Hypermethylation and Clinicopathological Significance of RASAL1 Gene in Gastric Cancer

Chen, Hong,Pan, Ying,Cheng, Zheng-Yuan,Wang, Zhi,Liu, Yang,Zhao, Zhu-Jiang,Fan, Hong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear. This study aimed to determine the methylation status and regulation of RASAL1 in gastric cancer. Materials and Methods: Using the methylation-specific polymerase chain reaction (MSP), the methylation status of CpG islands in the RASAL1 promoter in gastric cancers and paired adjacent non-cancerous tissues from 40 patients was assessed and its clinicopathological significance was analyzed. The methylation status of RASAL1 in gastric cancer lines MKN-28, SGC-790l, BGC-823, as well as in normal gastric epithelial cell line GES-l was also determined after treatment with a DNA methyltransferase inhibitor, 5-aza-2'-doexycytidine (5-Aza-CdR). RAS activity (GAS-GTP) was assessed through a pull-down method, while protein levels of ERK1/2, a downstream molecule of RAS signaling pathways, were determined by Western blotting. Results: The frequencies of RASAL1 promoter methylation in gastric cancer and paired adjacent non-cancerous tissues were 70% (28/40) and 30% (12/40) respectively (P<0.05). There were significantly correlations between RASAL1 promoter methylation with tumor differentiation, tumor size, invasive depth and lymph node metastasis in patients with gastric cancer (all P<0.05), but no correlation was found for age or gender. Promoter hypermethylation of the RASAL1 gene was detected in MKN-28, SGC-790l and BGC-823 cancer cells, but not in the normal gastric epithelial cell line GES-1. Elevated expression of the RASAL1 protein, a decreased RAS-GTP and p-ERK1/2 protein were detected in three gastric cancer cell lines after treatment with 5-Aza-CdR. Conclusions: Aberrant hypermethylation of the RASAL1 gene promoter frequently occurs in gastric cancer tissues and cells. In addition, the demethylating agent 5-Aza-CdR can reverse the hypermethylation of RASAL1 gene and up-regulate the expression of RASAL1 significantly in gastric cancer cells in vivo. Our study suggests that RASAL1 promoter methylation may have a certain relationship with the reduced RASAL1 expression in gastric cancer.

Three-dimensional modelling of water flow due to leakage from pressurized buried pipe

Zhu, Hong,Zhang, Limin,Chen, Chen,Chan, Kit Techno-Press 2018 Geomechanics & engineering Vol.16 No.4

A three-dimensional model is constructed to simulate water infiltration in an unsaturated slope from a leaking pipe. Adaptive mesh refinement and time stepping are used, assisted by an automatic procedure for progressive steepening of the hydraulic property function for better convergence. The model is justified by comparing the simulated results with experimental data. Steady-state flow is investigated considering various pipe water pressures, locations and sizes of the opening, and soil layering. The opening size significantly affects the soaked zone around the pipe. Preferential flow dominates along the pipe longitudinal direction in the presence of a loose backfill around the pipe.

Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta-Analysis Findings

Chen, Jia-Yan,Zhu, Hong-Cheng,Guo, Qing,Shu, Zheng,Bao, Xu-Hui,Sun, Feng,Qin, Qin,Yang, Xi,Zhang, Chi,Cheng, Hong-Yan,Sun, Xin-Chen Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Purpose: To investigate any potential association between wine and breast cancer risk. Materials and Methods: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. Results: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Conclusions: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

Current Evidence on the Association between rs3757318 of C6orf97 and Breast Cancer Risk: a Meta-Analysis

Hong, Yuan,Chen, Xue-Qin,Li, Jiao-Yuan,Liu, Cheng,Shen, Na,Zhu, Bei-Bei,Gong, Jing,Chen, Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: A common genetic variant rs3757318, located in intron of C6orf97, was firstly identified to be associated with breast cancer (BC) risk by a genome-wide association (GWA) study. However, subsequent validation studies with different ethnicities have yielded conflicting results. Materials and Methods: We performed a meta-analysis to synthesize all available data for evaluating the precise effect of this variant on BC susceptibility. Results: A total of 8 articles containing 11 studies with 62,891 cases and 65,635 controls were included in this meta-analysis. When compared to the G allele, the rs3757318-A allele was significantly associated with BC risk with the pooled OR of 1.21 (95% CI=1.15 - 1.29, P<0.001) but with obvious between-study heterogeneity (P=0.040). Stratified analysis suggested that diversity of ethnicity along with control source may explain part of the heterogeneity. Similarly, significant associations were also identified in heterozygote, homozygote, dominant and recessive genetic models. Sensitivity and publication bias analyses indicated robust stability of our results. Conclusions: Our present meta-analysis demonstrated that the variant rs3757318 is associated with increased BC risk. Nevertheless, further studies are needed to clarify the underlying biological mechanisms.

Efficacy of Pap Test in Combination with ThinPrep Cytological Test in Screening for Cervical Cancer

Chen, Hua,Shu, Hui-Min,Chang, Zhou-Lin,Wang, Zhi-Feng,Yao, Hai-Hong,Zhu, Hong-Mei,Lu, Tian-Mei,Ma, Qiang-Yan,Yang, Bin-Lie Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: Our aim was to investigate the efficacy of the Pap test in combination with the ThinPrep cytological test (TCT) in screening for cervical cancer in China. Design: From March 2006 to October 2008, 988 women with the mean age $46.4{\pm}10.5$ years (range, 23-80 years) were recruited to receive cervical cancer screening. Pap test results ${\geq}$ grade III and TCT findings ${\geq}$ ASCUS/AGUS were considered abnormal. Subjects with a Pap test result ${\geq}$ grade IIb received TCT. Colposcopy and biopsies were performed in all participants, and final diagnosis was based on pathological findings. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Youden index for predicting CIN I or above were determined. Results: The sensitivity, specificity, PPV, NPV and Youden index of the Pap test were 43.1%, 97.2%, 70.0%, 91.9%, and 40.3%, respectively. The same values for TCT in predicting CIN were 80.0%, 63.2%, 16.0%, 97.3%, and 43.2%, respectively. The two tests in combination gave values for predicting CIN of 64.8%, 87.6%, 43.6%, 94.4%, and 53.5%, respectively. Combined testing exhibited the highest Youden index (53.4%). Conclusion: The Pap test with a reduced threshold in combination with the TCT has high sensitivity and high specificity in screening for cervical cancer.

Expression Analysis of miRNAs in Porcine Fetal Skeletal Muscle on Days 65 and 90 of Gestation

Chen, Jian-hai,Wei, Wen-Juan,Xiao, Xiao,Zhu, Meng-Jin,Fan, Bin,Zhao, Shu-Hong Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.7

MiRNAs (microRNAs) are a class of small non-coding RNA molecules of ~21 nucleotides that down- regulate the expression of target genes at post-transcriptional level. In this study, we first accomplished a preliminary scan of miRNA expression using 65 and 90 day fetal pig skeletal muscle samples by microarray hybridization, and 34 miRNAs showed strong positive signals. Five of these miRNAs were selected for further investigation by real-time RT-PCR. The statistical analyses indicated that three miRNAs exhibited significant differential expression (p<0.05) during porcine muscle development from 65 to 90 days of gestation, e.g., miR-24 and miR-424 were down-regulated while miR-133a was up-regulated. Multi-tissue RT-PCR was performed to detect the expression patterns of the five miRNA precursors. The results showed that most of these precursor miRNAs were ubiquitously expressed in different porcine tissues.

Colloidal Suspension Properties of Carbonaceous Nanomaterials Enhanced by Using Li as Dopant

Zhu, L.,Meng, Z.-D.,Chen, M.-L.,Choi, J.-G.,Park, C.-Y.,Lee, S.-C.,Hong, D.-S.,Oh, W.-C. CHEMIC PUBLISHING COMPANY 2012 Asian Journal of Chemistry Vol.24 No.2

Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes

Zhu, Bing-Mei,Kang, Keunsoo,Yu, Ji Hoon,Chen, Weiping,Smith, Harold E.,Lee, Daeyoup,Sun, Hong-Wei,Wei, Lai,Hennighausen, Lothar Oxford University Press 2012 Nucleic acids research Vol.40 No.10

<P>Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild-type (WT) mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation, 23 827 and 111 939 STAT5A binding sites were detected in WT and STAT5A overexpressing MEFs, respectively. 13 278 and 71 561 peaks contained at least one GAS motif. 1586 and 8613 binding sites were located within 2.5 kb of promoter sequences, respectively. Stringent filtering revealed 78 genes in which the promoter/upstream region (−10 kb to +0.5 kb) was recognized by STAT5 both in WT and STAT5 overexpressing MEFs and 347 genes that bound STAT5 only in overexpressing cells. Genome-wide expression analyses identified that the majority of STAT5-bound genes was not under GH control. Up to 40% of STAT5-bound genes were not expressed. For the first time we demonstrate the magnitude of opportunistic genomic STAT5 binding that does not translate into transcriptional activation of neighboring genes.</P>

Comparative Analysis on Antioxidative Ability of Muscle between Laiwu Pig and Large White

Chen, Wei,Zhu, Hong-Lei,Shi, Yuan,Zhao, Meng-Meng,Wang, Hui,Zeng, Yong-Qing Asian Australasian Association of Animal Productio 2012 Animal Bioscience Vol.25 No.8

This study was conducted to evaluate effects of storage temperatures ($4^{\circ}C$ and $20^{\circ}C$) and pig breeds (Laiwu pig and Large White pig) on the main antioxidative enzymes (superoxide dismutase, catalase, and glutathione peroxidase) activity and lipid oxidation in porcine Longissimus dorsi muscle. Activities of antioxidative enzymes (AOE) decreased slightly during storage, regardless of storage temperatures. Muscle antioxidative enzymes activities stored at $4^{\circ}C$ were higher than that stored at $20^{\circ}C$. Laiwu pig's enzymes activities were significantly (p<0.01) higher than Large White's. The level of malondialdehyde is a direct expression of the grade of lipid oxidation in meat. In our study, the malondialdehyde contents increased after 6 days storage. However, malondialdehyde contents of Laiwu pig were significantly (p<0.01) lower than Large White's. A lower content of malondialdehyde corresponds to a lower oxidation of lipids. These results indicated the muscle antioxidative ability of Laiwu pig was higher than Large White pig. It also implied that antioxidative enzymes were involved in the essentials and deciding mechanisms of meat quality by quenching oxygen free radicals and inhibiting lipid oxidation in muscle.

Ischemic postconditioning protects cardiomyocytes against ischemia/reperfusion injury by inducing MIP2

Zhu, Hong-Lin,Wei, Xing,Qu, Shun-Lin,Zhang, Chi,Zuo, Xiao-Xia,Feng, Yan-Sheng,Luo, Qi,Chen, Guang-Wen,Liu, Mei-Dong,Jiang, Lei,Xiao, Xian-Zhong,Wang, Kang-Kai Korean Society for Biochemistry and Molecular Bion 2011 Experimental and molecular medicine Vol.43 No.8

Cardiomyocytes can resist ischemia/reperfusion(I/R) injury through ischemic postconditioning (IPoC) which is repetitive ischemia induced during the onset of reperfusion. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a member of the WD-40 family proteins, we previously showed that MIP2 was up-regulated during ischemic preconditioning (IPC). As IPC and IPoC engaged similar molecular mechanisms in cardioprotection, this study aimed to elucidate whether MIP2 was up-regulated during IPoC and contributed to IPoC-mediated protection against I/R injury. The experiment was conducted on two models, an $in$ $vivo$ open chest rat coronary artery occlusion model and an $in$ $vitro$ model with H9c2 myogenic cells. In both models, 3 groups were constituted and randomly designated as the sham, I/R and IPoC/hypoxia postconditioning (HPoC) groups. In the IPoC group, after 45 min of ischemia, hearts were allowed three cycles of reperfusion/ischemia phases (each of 30 s duration) followed by reperfusion. In the HPoC group, after 6 h of hypoxia, H9c2 cells were subjected to three cycles of 10 minute reoxygenation and 10 minute hypoxia followed by reoxygenation. IPoC significantly reduced the infarct size, plasma level of Lactate dehydrogenase and creatine kinase MB in rats. 12 h after the reperfusion, MIP2 mRNA levels in the IPoC group were 10 folds that of the sham group and 1.4 folds that of the I/R group. Increased expression of MIP2 mRNA and attenuation of apoptosis were similarly observed in the HPoC group in the $in$ $vitro$ model. These effects were blunted by transfection with MIP2 siRNA in the H9c2 cells. This study demonstrated that IPoC induced protection was associated with increased expression of MIP2. Both MIP2 overexpression and MIP2 suppression can influence the IPoC induced protection.