• Title/Summary/Keyword: STAT2

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Development of Data Mining Tool Using S-PLUS and StatServer (S-PLUS와 StatServer를 이용한 Data Mining 도구 개발)

  • 정인석;이재준
    • Journal of Intelligence and Information Systems
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    • v.4 no.2
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    • pp.129-139
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    • 1998
  • 통계 software에는 data mining에 필요한 다양한 모형과 함수들이 제공되고 있어 이를 이용한 data mining 도구가 소개되고 있다. 본 논문에서는 data mining을 수행하는데 효과적인 환경을 제공하는 S-Plus로 data mining 기법들을 구현하거나 재구성하였으며, StatServer를 이용하여 대용량의 data base를 직접 관리할 수 있게 하고, S-PLUS의 분석기능을 Internet을 통하여 사용할 수 있게 하여 원거리에서 data mining작업을 수행될 수 있도록 구성하였다. 또한 분석자는 찾아낸 모형을 복잡한 프로그래밍 작업 없이 새로운 웹 페이지를 만들 수 있으며, 이를 통해 운영계의 사용자가 최적 모형이 제시하는 결과를 실제 업무에 즉시 이용할 수 있도록 하였다.

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Synthesis of Thienopyrimidine Derivatives as Inhibitors of STAT3 Activation Induced by IL-6

  • Jang, Hyun-Jae;Kim, Sung Min;Rho, Mun-Chual;Lee, Seung Woong;Song, Yang-Heon
    • Journal of Microbiology and Biotechnology
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    • v.29 no.6
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    • pp.856-862
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    • 2019
  • A series of thienopyrimidine compounds (6Aa-g and 6Ba-d) were synthesized and characterized by NMR spectroscopy and mass spectrometry. These compounds (6Aa-g and 6Ba-d) potently inhibited STAT3 expression induced by IL-6 in a dose-dependent manner with $IC_{50}$ values of $5.73-0.32{\mu}M$. Among the prepared thienopyrimidine derivatives, 6Aa, 6Ab, 6Ba and 6Bc significantly suppressed the phosphorylation of STAT3 and ERK1/2 stimulated by IL-6 in Hep3B cells. Furthermore, the synthesized compounds might be useful remedies for the treatment of inflammatory diseases by inhibiting the action of IL-6.

Hydroxyzine Induces Cell Death in Triple-Negative Breast Cancer Cells via Mitochondrial Superoxide and Modulation of Jak2/STAT3 Signaling

  • Shakya, Rajina;Park, Gyu Hwan;Joo, Sang Hoon;Shim, Jung-Hyun;Choi, Joon-Seok
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.585-592
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    • 2022
  • Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay showed that hydroxyzine induced apoptosis. The hydroxyzine-induced apoptosis was accompanied down-regulation of cyclins and CDKs, as well as the generation of reactive oxygen species (ROS) without cell cycle arrest. The effect of hydroxyzine on the induction of ROS and apoptosis on TNBC cells was prevented by pre-treatment with ROS scavengers, N-acetyl cysteine or Mito-TEMPO, a mitochondria-targeted antioxidant, indicating that an increase in the generation of ROS mediated the apoptosis induced by hydroxyzine. Western blot analysis showed that hydroxyzine-induced apoptosis was through down-regulation of the phosphorylation of JAK2 and STAT3 by hydroxyzine treatment. In addition, hydroxyzine induced the phosphorylation of JNK and p38 MAPK. Our results indicate that hydroxyzine induced apoptosis via mitochondrial superoxide generation and the suppression of JAK2/STAT3 signaling.

Gamma Irradiation-reduced IFN-γ Expression, STAT1 Signals, and Cell-mediated Immunity

  • Han, Seon-Kyu;Song, Jie-Young;Yun, Yeon-Sook;Yi, Seh-Yoon
    • BMB Reports
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    • v.35 no.6
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    • pp.583-589
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    • 2002
  • The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon $\gamma$ (IFN-$\gamma$). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-$\gamma$-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-$\gamma$ mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.

MicroRNA 449c Mediates the Generation of Monocytic Myeloid-Derived Suppressor Cells by Targeting STAT6

  • Han, Xiaoqing;Luan, Tao;Sun, Yingying;Yan, Wenyi;Wang, Dake;Zeng, Xianlu
    • Molecules and Cells
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    • v.43 no.9
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    • pp.793-803
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    • 2020
  • Myeloid-derived suppressor cells (MDSCs) promote tumour progression by contributing to angiogenesis, immunosuppression, and immunotherapy resistance. Although recent studies have shown that microRNAs (miRNAs) can promote the expansion of MDSCs in the tumour environment, the mechanisms involved in this process are largely unknown. Here, we report that microRNA 449c (miR-449c) expression was upregulated in myeloid progenitor cells upon activation of C-X-C motif chemokine receptor 2 (CXCR2) under tumour conditions. MiR-449c upregulation increased the generation of monocytic MDSCs (mo-MDSCs). The increased expression of miR-449c could target STAT6 mRNA in myeloid progenitor cells to shift the differentiation balance of myeloid progenitor cells and lead to an enhancement of the mo-MDSCs population in the tumour environment. Thus, our results demonstrate that the miR-449c/STAT6 axis is involved in the expansion of mo-MDSCs from myeloid progenitor cells upon activation of CXCR2, and thus, inhibition of miR-449c/STAT6 signalling may help to attenuate tumour progression.

Effects of Raphani Semen Ethanol Extracts on Skin Inflammation in HaCaT Keratinocytes (나복자(萊菔子) 에탄올 추출물이 HaCaT 피부각질형성세포에서 피부염증 감소에 미치는 영향)

  • Kim, Keun-Lip;Hong, Chul-Hee;Lee, Kyou-Young
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.2
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    • pp.13-27
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    • 2022
  • 목적 : 본 연구는 인간피부각질형성세포(HaCaT keratinocytes) 모델을 TNF-α와 IFN-γ로 자극하여 내복자(萊菔子)의 피부염증 감소 및 만성 염증성 질환에 미치는 영향을 알아보고자 하였다. 방법 : 내복자(萊菔子) 에탄올 추출물(RSE)이 세포생존율에 미치는 영향을 확인하기 위하여 MTT assay를 시행하였다. 또한 RSE가 TNF-α와 IFN-γ로 자극한 HaCaT 세포에서 p-IκBα, p-ERK, p-JAK2, p-STAT1, p-STAT6의 발현과 periostin, TSLP 단백질 발현에 미치는 영향을 확인하였다. 결과 : RSE는 200㎍/㎖ 이하에서 세포 독성을 보이지 않았고, HaCaT keratinocytes에서 TNF-α와 IFN-γ자극에 의하여 증가된 IκBα, ERK의 인산화를 억제하였다. 또한 JAK2와 STAT1, STAT6의 인산화를 억제하였으며, periostin과 TSLP의 발현을 감소시켰다. 결론 : RSE는 HaCaT keratinocytes에서 pro-inflammatory cytokines 및 transcription factors의 발현을 감소시켜 피부염증 감소 효능을 보였고, 만성 염증성 질환에서 내복자(萊菔子)의 사용 가능성을 확인하였다.

A Study on the Effect of Liriopis tuber water extract on Hydrogen Peroxide-stimulated C6 Astrocyte Cells (과산화수소 자극으로 활성화된 C6 성상교세포에 대한 맥문동추출물의 조절 효능 연구)

  • Park, Ki Ho;Kang, Seok Yong;Jung, Hyo Won;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.35 no.4
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    • pp.9-16
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    • 2020
  • Objective : To identify the effects of the water extract of Liriope platyphylla tuber (Liriopis tuber, LT) on the activation of astocytes, we investigated the regulatory effects of LT extract on H2O2-induced oxidative damage in C6 rat astrocytes. Methods : LT extract was extracted with boiling water. C6 cell line were treated with LT extract at 1, 2, and 3 mg/㎖ or without for 30 min and then stimulated with H2O2 at 5 ㎛ for 24 hr. The cell viability was measured by MTT assay. The expression of glial fibrillary acidic protein (GFAP), signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (pSTAT3), cyclooxygenase (COX-2), Nuclear factor-κB (NF-κB), superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), catalase, Akt, phospho-Akt (p-Akt) phosphoinositide 3-kinases (PI3K), and protein kinase C alpha (PKCα) proteins were determined by Western blot, respectively. GFAP expression was also observed with immunocytochemistry under a fluorescence microscope. Results : LT extract induced cell proliferation in H2O2-stimulated C6 cells. LT extract significantly inhibited the expression of GFAP, NF-κB and COX-2 and increased the expression of HO-1 and the phosphorylation of STAT3 in H2O2-stimulated C6 cells. LT extract also significantly increased the phosphorylation of Akt and decreased the expression of PKCα in a dose-dependent manner in H2O2-stimulated C6 cells. Conclusions : LT extract can regulate H2O2-induced activation of astrocytes through inhibiting the expression of NF-κB, COX-2 and regulating Akt / HO-1, STAT3 or PKCα signaling pathway.

Serosurvey for antibodies against brucellosis in pigs (돼지 brucellosis에 대한 항체가 조사)

  • Hur, Jin;Baek, Byeong-Kirl
    • Korean Journal of Veterinary Service
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    • v.34 no.2
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    • pp.153-157
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    • 2011
  • In order to investigate serum antibodies for detection of brucellosis in pigs, a total of 1208 sera were tested by Rose Bengal test (RBT), the standard tube agglutination test (STAT) and competitive ELISA (cELISA). The sera were collected from pigs of Gyeonggi, Chungnam, Chungbuk, Jeonnam and Jeonbuk, provinces during the period 2002 to 2004. All the sera were screened by RBT, and were confirmed by STAT and cELISA. Among 1208 sera, 26 sera (2.2%) were positive in screening test. All the 26 positive sera were positive by STAT, while all the sera were negative by cELISA. On the basis of this study, farmed pigs may be exposed to Brucella species. Furthermore, these results suggest that establishment of diagnoses for detection of porcine brucellosis is necessary.

The Effects of Injinchunggantang on Interferon Signaling Pathway of HepG2 Cells (인진청간탕(茵蔯淸肝湯)이 HepG2 cell의 인터페론 신호전달계에 미치는 영향)

  • Yi, Jong-Hoon;Kim, Young-Chul;Lee, Jang-Hoon;Woo, Hong-Jung
    • The Journal of Internal Korean Medicine
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    • v.26 no.1
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    • pp.74-92
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    • 2005
  • Objectives/Methods : To analyze the effect of Injinchunggantang(IJCGT) to Interferon-${\alpha}/{\beta}$ signal transmission system in HepG2 cells, HepG2 Cell were treated with IJCGT. Also, revelation of MxA, 2'5'-OAS mRNA leaded by Interferon-${\alpha}/{\beta}$ and revelation and activation of Jak1, TYK1, and STAT 1, all main signal transmission factors, were analyzed. Results : The analysis resulted in the following 1. With interferon ${\alpha}/{\beta}$ there was no affect cell propagation of Hep G2 cells. With IJCGT alone, cell propagation of HepG2 was promoted, and cell propagation control function was recovered. 2. With interferon ${\alpha}/{\beta}$ cell death was unaffected. With IJCGT apoptosis of HepG2 cell was restrained, and the cell's reaction to interferon was unaffected. 3. With interferon ${\alpha}/{\beta}$ treatment mRNA revelation of MxA and 2'5'-OAS was induced. When HepG2 cells were injected with IJCGT without interferon ${\alpha}/{\beta}$ treatment, mRNA revelation of MxA and 2'5'-OAS increased in proportion to the treatment density. With pre-treatment of IJCGT, leaded with interferon ${\alpha}/{\beta}$, promoted revelation of MxA, 2'5' -OAS mRNA. 4. Though mRNA revelation of lakl, TYK1 and STAT1 was unaffected with IJCGT, activation of STAT1 was promoted with an increase of phosphorylation of STAT1 protein. With pre-treatment of IJCGT, Jak1, TYK2, STAT1 phosphorylation, leaded with interferon, strengthened. 5. TNF-a, IL-1b and LPS present, revelation of MxA and 2'5'-OAS mRNA leaded by interferon was restrained when HepG2 cells were treated with IJCGT, and the interferon signal transmission system restraint action leaded by inflammatory cytokines was moderated. Conclusion : These results support a role for IJGCT in promotion of anti-virus action through maintainance of the liver's sensibility toward interferon. A clinical study of an interferon treated patient treated also with IJGCT is needed to determine its efficacy.

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Evaluation on diagnostic efficiency of the standard tube agglutination test for bovine brucellosis (소 브루셀라병 표준시험관응집반응법 진단효율 평가)

  • Sung, So-Ra;Kim, Ji-Yeon;Her, Moon;Lee, Kichan;Gu, Jeong-Hui;Kang, Sung-Il;Lee, Hyang-Keun;Kim, Suk-Mi;Jung, Suk-Chan
    • Korean Journal of Veterinary Service
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    • v.35 no.4
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    • pp.269-273
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    • 2012
  • A confirmatory serological test, the standard tube agglutination test (STAT) is evaluated for the diagnostic efficiency in brucellosis Korea. A total of 345 bovine samples were collected from regional veterinary branch under national brucellosis monitoring program from January 2010 to June 2012 in Korea. These samples were diagnosed as suspected serum and brucellosis positive by the Rose Bengal test (RBT) and the STAT, respectively. The STAT was compared and evaluated with three serological test such as the indirect-enzyme linked immunosorbent assay (I-ELISA), competitive-enzyme linked immunosorbent assay (C-ELISA) and fluorescence polarisation assay (FPA) prescribed for international trade by OIE. Among the 345 bovine serum samples, 302 (87.5%) were diagnosed as positive in the STAT, while 215 (62.3%), 223 (64.6%) and 194 (56.2%) serum samples were diagnosed as positive for brucellosis in the I-ELISA, C-ELISA and FPA, respectively. The STAT showed quite high positive results as compared with three prescribed tests of OIE. FPA, I-ELISA and C-ELISA have shown 60.6%, 64.9% and 67.2% correlation, respectively as compared to the STAT. However correlations of three prescribed tests ranged high 84.1~97.7%. Especially, correlation between I-ELISA and C-ELISA is quite high, 97.7%. These results suggest that the STAT has shown many false-positive reactions. Therefore, additional serological test, such as ELISAs and FPA, would be necessary to adopt as a confirmatory test in the national surveillance program of bovine brucellosis in Korea.