• 제목/요약/키워드: TLR4

검색결과 317건 처리시간 0.025초

생물전환을 통한 음나무발효물의 LPS에 대한 경쟁적 억제제 효과 및 내독소혈증 억제 효과 (The Inhibitory Effect of Fermented Kalopanax pictus by Bioconversion on Endotoxemia and the Competitive Inhibitor Activity on LPS)

  • 김성필;이화영;인수아;성은영;김진만;남석현
    • 한국식품영양학회지
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    • 제32권2호
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    • pp.106-113
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    • 2019
  • The objective of this study was to evaluate the effect of fermented Kalopanax pictus (KP-F) on macrophage activation and its effect as a competitive inhibitor of LPS and inhibitory effect on endotoxemia. The results showed that KP-F could activate macrophage in a dose-dependent manner, and KP-F was confirmed to act as a ligand for TLR4. Also, it was found that KP-F did not exhibit the same biotoxicity as LPS in intraperitoneal injection, and that it could suppress the neutrophil migration induced by LPS administration. In normal mice, the body weight, tissue weight, and amount of nitrite and pro-inflammatory cytokines in serum showed no significant changes with KP-F diet for 2 weeks, confirming that administration of KP-F in normal mice did not lead to over activation of immune response and biotoxicity. In the mouse model of endotoxemia induced by LPS and D-galactosamine(D-GalN) in sub-lethal dose, the diet of KP-F effectively inhibited the amount of nitrite and cytokines in the blood, and thus was found to be able to relieve the hepatic and kidney injury. In addition, in the endotoxemia mouse model induced by LPS and D-GalN of lethal dose, the survival rate was increased by KP-F diet in a dose-dependent manner.

Tumor necrosis factor α - induced protein3의 발현과 NF-κB 활성 억제를 통한 동과자의 염증반응 억제 효과 (Donggwaja Suppresses Inflammatory Reaction Via Tumor Necrosis Factor α-induced Protein3 and NF-κB)

  • 김균하;최준용;주명수
    • 동의생리병리학회지
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    • 제35권1호
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    • pp.15-21
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    • 2021
  • Donggwaja (Benincasae Semen), the seed of Benincasa hispida (Thunb.) Cogn., has been used in Korean traditional medicine to control the body heat and water retention caused by various diseases. Both the symptoms targeted by the herbal medicine in clinic and studies with disease mouse models support the potential anti-inflammatory effect of Donggwaja. However, it is less understood how Donggwaja exerts its possible anti-inflammatory effect. Here, we present evidence that Donggwaja suppresses macrophage inflammatory reactions via expressing tumor necrosis factor a-induced protein 3 (TNFAIP3 or A20) and suppressing NF-kB activity. The ethanol extract of Donggwaja (EED) showed no toxicity when added to RAW 264.7 cells less than 100mg/ml. When treating the cells for 16 h, EED significantly suppressed the nuclear localization of NF-kB, suggesting that EED suppresses NF-kB activity. Concordantly, a semi-quantitative RT-PCR analysis showed that EED decreased the expression of prototypic pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-a, IL(interleukin)-6, and IL-1b. EED induced in RAW 264.7 cells the expression of A20, a ubiquitin modulator that suppresses inflammatory signaling cascades initiated from TLR4 and TNF and IL-1 receptors, while not affecting the induction of Nrf2, an anti-inflammatory factor that could suppress the effect of NF-kB. These results suggest that EED exerts its suppressive effect on inflammation, at least in part, by expressing anti-inflammatory factor A20 and suppressing pro-inflammatory factor NF-kB activity.

Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

  • Buddham, Richa;Chauhan, Sweety;Narad, Priyanka;Mathur, Puniti
    • Journal of Microbiology and Biotechnology
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    • 제32권3호
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    • pp.365-377
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    • 2022
  • Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

독성을 제거한 재조합 리신 백신 개발 및 효능평가 (Development of Non-toxic Recombinant Ricin Vaccine and Evaluation of Vaccine Efficacy)

  • 윤형석;조혜은;송동현;유치호;송영조;허경행
    • 한국군사과학기술학회지
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    • 제27권2호
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    • pp.304-310
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    • 2024
  • Ricin is a highly toxic protein which is produced in the seeds of the castor oil plant. Ricin toxin A chain has ribosomal RNA N-glycosylase activity that irreversibly hydrolyses the N-glycosidic bond of the adenine residue at position 4324 within the 28S rRNA. In this study, we developed non-toxic recombinant ricin vaccine(R51) in E. coli expression system, and evaluated efficacy of the R51 according to adjuvants. When the R51 was administered using aluminum hydroxide as an adjuvant, the vaccine efficacy was higher than that of TLR agonists or aluminum phosphate. Because it is time-consuming to administer the vaccine three times at three-week intervals, we investigated the survival rate and antibody titer of mice according to the change of time interval of vaccination. Interestingly, there was no difference in survival rate and antibody titer when R51 was administered at 0, 1, and 3 weeks or 0, 2, and 4 weeks compared to when administered at 0, 3, and 6 weeks. Therefore, the developed R51 vaccine is promising to protect soldiers from Ricin attack.

LPS로 염증 유도된 RAW 264.7세포에 대한 참콩풍뎅이(Popillia flavosellata) 에탄올 추출물의 항염증 효과 (Inhibition of Inflammation by Popillia flavosellata Ethanol Extract in LPSinduced RAW264.7 Macrophages)

  • 윤영일;황재삼;김미애;안미영;이영보;한명세;구태원;윤은영
    • 생명과학회지
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    • 제25권9호
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    • pp.993-999
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    • 2015
  • 본 연구에서는 참콩풍뎅이(Popillia flavosellata) 에탄올 추출물(PFE)의 항염증 효능을 분석하기 위해 PFE를 농도별(500, 1,000, 2,000 μg/ml)로 대식세포인 RAW 264.7에 처리 시 최고 처리농도인 2,000 μg/ml까지 통계적인 유의성 있는 독성이 없음을 확인하였다. LPS (100 ng/ml)로 염증 유도된 RAW 264.7 세포에 PFE를 농도별(500, 1,000, 2,000 μg/ml)로 동시 처리 시 농도 의존적으로 염증성사이토카인인 TNF-α와 IL-6의 단백질 생성을 통계적인 유의성(p<0.001)있게 억제함을 확인하였다. 또한 염증 유도된 RAW 264.7 세포에 PFE 동시 처리 시 NF-κB p65의 핵으로 이동이 차단됨과 iNOS와 COX-2의 단백질 발현을 감소시키는 것을 확인하였다. 이상의 연구결과를 통해 참콩 풍뎅이는 염증에 의해 활성화된 TLR-4 신호전달과정을 조절하는 NF-κB p65의 활성과 염증성사이토카인 TNF-α와 IL-6의 생성 및 염증성효소 iNOS와 COX-2의 생성을 억제하는 항염증 효능이 있음을 확인하였다.

스텐트 재협착 병변에서 약물코팅 풍선카테터과 약물용출 스텐트의 예후 분석 (Prognostic Analysis of Drug-Eluting Balloon Catheter and Drug-Eluting Stent for In-Stent Restenosis of Drug-Eluting Stent)

  • 이두환;송종남;박신의;최남길;한재복;김인수
    • 한국방사선학회논문지
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    • 제13권3호
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    • pp.381-389
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    • 2019
  • 약물용출 스텐트(drug-eluting stents, DES)는 일반 금속 스텐트에 비하여 재협착을 현저하게 줄였지만, 여전히 관상동맥 스텐트 재협착은 비율이 높다. 2012년 11월부터 2016년 12월까지의 일 대학교병원 심혈관센터에서 경피적 관상동맥 스텐트 삽입술 후 관상동맥 조영술에서 스텐트 재협착 환자 187명 그룹 I (약물코팅 풍선카테터 사용, n=127명), 그룹 II (약물용출 스텐트 사용, n=60명)로 분류하여 치료효과, 주요심장사건, 사망 발생률, 심근경색, 표적병변 재개통술 그리고 스텐트 혈전 등을 2년 동안 추적 분석하였다. 임상적 특성은 두 그룹간 차이는 없었고($21.1{\pm}5.3$ vs. $25.3{\pm}9.6 mm$, p<0.002), 혈관조영검사에서 약물코팅 풍선카테터 사용 그룹에서 스텐트 재협착 길이가 짧았다. 주요심장사건은 8.7%vs.10.0%, p=0.789, 사망발생률 0%vs. 0%,p=1.000, 심근경색 1.6%vs.6.7%, p=0.085, 표적병변 재개통술 8.7% vs. 10.0%, p=0.789 그리고 스텐트 혈전증 0% vs. 0%, p=1000에서 양군 간에 차이를 보이지 않았다. 약물코팅 풍선카테터가 약물방출 스텐트와 비교하여 2년 추적 검사 결과 주요심장사건에서 차이가 없었고, 약물코팅 풍선카테터는 스텐트 재협착 병변에서 약물방출 스텐트와 함께 선택할 수 있는 좋은 치료방법이라고 사료된다.

녹차, 우롱차 및 홍차의 용매별 추출물의 카테킨류 함량 및 항산화효과에 관한 연구 (A Study on the Catechins Contents and Antioxidative Effect of Various Solvent Extracts of Green, Oolong and Black Tea)

  • 이영자;안명수;오원택
    • 한국식품위생안전성학회지
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    • 제13권4호
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    • pp.370-376
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    • 1998
  • 대표적인 기호성 음료인 차의 발효정도에 따른 분류인 무발효차, 반발효차 및 발효차중 녹차, 우롱차 및 홍차, 그리고 녹차의 채엽 시기별에 따른 분류인 녹차 1번차, 녹차 2번차 및 녹차 3번차 등을 에탄올, 메탄올, 에틸아세테이트를 추출용매로 사용하여 얻은 각 추출물의 용매별 추출수율과 카테킨류 함량 분석 및 용매별 추출물의 항산화 효과를 측정하였다. 용매별 추출수율은 MeOH이 EtOH 및 EtAc 에 비하여 녹차류는 3~5배, 우롱차는 4~5배, 홍차는 5~7배 씩 각각 놓았다. 추출용매의 종류에 따른 총카테킨류 % 함량은 조카테킨이 EtOH 및 MeOH 추출물에 비해 홍차는 3배 , 녹차 및 우롱차는 2배정도 높은 것으로 EtOH이나 MeOH로 추출하는 것보다는 물추출물을 다시 에틸아세테이트로 추출·분리정제하여 얻은 조카테킨의 경우가 순도가 매우 높은 EC, EGC, ECG 및 EGCG를 얻을수 있었다. 용매별추출물을 200, 500, 1000ppm씩 기질대두유에첨가하여 항산화효과를 측정시 EtOH 추출물, MeOH 추출물, EtAc 추출물 모두가 기존의 항산화제인 BHT, dl-α-tocopherol보다 좋은 항산화효과를 보였으며, 첨가량이 많을 수혹 항산화효과가 증가하였다. 또한 EtOH 추출물을 200 및 5000ppm, MeOH 추출물을 200 및 500ppm , EtAc ncnfanf을 200ppmTlr 각각 첨가시의 항산화효과는 녹차I >녹차II>녹차 III> 우롱차>홍차의 순이었으며, 이때 항산화효과는 네가지 카테킨류 성분인 EGC 함량이 많을수록 비례하여 컸다. 그러나 , MeOH 추출물을 1000ppm, EtAc 추출물을 500 및 1,000 ppm씩 각각 첨가시의 항산화 효과는 카테킨류 성분인 EGC 및 EGCG 함량의 영향을 받지 않았다.

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RAW 264.7 대식세포에서 쑥부쟁이 추출물의 항산화 및 항염증 효능에 관한 연구 (Antioxidant and Anti-inflammatory Effects of Ethanol Extract of Aster yomena in RAW 264.7 Macrophages)

  • 김성옥;정지숙;최영현
    • 생명과학회지
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    • 제29권9호
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    • pp.977-985
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    • 2019
  • 쑥부쟁이는 국화과에 속하는 다년생 식물로서 다양한 질병의 예방 및 치료에 오랫동안 사용되어 왔다. 최근 연구에서 쑥부쟁이 잎 추출물이 항산화 및 항염증 효과가 있는 것으로 알려져 있지만, 정확한 효능 평가에 관한 연구는 여전히 미비한 실정이다. 본 연구에서는 RAW 264.7 대식세포에서 쑥부쟁이 잎 에탄올 추출물(EEAY)의 항산화 효능이 항염증 효능과 연관이 있는지의 여부를 조사하였다. 본 연구의 결과에 의하면, EEAY는 $H_2O_2$ 처리에 의한 RAW 264.7 세포의 세포 독성을 유의적으로 억제시켰으며, 이는 Nrf2 및 HO-1의 발현 증가와 관련이 있음을 보여 주었다. 또한 EEAY는 $H_2O_2$에 의한 apoptosis를 유의적으로 억제하였으며, 이는 caspase-3의 활성 억제에 따른 PARP의 분해 차단과 연관성이 있었다. 그리고 EEAY는 대표적인 항 염증성 사이토카인인 IL-10의 발현 및 생산을 증가시켰으며, 이는 전사 및 번역 수준에서의 TLR-4 및 Myd88 발현 증가와 관련이 있었다. 아울러 EEAY는 LPS에 의한 염증성 매개인자인 NO의 생성 증가를 현저히 억제하였으며, EEAY에 의한 NO 생성의 억제 효과는 HO-1 유도제인 hemin에 의해 더욱 증가되었다. 따라서 본 연구의 결과는 EEAY에 의한 산화적 및 염증성 스트레스에 대한 RAW 264.7 대식세포의 보호 효과에 최소한 Nrf2/HO-1 신호 경로의 활성화가 관여할 가능성을 보여주었다.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials

  • Hyeonjin Kim;Soohyun Jeong;Sung Wook Kim;Hyung-Jin Kim;Dae Yong Kim;Tae Han Yook;Gabsik Yang
    • 대한약침학회지
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    • 제27권2호
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    • pp.59-69
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    • 2024
  • This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

Effects of Vitamin C or E on the Pro-inflammatory Cytokines, Heat Shock Protein 70 and Antioxidant Status in Broiler Chicks under Summer Conditions

  • Jang, In-Surk;Ko, Young-Hyun;Moon, Yang-Soo;Sohn, Sea-Hwan
    • Asian-Australasian Journal of Animal Sciences
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    • 제27권5호
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    • pp.749-756
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    • 2014
  • The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between $32^{\circ}C$ to $34^{\circ}C$ at day to $27^{\circ}C$ to $29^{\circ}C$ at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-$1{\beta}$, IL-6, interferon (IFN)-${\gamma}$, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.