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CKD-712, (S)-1-(${\alpha}$-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-${\kappa}B$ Activation and Augments Akt Activation during TLR4 Signaling

  • Lee, Jeong-Gi;Yang, Eun-Jeong;Shin, Jeon-Soo;Kim, Dal-Hyun;Lee, Sung-Sook;Choi, In-Hong
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.420-423
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    • 2011
  • Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-${\kappa}B$ was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-${\kappa}B$ signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-${\kappa}B$ activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.

Plasma Nuclear Factor Kappa B and Serum Peroxiredoxin 3 in Early Diagnosis of Hepatocellular Carcinoma

  • Ismail, Saber;Mayah, Wael;Battia, Hassan El;Gaballah, Hanaa;Jiman-Fatani, Asif;Hamouda, Hala;Afifi, Mohamed A.;Elmashad, Nehal;Saadany, Sherif El
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1657-1663
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    • 2015
  • Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-${\kappa}B$ and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-${\kappa}B$) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-${\kappa}B$ and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-${\kappa}B$) as a target for treatment of liver fibrosis and HCC must be widely evaluated.

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines

  • Shafik, Noha M;Mohamed, Dareen A;Bedder, Asmaa E;El-Gendy, Ahmed M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8579-8587
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    • 2016
  • Background: The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), with the inflammatory markers nuclear factor kappa B/p65 (NF-${\kappa}B$/P65) and interleukin-1 beta (IL-$1{\beta}$) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-${\kappa}B$/P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-$1{\alpha}$ and IL-$1{\beta}$ were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma ($1.47{\pm}0.31$ and $184.98{\pm}18.18$, respectively) compared to low grade carcinoma ($1.21{\pm}0.32$ and $171.76{\pm}7.58$, respectively) and controls ($0.70{\pm}0.02$ and $65.34{\pm}6.41$, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-$1{\alpha}$ and IL-$1{\beta}$ as well as NF-${\kappa}B$/P65 DNA binding activity were significantly higher in high grade breast carcinoma ($148.54{\pm}14.20$, $0.79{\pm}0.03$ and $247.13{\pm}44.35$ respectively) than their values in low grade carcinoma ( $139.14{\pm}5.83$, $0.34{\pm}0.02$ and $184.23{\pm}37.75$, respectively) and controls ($33.95{\pm}3.11$, $0.11{\pm}0.02$ and $7.83{\pm}0.92$, respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-$1{\alpha}$ could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-$1{\beta}$ and NF-${\kappa}B$/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.

대기압 플라즈마 정밀 Etching 기술 개발

  • Im, Chan-Ju;Kim, Yun-Hwan;Lee, Sang-Ro;Ak, Heun
    • Proceedings of the Korean Vacuum Society Conference
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    • 2011.02a
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    • pp.263-263
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    • 2011
  • 본 연구에서는 DBD (Dielectric Barrier Discharge)방식의 상압 플라즈마를 이용하여 FPD (flat panel display) 공정에 사용되는 a-Si, Si3N4의 식각 공정 특성을 평가하였다. 사용된 DBD 반응기는 기존의 blank planar plate 형태의 Power가 인가되는 anode 부분과 Dielectric Barrier 사이 공간을 액상의 도전체로 채워 넣은 형태의 전극이 사용 하였으며, 인가 Power는 40kHz AC 최대인가 전압 15 kVp를 사용 하였다. 방전 가스는 N2, 반응가스로는 CDA (Clean Dry Air)와 NF3, 액상의 Etchant를 사용 하였으며 모든 공정은 In-line type으로 시편을 처리 하였다. NF3의 경우 30 mm/sec 이송속도 1회 처리 기준 a-Si 1300${\AA}$, Si3N4 1900${\AA}$의 식각 두께를 보였으며 a-Si : Si3N4 선택비는 N2, CDA의 조절을 통하여 최대 1:2에서 4:1 정도까지 변화가 가능하였다. 균일도는 G2 (370 mm${\times}$470 mm)의 경우 5.8 %의 균일도를 보이고 있다. 이외에도 NF3 공정의 경우 실제 TFT-LCD 공정 중 n+ channel (n+ a-Si:H)식각 공정에 적용하여 5.5 inch LCD panel feasibility를 확인 할 수 있었다. 액상 Etchant (HF수용액, NH4HF2)는 버블러를 사용하여 기화 시켜 플라즈마 소스를 통해 1차적으로 활성화 시키고 기존 DBD 반응기에 공급해 주는 형태로 평가를 진행하였다. 식각 특성은 30mm/sec 이송속도에서 a-Si $25{\AA}$ 정도로 가스 형태의 Etchant에 비해 매우 낮은 수준이나 Etching rate 향상을 위한 factor 파악 및 개선을 위한 연구를 진행 하였다.

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Antistress effect of red ginseng in brain cells is mediated by TACE repression via PADI4

  • Kim, Eun-Hye;Kim, In-Hye;Ha, Jung-Ah;Choi, Kwang-Tae;Pyo, Suhkneung;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • v.37 no.3
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    • pp.315-323
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    • 2013
  • Ginseng is known to have antistress effects. Previously, red ginseng (RG) was shown to repress stress-induced peptidyl arginine deiminase type IV (PADI4) via estrogen receptor ${\beta}$ ($ER{\beta}$) in the brain, thus inhibiting brain cell apoptosis. Moreover, tumor necrosis factor (TNF)-${\alpha}$ plays a critical role in immobilization (IMO) stress. However, the signaling pathway of RG-mediated repressesion of inflammation is not completely understood. In this study, we determined how RG modulated gene expression in stressed brain cells. Since secretion of TNF-${\alpha}$ is modulated via TNF-${\alpha}$ converting enzyme (TACE) and nuclear factor (NF)-${\kappa}B$, we examined the inflammatory pathway in stressed brain cells. Immunohistochemistry revealed that TACE was induced by IMO stress, but RG repressed TACE induction. Moreover, PADI4 siRNA repressed TACE expression compared to the mock transfected control suggesting that PADI4 was required for TACE expression. A reporter assay also revealed that $H_2O_2$ oxidative stress induced NF-${\kappa}B$ in neuroblastoma SK-N-SH cells, however, RG pretreatment repressed NF-${\kappa}B$ induction. These findings were supported by significant induction of nitric oxide and reactive oxygen species (ROS) by oxidative stress, which could be repressed by RG administration. Taken together, RG appeared to repress stress-induced PADI4 via TACE and NF-${\kappa}B$ in brain cells thus preventing production of ROS and subsequently protecting brain cells from apoptosis.

Characterization of Heterologously Expressed Acetyl Xylan Esterase1 Isolated from the Anaerobic Rumen Fungus Neocallimastix frontalis PMA02

  • Kwon, Mi;Song, Jaeyong;Park, Hong-Seog;Park, Hyunjin;Chang, Jongsoo
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.11
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    • pp.1576-1584
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    • 2016
  • Acetyl xylan esterase (AXE), which hydrolyzes the ester linkages of the naturally acetylated xylan and thus known to have an important role for hemicellulose degradation, was isolated from the anaerobic rumen fungus Neocallimastix frontatlis PMA02, heterologously expressed in Escherichi coli (E.coli) and characterized. The full-length cDNA encoding NfAXE1 was 1,494 bp, of which 978 bp constituted an open reading frame. The estimated molecular weight of NfAXE1 was 36.5 kDa with 326 amino acid residues, and the calculated isoelectric point was 4.54. The secondary protein structure was predicted to consist of nine ${\alpha}$-helixes and 12 ${\beta}$-strands. The enzyme expressed in E.coli had the highest activity at $40^{\circ}C$ and pH 8. The purified recombinant NfAXE1 had a specific activity of 100.1 U/mg when p-nitrophenyl acetate (p-NA) was used as a substrate at $40^{\circ}C$, optimum temperature. The amount of liberated acetic acids were the highest and the lowest when p-NA and acetylated birchwood xylan were used as substrates, respectively. The amount of xylose released from acetylated birchwod xylan was increased by 1.4 fold when NfAXE1 was mixed with xylanase in a reaction cocktail, implying a synergistic effect of NfAXE1 with xylanase on hemicellulose degradation.

Anti-inflammatory Effects of the Water Extract of Phyllostachys Folium via NF-κB Inhibition (죽엽 열수추출물의 염증억제 효과)

  • Son, Jin Won;Park, Sang Mi;Jung, Ji Yun;Hwangbo, Min;Cho, Il Je;Jung, Tae Young;Park, Chung A;Kim, Sang Chan;Jee, Seon Young
    • Herbal Formula Science
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    • v.24 no.4
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    • pp.259-269
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    • 2016
  • Objectives : Phyllostachys Folium is leaves of Phyllostachys nigra var. henesis $S_{TAPF}$. In the East Asian traditional medicine, the herb has been used to treat nasal bleeding, dysuria, epilepsy and etc. The present study was conducted to evaluate the anti-inflammatory effects of the Phyllostachys Folium water extracts (PFE) in vitro and in vivo model. Methods : Cell viability was measured by MTT assay after the treatment of PFE and NO production was monitored by measuring the nitrite content in culture medium. iNOS, COX-2, $I{\kappa}B$, $p-I{\kappa}B{\alpha}$ amd $NF{\kappa}B$ were detected by immunoblot analysis, and levels of cytokine were analyzed by sandwich ELISA kit. Anti-edema effect of PFE was determined in the carrageenan-induced paw edema model in rats. Results : LPS increased NO and cytokines levels compared with control, these increases were attenuated by PFE. In addition, LPS-induced pro-inflammatory proteins such as iNOS, COX-2 were down regulated by PFE. These anti-inflammatory effect of PFE results from inhibition of phosphorylation of $I{\kappa}B$ and translocation of $NF-{\kappa}B$. Conclusion : These results show that PFE has some anti-inflammatory effects which might play a role in gram-negative bacterial infection inflammation and $NF{\kappa}B$ activated diseases.

Viridicatol from Marine-derived Fungal Strain Penicillium sp. SF-5295 Exerts Anti-inflammatory Effects through Inhibiting NF-κB Signaling Pathway on Lipopolysaccharide-induced RAW264.7 and BV2 Cells

  • Ko, Wonmin;Sohn, Jae Hak;Kim, Youn-Chul;Oh, Hyuncheol
    • Natural Product Sciences
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    • v.21 no.4
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    • pp.240-247
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    • 2015
  • Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 ($PGE_2$) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B ($NF-{\kappa}B$) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B $(I{\kappa}B)-{\alpha}$ in the cytoplasm, and suppressed the translocation of $NF-{\kappa}B$ p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of $NF-{\kappa}B$ in LPS-stimulated RAW264.7 and BV2 cells.

Comparison of Nitrate and Fluoride Removals between Reverse-Osmosis, Nano-Flitration, Electro-Adsorption, Elecero-Coagulation in Small Water Treatment Plants (소규모 수도시설의 역삼투(RO), 나노여과(NF), 전기흡착(EA), 전기응집(EC) 공정의 질산성 질소 및 불소 이온 제거 성능 비교)

  • Han, Song-Hee;Chang, In-Soung
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.4
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    • pp.2027-2036
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    • 2013
  • Comparison of removal performance between reverse osmosis(RO), nanofiltration(NF), electrocoagulation(EC) and electroadsorption(EA) for removal of nitrate and fluoride often exceeded the limits of water quality in small water treatment plants. Removals of nitrate and fluoride were 72-92% and 74-85% in RO, 5-15% and 1% in NF, 99% and 44% in EA equipped with MWCNT coated electrodes, 82% and 77% in EA equipped with Cu-MWCNT electrodes, and 11-46% and 69-99% in EC. Consequently, high removals of both ions were anticipated in RO. Effective removal of both ions are possible for EC, but great production of sludge is a big burden. EA equipped with the MWCNT electrodes showed a great fluctuation in removal efficiency, and electrode stability should be upgraded.

Curcumin Inhibits Ovalbumin-Induced Inducible Nitric Oxide Synthase Expression (Curcumin은 ovalbumin에 의해서 유도된 inducible nitric oxide synthase 억제)

  • Kim, Ji-Soo;Ahn, Hee-Jin;Shin, Hwa-Jeong;Gu, Gyo-Jeong;Eum, Sang-Hoon;Lee, Chung-Ho;Min, In-Soon;Youn, Hyung-Sun
    • Korean Journal of Food Science and Technology
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    • v.44 no.4
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    • pp.498-501
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    • 2012
  • Egg allergy has been reported as the most prevalent food hypersensitivity among children. One of the major egg allergens is ovalbumin (OVA). OVA is the major protein in the egg white, comprising 54% of its total protein content. Curcumin isolated from Curcuma longa has been used as folk remedies in order to treat many chronic diseases for many years. In the present report, we present biochemical evidence that curcumin inhibits the NF-${\kappa}B$ activation induced by OVA. Curcumin also inhibits OVA-induced iNOS expression and nitrite production. These data suggest new approaches for the development of efficient anti-allergic strategies.