• 제목/요약/키워드: Stat4

검색결과 253건 처리시간 0.024초

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

  • Chanthra, Nawin;Payungporn, Sunchai;Chuaypen, Natthaya;Pinjaroen, Nutcha;Poovorawan, Yong;Tangkijvanich, Pisit
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권12호
    • /
    • pp.5069-5073
    • /
    • 2015
  • The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.

TNF-α/IL-17A 유도된 HaCaT 세포주에서 Quercetin의 IκBα/STAT3 인산화 조절에 의한 CCL20 발현 억제 (Quercetin suppress CCL20 by reducing IκBα/STAT3 phosphorylation in TNF-α/IL-17A induced HaCaT cells)

  • 김미란;김민영;황형서
    • Journal of Applied Biological Chemistry
    • /
    • 제63권3호
    • /
    • pp.211-219
    • /
    • 2020
  • Quercetin은 항산화 및 항염증 활성이 잘 알려져 있으나, 건선 피부염 조절에 대한 효능 연구는 거의 보고된 것이 없어, in vitro 건선 피부염 시험 모델인 TNF-α/IL-17A 유도 HaCaT 세포주를 이용해 quercetin에 의한 건선 피부염 개선 효과를 규명하였다. 먼저, TNF-α에 의해 활성화된 HaCaT 세포주에 quercetin을 처리한 결과, IL-1α, IL-1β, IL-6 등 염증성 사이토카인 발현이 TNF-α 처리군 대비 각각 49.1±7.14, 42.8±8.16, 34.5±2.52% 억제되었다. Th17세포 및 수지상세포 등 면역세포를 염증 반응 부위로 유인하는 케모카인 IL-8 및 CCL20의 mRNA 발현량 또한 TNF-α 처리군 대비 38.4±5.83, 52.9±4.59% 감소하였다. TNF-α 자극에 의해 건선피부에서 비특이적으로 증가되는 케라틴 단백질 KRT6A 및 KRT16 발현뿐만 아니라, IκBα 및 STAT3 단백질의 인산화 또한 quercetin에 의해 유의적으로 억제되었다. 또 다른 건선 유발 사이토카인으로 알려진 IL-17A로 HaCaT 세포주를 자극한 후 quercetin에 의한 영향을 관찰한 결과, IκBα mRNA 발현은 55.8±5.28% 감소하였고, STAT3 인산화는 36.3±6.81% 하향 조절되었다. 마지막으로 TNF-α/IL-17A를 동시 자극한 HaCaT 세포주에 quercetin을 처리한 결과, IL-1α, IL-1β, IL-6, TNF-α, CCL20 유전자 발현이 모두 억제되는 것을 확인하였다. 이를 통해 quercetin은 기존 항산화, 항염증 활성뿐만 아니라 건선 피부염 개선에 활성을 갖는 소재임을 확인할 수 있었다.

Pseudomonas oleovorans의 유가식 배양에 의한 medium chain length Polyhydroxyalkanoates (MCL-PHA) 생산

  • 김범수;임희연
    • 한국생물공학회:학술대회논문집
    • /
    • 한국생물공학회 2000년도 춘계학술발표대회
    • /
    • pp.207-210
    • /
    • 2000
  • P. oleovorans의 유가식 배양에서 탄소원으로 octanoic acid, 질소원으로 $NH_4NO_3$를 이용한 혼합기질을 배양액의 pH 변화에 따라 공급하는 pH-stat 기질공급전략을 개발하였다. 공급기질의 탄소원/질소원 비 (C/N 비)를 변화시킴으로써 최종 균체농도, PHA 농도, PHA 함량 등을 변화시킬 수 있었으며, 최대 균체농도는 C/N 비가 10 (g octanoic acid/g $NH_4NO_3$)일 때 65 g/L, 최대 PHA 농도는 C/N 비가 20일 때 41 g/L, 최대 PHA 함량은 C/N 비가 20일 때 75%였으며 최대 PHA 생산성은 C/N 비가 10일 때 1.03 g/L/h였다.

  • PDF

On Asymptotic Property of Matheron′s Spatial Variogram Estimators

  • Lee, Yoon-Dong;Lee, Eun-Kyung
    • Journal of the Korean Statistical Society
    • /
    • 제30권4호
    • /
    • pp.573-583
    • /
    • 2001
  • A condition in which the covariances of Matheron's variogram estimators are expressed in a simple form is reviewed. An asymptotic property of the covariances of the variogram estimators is examined, and a sufficient condition that guaranties the finiteness of the asymptotic variance of the normalized variogram estimators is provided.

  • PDF

결핵환자에서 IFN-${\gamma}$ 수용체의 기능적 및 유전적 이상에 관한 연구 (The Functional and Genetic Defects of IFN-${\gamma}$ Receptor in the Patients with Tuberculosis)

  • 박계영;황유진;임영희;안창혁;박정웅;정성환
    • Tuberculosis and Respiratory Diseases
    • /
    • 제52권5호
    • /
    • pp.497-505
    • /
    • 2002
  • 연구배경 : 결핵의 방어면역에서 IFN-${\gamma}$는 매우 중요한 역할을 한다. IFN-${\gamma}$ 수용체의 완전결손이 있는 환자는 Mycobacterium 감염에 감수성이 높아서 매우 치명 적이다. 매우 드문 일부 Mycobacterium 감염에서 IFN-${\gamma}$ 수용체의 완전결손 외에 여러 종류의 부분결손들과 STAT1의 돌연변이들이 알려져 있다. 특히, IFN-${\gamma}$ 수용체의 부분결손이 있는 환자들의 경우 병리학적 소견파 임상적 경과가 일반적 결핵과 유사한 소견을 보이는 것으로 알려져 있다. 방 법 : 임상적 결핵환자에서 IFN-${\gamma}$ 수용체의 기능을 평가하여 대조군과 비교하였다. IFN-${\gamma}$ 수용체의 이상이 있을 가능성이 가장 높은 파종성 결핵환자의 DNA에서 앞서 발표된 증례들에서 확인된 IFN-${\gamma}$ 수용제와 STAT1의 유전적 이상을 확인하였다. 결 과 : 말초혈액 단핵구를 recombinant IFN-${\gamma}$ (100, 1000IU/ml)로 자극하였을 때 대조군과 환자군에 모두 HLA-DR과 CD64의 발현이 증가하였으나, 두 군간의 차이는 없었다. 대조군과 환자군에서 모두 LPS자극하였을 때 TNF-${\alpha}$의 생산이 증가하였으며 IFN-${\gamma}$로 전처치 후에 다시 LPS로 자극하였을 때 TNF-${\alpha}$의 생산은 더욱 더 증가하였다. 그러나, 두 군간의 통계적으로 유의한 차이는 없었다. 파종성 결핵 환자에서 기존에 알려진 IFNgR1과 STAT1의 돌연 변이를 확인하였을 때 특이한 이상소견을 발견할 수 없었다. 결 론 : 임상적 결핵에서 IFN-${\gamma}$ 수용체의 기능적 및 유전적 이상을 확인할 수 없었다. 기존의 연구에서 BCG와 NTM 감염과 관련 있는 것으로 알려진 IFN-${\gamma}$수용체의 이상 만으로는 임상적 결핵의 개체감수성을 설명할 수 없었다.

4-(Tert-butyl)-2,6-bis(1-phenylethyl)phenol induces pro-apoptotic activity

  • Kim, Jun Ho;Lee, Yunmi;Kim, Mi-Yeon;Cho, Jae Youl
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제20권3호
    • /
    • pp.253-259
    • /
    • 2016
  • Previously, we found that KTH-13 isolated from the butanol fraction of Cordyceps bassiana (Cb-BF) displayed anti-cancer activity. To improve its antiproliferative activity and production yield, we employed a total synthetic approach and derivatized KTH-13 to obtain chemical analogs. In this study, one KTH-13 derivative, 4-(tert-butyl)-2,6-bis(1-phenylethyl)phenol (KTH-13-t-Bu), was selected to test its anti-cancer activity. KTH-13-t-Bu diminished the proliferation of C6 glioma, MDA-MB-231, LoVo, and HCT-15 cells. KTH-13-t-Bu induced morphological changes in C6 glioma cells in a dose-dependent manner. KTH-13-t-Bu also increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, KTH-13-t-Bu increased the levels of cleaved caspase-3 and -9. In contrast, KTH-13-t-Bu upregulated the levels of pro- and cleaved forms of caspase-3, -8, and -9 and Bcl- 2. Phospho-STAT3, phospho-Src, and phospho-AKT levels were also diminished by KTH13-t-Bu treatment. Therefore, these results strongly suggest that KTH-13-t-Bu can be considered a novel anti-cancer drug displaying pro-apoptotic activity.

Effect of Environmental pH on End Products, Fermentation Balances and Bioenergetic As-pects of Lactobacillus bulg-aricus in a Glucose-limited “pH Stat” Continuous Culture.

  • Rhee, Sang-Ki;Pack, Moo-Young
    • 한국미생물생명공학회:학술대회논문집
    • /
    • 한국미생물생명공학회 1979년도 추계학술대회 심포지움
    • /
    • pp.246.1-246
    • /
    • 1979
  • A glucose-limited “pH-stat” continuous culture study of Lactobacillus bulgaricus NLS-4 in an anaerobic condition showed the marked effects of environmental pH on end products, fermentation blances and bioenergetic aspects of the organism. Lactic acid was the major end product of fermentation with minor products, such as acetic acid, formic acid and ethanol throughout the pH range tested. In acidic conditions below pH 6.5, a typi-cal pattern of homofermentation was revealed whereas in alkaline conditions, the metabolic pattern was changed from homofermentation to heterofermentation and led to acquire much energy. This metabolic change was likely due to the pH-dependent lactate dehydrogenase activity. Molar growth yields (Yglc=35.5-44.4) and YATP, $18.5\pm2.5$ in average which was 80% higher than the value ever postulated seemed to be accounted for less requirement of maintenance energy of the organism in the culture conditions.

  • PDF

디엠프리(녹차추출물)에 의한 나균 감염 중간엽줄기세포의 IL-6 생산 억제 (DMfree®(Green Tea Extract) Inhibits IL-6 of Mycobacterium leprae Infected Mesenchymal Stem Cells)

  • 박란숙
    • 한국식품영양학회지
    • /
    • 제28권4호
    • /
    • pp.695-701
    • /
    • 2015
  • Previous reports revealed that DMfree (green tea extract) inhibited expression of the IL-6 gene in Mycobacterium lepraeinfected MSCs (mesenchymal stem cells). This study aimed to measure IL-6, $IL-1{\beta}$, $TNF-{\alpha}$ and PGE2 production in M. leprae-infected MSCs using ELISA. To confirm the effect of DMfree on IL-6 and signal transduction, a western blotting test was performed. DMfree inhibited the expression of IL-6 in the MSCs and the heterodimer of STAT3, which also affects the expression of multiple genes. Though DMfree pre-treatment of control MSCs produced a baseline level of IL-6, it significantly inhibited the production of IL-6 in M. leprae-infected MSCs. There was no significant difference in IL-6 production between 1 and 7 day treatment groups. M. leprae-infected MSCs produced more $IL-1{\beta}$, $TNF-{\alpha}$ and PGE2, but DMfree could not inhibit their production at a physiological concentration. This is different from other reports that used higher concentration of EGCG treatment, resulting in significant inhibition of the cytokines. The inhibition appears to be related to the concentration of EGCG. These results indicate that DMfree can alleviate inflammation involving IL-6.

Development and Characterization of a Novel Anti-idiotypic Monoclonal Antibody to Growth Hormone, Which Can Mimic Physiological Functions of Growth Hormone in Primary Porcine Hepatocytes

  • Lan, Hai-Nan;Jiang, Hai-Long;Li, Wei;Wu, Tian-Cheng;Hong, Pan;Li, Yu Meng;Zhang, Hui;Cui, Huan-Zhong;Zheng, Xin
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제28권4호
    • /
    • pp.573-583
    • /
    • 2015
  • B-32 is one of a panel of monoclonal anti-idiotypic antibodies to growth hormone (GH) that we developed. To characterize and identify its potential role as a novel growth hormone receptor (GHR) agonist, we determined that B-32 behaved as a typical $Ab2{\beta}$ based on a series of enzyme-linked immunosorbent assay assays. The results of fluorescence-activated cell sorting, indirect immunofluorescence and competitive receptor binding assays demonstrated that B-32 specifically binds to the GHR expressed on target cells. Next, we examined the resulting signal transduction pathways triggered by this antibody in primary porcine hepatocytes. We found that B-32 can activate the GHR and Janus kinase (2)/signal transducers and activators of transcription (JAK2/STAT5) signalling pathways. The phosphorylation kinetics of JAK2/STAT5 induced by either GH or B-32 were analysed in dose-response and time course experiments. In addition, B32 could also stimulate porcine hepatocytes to secrete insulin-like growth factors-1. Our work indicates that a monoclonal anti-idiotypic antibody to GH (B-32) can serve as a GHR agonist or GH mimic and has application potential in domestic animal (pig) production.

매실 혼합물이 DSS로 유도된 염증성 장질환 동물모델의 면역조절에 미치는 활성 (Anti-Inflammatory Effects of Prunus mume Mixture in Colitis Induced by Dextran Sodium Sulfate)

  • 김해란;이보람;임경직;;신흥묵;임병우
    • 한국약용작물학회지
    • /
    • 제19권1호
    • /
    • pp.16-23
    • /
    • 2011
  • This study was conducted to investigate the anti-inflammatory effects of Pruns mume, Schisandra chinensis, Chaenomeles sinensis-- Prunus mume mixtrue (PM) treatment on colitis induced in mice by dextran sodium sulfate (DSS) treatment. A total of 25 male BALB/c mice (average weight $20.7\;{\pm}\; 1.6 \;g$) were divided into 5 treatment groups and fed a commercial diet (A), PM administration (B), commercial diet + induced colitis by DSS (C), PM administration + induced colitis by DSS (D) and sulfasalazine + induced colitis by DSS (E). We found that PM treatment (D) and sulfasalazine (E) decreased the expression of $TNF-{\alpha}$ and COX-2 compared to the DSS-induced colitis group (C). The expression of IL-4, STAT6, $IFN-{\gamma}$, STAT1 was decreased in group D and group E compared to the colitis group (C), COX-2 and STAT1 were more decreased in group D. The serum IgE levels decreased in the PM treatment groups (C and D) compared to the non-PM treatment groups (A and B) although there was no significant difference between the PM treatment groups. It is notable that a therapeutic application of the PM extracts ameliorated DSS-induced colitis in mice.