• Title/Summary/Keyword: Degradation factor

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Dermal Absorption and Body Distribution of $^{125}I-rhEGF$ in Hairless Mice (헤어리스마우스 피부 국소에 적용된 $^{125}I-rhEGF$의 피부흡수 및 체내 분포)

  • Lee, Jeong-Uk;Chung, Seok-Jae;Lee, Min-Hwa;Shim, Chang-Koo
    • YAKHAK HOEJI
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    • v.41 no.6
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    • pp.737-748
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    • 1997
  • Distribution of rhEGF in the skin, plasma and several organ tissues following topical application of $^{125}I-rhEGF$ (0.4${\mu}$Ci) solution in 25% Pluronic F-127 on 154$mm^2$ normal and damaged (burned and stripped) skins of hairless mice was examined. The radioactivity in the stripped skin tissues increased as a function of time, and was 10-20 times higher than that in the normal and burned skins. The fractions of intact drug in the skin tissues were 40-60% for the normal and burned skins, and 60-80% for the stripped skin. It indicates that the stratum corneum layer behaves as a barrier for the dermal penetration of the drug. The radioactivity in the plasma was much higher for the stripped skin than for the normal and burned skins. However, the concentration of intact drug in the stripped skin was comparable to those in the normal and burned skins indicating most severe degradation (or metabolism) of the drug in the stripped skin. As a result, the fraction of intact drug in the plasma was lowest for the stripped skin (<10%). Body organ distribution of the drug was much higher for the stripped skin. The concentration in the stomach. Both in total radioactivity and intact drug, showed more than 10-times higher value than in the other organs (liver, kidney and spleen). The fraction of intact drug in each organ tissue was below 10-20%. And generally lowest for the stripped skin. The lowest fraction of the drug for the stripped skin could not be explained by the activity of the aminopeptidases in the skin since it was lower for the stripped skin than for the normal skin. Thereover, the fraction of intact drug appears to be determined by the balance between dermal uptake and systemic elimination of the drug, for example. The mechanism of dermal uptake of rhEGF was examined by topical applying 200${\mu}$l of 25% Pluronic F-127 solution containing 0.4 ${\mu}$Ci of $^{125}I-rhEGF$ and 0.14${\mu}$Ci of $^{14}C$-inulin (a marker of passive diffusion). The radioactivity of $^{125}I-rhEGF$ at each sampling time point (0.5, 1, 2, 4 and 8hr) was correlated (p<0.05) with the corresponding radioactivity of $^{14}C$-inulin. It appears to indicate the rhEGF may be uptaken into the skins mainly by the passive diffusion. This hypothesis was supported by the constant specific binding of EGF to the skin homogenates regardless of the skin models. Receptor mediated endocytosis (RME) appears to contribute negligibly, if any, to the overall uptake process.

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Inhibitory Effect of Extract of Teucrium veronicoides on the Production of Inflammatory Cytokines (곽향 추출물의 염증성세포활성물질 억제효과)

  • Bae, Gi-Sang;Park, Hee-Je;Kim, Do-Yun;Seo, Sang-Wan;Park, Kyung-Bae;Kim, Byung-Jin;Song, Je-Moon;Lee, Kyung-Yong;Na, Chul;Shin, Byung-Chul;Park, Sung-Joo;Song, Ho-Joon;Hwang, Sung-Yeon
    • The Korea Journal of Herbology
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    • v.23 no.3
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    • pp.119-125
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    • 2008
  • Objectives : The purpose of this paper was to investigate the anti-inflammatory effects of extract from Teucrium veronicoides (TV) on the RAW 264.7 cells. Methods : To evaluate of anti-inflammatory of TV, we examined the cytokine productions on lipopolysacchride (LPS)-induced RAW 264.7 cells and also inhibitory mechanisms using Western blot. Furthermore, We examined LPS-induced endotoxin shock. Results : 1. Extract from TV itself does not have any cytotoxic effect. 2. Extract from TV reduced LPS-induced Nitric oxide (NO),interleukin (IL)-1b, IL-6 and IL-10, tumor necrosis factor-a (TNF-a) production in RAW 264.7 cells. 3. TV inhibited the activation of mitogen-activated protein kinases (MAPKs) such as p38, extracelluar signal-regulated kinase (ERK 1/2) and c-Jun NH2-terminal kinase (JNK) and also the degradation of inhibitory kappa B a (Ik-Ba) in the LPS-stimulated RAW 264.7 cells. 3. TV slightly increased the duration of survival after LPS-induced endotoxin shock. Conclusions : TV down-regulated LPS-induced NO and cytokines production, which could provide a clinical basis for anti-inflammatory properties of TV.

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Eupatorium chinensis var. simplicifolium Root Extract Inhibits the Lipopolysaccharide-Induced Inflammatory Response in Raw 264.7 Macrophages by Inhibiting iNOS and COX-2 Expression (Raw 264.7 대식세포에서 등골나물 뿌리 추출물의 염증반응 조절 분자 iNOS와 COX-2 발현 억제 효과)

  • Lee, Jin-Ho;Kim, Dae-Hyun;Shin, Ji-Won;Park, Sae-Jin;Kim, Yoon-Suk;Shin, Yu-Su;Yu, Ji-Yeon;Kim, Tack-Joong
    • Journal of Life Science
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    • v.22 no.9
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    • pp.1137-1144
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    • 2012
  • Inflammation is a host defense mechanism that is activated in response to harmful substances or pathogens. However, an excessive inflammatory response is a problem in itself. Macrophages secrete inflammatory mediators such as nitric oxide (NO) or cytokines through various pathways such as the nuclear factor kappa B (NF-${\kappa}B$)-activated pathway after recognizing pathogen-like lipopolysaccharides (LPSs). In this study, anti-inflammatory effects of Eupatorium chinensis var. simplicifolium (EUC) extracts were investigated using LPS-stimulated RAW 264.7 macrophages. The EUC root extract significantly reduced NO production, inducible nitric oxide synthase (iNOS) expression, and cyclooxygenase-2 expression in a concentration-dependent manner. In addition, the EUC root extract reduced phosphorylation of mitogen-activated protein kinases and protein kinase B, which is upstream of NF-${\kappa}B$. The EUC root extract also reduced the degradation of inhibitory kappa B. These results indicate that EUC root extract exerts anti-inflammatory effects, which are mediated by inhibition of iNOS expression and the NF-${\kappa}B$ pathway.

Tristetraprolin Overexpression in Gastric Cancer Cells Suppresses PD-L1 Expression and Inhibits Tumor Progression by Enhancing Antitumor Immunity

  • Guo, Jian;Qu, Huiheng;Shan, Ting;Chen, Yigang;Chen, Ye;Xia, Jiazeng
    • Molecules and Cells
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    • v.41 no.7
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    • pp.653-664
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    • 2018
  • The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

Effects of pH Control Methods on Removal Efficiency in Electrokinetic Bioremediation of Phenanthrene-contaminated Soil (Phenanthrene-오염토양의 동전기 생물학적 복원에서 pH 조절방법이 제거효율에 미치는 영향)

  • Kim, Sang-Joon;Park, Ji-Yeon;Lee, You-Jin;Yang, Ji-Won
    • KSBB Journal
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    • v.21 no.3
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    • pp.181-187
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    • 2006
  • In this study, problems related with pH control in electrokinetic(EK) bioremediation of phenanthrene contaminated soil were observed, and the effects of pH control methods on the removal efficiency were investigated to search a further application strategy. In a preliminary experiment, it was found out by flask cultivation that a certain sulfate concentration was needed to degrade phenanthrene well using Sphingomonas sp. 3Y. However, when $MgSO_4$ was used as sulfate source in EK bioremediation, the bacterial activity reduced seriously due to the abrupt decrease of pHs in soil and bioreactor by the combination of magnesium and hydroxyl ions. When another strong buffering compound was used to control the pH problem, the good maintenance of the bacterial activity and pHs could be observed, but the removal efficiency decreased largely. When a low concentration of $MgSO_4$ was added, the removal efficiency decreased somewhat in spite of the good maintenance of neutral pHs. With the addition of NaOH as a neutralizing agent, the removal efficiency also decreased because of the increase of soil pH. Consequently the selection of electrolyte composition was a very important factor in EK bioremediation and some sulfate sources suitable for both bacterial activity and contaminant degradation should be investigated.

Inhibition of Inflammatory-cytokines Production and Prostaglandin E2 Activity by Puerariae Radix Extracts (갈근 추출물에 의한 염증성 Cytokine 생성 억제 및 Prostaglandin E2 활성 저해에 관한 연구)

  • Kim, Si-Na;Kim, Hee-Seok;Nam, Gyeong-Sug;Hwang, Sung-Wan;Hwang, Sung-Yeoun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.1
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    • pp.28-34
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    • 2006
  • The ethanol extracts of Puerariae Radix inhibited cyclooxygenase-2 (COX-2) activity in bone marrow derived mast cells (BMMC). COX-2 is responsible for the production of large amounts of proinflammatory prostaglandins (PGs) at the inflammatory site. We have investigated the anti-inflammatory effect of ethyl acetate fraction from $70\%$ ethanol extract of Puerariae Radix (EPR), and attempted acetic acid induced writhing to verify the analgesic effect. Inflammation was induced by interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), $inteferon-\gamma$ $(IFN-\gamma)$ and lipopolysaccharide (LPS). EPR showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, prostaglandin $E_2\;(PGE_2)$ production, nitric oxide (NO) production, and matrix-metalloproteinases (MMPs) expression in mouse macrophage and rabbit articular chondrocyte. In the writhing test, EPR $(200\~400\;mg/kg)$ exhibited a dose-dependent inhibition of writhing. The results indicate that EPR have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for treating of osteoarthritis (OA).

Characteristics of Nickel_Titanium Dual-Metal Schottky Contacts Formed by Over-Etching of Field Oxide on Ni/4H-SiC Field Plate Schottky Diode and Improvement of Process (Ni/4H-SiC Field Plate Schottky 다이오드 제작 시 과도 식각에 의해 형성된 Nickel_Titanium 이중 금속 Schottky 접합 특성과 공정 개선 연구)

  • Oh, Myeong-Sook;Lee, Jong-Ho;Kim, Dae-Hwan;Moon, Jeong-Hyun;Yim, Jeong-Hyuk;Lee, Do-Hyun;Kim, Hyeong-Joon
    • Korean Journal of Materials Research
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    • v.19 no.1
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    • pp.28-32
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    • 2009
  • Silicon carbide (SiC) is a promising material for power device applications due to its wide band gap (3.26 eV for 4H-SiC), high critical electric field and excellent thermal conductivity. The Schottky barrier diode is the representative high-power device that is currently available commercially. A field plate edge-terminated 4H-SiC was fabricated using a lift-off process for opening the Schottky contacts. In this case, Ni/Ti dual-metal contacts were unintentionally formed at the edge of the Schottky contacts and resulted in the degradation of the electrical properties of the diodes. The breakdown voltage and Schottky barrier height (SBH, ${\Phi}_B$) was 107 V and 0.67 eV, respectively. To form homogeneous single-metal Ni/4H-SiC Schottky contacts, a deposition and etching method was employed, and the electrical properties of the diodes were improved. The modified SBDs showed enhanced electrical properties, as witnessed by a breakdown voltage of 635 V, a Schottky barrier height of ${\Phi}_B$=1.48 eV, an ideality factor of n=1.04 (close to one), a forward voltage drop of $V_F$=1.6 V, a specific on resistance of $R_{on}=2.1m{\Omega}-cm^2$ and a power loss of $P_L=79.6Wcm^{-2}$.

Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells

  • Lee, Jae-Won;Choi, Yong-Joon;Kim, Song-In;Lee, Sue-Young;Kang, Sang-Soo;Kim, Nam-Ho;Kwon, Yong-Soo;Lee, Hee-Jae;Chun, Wan-Joo;Kim, Sung-Soo
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.431-437
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    • 2011
  • Aberrant activation of microglia has been reported to cause neuronal damages by releasing a variety of pro-inflammatory cytokines. Besides where microglia become active, damages have been also observed in remote places, which is considered due to the migration of activated microglia. Therefore, an agent that could suppress abnormal activation of microglia and their subsequent migration might be valuable in activated microglia-related brain pathologies. The objective of the present study was to evaluate anti-inflammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid significantly attenuated LPS-induced NO production and protein expression of iNOS. Betulinic acid also significantly suppressed LPS-induced release and expression of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Furthermore, betulinic acid significantly uppressed LPS-induced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major pro-inflammatory transcription factor, was examined. Betulinic acid significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was significantly suppressed with betulinic acid. Taken together, the present study for the first time demonstrates that betulinic acid possesses anti-inflammatory activity through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.

Effect of Screw Configurations and Process Parameters on Characteristics of Wheat Bran Extrudates (스크류 조합과 공정변수 조절에 따른 밀기울 압출물의 특성)

  • Kim, Chong-Tai;Hwang, Jae-Kwan;Cho, Sung-Ja;Kim, Chul-Jin;Kim, Hae-Sung
    • Korean Journal of Food Science and Technology
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    • v.28 no.1
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    • pp.169-178
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    • 1996
  • Target parameters such as water solubility index (WSI), intrinsic viscosity (IV), water holding capacity (WHC), oil holding capacity (OHC), soluble dietary fiber (SDF) and microstructure were investigated on three different screw configurations during twin-screw extrusion of wheat bran. WSI of raw wheat bran (RWB) was 13.7%, while that of extrudates ranged $16.3{\sim}23.2%$ when extruded using screw configurations with 5 reverse screw elements (RSE). It was found that the moisture content of RWB greatly affected WSI of extrudates. IV of wheat bran extrudates increased from 10.6 ml/g of RWB to $37.86{\sim}44.37\;ml/g$ of extrudates extruded using 3, 4 and 5 RSE, whose trend was highly related to the moisture content of RWB and the extrusion pressure. Multiplication of IV and soluble solid (SS) content exhibited good correlation $(R^2=0.85)$ with specific mechanical energy (SME). The results suggested that SS and molecular size are an important factor governed by the SME in solubilization of wheat bran. WHC increased with increasing feed rate and moisture content, while OHC decreased. SDF increased from 2.68% of RWB to $4.32{\sim}6.48%$ of extruded wheat bran, indicating the significant breakdown of cell wall components. Microstructure of the extrudates showed the distinct patterns of degradation and solubilization of cell wall structure, depending on the moisture content of RWB.

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Analysis on Priority of Influence Factors for Management of Vertical-extension Remodeling Project (수직증축 리모델링공사의 효율적 관리를 위한 영향요인 분석)

  • Lee, Dong-Heon;Lim, Hyoung-chul
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.9
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    • pp.314-321
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    • 2016
  • After the 1980s, as the economy was growing rapidly and the real estate market was active, a large increase in population was supplied to the city. Accordingly, the national apartment housing market is located in the form of Urban Housing Culture. On the other hand, with time, the supply apartment houses became superannuated and the residential environment became poor. Therefore, the environment of old apartment houses has been changed to improve by reconstruction. Despite this, reconstruction incurred not only a lot of construction waste, but also problems of environmental degradation, noise, traffic congestion, increasing number of households, and so on. Recently, the housing law has changed, and vertical extension remodeling focused on Small/Medium Town House is underway. This has been changed in response to the demand. This is one of essential parts in the remodeling field for the future, even though it has some problems in how uses existing buildings. Therefore, this study analyzed occurrence risk factor for each type through research materials and case analysis regarding the vertical extension remodeling of apartment housing. In addition, the relative importance was determined through questionnaires and interviews from constructors, designers, and experts in the field.