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Expression of hepatitis C virus nonstructural 4B in transgenic mice
Ai-Guo Wang,문형배,김진만,황순봉,유대열,이동석 생화학분자생물학회 2006 Experimental and molecular medicine Vol.38 No.3
Hepatitis C virus (HCV) is a pathogen that is of great cirrhosis, and hepatocellular carcinoma worldwide. Although the HCV proteins have been intensively investigated over the past decade, the biochemical functions of the NS4B protein are still largely unknown. To investigate NS4B as a potential cau-sative agent of liver disease, transgenic mice expressing the NS4B protein in liver tissue were produced. The transgenic animals were phenoty-pically similar to their normal littermates for up to 18 months of age. Our results suggest that the HCV NS4B protein is not directly cytopathic or oncogenic in our transgenic mice model.
Gender-dependent hepatic alterations in H-<i>ras</i>12V transgenic mice
Wang, Ai-Guo,Moon, Hyung-Bae,Lee, Mi-Ran,Hwang, Chae Young,Kwon, Ki-Sun,Yu, Seong-Lan,Kim, Yong-Sung,Kim, Mirang,Kim, Jin-Man,Kim, Sang-Keun,Lee, Tae-Hoon,Moon, Eun-Yi,Lee, Dong-Seok,Yu, Dae-Yeul Elsevier 2005 Journal of hepatology Vol.43 No.5
<P><B>Background/Aims</B></P><P>Although it has been proposed that Ras and related signal pathways play important roles in hepatocarcinogenesis, appropriate in vivo models are lacking.</P><P><B>Methods</B></P><P>Two hepatocellular carcinoma lines were established using pronuclear microinjection techniques to create an insertion of the H-<I>ras</I>12V transgene under the control of the albumin enhancer/promoter. The resulting phenotypes and related molecular events were then examined.</P><P><B>Results</B></P><P>Male (but not female) transgenic mice older than 2 months showed hepatic alterations with a high degree of reproducibility, as compared to the wild-type mice. The liver/body-weight ratios were lower for the females than for the males. The transgene-carrying line 28 was investigated extensively with respect to molecular differences between the genders. Male hepatocytes showed higher Ras activity and higher reactive oxygen species (ROS) levels than female hepatocytes. The female hepatocytes showed higher expression levels of p53 and p21<SUP>Waf1/Cip1</SUP>, enhanced cytochrome <I>c</I> release, which correlated with cell cycle arrest, and higher levels of hypodiploid cell formation, as compared to the male hepatocytes.</P><P><B>Conclusions</B></P><P>The gender-related differences in molecular responses to activated Ras may have implications for the prevalence of hepatic alterations in males. Our transgenic mice represent a potentially valuable animal model for future investigations.</P>
Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice
Wang, Ai-Guo,Lee, Dong-Seok,Moon, Hyung-Bae,Kim, Jin-Man,Cho, Kyung-Hyun,Choi, Soo-Ho,Ha, Hye-Lin,Han, Ying-Hao,Kim, Dae-Ghon,Hwang, Soon B.,Yu, Dae-Yeul John Wiley Sons, Ltd. 2009 The Journal of pathology Vol.219 No.2
<P>Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). However, the mechanism of HCV pathogenesis is not well understood. Our previous in vitro studies suggested that non-structural 5A (NS5A) protein may play an important role in liver pathogenesis. To elucidate the mechanism of HCV-induced liver pathogenesis, we investigated the histopathological changes of liver in transgenic mice harbouring the NS5A gene. We generated transgenic mice harbouring HCV NS5A gene under the control of hepatitis B virus (HBV) enhancer. Pathological changes were analysed by immunohistochemical staining and western blot analysis. Lipid composition and reactive oxygen species (ROS) production in NS5A transgenic mice were analysed. HCV NS5A transgenic mice developed extraordinary steatosis over 6 months old and induced HCC in some mice. NS5A was co-localized with apolipoprotein A-I in fatty hepatocytes. In addition, the extraordinarily high levels of ROS, NF-κB and STAT3 were detected in hepatocytes of NS5A transgenic mice. These data suggest that NS5A, independent of other HCV viral proteins, may play an important role in the development of hepatic pathologies, including steatosis and hepatoceullular carcinoma in transgenic mice. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>
The Expression of Estrogen Receptors in Hepatocellular Carcinoma in Korean Patients
Ai Guo Wang,이기영,김성용,최종영,이기호,김욱환,왕희정,김진만,박문기,염영일,김남순,유대열,이동석 연세대학교의과대학 2006 Yonsei medical journal Vol.47 No.6
Expression of estrogen receptors (ER)- and - , as well as androgen receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with prognosis, survival, and male prevalence of HCC. These hypotheses are based on investigations of European patients; however the expression patterns of these receptors in Asian patients are largely unknown. In this study, we collected liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males) in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type ER- and AR were expressed in all of the samples investigated, and their expression was independent of the causal virus or patient sex. Expression of the ER- variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER- was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p 0.05). In conclusion, the stronger ER- variant expression in HCC tissues implies that this variant has an important role in HCC development. However, at least in Korean patients, expression of the ER- variant (vER- ) is not related to male HCC prevalence. In addition, the predominant expression of ER- in HCV patients suggests that it plays an important role in HCV-induced liver disease.
Reactive Oxygen Species Co-Operated with Sex Hormones Inhibit Proliferation of Hepal-6 Cells
Wang Ai-Guo,Kim Nam-Soon,Lee Dong-Seok The Korean Society for Biomedical Laboratory Scien 2005 Journal of biomedical laboratory sciences Vol.11 No.3
Reactive oxygen species (ROS) and sex hormones affect the proliferation of cells and are believed to play important roles in tumorigenesis. However, little is known regarding how these two factors interact to affect cell proliferation. In this study, hepal-6 cells were treated with ROS and sex hormones (testosterone and steroidal) either separately or in combination. The sex hormones had no significant influence the cell proliferation up to a concentration of $1{\mu}M$. However, cell proliferation was inhibited when the cells were treated simultaneously with $H_2O_2$, which alone was found to promote cell proliferation at the concentrations of $15{\mu}M$. In conclusion, this study indicates that instead of promoting the cell proliferation, ROS interact with sex hormones to inhibit the Hepa 1-6 cell proliferation.
Wang, Ai-Guo,Fang, Wan,Han, Ying-Hao,Cho, Sang-Mi,Choi, Jong Young,Lee, Kee Ho,Kim, Wook Hwan,Kim, Jin Man,Park, Moon Gi,Yu, Dae-Yeul,Kim, Nam-Soon,Lee, Dong-Seok The Korean Academy of Medical Sciences 2006 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.21 No.5
<P>Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel gene that was first reported in breast cancer. However, the functions of RERG are largely unknown in other tumor types. In this study, RERG expression was analyzed in hepatocellular carcinomas of human patients using reverse transcriptase PCR analysis. In addition, the possible regulation of RERG expression by histone deacetyltransferases (HDACs) was studied in several cell lines. Interestingly, the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of male patients (57.9%) but decreased in HCC of females (87.5%) comparison with paired peri-tumoral tissues. Moreover, RERG gene expression was increased in murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A. Our results suggest that RERG may function in a gender-dependent manner in hepatic tumorigenesis and that the expression of this gene may be regulated by an HDAC-related signaling pathway.</P>
Yi, Wei-Min,Wang, Feige,Wu, Xue-Bing,Yang, Jinyi,Bai, Jin-Ming,Fan, Xiaohui,Brandt, William N.,Ho, Luis C.,Zuo, Wenwen,Kim, Minjin,Wang, Ran,Yang, Qian,Zhang, Ju-jia,Wang, Fang,Wang, Jian-Guo,Ai, Yanl IOP Publishing 2014 ASTROPHYSICAL JOURNAL LETTERS - Vol.795 No.2
<P>Very few of the z > 5 quasars discovered to date have been radio-loud, with radio-to-optical flux ratios (radio-loudness parameters) higher than 10. Here we report the discovery of an optically luminous radio-loud quasar, SDSS J013127.34-032100.1 (J0131-0321 in short), at z = 5.18 +/- 0.01 using the Lijiang 2.4 m and Magellan telescopes. J0131-0321 has a spectral energy distribution consistent with that of radio-loud quasars. With an i-band magnitude of 18.47 and a radio flux density of 33 mJy, its radio-loudness parameter is similar to 100. The optical and near-infrared spectra taken by Magellan enable us to estimate its bolometric luminosity to be L-bol similar to 1.1 x 10(48) erg s(-1), approximately 4.5 times greater than that of the most distant quasar known to date. The black hole mass of J0131-0321 is estimated to be 2.7 x 10(9) M-circle dot, with an uncertainty up to 0.4 dex. Detailed physical properties of this high-redshift, radio-loud, potentially super-Eddington quasar can be probed in the future with more dedicated and intensive follow-up observations using multi-wavelength facilities.</P>
Ai-Hong Yu,Yang-Yang Duan-Mu,Yong Zhang,Ling Wang,Zhe Guo,Yong-Qiang Yu,Yu-Sheng Wang,Xiao-Guang Cheng 대한영상의학회 2018 Korean Journal of Radiology Vol.19 No.5
Objective: To investigate the correlation between non-alcoholic fatty liver disease and visceral adipose tissue in non-obese Chinese adults using computed tomography (CT). Materials and Methods: The study included 454 subjects undergoing abdominal CT scan. Degree of CT attenuation in liver and spleen, and the degree of fat infiltration in liver were evaluated according to three indices: the attenuation value of liver parenchyma (CTLP), the attenuation ratio of liver and spleen (LSratio) and the attenuation difference between liver and spleen (LSdif). Visceral fat area (VFA) and total fat area (TFA) at L2/3 and L4/5 levels were measured, and the abdominal subcutaneous fat area (SFA) was calculated. Bivariate correlation analysis was carried out to determine the correlation among these factors. Results: In men, VFA, SFA and TFA at L2/3 and L4/5 levels showed significant differences in terms of the three indices to distinguish fatty liver from non-fatty liver (all, p < 0.001). In men, all the three indices showed negative correlation with TFA, SFA and VFA (all, p < 0.001). The negative correlation between the three indices and VFA at the L2/3 level was higher than at L4/5 level (r = -0.476 vs. r = -0.340 for CTLP, r = -0.502 vs. r = -0.413 for LSratio, r = -0.543 vs. r = -0.422 for LSdif, p < 0.001, respectively). The negative correlation between LSratio, LSdif and VFA at L2/3 and L4/5 levels was higher than SFA at the corresponding level. In women, all the three indices showed negative correlation with VFA and TFA at L2/3 and L4/5 levels, and the negative correlation between CTLP and VFA was higher at L2/3 level than at L4/5 level (r = -0.294 vs. r = -0.254, p < 0.001). Conclusion: In non-obese Chinese adults, the degree of hepatic fatty infiltration showed a strong correlation with abdominal fat on CT. VFA at L2/3 level was more closely related to fatty liver compared with VFA at L4/5 level.