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Gleditsia Spina Extract Protects Hepatocytes from Oxidative Stress through Nrf2 Activation (皂角刺 추출물의 Nrf2 활성화를 통한 간세포 보호 효과)

  • Kim, Jae Kwang;Park, Sang Mi;Jegal, Kyung Hwan;Kim, Young Woo;Byun, Sung Hui;Kim, Sang Chan;Cho, Il Je
    • The Korea Journal of Herbology
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    • v.30 no.4
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    • pp.57-64
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    • 2015
  • Objectives : Oxidative stress is one of the most causes of hepatocyte injury. Gleditsia spina, the thorns ofGleditsia sinensisLam., has been known for its anti-cancer and anti-inflammatory effects in Korean medicine. The present study investigated hepatoprotective effect of Gleditsia spina water extract (GSE) against oxidative stress induced by arachidonic acid (AA) + iron in HepG2 cells.Methods : To investigate cytoprotective effect of GSE, cells were pretreated with GSE and then subsequently exposed to 10 μM AA for 12 h, followed by 5 μM iron. Cell viability was monitored by MTT assay, and expression of apoptosis-related proteins was examined by immunoblot analysis. To identify responsible molecular mechanisms, reactive oxygen species (ROS) production, GSH contents, and mitochondrial membrane potential were measured. In addition, effect of GSE on nuclear factor erythroid 2-related factor 2 (Nrf2) activation was determined by immunoblot and antioxidant response element (ARE)-driven reporter gene assays.Results : GSE pretreatment prevented AA + iron-mediated cytotoxicity in concentration dependent manner. In addition, ROS production, glutathione depletion, and mitochondrial impairment by AA + iron were significantly inhibited by GSE. Furthermore, GSE promoted translocation of Nrf2 to nucleus, which acts as essential transcription factor for induction of antioxidant genes. Increased nuclear Nrf2 that caused by GSE treatment promoted transcriptional activity of ARE. Finally, GSE up-regulated sestrin-2 which was widely recognized as target gene of Nrf2.Conclusions : This study demonstrates that GSE protects hepatocytes from oxidative stress via activation of Nrf2 signaling pathway.

Mechanism Underlying the Anti-Inflammatory Action of Piceatannol Induced by Lipopolysaccharide (당지질로 유도한 염증반응에서 Piceatannol의 항염증 기전 연구)

  • Cho, Han-Jin;Shim, Jae-Hoon;So, Hong-Seob;YoonPark, Jung-Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.9
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    • pp.1226-1234
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    • 2012
  • 3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.

A Study on Kim Dong-Seong's Activities as Journalist in 1920-30's (일제하 언론이 김동성의 언론활동에 관한 연구)

  • Kim, Ug-Young
    • Korean journal of communication and information
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    • v.26
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    • pp.83-104
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    • 2004
  • Most studies of Korean Newspaper in historical view have focused on the news writing form and editorial practice. Those studies have much rely on the memories of ex-journalist or the impression of scholars. So this study aims to give the concrete figures of news writing forms and editing practices in 1920-30's by investigating Kim Dong-Seong's activities as a journalist. He was a first journalist who studies journalism. He studied journalism during his stay in the Ohio State University as an english department student. After he came back to Seoul, he worked at the Dong-A Il Bo as an one of the first publish members. His activities as a journalist have much important meanings because of his varied works and careers. He also wrote a practical affair book for reporters which was the first book in Korea. As a result of research about Kim Dong-Seong's activities in 1920-30's, the feature of edit practice in 1920's had much emphasis not only on the headline but on the relation between type and print, and at the same time the combination of news or the change of typography was one of methods which make the editing more variety. News materials were collected varied news sources and legworks by reporter. These results show us that such a news reporting practice in 1920-30's is similar co the contemporary.

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An Analysis on the Contents of the Health Related Articles in the Newspapers. (From the points of view of Health Education) (주요일간지의 건강관련기사내용 분석)

  • 김지미
    • Korean Journal of Health Education and Promotion
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    • v.3 no.1
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    • pp.29-42
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    • 1985
  • The purpose of this study was to evaluate the educatconal function of the health related articles. The health articles of the four major daily newspapers from Jan. 1st, 1980 to Dec. 31th, 1984 were used and examined for the study. Editorials were excluded. The major results were summarized as follows: 1. The total number of the health articles subjected to the study in the four major daily newspapers was 4,431. On the whole, the health articles were appeared most frequently in 1981. As for monthly distribution, the health articles were appeared most frequently on June.(9.3%). As for weekly distribution, the health articles were appeared most frequently on wednesday and saturday(50.8%). As for the subjects of content; the health articles related to the health & disease management were appeared most frequently(52.8%), but the health articles on industrial health were showed least frequently(0.6%). 2. Reviewing the chronological trend of the health articles, the frequency of appearance of the public health administration was tended to increase year by year, whereas that of enviornmental health, industrial health and population decrease relatively. As for appealing method, it was observed that the articles providing health information were steadily increasing. As for the motives of writing the health articles, there was a tendency that seasonal motive, symphosium & seminar and compaign were increasing, but motive of legislative action and administrative action were gradually decreasing. As for type of the health articles, it was observed that interpretation and research result were steadily increasing. As for the writer of the health articles, there was a tendency that writing by reporter was increasing, whereas writing by experts was decreasing. As for tone of head, the health articles written by identification statement was tended to increase. As for the appearance of photograph & cut, it was observed that the health articles excluding photograph & cut were increasing. 3. When contents were analyzed by subjects, for the purpose of providing information was used most frequently as appealing method for all subjects. As for the motive of writing, "from the interest of writers" was most frequent. As for the type of articles, interpretation type was most prevalent for the public health administration, enviornmental health, food hygrene & nutrition, population and health behavior, while contribution by experts was most frequent for the health & disease management. As for the size of articles, all subjects except the population were appeared most frequently on the column. size between 100㎠ and 199㎠.

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Study on Preventing Retaliation against Crime Victims (범죄피해자에 대한 보복범죄 방지 대책에 관한 연구)

  • Choi, KeeNam
    • Convergence Security Journal
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    • v.16 no.7
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    • pp.129-137
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    • 2016
  • The guarantee of citizens' safety from crime is the reason for a nation's existence according to the social contract, and it is also a salient task in securing the citizens' right to the pursuit of happiness, which is a constitutional right expressing the nation's duty to its citizens. First, a procedure must be made mandatory that corresponds to the Miranda rule applied during the arrest of criminal suspect, which verifies whether there exists a risk of retaliatory crime to the victim of crime, crime reporter, or witness following their report of a crime or testimony. A measure to punish those who violate this should be devised. The second is the improvement of related laws and systems, such as expanding the scope of persons subject to protection from retaliatory crimes under the current law and strengthening information protection. Third, a retaliatory crime risk evaluation index must be developed, and the evaluation results must be quantified to clearly state measures and responsibilities, in detail, for personal safety at each level of intensity. The fourth is the expanded implementation of proactive personal safety measures for victims of crime and witnesses, as well as the development and application of advanced techniques. The last is a change in the perception s of those working for the judicial body. From the initial investigation stage of the crime to the diagnosis regarding the possibility of retaliation perpetrated on an ex-convict through psychological tests, systems of general cooperation, and mutual assistance must be established.

Characterization of the Nar Promoter Modified by Site-directed Mutagenesis to Use as an Expression Promoter (특정부위돌연변이화에 의해 변형된 nar 프로모터를 발현 프로모터로 이용하기 위한 특성연구)

  • 이종원
    • KSBB Journal
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    • v.11 no.4
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    • pp.431-437
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    • 1996
  • The nar promoter of Escherichta coli, which is maximally induced under anaerobic conditions in the presence of nitrate, was characterized to see whether the nar promoter cloned onto pBR322 can be used as an expression promoter. The modified nar promoter, in which several bases in the -10 region was mutated to the consensus sequence by site-directed mutagenesis, was characterized in E. coli, on which chromosome the fnr gene affecting expression of the nar promoter according to dissolved oxygen level was mutated. The E. coli lacZ gene was used as a reporter gene. The following effects were investigated to find optimal conditions to induce the modified nar promoter: induction methods, optimal nitrate concentrations, the amount of ${\beta}$-galactosidase expressed at the different growth conditions, and induction characteristics. The following results were obtained from the experiments : expression of ${\beta}$-galactosidase from the modified nar promoter was not affected much by nitrate concentrations. The maximal specific ${\beta}$-galactosidase activity was obtained when E. coli was grown under aerobic conditions, and then the modified nar promoter was induced at OD600=2.2 under microaerobic conditions (DO=1∼2%), under which conditions the maximal specific ${\beta}$-galactosidase activity was 13,000 Miller units. However, the specific ${\beta}$-galactosidase activity was approximately 6,000 Miller units even before the modified nar promoter was induced. Therefore, the modified nar promoter seemed to be useful when the cloned gene wants to be expressed in E. coli constitutively.

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Inhibitory Mechanism on NF-${\kappa}B$ Transactivation by Dexamethasone in Pulmonary Epithelial Cells (폐상피세포에서 Dexamethasone에 의한 NF-${\kappa}B$ Transactivation 억제기전에 관한 연구)

  • Lee, Kye-Young;Kim, Yoon-Seop;Ko, Mi-Hye;Park, Jae-Seok;Jee, Young-Koo;Kim, Keun-Youl;Kwak, Sahng-June
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.5
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    • pp.682-698
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    • 2000
  • Glucocorticoid receptor (GR) functions as a suppressor of inflammation by inhibiting the expression of many cytokine genes activated by NF-${\kappa}B$. The goal of this study is to investigate the mechanism by which GR repress NF-${\kappa}B$ activation in lung epithelial cells. We used A549 and BEAS-2B lung epithelia! cell lines. Using Ig$G{\kappa}$-NF-${\kappa}B$ luciferase reporter gene construct, we found that dexamethasone significantly suppressed TNF-$\alpha$-induced NF-${\kappa}B$ activation and the overexpression of GR showed dose-dependent reduction of TNF-$\alpha$-induced NF-${\kappa}B$ activity in both cell lines. However, DNA binding of NF-${\kappa}B$ induced by TNF-$\alpha$ in electromobility shift assay was not inhibited by dexamethasone. Super shift assay with anti-p65 antibody demonstrated the existence of p65 in NF-${\kappa}B$ complex induced by $\alpha$ Western blot showed that $I{\kappa}B{\alpha}$ degradation induced by TNF-$\alpha$ was not affected by dexamethasone and $I{\kappa}B{\kappa}$ was not induced by dexamethasone, neither. To evaluate p65 specific transactivation, we adopted co-transfection study of Gal4-p65TA1 or TA2 fusion protein expression system together with 5xGal4-luciferase vector. Co-transfection of GR with Gal4-p65TA1 or TA2 repressed luciferase activity profoundly to the level of 10-20% of p65TA1- or TA2-induced transcriptional activity. And this transrepressional effect was abolished by co-transfection of CBP of SRC-1 expression vectors. These results suggest that GR-mediated transrepression of NF-${\kappa}B$ in lung epithelial cells is through competing for binding to limiting amounts of transcriptional coactivators, CBP or SRC-1.

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Characterization and Antiviral Effects of Mx Proteins from Various MHC Haplotype Chickens Showing Different Susceptible to Marek's Disease Virus

  • Chang, Kyuug-Soo
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.229-238
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    • 2010
  • Chicken Mx protein (cMx) induced interferon (IFN) is an antiviral protein to inhibit replication of RNA virus, particularly negative stranded RNA virus, through blockage of transfortation of viral RNA and proteins. In order to determine antiviral effects of cMx from different MHC haplotype chicken, we characterized cMx gene by studying on nucleotide sequencing, antiviral effects to Newcastle disease virus, VSV and MDV, and transcription activities. Three types of eMx genes (2,118 bp) were detected from the different MHC haplotype chickens [B19 (N), B15(F) and B21 (GSP)] chickens, which have showed different susceptible to Marek's disease (MD). Several amino acid substitutions were showed in the cMx. The amino acid 548 and 631 in the cMxs from N and F, chickens susceptible to MD, was Val and Asn which was important on antiviral effects, and showed in resistant cMx. Those in the cMx from GSP, chicken resistant to MD, were same that showed in susceptible cMx. Though every cMx transactivated the expression of the reporter gene, the transcription activation by resistant cMx from N and F was lower compared to that by susceptible cMx from GSP. The decease of the cell growth in the resistant cMx cloned cells was seen in comparison with another cMx clone cells. Replication of NDV and VSV was suppressed in the clones with resistant cMx from N and F. NMx258-transducted cells lack of antiviral effects, and NMx437 or NMx646-transducted cells was showed 60% of antiviral effects compared to NMx705. Mean death time (MDT) and hemaggutination (HA) titer to NDV was long and low in the eggs of N and F lines, but short and high in the egg of GSP line. Interestingly, strong suppression to NDV was observed in the clone with N-Mx and in the eggs of N line. However, the effects of Mx for replication of vvMDV1 have not been. Thus, resistant types of cMx, N- and F-Mx, have showed the anti-viral effects to only RNA virus including NDV and VSV, but not to DNA virus. Antiviral effects of cMx were required whole length of amino acid including Val and Asn in amino acid 548 and 631.

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

  • Ahn, Hye-Na;Jeong, Si-Yeon;Bae, Gyu-Un;Chang, Minsun;Zhang, Dongwei;Liu, Xiyuan;Pei, Yihua;Chin, Young-Won;Lee, Joongku;Oh, Sei-Ryang;Song, Yun Seon
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.347-354
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    • 2014
  • Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

  • Yang, Sungjae;Kim, Yong;Jeong, Deok;Kim, Jun Ho;Kim, Sunggyu;Son, Young-Jin;Yoo, Byong Chul;Jeong, Eun Jeong;Kim, Tae Woong;Han Lee, In-Sook;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.595-603
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    • 2016
  • (E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.