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.

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.

Characterizing Size and Porosity of Hollow Nanoparticles: SAXS, SANS, TEM, DLS, and Adsorption Isotherms Compared

Chen, Zhi Hong,Kim, Chanhoi,Zeng, Xiang-bing,Hwang, Sun Hye,Jang, Jyongsik,Ungar, Goran American Chemical Society 2012 Langmuir Vol.28 No.43

<P>A combination of experimental methods, including transmission and grazing incidence small-angle X-ray scattering (SAXS and GISAXS), small-angle neutron scattering (SANS), transmission electron microscopy (TEM), dynamic light scattering (DLS), and N<SUB>2</SUB> adsorption–desorption isotherms, was used to characterize SiO<SUB>2</SUB>/TiO<SUB>2</SUB> hollow nanoparticles (HNPs) of sizes between 25 and 100 nm. In the analysis of SAXS, SANS, and GISAXS data, the decoupling approximation and the Percus–Yevick structure factor approximation were used. Brunauer–Emmett–Teller, <I>t</I>-plot, and a spherical pore model based on Kelvin equation were applied in the treatment of N<SUB>2</SUB> isotherms. Extracted parameters from the scattering and TEM methods are the average outer and inner diameters and polydispersity. Good agreement was achieved between different methods for these extracted parameters. Merits, advantages, and disadvantages of the different methods are discussed. Furthermore, the combination of these methods provided us with information on the porosity of the shells of HNPs and the size of intrawall pores, which are critical to the applications of HNPs as drug delivery vehicles and catalyst supports.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2012/langd5.2012.28.issue-43/la302236u/production/images/medium/la-2012-02236u_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/la302236u'>ACS Electronic Supporting Info</A></P>

A Study on the Strain Stability of Si/SiGe Layer Structure in a Heterojunction Bipolar Transistor during Thermal Processing

Zhi Hong Liu,Chang Chun Chen,Wen Tao Huang,Wei Zhi Dou,Yi Lin Shan,Wei Zhang,Jun Zhu,Pei Hsin Tsien 대한금속학회 2004 METALS AND MATERIALS International Vol.10 No.3

Isolation and Characterization of Bacillus sp. Producing Broad-Spectrum Antibiotics Against Human and Plant Pathogenic Fungi

( Na Chen ),( Min Jin ),( Hong Mei Qu ),( Zhi Qiang Chen ),( Zhao Li Chen ),( Zhi Gang Qiu ),( Xin Wei Wang ),( Jun Wen Li ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.2

A strain of bacterium producing antifungal antibiotic was isolated and identification of the strain was attempted. We could identify the bacterium as being a Bacillus sp., based on morphological observation, physiological characteristics, and 16S rDNA sequence analysis, thus leading us to designate the strain as Bacillus sp. AH-E-1. The strain showed potent antibiotic activity against phytopathogenic and human pathogenic fungi by inducing mycelial distortion and swelling and inhibiting spore germination. The antibiotic metabolite produced by the strain demonstrated excellent thermal and pH (2-11) stability, but was labile to autoclaving. From these results, we could find a broader antifungal activity of Bacillus genus. Isolation and characterization of the active agent produced by the strain are under progress.

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.

Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma

Liu Ying,Zhang Xin,Zhang Li,Oliver Brian G,Wang Hong Guang,Liu Zhi Peng,Chen Zhi Hong,Wood Lisa,Hsu Alan Chen-Yu,Xie Min,McDonald Vanessa,Wan Hua Jing,Luo Feng Ming,Liu Dan,Li Wei Min,Wang Gang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.4

Purpose: The molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes. Methods: In the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations. Results: Seventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5′-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000–1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000–1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000–1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates. Conclusions: Different inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.

The effects of LNG-tank sloshing on the global motions of FLNG system

Zhi-Qiang Hu,Shu-Ya Wang,Gang Chen,Shu-Hong Chai,Yu-Ting Jin 대한조선학회 2017 International Journal of Naval Architecture and Oc Vol.9 No.1

This paper addresses a study of inner-tank sloshing effect on motion responses of a Floating Liquefied Natural Gas (FLNG) system, through experimental analysis and numerical modeling. To investigate hydrodynamic characteristics of FLNG under the conditions of with and without LNG-tank sloshing, a series of numerical simulations were carried out using potential flow solver SESAM. To validate the numerical simulations, model tests on the FLNG system was conducted in both liquid and solid ballast conditions with 75% tank filling level in height. Good correlations were observed between the measured and predicted results, proving the feasibility of the numerical modeling technique. On the verified numerical model, Response Amplitude Operators (RAOs) of the FLNG with 25% and 50% tank filling levels were calculated in six degrees of freedom. The influence of tank sloshing with varying tank filling levels on the RAOs has been presented and analyzed. The results showed that LNG-tank sloshing has a noticeable impact on the roll motion response of the FLNG and a moderate tank filling level is less helpful in reducing the roll motion response.

The infection status of anisakid larvae in marine fish and cephalopods from the Bohai Sea, China and their taxonomical consideration

Hong-Wei MA,Tai-Jing JIANG,Fu-Shi QUAN,Xiao-Guang CHEN,Hui-dong WANG,Yun-Shu ZHANG,Ming-Shan CUI,Wen-Yan ZHI,Dian-Chen JIANG 대한기생충학열대의학회 1997 The Korean Journal of Parasitology Vol.35 No.1

Effects of Lignocellulose-derived Inhibitors on Growth and Succinic Acid Accumulation by Corynebacterium glutamicum

Hong-Tao Xu,Chen Wang,Zhi-Hui Zhou,Zhong-Jun Chen,Heng Cai 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.4

Succinic acid production by genetically engineered C. glutamicum from lignocellulosic biomass requires the hydrolysis of carbohydrate polymers into fermentable syrup. A variety of toxic compounds are produced such as aldehydes and organic acids, while the hydrolysis of hemicellulose with dilute acid. In this study, we have investigated the toxicity of representative aldehydes (furfural, 5-hydroxymethylfurfural, syringaldehyde, and vanillin) and organic acids (ferulic, 4-hydroxybenzic, vanillic, protocatechuic acid) on growth and succinic acid accumulation of C. glutamicum NC-1. In the presence of various inhibitors of growth experiment, furfural, 5- hydroxymethylfurfural appeared less toxic to growth of C. glutamicum NC-1, syringaldehyde almost completely inhibitor growth of C. glutamicum NC-1, vanillin has inhibited the growth of 67%, of organic acids, only ferulic appeared toxic to growth of C. glutamicum NC-1. Of succinic acid accumulation experiment under oxygen deprivation, all the organic acids compounds showed little inhibition on the glocuse consumption and succinic acid accumulation of C. glutamicum NC-1, but furfural, 5- hydroxymethylfurfural and vanillic have decreased the production of succinic acid. In addition, the actual inhibitor mixtures from the acid hydrolysate of corn cobs have reduced the accumulation of succinic acid. Across further research showed, a reason of succinic acid yield decrease was the malic enzyme activity was inhibited.