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Tang Y.,Hubei University of Medicine | Tang Y.,Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control | Zheng S.-J.,Hubei University of Medicine | Qi C.-B.,Hubei University of Medicine | And 2 more authors.
Analytical Chemistry | Year: 2015

(Chemical Equation Presented) Cytosine methylation (5-methylcytosine, 5-mC) in genomic DNA is an important epigenetic mark that has regulatory roles in diverse biological processes. 5-mC can be oxidized stepwise by the ten-eleven translocation (TET) proteins to form 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC), which constitutes the active DNA demethylation pathway in mammals. Owing to the extremely limited contents of endogenous 5-mC oxidation products, no reported method can directly determine all these cytosine modifications simultaneously. In the current study, we developed selective derivatization of cytosine moieties with 2-bromo-1-(4-dimethylamino-phenyl)-ethanone (BDAPE) coupled with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the simultaneous determination of these cytosine modifications in genomic DNA. The chemical derivatization notably improved the liquid chromatography separation and dramatically increased detection sensitivities of these cytosine modifications. The limits of detection (LODs) of the derivatives of 5-mC, 5-hmC, 5-foC, and 5-caC were 0.10, 0.06, 0.11, and 0.23 fmol, respectively. Using this method, we successfully quantified 5-mC, 5-hmC, 5-foC, and 5-caC in genomic DNA from human colorectal carcinoma (CRC) tissues and tumor-adjacent normal tissues. The results demonstrated significant depletion of 5-hmC, 5-foC, and 5-caC in tumor tissues compared to tumor-adjacent normal tissues, and the depletion of 5-hmC, 5-foC, and 5-caC may be a general feature of CRC; these cytosine modifications could serve as potential biomarkers for the early detection and prognosis of CRC. Moreover, the marked depletion of 5-hmC, 5-foC, and 5-caC may also have profound effects on epigenetic regulation in the development and formation of CRC. © 2015 American Chemical Society.

Zeng X.,Guangxi Medical University | Liu S.,Guangxi Medical University | Yu H.,Guangxi Medical University | Ji L.,Taishan Medical College | And 4 more authors.
DNA and Cell Biology | Year: 2012

The associations between DNA repair capacity (DRC), DNA repair gene polymorphisms, and the incidence of hepatocellular carcinoma (HCC) have not been determined in high-risk areas. The aims of this study were to investigate whether DRC is related to the incidence of HCC and to determine whether polymorphisms in the DNA repair genes that regulate DRC are associated with the risk of HCC. First, a small case-control study was conducted to examine the association between DRC and the incidence of HCC and the environmental and genetic factors regulating DRC. Then, a large case-control study was conducted to determine whether those DNA repair gene polymorphisms shown to regulate DRC were related to the risk of HCC. The median DRC was significantly lower among the cases (0.80) than the controls (0.93). A multivariate linear regression analysis showed that the HBsAg status (p<0.01), ethnicity (p=0.01), and polymorphisms in the XRCC3-241 (p=0.01) and APE1-148 (p=0.03) gene loci may be impact factors for DRC. In the large case-control study, a stratified analysis showed that individuals with the APE1-148-combined genotype GT+TT likely had a significantly higher HCC risk compared with those with only the GG genotype (crude odds ratio=1.93, 95% confidence interval=1.17-3.17) among the Zhuang ethnicity. However, nonsignificant differences were observed between XRCC3-241 polymorphisms and the HCC risk. DRC may be related to the incidence of HCC as determined by environmental and genetic factors found in southwestern part of the Guangxi Province. Gene-environment interactions play an important role in the incidence and progression of HCC. © Copyright 2012, Mary Ann Liebert, Inc.

Zeng X.,Medical Scientific Research Center | Zeng X.,Guangxi Medical University | Yin F.,Medical Scientific Research Center | Liu X.,Guangxi Medical University | And 5 more authors.
Oncology Reports | Year: 2014

E2F transcription factor 3 (E2F3), a member of the E2F transcription factor family and a member of the genes involved in the regulation of cell cycle, is an oncogene with strong proliferative potential. E2F3 is involved in many processes and plays important roles in the development of several types of cancer, while its relationship with prognosis in hepatocellular carcinoma (HCC) has yet to be reported. In the present study, based on 4 independent microarray data sets which covered 385 cases of HCC and 327 cases of normal livers retrieved from the Oncomine database, we demonstrated that E2F3 was upregulated at least 1.5-fold and on average 2.3-fold in HCC when compared with normal controls. Comprehensive bioinformatics analysis consisting of protein-protein interaction, gene co-occurrence, microRNA-mRNA interaction and biological process annotation indicated that E2F3 interacted with a large number of genes, proteins and microRNAs which were all associated with poor prognosis in patients with HCC and other types of cancer, suggesting that E2F3 may also serve as a biomarker for poor prognosis. Taken together, for the first time, we show that the overexpression of E2F3 may be associated with unfavorable prognosis in HCC.

Shen J.-Q.,Guangxi Medical University | Yang Q.-L.,National Institute of Parasitic Disease | Xue Y.,Guangxi Medical University | Cheng X.-B.,Guangxi Medical University | And 4 more authors.
Parasitology Research | Year: 2015

Clonorchis sinensis is a food-borne parasite that induces a permanent increase of nitrosation in the body upon infection. The spleen is an important secondary lymphoid organ for the regulation of immune responses locally and in the whole body. However, the functions and mechanisms of the spleen in nitric oxide (NO) responses after C. sinensis infection remain unknown. In this study, BALB/c mice were infected with 20, 40, and 80 C. sinensis metacercariae to simulate mild, moderate, and severe infections, respectively. We examined the expression of inducible nitric oxide synthase (iNOS) in the spleen and the relevant cytokine transcription in splenocytes from the mice infected with different amounts of metacercariae. The iNOS of the mice infected with 80 metacercariae was expressed in the spleen as early as 10 days post-infection (dpi) and gradually increased until 90 dpi. The iNOS expression in the mice infected with 40 metacercariae was detected only at 45 and 90 dpi, but not in the mice infected with 20 metacercariae. The level of interferon (IFN)-γ messenger RNA (mRNA) transcription in splenocytes significantly increased at 10 and 20 dpi (P < 0.05) in response to mild/moderate infection but gradually decreased to normal levels after 45 dpi. The level of IL-12p35 mRNA transcription did not change at 10 and 20 dpi but significantly decreased after 45 dpi under moderate/severe infection (P < 0.05/0.01/0.001). The level of IL-18 mRNA transcription significantly increased at 10 dpi (P < 0.05/0.01) but significantly decreased after 20 dpi (P < 0.05/0.01/0.001). These results suggest that spleen is an important organ for iNOS/NO responses, which correspond to the severity of C. sinensis infection, but cannot be attributed to the expression of the Th1 cytokines. © 2015, The Author(s).

Harrison T.J.,University College London | Yang J.-Y.,Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control | Chen Q.-Y.,Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control | Wang X.-Y.,Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control | Fang Z.-L.,Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control
Liver International | Year: 2013

Background: Although persistent hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), the mechanisms of oncogenesis remain obscure. Aims: To determine whether the findings that HBV basal core promoter (BCP) A1762T, G1764A double mutations, pre-S deletions and a combination of both are risk factors of HCC are supported by geographical epidemiology. Methods: Study subjects were recruited from Long An county, where the incidence of HCC is the highest, and five other counties in Guangxi, where the HCC incidence is lower and varies among them. The Pre-S region and BCP of HBV from all study subjects were amplified and sequenced and the data were analysed using chi-squared tests. Results: The prevalence of BCP and pre-S mutations differs significantly (χ2 = 9.850, 5.135, respectively, all P < 0.01) between Long An and the other counties. However, the prevalence of combined BCP and pre-S mutations does not differ significantly (χ2 = 1.510, P > 0.05). These mutations are less frequent in the young but the prevalence of pre-S deletions does not increase with age. The prevalence of these mutations does not differ significantly between men and women but is significantly higher in Zhuang than the other ethnic populations. Among the other five counties, the prevalence of BCP mutations in counties where the HCC incidence is high is significantly higher than that of counties where the HCC incidence is low. Conclusions: Combined BCP double mutations and pre-S deletion may not increase the risk of HCC, although these mutations are a risk factor of HCC when they present alone. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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