• Title/Summary/Keyword: pre-activation

Search Result 494, Processing Time 0.033 seconds

The Role of NF-${\kappa}B$ in the TNF-$\alpha$-induced Apoptosis of Lung Cancer Cell Line (폐암세포주의 TNF-$\alpha$ 유발 apoptosis에서 NF-${\kappa}B$의 역할)

  • Kim, J.Y.;Lee, S.H.;HwangBo, B.;Lee, C.T.;Kim, O.H.;Han, S.K.;Shim, O.S.;Yoo, C.G.
    • Tuberculosis and Respiratory Diseases
    • /
    • v.48 no.2
    • /
    • pp.166-179
    • /
    • 2000
  • Background: The main reason for the failure of anti-cancer chemotherapy is the build up of resistance by cancer cells to apoptosis. The activation of NF-${\kappa}B$ in many cancer cell lines is reported to be underlying mechanism behind the build up of resistance of cancer cells to apoptosis. However, this relationship varied depending on the cells used in the experiments. In this study, the role of NF-${\kappa}B$ activation in the TNF-$\alpha$-induced apoptosis in lung cancer cell line was evaluated. Methods: NCI-H157 cells were used in all experiments. Cells were exposed to a high dose of TNF-$\alpha$(20 ng/ml) for 24 or 48 hours with or without blocking NF-${\kappa}B$ activation. TNF-$\alpha$-induced activation of NF-${\kappa}B$ was inhibited either by overexpression of $I{\kappa}B{\alpha}$-super repressor($I{\kappa}B{\alpha}$-SR) or by pre-treatment with proteasome inhibitor. Cell viability and apoptosis were evaluated with MTT assay and Western blot analysis for PARP fragment, respectively. Results: Cell viability of NCI-H157 cells was not affected by TNF-$\alpha$ treatment alone; however, combined treatment with TNF-$\alpha$ and cycloheximide reduced cell viability significantly, indicating that resistance to TNF-$\alpha$ is mediated by the new proteins synthesized after TNF-$\alpha$ stimulation. To evaluate the role of NF-${\kappa}B$ in the transcription of anti-apoptotic proteins. delete NF-${\kappa}B$ activation was inhibited before TNF-$\alpha$ stimulation. as described above. $AD5I{\kappa}B{\alpha}$-SR-transduction inhibited TNF-$\alpha$-induced nuclear translocation of p65. TNF-$\alpha$-induced cell death and apoptosis increased after inhibition of TNF-$\alpha$-induced activation of NF-${\kappa}$ by methods. Conclusion: These results suggest that TNF-$\alpha$-induced activation of NF-${\kappa}B$ may be closely related to the acquisition of the resistance to TNF-$\alpha$-induced apoptosis in lung cancer cells. Therefore. blocking of NF-${\kappa}B$ pathway can be a useful therapeutic modality in the treatment of lung cancer.

  • PDF

Design of Client-Server Model For Effective Processing and Utilization of Bigdata (빅데이터의 효과적인 처리 및 활용을 위한 클라이언트-서버 모델 설계)

  • Park, Dae Seo;Kim, Hwa Jong
    • Journal of Intelligence and Information Systems
    • /
    • v.22 no.4
    • /
    • pp.109-122
    • /
    • 2016
  • Recently, big data analysis has developed into a field of interest to individuals and non-experts as well as companies and professionals. Accordingly, it is utilized for marketing and social problem solving by analyzing the data currently opened or collected directly. In Korea, various companies and individuals are challenging big data analysis, but it is difficult from the initial stage of analysis due to limitation of big data disclosure and collection difficulties. Nowadays, the system improvement for big data activation and big data disclosure services are variously carried out in Korea and abroad, and services for opening public data such as domestic government 3.0 (data.go.kr) are mainly implemented. In addition to the efforts made by the government, services that share data held by corporations or individuals are running, but it is difficult to find useful data because of the lack of shared data. In addition, big data traffic problems can occur because it is necessary to download and examine the entire data in order to grasp the attributes and simple information about the shared data. Therefore, We need for a new system for big data processing and utilization. First, big data pre-analysis technology is needed as a way to solve big data sharing problem. Pre-analysis is a concept proposed in this paper in order to solve the problem of sharing big data, and it means to provide users with the results generated by pre-analyzing the data in advance. Through preliminary analysis, it is possible to improve the usability of big data by providing information that can grasp the properties and characteristics of big data when the data user searches for big data. In addition, by sharing the summary data or sample data generated through the pre-analysis, it is possible to solve the security problem that may occur when the original data is disclosed, thereby enabling the big data sharing between the data provider and the data user. Second, it is necessary to quickly generate appropriate preprocessing results according to the level of disclosure or network status of raw data and to provide the results to users through big data distribution processing using spark. Third, in order to solve the problem of big traffic, the system monitors the traffic of the network in real time. When preprocessing the data requested by the user, preprocessing to a size available in the current network and transmitting it to the user is required so that no big traffic occurs. In this paper, we present various data sizes according to the level of disclosure through pre - analysis. This method is expected to show a low traffic volume when compared with the conventional method of sharing only raw data in a large number of systems. In this paper, we describe how to solve problems that occur when big data is released and used, and to help facilitate sharing and analysis. The client-server model uses SPARK for fast analysis and processing of user requests. Server Agent and a Client Agent, each of which is deployed on the Server and Client side. The Server Agent is a necessary agent for the data provider and performs preliminary analysis of big data to generate Data Descriptor with information of Sample Data, Summary Data, and Raw Data. In addition, it performs fast and efficient big data preprocessing through big data distribution processing and continuously monitors network traffic. The Client Agent is an agent placed on the data user side. It can search the big data through the Data Descriptor which is the result of the pre-analysis and can quickly search the data. The desired data can be requested from the server to download the big data according to the level of disclosure. It separates the Server Agent and the client agent when the data provider publishes the data for data to be used by the user. In particular, we focus on the Big Data Sharing, Distributed Big Data Processing, Big Traffic problem, and construct the detailed module of the client - server model and present the design method of each module. The system designed on the basis of the proposed model, the user who acquires the data analyzes the data in the desired direction or preprocesses the new data. By analyzing the newly processed data through the server agent, the data user changes its role as the data provider. The data provider can also obtain useful statistical information from the Data Descriptor of the data it discloses and become a data user to perform new analysis using the sample data. In this way, raw data is processed and processed big data is utilized by the user, thereby forming a natural shared environment. The role of data provider and data user is not distinguished, and provides an ideal shared service that enables everyone to be a provider and a user. The client-server model solves the problem of sharing big data and provides a free sharing environment to securely big data disclosure and provides an ideal shared service to easily find big data.

Hematologic Changes and Factors Related to Postoperative Hemorrhage Following Cardiopulmonary Bypass (체외순환에 따른 혈액학적 변화와 술후 출혈에 관계하는 인자에 관한 연구)

  • 김하늘루;황윤호;최석철;최국렬;김승우;조광현
    • Journal of Chest Surgery
    • /
    • v.31 no.10
    • /
    • pp.952-963
    • /
    • 1998
  • Background: Cardiopulmonary bypass(CPB)-induced hemostatic defects may result increased possibility of excessive hemorrhage and additional multiple transfusion reactions or reoperation. Particularly, fibrinolytic activation and decreased platelet count and function by CPB were proposed as a predictor of hemorrhage during postoperative periods in several reports. Materials and methods: Present study, which was conducted in 20 adult patients undergoing CPB, was prospectively designed to examine the hematologic changes, including fibrinolytic activation during and after CPB and to clarify the relationships between these changes and the magnitude of the postoperative nonsurgical blood loss. The serial blood samples for measurment of hematologic parameters were taken during operation and postoperative periods. Blood loss was respectively counted via thoracic catheter drainage at postoperative 3, 6, 12, 24, 48 hours and total period. Results: The results were obtained as follows:Platelet count rapidly declined following CPB(p<0.01), which its decreasing rate was an inverse proportion to total bypass time(TBT, r=0.55, p=0.01), And platelet count in postoperative 7th day was barely near to its control value. Fibrinogen degradating product(FDP) and D-dimer level significantly increased during CPB(p<0.0001, p<0.0001, respectively), and both of fibrinogen and plasminogen concentration correlatively decreased during CPB(r=0.57, p<0.01), implying activation of fibrinolytic system. Postoperative bleeding time (BT), postoperative activated partial thromboplastin time(aPTT) and postoperative prothrombin time (PT) were significantly prolonged as compare with each control value (p=0.05, p<0.0001, p<0.0001, respectively). Total blood loss was positively correlated with patient's age, aortic clamping time (ACT) and TBT, while there was negative correlation between platelet count and blood loss at pre-CPB, CPB-off and the 1st postoperative day, and in some periods. Postoperative aPTT and postoperative PTwere positively related to postoperative 6 hr and 48 hr blood loss(r=0.53, p=0.02; r=0.43, p=0.05) but not to total blood loss, whereas there was no relationship between postoperative BT and blood loss at any period. Conclusions: These observations suggest that CPB results various hematologic changes, including fibrinolytic activation and severe reduction in platelet count. Diverse factors such as age, platelet count, ACT, TBT and postoperative aPTT and PT may magnify the postoperative bleeding. This study will be a basic reference in understanding CPB-induced hemostatic injuries and in decreasing the postoperative hemorrhage

  • PDF

Effects of TRPV1 in formalin-induced nociceptive behavior in the orofacial area of rats (흰쥐의 구강악안면 영역에서 포르말린 통증행위반응에 TRPV1 채널의 영향)

  • Park, Min-Kyoung;Seong, Mi-Gyung;Lee, Min-Kyung
    • Journal of the Korea Academia-Industrial cooperation Society
    • /
    • v.15 no.1
    • /
    • pp.316-322
    • /
    • 2014
  • The present study investigated the inflammatory hypersensitivity following activation of the transient receptor potential vanilloid receptor-1(TRPV1) in rats. Experiments were carried out on male Sprague-Dawley rats weighing 220-260g. Following an subcutaneous injection of 5% formalin in the orofacial area, nociceptive scratching behavior was recorded for 9 successive 5-min intervals in rats. The subcutaneous injection of $25{\mu}L$ of 5% formalin produced noxious scratching behavior. Injection of capsaicin, TRPV1 agonist, alone into the vibrissa pad did not produced nociceptive behavior. After subcutaneous injection of capsaicin(0$0.1{\mu}g$, $1{\mu}g/10{\mu}L$) in the formalin-treated rats, nociceptive scratching behavior was recorded for 9 successive 5-min internals. Injection of capsaicin into the vibrissa pad significantly increased the number of scratches at 1 hours after injection. Noxious behavioral responses induced by subcutaneous capsaicin injection were significantly potentiated in formalin-treated rats. Pre or post-treatment with iodo-resinaferatoxin(IRTX), TRPV1 antagonist, significantly attenuated increased nociceptive behavior. These findings suggest that activation of the TRPV1 enhanced formalin-induced inflammatory pain in the orofacial area of rats.

Protective Effects of Chijabaegpi-tang on Atopic Dermatitis in TNF-α/IFNγ-induced HaCaT Cells (피부각질세포에서 치자백피탕(梔子柏皮湯)의 아토피 피부염 개선효과)

  • Eun, So Young;Yoon, Jung Joo;Kim, Hye Yoom;Ahn, You Mee;Han, Byung Hyuk;Hong, Mi Hyeon;Son, Chan Ok;Na, Se Won;Lee, Yun Jung;Kang, Dae Gill;Lee, Ho Sub
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.32 no.4
    • /
    • pp.226-231
    • /
    • 2018
  • Chijabaegpi-tang (CHG) is an oriental herbal medicine that has been used for its various pharmacological effects, which include anti-inflammatory, anti-oxidant and immunoregulation activities. In the present study, we investigated which skin inflammations are involved in the $TNF-{\alpha}/IFN{\gamma}$-induced HaCaT cells. We investigated the suppressive effect of CHG on $TNF-{\alpha}/IFN{\gamma}$-induced HaCaT cell production of the following chemokines: macrophage-derived chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTES)/CCL5; and interleukin-8 (IL-8); thymus and activation-regulated chemokine (TARC)/CCL17. The pre-treatment of HaCaT cells with CHG suppressed $TNF-{\alpha}/IFN{\gamma}$-induced nuclear transcription factor kappa-B ($NF-{\kappa}B$). In addition, CHG inhibited $TNF-{\alpha}/IFN{\gamma}$-induced phosphorylation of ERK and p38. $TNF-{\alpha}/IFN{\gamma}$ suppressed the expression of skin barrier proteins, including filaggrin (FLG), Involucrin (IVL) and loricrin (LOR). By contrast, CHG restored the expression of FLG, IVL and LOR. Taken together, our findings suggest that CHG could be a therapeutic agent for prevention of skin disease, including atopic dermatitis.

Synthesis of Low-Priced Catalyst from Coal Fly Ash for Pyrolysis of Waste Low Density Polyethylene (석탄비산재(石炭飛散災)로부터 저밀도(低密度) 폴리에틸렌 폐기물(廢棄物) 열분해용(熱分解用) 저가(低價) 촉매(觸媒) 합성(合成))

  • Jeong, Byung-Hwan;Na, Jeong-Geol;Kim, Sang-Guk;Mo, Se-Young;Chung, Soo-Hyun
    • Resources Recycling
    • /
    • v.16 no.2 s.76
    • /
    • pp.48-55
    • /
    • 2007
  • A low-priced catalyst for pyrolysis of LDPE has been synthesized. Fly ash, which is waste material generated from coal-fired power plants was used as silica and alumna sources for solid acid catalyst. Amorphous silica-alumina catalysts (FSAs) were pre-pared by dissolution of silica and alumina from fly ash, followed by co-precipitation of the dissoluted ions. A series of LDPE pyrolysis were carried out in a thermogravimetric analyzer to investigate the effects of synthesis conditions such as NaOH/fly ash weight ratio and activation time one catalytic performance of FSAs. The physical properties of FSAs were examined and related to their catalytic performances. FSA(1.2-8) synthesized with NaOH/fly ash weight ratio of 1.2 and the activation time of 8 hours showed the best catalytic performance. The catalytic performance of FSA(1.2-8) was comparable with that of commercial catalysts and it was concluded that the FSA could be a good candidate for catalytic use in the recycling of waste polyolefins.

Structural Origin for the Transcriptional Activity of Human p53

  • Lee, Si-Hyung;Park, Kyu-Hwan;Kim, Do-Hyung;Choung, Dong-Ho;Suk, Jae-Eun;Kim, Do-Hyung;Chang, Jun;Sung, Young-Chul;Choi, Kwan-Yong;Han, Kyou-Hoon
    • BMB Reports
    • /
    • v.34 no.1
    • /
    • pp.73-79
    • /
    • 2001
  • Transcriptional activation domains are known to be inherently "unstructured" with no tertiary structure. A recent NMR study, however, has shown that the transactivation domain in human p53 is populated with an amphipathic helix and two nascent turns. This suggests that the presence of such local secondary structures within the overall "unstructured" structural framework is a general feature of acidic transactivation domains. These pre-existing local structures in p53, formed selectively by positional conserved hydrophobic residues that are known to be critical for transcriptional activity, thus appear to constitute the specific structural motifs that regulate recognition of the p53 transactivation domain by target proteins. Here, we report the results of a NMR structural comparison between the native human p53 transactivation domain and an inactive mutant (22L,23W$\rightarrow$22R,23S). Results show that the mutant has an identical overall structural topology as the native protein, to the extent that the amphipathic helix formed by the residues 18T 26L within the native p53 transactivating domain is preserved in the double mutant. Therefore, the lack of transcriptional activity in the double mutant should be ascribed to the disruption of the essential hydrophobic contacts between the p53 transactivation domain and target proteins due to the (22L,23W$\rightarrow$22R,23S) mutation.

  • PDF

Anti-inflammatory effects of Sparassis crispa extracts (꽃송이버섯 추출물의 항염활성 효과)

  • Choi, Woo-Suk;Shin, Pyung-Gyun;Bok, Yoo Young;Jun, Noh Hyung;Kim, Gun-Do
    • Journal of Mushroom
    • /
    • v.11 no.1
    • /
    • pp.46-51
    • /
    • 2013
  • Sparassis crispa is a medicinal mushroom, which has been reported to have anti-cancer effect. In this study, we designed to investigate the effects of Sparassis crispa extracts on the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells. The pre-treatment of the extracts prior to add LPS in RAW264.7 cells suppressed NO production and iNOS expression at protein and mRNA levels. The phosphorylation of $I{\kappa}B{\alpha}$ was inhibited by the extracts, which was induced through suppressing the activation of $NF-{\kappa}B$. Sparassis crispa extracts showed the effect on the down-regulation of STAT-1 activation in a dose-dependent manner. In LPS-stimulated RAW264.7 cells, $NF-{\kappa}B$ was translocated into the nucleus, while the treatment of Sparassis crispa extracts induced to sequestered $NF-{\kappa}B$ in the cytosol. These experimental results determined that Sparassis crispa extracts play a inhibitory role in inflammatory reactions via regulating NO production, which suggests potential as a component of inflammatory drugs.

The Stimulatory Effect of Essential Fatty Acids on Glucose Uptake Involves Both Akt and AMPK Activation in C2C12 Skeletal Muscle Cells

  • Park, So Yeon;Kim, Min Hye;Ahn, Joung Hoon;Lee, Su Jin;Lee, Jong Ho;Eum, Won Sik;Choi, Soo Young;Kwon, Hyeok Yil
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.18 no.3
    • /
    • pp.255-261
    • /
    • 2014
  • Essential fatty acid (EFA) is known to be required for the body to function normally and healthily. However, the effect of EFA on glucose uptake in skeletal muscle has not yet been fully investigated. In this study, we examined the effect of two EFAs, linoleic acid (LA) and ${\alpha}$-linolenic acid (ALA), on glucose uptake of C2C12 skeletal muscle cells and investigated the mechanism underlying the stimulatory effect of polyunsaturated EFAs in comparison with monounsaturated oleic acid (OA). In palmitic acid (PA)-induced insulin resistant cells, the co-treatment of EFAs and OA with PA almost restored the PA-induced decrease in the basal and insulin-stimulated 2-NBDG (fluorescent D-glucose analogue) uptake, respectively. Two EFAs and OA significantly protected PA-induced suppression of insulin signaling, respectively, which was confirmed by the increased levels of Akt phosphorylation and serine/threonine kinases ($PKC{\theta}$ and JNK) dephosphorylation in the western blot analysis. In PA-untreated, control cells, the treatment of $500{\mu}M$ EFA significantly stimulated 2-NBDG uptake, whereas OA did not. Phosphorylation of AMP-activated protein kinase (AMPK) and one of its downstream molecules, acetyl-CoA carboxylase (ACC) was markedly induced by EFA, but not OA. In addition, EFA-stimulated 2-NBDG uptake was significantly inhibited by the pre-treatment of a specific AMPK inhibitor, adenine 9-${\beta}$-D-arabinofuranoside (araA). These data suggest that the restoration of suppressed insulin signaling at PA-induced insulin resistant condition and AMPK activation are involved at least in the stimulatory effect of EFA on glucose uptake in C2C12 skeletal muscle cells.

Vasorelaxing Activity of Ulmus davidiana Ethanol Extracts in Rats: Activation of Endothelial Nitric Oxide Synthase

  • Cho, Eun-Jung;Park, Myoung-Soo;Kim, Sahng-Seop;Kang, Gun;Choi, Sung-A;Lee, Yoo-Rhan;Chang, Seok-Jong;Lee, Kwon-Ho;Lee, Sang-Do;Park, Jin-Bong;Jeon, Byeong-Hwa
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.15 no.6
    • /
    • pp.339-344
    • /
    • 2011
  • Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD ($10{\sim}100{\mu}g/ml)$ did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of $0.1{\sim}10{\mu}g/ml$ with an $ED_{50}$ value of $2{\mu}g/ml$. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high $K^+$ and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium.