• Title/Summary/Keyword: Up-regulated

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Identification of key genes and carcinogenic pathways in hepatitis B virus-associated hepatocellular carcinoma through bioinformatics analysis

  • Sang-Hoon Kim;Shin Hwang;Gi-Won Song;Dong-Hwan Jung;Deok-Bog Moon;Jae Do Yang;Hee Chul Yu
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.26 no.1
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    • pp.58-68
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    • 2022
  • Backgrounds/Aims: Mechanisms for the development of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients remain unclear. The aim of the present study was to identify genes and pathways involved in the development of HBV-associated HCC. Methods: The GSE121248 gene dataset, which included 70 HCCs and 37 adjacent liver tissues, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in HCCs and adjacent liver tissues were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were then performed. Results: Of 134 DEGs identified, 34 were up-regulated and 100 were down-regulated in HCCs. The 34 up-regulated DEGs were mainly involved in nuclear division, organelle fission, spindle and midbody formation, histone kinase activity, and p53 signaling pathway, whereas the 100 down-regulated DEGs were involved in steroid and hormone metabolism, collagen-coated extracellular matrix, oxidoreductase activity, and activity on paired donors, including incorporation or reduction of molecular oxygen, monooxygenase activity, and retinol metabolism. Analyses of protein-protein interaction networks with a high degree of connectivity identified significant modules containing 14 hub genes, including ANLN, ASPM, BUB1B, CCNB1, CDK1, CDKN3, ECT2, HMMR, NEK2, PBK, PRC1, RACGAP1, RRM2, and TOP2A, which were mainly associated with nuclear division, organelle fission, spindle formation, protein serine/threonine kinase activity, p53 signaling pathway, and cell cycle. Conclusions: This study identified key genes and carcinogenic pathways that play essential roles in the development of HBV-associated HCC. This may provide important information for the development of diagnostic and therapeutic targets for HCC.

Differential Expressions of Adhesion Receptor Genes in the Rat Uterus Associated with Ovarian Steroid Hormone (흰쥐 자궁에서 난소 스테로이드 호르몬에 의한 Adhesion 수용체 유전자 발현조절에 대한 연구)

  • Kang Han Seung;Lee Chae Kwan;Moon Deog Hwan;Kang Sung Goo
    • Development and Reproduction
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    • v.7 no.1
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    • pp.41-48
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    • 2003
  • This report aimed at investigating the differential gene expressions of the adhesion receptors between ovariectomized (OVX) and estrus stage rat uteri (OVX vs. estrus pair) using the cDNA expression away analysis. In addition, this report aimed at confirming of the differential gene expressions of the adhesion receptors between OVX and progesterone (P$_4$) injected OVX rat uteri (OVX vs. OVX+P$_4$ pair). RNA samples were extracted from the uterus and reverse-transcribed in the presence of [$\alpha$$^{32}$ P]-dATP. Membrane sets of Rat Atlas array 1.2 II (Clontech) were hybridized with CDNA probe sets. RT-PCR was employed to validate the relative gene expression patterns obtained by the cDNA array. The results were well consistent to cDNA array analysis data except the fold changes of gene expression. Among a total of 1176 cDNAs, 5 genes of adhesion receotor including embigin protein, activated leukocyte cell adhesion molecule, afadin, neuroligin 2, semaphorin Z showed significant (more than 2-fold) changes in the OVX vs. late estrus pair. All of these genes were up regulated in estrus stage than OVX rat uterus. In the OVX vs. OVX+P$_4$ pair, 4 genes including osteonectin, afadin, neuroligin 2, semaphorin Z showed significant changes. All of these genes were also up regulated in OVX+P$_4$ injected rat uterus than OVX control. Three genes including afadin, neuroligin 2, semaphorin Z which were up regulated in estrus and OVX+P$_4$ injected rat uteri of both experimental pairs than OVX rat uteri. These genes seem to be under the control of P$_4$.

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Anti-apoptotic Activity of Heme Oxygenase-1 Up-regulated by Etoposide in Human Retinal Pigment Epithelial Cells (Etoposide에 의한 인간 망막색소상피세포인 ARPE-19 세포의 아폽토시스 과정에서 Heme oxygenase-1의 항아폽토시스 기능에 대한 연구)

  • Lee, Sang-Kwon;Song, Ju-Dong;Kim, Kang-Mi;Kim, Jong-Min;Lee, Sang-Yull;Yoo, Young-Hyun;Park, Young-Chul
    • Journal of Life Science
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    • v.17 no.9 s.89
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    • pp.1204-1210
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    • 2007
  • The topoisomerase II inhibitor etoposide causes an accumulation of DNA double strand breaks within the nuclei of cells. In this study, we investigated the effect of etoposide on the cell growth and apoptosis of human RPE cells. Etoposide evoked a significant inhibition of cell growth, and also induced DNA fragmentation in ARPE-19 cells. In addition, etoposide significantly up-regulated the expression of heme oxygenase-1 (HO-1), which is a stress-responsive protein and is known to play a protective role against the oxidative injury. And, etoposide-induced HO-1 expression was affected by the ROS scavenger N-acetyl cysteine. We also used oligonucleotides interfering with HO-1 mRNA (siRNA) for the inhibition of HO-1 expression. Interestingly, knock-down of the HO-1 gene significantly increased the level of DNA fragmentation in etoposide-treated ARPE-19 cells. In conclusion, these results suggest that up-regulated HO-1 plays as an anti-apoptotic factor in the process of apoptosis of ARPE-19 cells stimulated by etoposide.

Proteomic Profiles of Mouse Neuro N2a Cells Infected with Variant Virulence f Rabies Viruses

  • Wang, Xiaohu;Zhang, Shoufeng;Sun, Chenglong;Yuan, Zi-Guo;Wu, Xianfu;Wang, Dongxia;Ding, Zhuang;Hu, Rongliang
    • Journal of Microbiology and Biotechnology
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    • v.21 no.4
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    • pp.366-373
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    • 2011
  • We characterized the proteomes of murine N2a cells following infection with three rabies virus (RV) strains, characterized by distinct virulence phenotypes (i.e., virulent BD06, fixed CVS-11, and attenuated SRV9 strains), and identified 35 changes to protein expression using two-dimensional gel electrophoresis in whole-cell lysates. The annotated functions of these proteins are involved in various cytoskeletal, signal transduction, stress response, and metabolic processes. Specifically, a-enolase, prx-4, vimentin, cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and prx-6 were significantly up-regulated, whereas Trx like-1 and galectin-1 were down-regulated following infection of N2a cells with all three rabies virus strains. However, comparing expressions of all 35 proteins affected between BD06-, CVS-11-, and SRV9-infected cells, specific changes in expression were also observed. The up-regulation of vimentin, CIAPIN1, prx-4, and 14-3-3 ${\theta}/{\delta}$, and down-regulation of NDPK-B and HSP-1 with CVS and SRV9 infection were ${\geq}2$ times greater than with BD06. Meanwhile, Zfp12 protein, splicing factor, and arginine/serine-rich 1 were unaltered in the cells infected with BD06 and CVS-11, but were up-regulated in the group infected with SRV9. The proteomic alterations described here may suggest that these changes to protein expression correlate with the rabies virus' adaptability and virulence in N2a cells, and hence provides new clues as to the response of N2a host cells to rabies virus infections, and may also aid in uncovering new pathways in these cells that are involved in rabies infections. Further characterization of the functions of the affected proteins may contribute to our understanding of the mechanisms of RV infection and pathogenesis.

Immunohistochemical Study on the Hair Growth Promoting Effect of Yonnyuniksoogobon-dan

  • Jeong, Chun-Geun;Park, Min-Hee;Seong, Ju-Won;Lee, Hyun-Sam;Park, Seong-Kyu;Kim, Sun-Yeou;Kim, Yoon-Bum;Jung, Hyuk-Sang;Sohn, Nak-Won;Sohn, Young-Joo
    • The Journal of Korean Medicine
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    • v.29 no.5
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    • pp.77-89
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    • 2008
  • Objectives : This study evaluates the hair growth promoting effect of Yonnyuniksoogobon-dan on shaved C57BL6 mice. Methods : Yonnyuniksoogobon-dan was administered orally (Group I) and both orally and by skin application (Group II) once a day for 12 days. The experimental groups were compared to Control, which was orally administered physiological saline solution. Hair regrowth was photographically and histologically determined during the experimental period. The levels of hair growth cycle related factors (EGF, TGF-${\beta}$1) and vascular factors (VEGF, iNOS) were also determined by immunohistochemistry. On gross observation of hair growth, both Group I and Group II shaved C57BL6 mice showed accelerated hair regrowth. Results : The hair regrowth index of Group I increased significantly from 7 days (P<0.05) to 12 days (P<0.01) after shaving and that of Group II was significantly higher at 12 days (P<0.05). On histological observation, both Group I and Group II demonstrated histological improvement and increases in the number and diameter of the hair follicles. EGF expression on the root sheath of hair follicles was up-regulated in both Group I and II. TGF-${\beta}$1 expression on the root sheath of hair follicles was unchanged in both Group I and II. VEGF expression in the tissues surrounding hair follicles was up-regulated in both groups. iNOS expression in the tissues surrounding hair follicles was down-regulated in both groups. Conclusions : These results suggest that Yonnyuniksoogobon-dan promotes hair growth and this effect is related to up-regulation of EGF and VEFG expression and down-regulation of TGF-${\beta}$1 and iNOS expression on hair roots.

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A 0.2V DC/DC Boost Converter with Regulated Output for Thermoelectric Energy Harvesting (열전 에너지 하베스팅을 위한 안정화된 출력을 갖는 0.2V DC/DC 부스트 변환기)

  • Cho, Yong-hwan;Kang, Bo-kyung;Kim, Sun-hui;Yang, Min-Jae;Yoon, Eun-jung;Yu, Chong-gun
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2014.10a
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    • pp.565-568
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    • 2014
  • This paper presents a 0.2V DC/DC boost converter with regulated output for thermoelectric energy harvesting. To use low voltages from a thermoelectric device, a start-up circuit consisting of native NMOS transistors and resistors boosts an internal VDD, and the boosted VDD is used to operate the internal control block. When the VDD reaches a predefined value, a detector circuit makes the start-up block turn off to minimize current consumption. The final boosted VSTO is achieved by alternately operating the sub-boost converter for VDD and the main boost converter for VSTO according to the comparator outputs. When the VSTO reaches 2.4V, a buck converter starts to operate to generate a stabilized output VOUT. Simulation results shows that the designed converter generates a regulated 1.8V output from an input voltage of 0.2V, and its maximum power efficiency is 60%. The chip designed using a $0.35{\mu}m$ CMOS process occupies $1.1mm{\times}1.0mm$ including pads.

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The Differentially Expressed Genes by Radiotherapy in the Patients with Uterine Cervix Cancer (자궁경부암 환자에서 방사선치료 시 발현되는 유전자의 규명)

  • Seo Eun Young;Cho Moon-June;Lee Jeung Hoon;Lee Young-Sook;Na Myung-Hoon;Lee Woong-Hee;Kim Jun-Sang;Kim Jae-Sung
    • Radiation Oncology Journal
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    • v.19 no.4
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    • pp.389-396
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    • 2001
  • Purpose : To detect differentially expressed genes in the patients with uterine cervical cancer during the radiation therapy. Materials and Methods : In patients with biopsy proven uterine cervical cancer, we took tumor tissue just before radiation therapy and at 40 minutes after external irradiation of 1.8 Gy. Total RNAs isolated from non-irradiated and irradiated tumor tissue samples were analyzed using the differential-display reverse transcription-polymerase chain reaction (DDRT-PCR). Complementary DNA (cDNA) fragments corresponding to differentially expressed messenger RNAs(mRNAs) were eluted, and cloned. The differential expression of the corresponding mRNAs was confirmed by reverse northern blot. Differentially expressed cDNA bands were sequenced. Nucleotide sequence data were analyzed in the Gene Bank and EMBL databases via the BLAST network sewer to identify homologies to known genes or cDNA fragments. Expression pattern of down-regulated clone was examined using RT-PCR in S patients undergoing radiotherapy. Results : We identified 18 differentially expressed bands by DDRT-PCR, which were eluted and cloned. There were 10 up-regulated clones and 1 down-regulated clone in reverse northern blot. One cDNA fragment had homology to chemokine receptor CXCR4, four were identified as Human ESTs in the EMBL database in EST clones. Down-regulated CxCa-11 was also down regulated in all patients. Conclusion : Using the DDRT-PCR, we have identified 10 up-regulated and 1 down-regulated clone(s) in the patients with uterine cervical cancer during the radiation therapy. The clinical relevance and the functions of these genes will be further investigated.

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Metabolic Engineering of the Thermophilic Bacteria, Bacillus stearothermophilus, for Ethanol Production

  • Jo, Gwang-Myeong;Ingram, Lonnie O.
    • 한국생물공학회:학술대회논문집
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    • 2000.11a
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    • pp.56-59
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    • 2000
  • Thermophilic bacterium, Bacillus stearothermophilus NUB3621, was engineered to produce ethanol from glucose by introducing cloned thermostable pyruvate decarboxylase and alcohol dehydrogenase genes. A novel promoter sequence was screened and used for the enhancement of these two enzymes. Successful redirection of metabolic flux into ethanol was obtained. In addition, gene expression profiling using Bacillus subtilis DNA microarray was analyzed to overcome the intrinsic low glucose utilization of B.stearothermophilus. Many known and unknown genes were identified to be up or down regulated under glucose-containing media.

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Clinical Significance of Upregulation of mir-196a-5p in Gastric Cancer and Enriched KEGG Pathway Analysis of Target Genes

  • Li, Hai-Long;Xie, Shou-Pin;Yang, Ya-Li;Cheng, Ying-Xia;Zhang, Ying;Wang, Jing;Wang, Yong;Liu, Da-Long;Chen, Zhao-Feng;Zhou, Yong-Ning;Wu, Hong-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1781-1787
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    • 2015
  • Background: miRNAs are relatively recently discovered cancer biomarkers which have important implications for cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics and generate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker in gastric cancer. Materials and Methods: The expression of mir-196a-5p in poorly, moderate and well differentiated gastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RT-qPCR. Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGG pathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0. Results: RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associated with more extensive degree of lymph node metastasis and clinical stage (P < 0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the targeted genes regulated by mir-196a-5p were involved in malignancy associated biology. Conclusions: Overexpression of mir-196a-5p is associated with lymph node metastasis and clinical stage, and enriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute to tumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer.