• Title/Summary/Keyword: regulatory factor

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Forsythiae Fructus Induces VEGF Production via p38 MAPK Activation in Human Keratinocytes (각질형성세포에서 p38 MAPK 활성을 통한 연교의 VEGF 생성 효과)

  • Kim, Mi-Sun;Choi, Yun Ho;Park, Sun Gyoo;Lee, Cheon Koo;Lee, Sang Hwa
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.4
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    • pp.329-336
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    • 2016
  • Cutaneous microvasculature plays a critical role in age-associated skin changes. A considerable reduction of number and size of vessels has been observed in the upper dermis of elderly skin. Forsythiae fructus (FF), the dried fruit of plant Forsythia suspensa (F. suspensa), has been traditionally used as an herbal medicine to treat inflammatory diseases and bacterial diseases. However, its regulatory effect on angiogenic responses has not been elucidated in skin. Therefore, we analyzed secretory profiles upon treatment of FF extract using array designed to detect angiogenesis-associated mediators in human keratinocytes. Because keratinocyte-derived VEGF (vascular endothelial growth factor) has been regarded as a potent factor for new microvasculature under the epidermis, we further investigated the effect of FF extract on VEGF production. We observed that the VEGF expression of mRNA and protein level was increased by about 2 folds in a dose-dependent manner after FF extract treatment. In signaling experiments, FF extract induced rapid p38 MAPK activation within 5 min, and the activation was totally abrogated by pretreatment with a p38 MAPK specific inhibitor. The FF-induced VEGF upregulation was also significantly attenuated by a p38 MAPK inhibition. Taken together, FF extract induces VEGF production via p38 MAPK activation in human epidermal keratinocytes. These novel findings suggest that FF is useful as a potential agent with pro-angiogenic activity and may help to improve age-dependent reduction of the microvasculature in aged skin or to heal skin wound.

Isolation and characterization of sigH from Corynebacterium glutamicum (Corynebacterium glutamicum의 sigH 유전자의 분리 및 기능분석)

  • Kim Tae-Hyun;Kim Hyung-Joon;Park Joon-Sung;Kim Younhee;Lee Heung-Shick
    • Korean Journal of Microbiology
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    • v.41 no.2
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    • pp.99-104
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    • 2005
  • Corynebacterial clones which exert regulatory effects on the expression of the glyoxylate bypass genes were isolated using a reporter plasmid carrying the enteric lacZ fused to the aceB promoter of Corynebacterium glutamicum. Some clones carried common fragments as turned out by DNA mapping technique. Subcloning analysis followed by the measurement of $\beta-galactosidase$ activity in Escherichia coli identified the region responsible for the aceB-repressing activity. Sequence analysis of the DNA fragment identified two independent ORFs of ORF1 and ORF2. Among them, ORF2 was turned out to be responsible for the aceB-repressing activity. ORF1 encoded a 23,216 Da protein composed of 206 amino acids. Sequence similarity search indicated that the ORF may encode a ECF-type $\sigma$ factor and designated sigH. To identify the function of sigH, C. glutamicum sigH mutant was constructed by gene disruption technique and the sigH mutant showed growth retardation as compared to the wild type strain. In addition, the mutant strain showed sensitivity to oxidative-stress generating agent plumbagin. This result imply that sigH is probably involved in the stress response occurring during normal cell growth.

IP-10 Decreases TNF-α Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis (IP-10에 의한 기도상피세포에서의 TNF-α 유도 MUC5AC발현 억제: 특발성폐섬유증 환자의 적은 객담과의 연관성)

  • Kim, Seung Joon;Kang, Chun Mi;You, Moon Bin;Yoon, Hyung Kyu;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.5
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    • pp.347-355
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    • 2008
  • Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

Transcriptome Analyses for the Anti-Adipogenic Mechanism of an Herbal Composition (생약복합물의 지방세포형성억제 기전규명을 위한 전사체 분석)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Bae, Sung-Min;Chae, Soo-Ahn;Lee, Jung-Ju;Oh, Dong-Jin;Park, Suk-Won;Cho, Soo-Hyun;Shim, Yae-Jie;Yoon, Yoo-Sik
    • Journal of Life Science
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    • v.20 no.7
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    • pp.1054-1065
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    • 2010
  • SH21B is a natural composition composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). In our previous study, we reported that SH21B inhibited adipogenesis and fat accumulation in 3T3-L1 cells through modulation of various regulators in the adipogenesis pathway. The aim of this study was to analyze the transcriptome profiles for the anti-adipogenic effects of SH21B in 3T3-L1 cells. Total RNAs from SH21B-treated 3T3-L1 cells were reverse-transcribed into cDNAs and hybridized to Affymetrix Mouse Gene 1.0 ST array. From microarray analyses, we identified 2,568 genes of which expressions were changed more than two-fold by SH21B, and the clustering analyses of these genes resulted in 9 clusters. Three clusters among the 9 showed down-regulation by SH21B (cluster 4, cluster 6 and cluster 9), and two clusters showed up-regulation by SH21B (cluster 7 and cluster 8) during the adipogenesis of 3T3-L1 cells. It was found that many genes related to cell proliferation and adipogenesis were included in these clusters. Clusters 4, 6 and 9 included genes which were related with adipogenesis induction and cell cycle arrest. Clusters 7 and 8 included genes related to cell proliferation as well as adipogenesis inhibition. These results suggest that the mechanisms of the anti-adipogenic effects of SH21B may be the modulation of genes involved in cell proliferation and adipogenesis.

Brazilin downregulates CCL20 expression via regulation of STAT3 phosphorylation in TNF-α/IL-17A/IFN-γ-induced HaCaT cells (TNF-α/IL-17A/IFN-γ 유도된 HaCaT 세포에서 브라질린의 STAT3 인산화 억제를 통한 CCL20 저해 효과)

  • Kim, Mi Ran;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.64 no.2
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    • pp.185-192
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    • 2021
  • Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

Regulatory Mechanism of Insulin-Like Growth Factor Binding Protein-3 in Non-Small Cell Lung Cancer (비소세포성 폐암에서 인슐린 양 성장 인자 결합 단백질-3의 발현 조절 기전)

  • Chang, Yoon Soo;Lee, Ho-Young;Kim, Young Sam;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Kim, Se Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.5
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    • pp.465-484
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    • 2004
  • Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

Inhibitory Effect of Jeungaektang Water Extract on Nitric Oxide and Cytokine Production in Lipopolysaccharide - activated RAW 264.7 Cells (증액탕(增液湯) 물추출물이 LPS로 유도된 RAW 264.7 cell에서의 Nitric Oxide 및 Cytokine에 미치는 영향)

  • Ahn, Sun-June;Lee, Jong-Rok;Kim, Sang-Chan;Jee, Seon-Young
    • Herbal Formula Science
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    • v.15 no.1
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    • pp.163-173
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    • 2007
  • Jeungaektang (JAT) is the herbal formula, has the effect of moistening the dryness by activating lung Qi and by nourishing Yin, has being used for dryness syndromes. Generally the herbal formulae for moistening dryness are used for exogenous or endogenous dryness syndromes. JAT has been clinically used for the treatment of endogenous dryness syndromes. It is composed of Scrophulariae Radix. Rehmanniae Radix and Liriopis Tuber. Recent studies showed that JAT has a protective effect against $CCl_{4}-induced$ hepatotoxicity and anti-inflammatory effects against ear swelling of mouse induced by Crotonis Fructus. However, the effect of JAT on the immunological activity was rarely studied. Therefore, this study evaluated the effects of JAT the regulatory mechanism of nitric oxide (NO) and cytokines in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. After the treatment of JAT water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Cyclooxygenase-2 (COX -2) and inducible nitric oxide synthase (iNOS) were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidence that JAT inhibited the production of nitrite and nitrate ($0.1{\sim}1.0$ mg/ml), iNOS ($0.1{\sim}1.0$ mg/ml), $interleukin-1{\beta}$ ( $0.1{\sim}1.0$ mg/ml) and tumor necrosis $factor-{\alpha}$ ($0.1{\sim}1.0$ mg/ml) in RAW 264.7 cells activated with LPS. Furthermore, JAT inhibited the expression of COX-2 expression and production of prostagladin E2 ($0.1{\sim}1.0$ mg/ml). These findings suggest that JAT can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

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Bee Venom-induced Growth Inhibition of Human Lung Cancer Cells was Associated with Inhibition of Prostagladin E2 Production and Telomerase Activity. (인체폐암세포에서 봉독에 의한 prostagladin E2 생성 및 telomerase 활성 저하)

  • Kim, Jong-Hwan;Hwang, Won-Deuk;Kim, Byung-Woo;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.4
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    • pp.502-507
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    • 2009
  • In modern oriental medicine, bee venom therapy is being used for aqua-acupuncture to relieve pain and to cure inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and gout. Bee venom therapy has been processed and reported in many experimental studies, with regard to its effects on pain alleviation, anti-inflammation, removal of fever, anti-convulsion, suppression of tumor and immunity strengthening, etc., however, its mechanism of action, molecular targeting on prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remains unclear. In this study, we investigated the effect of bee venom on the levels of cyclooxygenases (COXs) and telomere regulatory components of A549 human lung cancer cells. Bee venom-induced anti-proliferative effects of A549 cells were associated with the inhibition of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR), transcription factor c-myc and the activity of telomerase. In addition, bee venom treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of bee venom.

Sequence and Expression Analysis of c-fos Proto-oncogene in Korean Cattle (HANWOO) (한우 c-fos 유전자의 염기서열 및 발현분석)

  • Yu, S.L.;Chung, H.J.;Jung, K.C.;Lee, J.H.;Cho, K.W.;Choi, J.G.;Na, K.J.;Sang, B.C.
    • Journal of Animal Science and Technology
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    • v.45 no.6
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    • pp.891-900
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    • 2003
  • Cellular FOS(c-fos) protein is a transcription factor that forms heterodimers mostly with c-jun family and stimulates the transcription of genes containing AP-1 regulatory elements. This c-fos expression can control growth and differentiation of various precursor cells including myoblasts. The controls by c-fos gene have been identified for affecting skeletal muscle fiber traits which are the key determinants of meat quality in pigs. As a first step for identifying the relationship between c-fos gene and meat quality traits in cattle, we fully sequenced 1,443 bp of Hanwoo c-fos mRNA and analyzed expression patterns from various organs and muscle tissues. The sequence identities of Hanwoo c-fos with that of human, pig and mouse showed 89.8%, 93.3% and 87%, respectively. Analyses of the northern blot showed high c-fos expressions were obtained in spleen and rib muscle from 7 organs and 9 different parts of muscles investigated. These results presented here can be used as a valuable marker for meat quality related traits in cattle with further verification.

The risk of the Information-oriented society and the role of private security (정보화 사회의 위험적 요소와 민간시큐리티의 역할)

  • Gong, Bae Wan
    • Journal of the Society of Disaster Information
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    • v.8 no.1
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    • pp.1-9
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    • 2012
  • Informatization of society through the computer and the Internet, because large amounts of information production and exchange and new way of communicating is born. Passive way past the one-sided information flows actively interact to evolve in a manner of information producers and information consumers distinction and personal relationships that enhance the online Social Networking Service (SNS) has developed into the social structure of. Thus, the spread of information work closely with the social network structure spark social conflict may act as a factor, and systems and the environment, personal and cultural adaptation of speed to keep up with the rapid development of science and technology as the inability conflict and confusion should lead to even. This paper the characteristics of the information society, with a look at the evolution of social risk factors as the wavelength of information about this look at the role of private security sought to evaluate. Information Society in time and space by shrinking the area of human life that has brought the convenience and simplicity, whereas the non-performance due to the nature of anonymous raises many social side-effects are. This made the preparation of national regulatory measures, but for the protection of personal protection devices in the private sector has not yet been discussed. Way of life and property of the purchaser to protect an individual's private security will have to charge it.