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.

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.

Baicalin Induces Apoptosis in Leukemia HL-60/ADR Cells via Possible Down-regulation of the PI3K/Akt Signaling Pathway

Zheng, Jing,Hu, Jian-Da,Chen, Ying-Yu,Chen, Bu-Yuan,Huang, Yi,Zheng, Zhi Hong,Liu, Ting-Bo Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: The effect and possible mechanism of traditional Chinese medicine, baicalin, on the PI3K/Akt signaling pathway in drug-resistant human myeloid leukemia HL-60/ADR cells have been investigated in this current study. Methods: HL-60/ADR cells were treated by 20, 40, $80\;{\mu}mol/L$ baicalin followed by cell cycle analysis at 24h. The mRNA expression level of the apoptosis related gene, Bcl-2 and bad, were measured by RT-PCR on cells treated with $80\;{\mu}mol/L$ baicalin at 12, 24 and 48hr. Western blot was performed to detect the changes in the expression of the proteins related to HL-60/ADR cell apoptosis and the signaling pathway before and after baicalin treatment, including Bcl-2, PARP, Bad, Caspase 3, Akt, p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR. Results: Sub-G1 peak of HL-60/ADR cells appeared 24 h after $20\;{\mu}mol/L$ baicalin treatment, and the ratio increased as baicalin concentration increased. Cell cycle analysis showed 44.9% G0/G1 phase cells 24 h after baicalin treatment compared to 39.6% in the control group. Cells treated with $80\;{\mu}mol/L$ baicalin displayed a trend in decreasing of Bcl-2 mRNA expression over time. Expression level of the Bcl-2 and PARP proteins decreased significantly while that of the PARP, Caspase-3, and Bad proteins gradually increased. No significant difference in Akt expression was observed between treated and the control groups. However, the expression levels of p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR decreased significantly in a time-dependent manner. Conclusions: We conclude that baicalin may induce HL-60/ADR cell apoptosis through the PI3K/AKT signaling pathway.

Isolation, Purification, and Characterization of a Thermostable Xylanase from a Novel Strain, Paenibacillus campinasensis G1-1

( Hong Chen Zheng ),( Yi Han Liu ),( Xiao Guang Liu ),( Jian Ling Wang ),( Ying Han ),( Fu Ping Lu ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.7

High levels of xylanase activity (143.98 IU/ml) produced by the newly isolated Paenibacillus campinasensis G1-1 were detected when it was cultivated in a synthetic medium. A thermostable xylanase, designated XynG1-1, from P. campinasensis G1-1 was purified to homogeneity by Octyl-Sepharose hydrophobic-interaction chromatography, Sephadex G75 gel-filter chromatography, and Q-Sepharose ion-exchange chromatography, consecutively. By multistep purification, the specific activity of XynG1-1 was up to 1,865.5 IU/mg with a 9.1-fold purification. The molecular mass of purified XynG1-1 was about 41.3 kDa as estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Sequence analysis revealed that XynG1-1 containing 377 amino acids encoded by 1,134 bp genomic sequences of P. campinasensis G1-1 shared 96% homology with XylX from Paenibacillus campinasensis BL11 and 77%~78% homology with xylanases from Bacillus sp. YA- 335 and Bacillus sp. 41M-1, respectively. The activity of XynG1-1 was stimulated by Ca2+, Ba2+, DTT, and β- mercaptoethanol, but was inhibited by Ni2+, Fe2+, Fe3+, Zn2+, SDS, and EDTA. The purified XynG1-1 displayed a greater affinity for birchwood xylan, with an optimal temperature of 60oC and an optimal pH of 7.5. The fact that XynG1-1 is cellulose-free, thermostable (stability at high temperature of 70oC~80oC), and active over a wide pH range (pH 5.0~9.0) suggests that the enzyme is potentially valuable for various industrial applications, especially for pulp bleaching pretreatment.

RASAL1 Attenuates Gastric Carcinogenesis in Nude Mice by Blocking RAS/ERK Signaling

Chen, Hong,Zhao, Ji-Yi,Qian, Xu-Chen,Cheng, Zheng-Yuan,Liu, Yang,Wang, Zhi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.

Biocatalysis and Fermentation Technology : Purification and Characterization of a Thermostable Xylanase from Paenibacillus sp. NF1 and its Application in Xylooligosaccharides Production

( Hong Chen Zheng ),( Ming Zhe Sun ),( Ling Cai Meng ),( Hai Sheng Pei ),( Xiu Qing Zhang ),( Zheng Yan ),( Wen Hui Zeng ),( Jing Sheng Zhang ),( Jin Rong Hu ),( Fu Ping Lu ),( Jun She Sun ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.4

High levels of extracellular xylanase activity (211.79 IU/mg) produced by Paenibacillus sp. NF1 were detected when it was submerged-cultured. After three consecutive purification steps using Octyl-Sepharose, Sephadex G75, and Q-Sepharose columns, a thermostable xylanase (XynNF) was purified to homogeneity and showed a molecular mass of 37 kDa according to SDS-PAGE. The specific activity of the purified XynNF was up to 3,081.05 IU/mg with a 14.55-fold purification. The activity of XynNF was stimulated by Ca2+, Ba2+, DTT, and β-mercaptoethanol, but was inhibited by Fe3+, Zn2+, Fe2+, Cu2+, SDS, and EDTA. The purified XynNF displayed a greater affinity for oat spelt xylan with the maximal enzymatic activity at 60°C and pH 6.0. XynNF, which was shown to be cellulose-free, with high stability at high temperature (70°C-80°C) and low pH range (pH 4.0-7.0), is potentially valuable for various industrial applications. The enzyme hydrolyzed oat spelt xylan to yield mainly xylooligosaccharides (95.8%) of 2-4 degree of polymerization (DP2-4). Moreover, the majority of the xylooligosacharides (DP2- 4) products was xylobiose (61.5%). The thermostable xylanase (XynNF) thus seems potentially usefull in the production of xylooligosaccharides.

日本慶應大學圖書館藏朝鮮銅活字本《史記》初探

진정굉 ( Zheng Hong Chen ) 한국중문학회 2009 中國文學硏究 Vol.38 No.-

Risk Factors for Anxiety in Major Depressive Disorder Patients

Li-Min Xin,Lin Chen,Zhen-Peng Ji,Suo-Yuan Zhang,Jun Wang,Yan-Hong Liu,Da-Fang Chen,Fu-De Yang,Gang Wang,Yi-Ru Fang,Zheng Lu,Hai-Chen Yang,Jian Hu,Zhi-Yu Chen,Yi Huang,Jing Sun,Xiao-Ping Wang,Hui-Chun 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.3

Objective: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). Methods: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. Results: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=−4.39, p<0.001), were older (t=−4.69, p<0.001), reported more lifetime depressive episodes (z=−3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ2=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. Conclusion: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.

Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia

Hosgood III, H. Dean,Wang, Wen-Chang,Hong, Yun-Chul,Wang, Jiu-Cun,Chen, Kexin,Chang, I-Shou,Chen, Chien-Jen,Lu, Daru,Yin, Zhihua,Wu, Chen,Zheng, Wei,Qian, Biyun,Park, Jae Yong,Kim, Yeul Hong,Chatterje Springer-Verlag 2012 HUMAN GENETICS Vol.131 No.7

<P>A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 10(-12)); however, this association did not achieve genome-wide significance (p 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.</P>

Study on the transient flow induced by the windbreak transition regions in a railway subject to crosswinds

Zheng-Wei Chen,Syeda Anam Hashmi,Tanghong Liu,Wenhui Li,Zhuang Sun,Dongrun Liu,Hassan Hemida,Hong-Kang Liu 한국풍공학회 2022 Wind and Structures, An International Journal (WAS Vol.35 No.5

Due to the complex terrain around high-speed railways, the windbreaks were established along different landforms, resulting in irregular windbreak transition regions between different subgrade infrastructures (flat ground, cutting, embankment, etc). In this paper, the effect of a windbreak transition on the wind flow around railways subjected to crosswinds was studied. Wind tunnel testing was conducted to study the wind speed change around a windbreak transition on flat ground with a uniform wind speed inflow, and the collected data were used to validate a numerical simulation based on a detached eddy simulation method. The validated numerical method was then used to investigate the effect of the windbreak transition from the flat ground to cutting (the “cutting” is a railway subgrade type formed by digging down from the original ground) for three different wind incidence angles of 90º, 75º, and 105º. The deterioration mechanism of the flow fields and the reasons behind the occurrence of the peak wind velocities were explained in detail. The results showed that for the windbreak transition on flat ground, the impact was small. For the transition from the flat ground to the cutting, the influence was relatively large. The significant increase in the wind speeds was due to the right-angle structure of the windbreak transition, which resulted in sudden changes of the wind velocity as well as the direction. In addition, the height mismatch in the transition region worsened the protective effect of a typical windbreak.