupational Disease | Mai J.-R.,Sun Yat Sen University | Wan J.-X.,Sun Yat Sen University | And 12 more authors.
PLoS ONE | Year: 2013

Previously, we identified the genetic variant -241 (-/G) (rs11453459) in the PP2A-Aα gene (PPP2R1A) promoter and demonstrated that this variant influences the DNA-binding affinity of nuclear factor-kappa B (NF-κB). In this study, we further confirmed that the transcriptional activity of PPP2R1A may be regulated by NF-κB through the functional genetic variant -241 (-/G). Moreover, we also demonstrated that the methylation status of CpG islands in the promoter of PPP2R1A influences the activity of this gene promoter. Few studies have examined the role of this -241 (-/G) variant in genetic or epigenetic regulation in hepatocellular carcinoma (HCC). To investigate whether this functional variant in the PPP2R1A promoter is associated with the risk of HCC and confirm the function of the -241 (-/G) variant in the HCC population, we conducted a case-control study involving 251 HCC cases and 252 cancer-free controls from a Han population in southern China. Compared with the -241 (--) homozygote, the heterozygous -241 (-G) genotype (adjusted OR = 0.32, 95% confidence interval (CI) = 0.17-0.58, P<0.001) and the -241 (-G)/(GG) genotypes (adjusted OR = 0.38, 95% CI = 0.22-0.67, P = 0.001) were both significantly associated with a reduced risk of HCC. Stratification analysis indicated that the protective role of -241 (-G) was more pronounced in individuals who were ≤ 40 years of age, female and HBV-negative. Our data suggest that the transcriptional activity of PPP2R1A is regulated by NF-κB through the -241 (-/G) variant and by the methylation of the promoter region. Moreover, the functional -241 (-/G) variant in the PPP2R1A promoter contributes to the decreased risk of HCC. These findings contribute novel information regarding the gene transcription of PPP2R1A regulated by the polymorphism and methylation in the promoter region through genetic and epigenetic mechanisms in hepatocarcinogenesis. © 2013 Chen et al. Source


Li X.D.,Guangdong 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 observe the association between SNPs in SOD1 (rs1041740, rs2070424, rs10432782 and rs4998557) and noise-induced hearing loss in Chinese Han population. A case-control study was used to study the effects of environmental risk factors on the susceptibility to noise induced hearing loss (NIHL) in 201 sensitive workers and 202 resistant workers. A questionnaire was designed to carry out an investigation, and an occupational health survey was used to identify the occupational risk factors. Genomic DNA was extracted from peripheral blood cells using standard procedures of Takara kit, and 5 ml blood was from each subject. SNPs were detected using standard procedures of TaqMan probe allele identification method. In SOD1 gene, the A allele of rs2070424 was a protective factor of NIHL, compared with the G allele (OR = 0.67, 95%CI: 0.50 approximately 0.88). The risk with NIHL in subjects with AA genotype was significantly lower than that in subjects with GG genotype (OR = 0.48, 95%CI: 0.26 approximately 0.79). After adjusting the confusion factors, OR was 0.44 and 95%CI was 0.25 approximately 0.78. In Chinese Han population, the SNP of rs2070424 in SOD1 may be associated with the susceptibility to NIHL. Source


Zhu W.,U.S. Center for Disease Control and Prevention | Zhu W.,Guangzhou University | Liu Y.,Guangzhou University | Hu K.,Shantou University | And 8 more authors.
Canadian Journal of Physiology and Pharmacology | Year: 2014

This study sought to understand the effects of vitronectin (VTN) on the growth of SMMC-7721 hepatoma cells. In addition, this study examined how VTN inhibits the induction of apoptosis in SMMC-7721 cells by 3,3′-diindolylmethane (DIM), a metabolite of natural phytochemicals, and preliminarily investigated the signaling molecules involved in this process. A cell proliferation reagent was used to observe the effects of VTN on cell proliferation rates. Laser scanning confocal microscopy was performed to observe the effects of VTN on the morphology of tubulin, a component of the cytoskeleton. Flow cytometry and Western blotting assays were used to observe the inhibitory effects of VTN on DIM-induced apoptosis in SMMC-7721 cells and changes in the expression levels of the signaling molecules involved in this process. VTN promoted tumor cell growth in a concentration-dependent manner and inhibited apoptosis caused by the effects of apoptosis-inducing agents. Under in vitro experimental conditions, VTN contributed to the growth of SMMC-7721 hepatoma cells and protected them from the effects of an apoptosis-inducing agent. These findings suggest that during hepatocellular carcinogenesis, VTN may promote tumor cell growth and inhibit chemically induced apoptosis. Source


Chen L.M.,Guangdong 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: 2012

To establish the oxidative damage model of cochlea hair cells using organic oxidant t-BHP in vitro. HEI-OC1 cells were exposed to t-BHP at 8 doses (30~4000 μmol/L) for 12 h. Trypan blue test was used to detected the cellular viability and MTT assay was utilized to measured the cellular proliferation. The intracellular ROS levels were determined by 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA). The survival rates of HEI-OC1 cells started decrease significantly at the dose of 100 μmol/L t-BHP, the peak of decreased survival rates appeared at the doses of 200~800 μmol/L. The results of MTT assay demonstrated that 30 μmol/L t-BHP could promote cellular proliferation ability, when t-BHP concentrations were higher than 200 μmol/L, the cellular proliferation ability was inhibited. The results of DCFH-DA assay showed that there was no fluorescence in control group, the strong fluorescence was observed in positive control group, the weak fluorescence was observed in 30~50 μmol/L t-BHP groups, the bright fluorescence was observed in 100 μmol/L t-BHP group, still the stronger fluorescence was observed in 200~1000 μmol/L groups, but the cellular number decreased with the doses because of the lower cellular viability. The exposure to 100 μmol/L t-BHP for 12 h could simulate the oxidative damage induced by noise in cochlear hair cells. Source


Chen Q.S.,Guangdong 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: 2012

To measure and assess the levels of occupational exposure to power frequency electromagnetic fields in workers of power grid. PMM8053 electromagnetic fields measuring system with EHP-50 probe was used to measure the levels of electromagnetic fields at working place. Personal dosimeters (EMDEX LITE) were utilized to measure the individual exposure levels of power frequency magnetic field. The results were evaluated with the limitation criteria of GBZ2.2 and ICNIRP. In the 500 kV ultra high voltage substation, the intensity at 90% measure points of power electric field was more than 5 kV/m. The magnetic field intensity in the areas nearby reactors and capacitors was often higher than 100 μT, even several hundreds μT. The mean daily exposure levels of workers in power grid were between 0.04 and 5.0 μT, and the exposure levels of 70% workers were higher than 0.4 μT. In the areas of ultra high voltage and nearby the reactors and capacitors are the key control points for occupational health in power grid. There is acute health risk of workers exposed to high accumulative exposure levels. Source

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