• 제목/요약/키워드: Stat4

검색결과 253건 처리시간 0.023초

5,8-Dimethoxy-2-Nonylamino-Naphthalene-1,4-Dione Inhibits Vascular Smooth Muscle Cell Proliferation by Blocking Autophosphorylation of PDGF-Receptor ${\beta}$

  • Kim, Yohan;Lee, Jung-Jin;Lee, Sang-Gil;Jung, Sang-Hyuk;Han, Joo-Hui;Yang, So Young;Yun, Eunju;Song, Gyu-Yong;Myung, Chang-Seon
    • The Korean Journal of Physiology and Pharmacology
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    • 제17권3호
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    • pp.203-208
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    • 2013
  • As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced $[^3H]$-thymidine incorporation, cell cycle progression from $G_0/G_1$ to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptor${\beta}$(PDGF-$R{\beta}$) enhanced by PDGF at $Tyr^{579}$, $Tyr^{716}$, $Tyr^{751}$, and $Tyr^{1021}$ residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and $PLC{\gamma}1$. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-$R{\beta}$ autophosphorylation, and subsequently PDGF-$R{\beta}$-mediated downstream signaling pathways.

Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana

  • Kim, Mi Seon;Lee, Yunmi;Sung, Gi-Ho;Kim, Ji Hye;Park, Jae Gwang;Kim, Han Gyung;Baek, Kwang Soo;Cho, Jae Han;Han, Jaegu;Lee, Kang-Hyo;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • 제23권4호
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    • pp.367-373
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    • 2015
  • Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

국내 비만아동의 비만관리프로그램의 효과에 대한 메타분석 (Meta-analysis of the Effects of Obesity Management Program for Children)

  • 성경숙;윤영미;김은주
    • Child Health Nursing Research
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    • 제19권4호
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    • pp.262-269
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    • 2013
  • 목적 국내에서 연구된 비만 아동의 관리프로그램의 효과를 확인하고 프로그램의 종류별, 종속변수별 효과크기를 산출하여 효과적인 아동의 비만관리프로그램의 형태를 파악하기 위함이다. 방법 본 연구에서는 2000년에서 2010년까지 비만 아동을 대상으로 운동 및 다양한 중재의 효과를 검증한 연구들이 주요 대상이었다. 본 연구에 포함된 연구는 대조군이 있는 실험연구, 비만 아동에게 중재를 제공한 연구, 서술 통계치와 추론 통계치가 사용가능한 연구들이 포함되었다. 선정기준에 적합한 연구들은 신뢰구간 95%, 통계적 유의수준 5%로 정하며 이용된 프로그램은 STATA 10.0을 이용하였다. 결과 총 61편의 연구가 분석에 이용되었으며 개별연구들의 결과를 결합한 효과크기는 -0.23 (95% CI, -0.32 ~ -0.15)로 중간 이하의 효과를 보였다. 중재별 결합추정치 중에서는 운동요법과 영양교육을 포함한 중재 방법이 중간 이상의 효과를 보였으며 종속변수 중에서는 혈중 렙틴, 인슐린이 큰 효과가 있었으며 중성지방, 혈당, 체지방률, 자아존중감이 중간크기의 효과가 있었다. 마지막으로 분석에 이용된 논문들은 출판상의 편향을 보이지 않았다. 결론 확인된 비만 아동의 관리프로그램을 각 지역사회기반을 둔 프로토콜 개발이 필요할 것이다. 비만아동의 지속적인 체중 및 건강유지를 위한 지속적인 연구가 진행되어야 할 것이다.

HGFK1 is Associated with a Better Prognostis and Reverses Inhibition by Gefitinib in NSCLC Cases

  • Zhou, Xiao-Hui;Tang, Li-Na;Yue, Lu;Min, Da-Liu;Yang, Yi;Huang, Jian-An;Shen, Zan
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권4호
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    • pp.1457-1461
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    • 2012
  • Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

초등학교 저학년 대상 ADHD 단독군, 동반 질환을 가진 ADHD군에서의 10회기 사회기술 훈련의 효과 비교 (Compared Effectiveness of 10-Session Social Skill Training for Korean Early Elementary School Children in Two Groups Diagnosed as Pure ADHD and ADHD with Comorbidity)

  • 이소희;정운선;황선영;정재훈;김은지;우정민;조현영
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • 제26권4호
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    • pp.258-265
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    • 2015
  • Objectives : Children with attention-deficit hyperactivity disorder (ADHD) have problems in social interactions. We compared the effect of 10-session social skill training (SST) among two groups, children with pure ADHD, and those with ADHD with comorbidity. Methods : Consecutive 10-session SST was conducted for 34 children from 2006 to 2012. There were 22 children with pure ADHD (male 20, female 2), and 12 children suffering from ADHD with comorbidity (male 11, female 1). All children took medication as prescribed by their doctors before the start of SST. The Child Behavior Checklist (CBCL), the Korean Personality Inventory for Children (K-PIC), the Conner's Rating Scale, the ADHD Rating Scale, and the Home Situation Questionnaire were completed by mothers before and after the SST. All children completed the Child Depression Inventory, the Stat-Trait Anxiety Inventory for Children, the Self-Concept Scale and the ADHD Diagnostic System before and after the SST. Results : Only children with pure ADHD showed improvement in anxiety and self-concept in scales rated by children. In the CBCL rated by parents, the pure ADHD group and the ADHD with comorbidity showed improvement in both externalizing and internalizing subscales. In the K-PIC rated by parents, the pure ADHD group showed improvement in most outcomes and ADHD with comorbidity showed positive change in verbal development. Conclusion : These results suggest that SST has significant positive effects on both the pure ADHD and ADHD with comorbidity group. Further research is needed in order to target diverse comorbidity groups with ADHD to improve the effectiveness of the SST.

간호대학생의 우울, 불안, 수면의 질이 주간과다졸림에 미치는 영향 (Effects of Depression, Anxiety, Quality of Sleep on Excessive Daytime Sleepiness in nursing students)

  • 이은하
    • 한국산학기술학회논문지
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    • 제20권12호
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    • pp.148-156
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    • 2019
  • 본 연구는 간호대학생의 우울, 불안, 수면의 질과 주간과다졸림의 정도를 확인하고, 주간과다졸림에 영향을 미치는 요인을 파악하여 중재방안 마련을 위한 근거자료를 제공하기 위해 수행되었다. 연구대상자는 일 대학에 재학 중인 간호대학생 213명으로, 2019년 5월 20일부터 5월 30일까지 구조화된 설문지를 통하여 자료 수집하였다. 수집된 자료는 SPSS/WIN 25.0 통계프로그램을 이용하여, 실수, 백분율, 평균, 표준편차, χ2 검정, Paired t-test, Pearson's Correlation, Multiple logistic regression으로 분석하였다. 연구결과 간호대학생의 주간과다졸림 평균 점수는 8.95(±4.56)점이었고 주간과다졸림군은 40.8%이었다. 대상자의 우울 평균 점수는 10.05(±7.85)점, 상태불안 평균점수는 46.09(±9.50)점, 특성불안 평균점수는 46.47(±9.93)점, 수면의 질 평균점수는 6.51(±2.95)점)이었다. 주간과다졸림 유무에 따라 대상자의 우울(t=1.955, p=.024), 상태불안(t=5.446, p<.001), 특성불안(t=1.716, p=.007), 수면의 질(t=2.168, p<.001)의 평균 점수에는 유의한 차이가 있었다. 주간과다졸림에 영향을 미치는 요인으로는 상태불안, 수면의 질로 나타났으며, 주간과다졸림에 대한 상태불안의 오즈비는 1.04(95% Confidence Interval=1.01-1.08), 수면의 질은 1.16(95% Confidence Interval=1.04-1.29)로 나타났다. 이상의 결과를 바탕으로 우선적으로, 간호대학생의 주간과다 졸림에 대한 관심을 높이고, 주간과다졸림을 줄이기 위해 불안완화를 위한 중재방안마련과 수면의 질에 대한 관리가 필요할 것이다.

Agaricus blazei의 유가식 배양을 통한 균사체 및 세포외 다당체 생산 (Production of Mycelium and Expolysaccharides by Fed-batch Culture of Agaricus blazei)

  • 김현한;나정걸;장용근;이상종
    • KSBB Journal
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    • 제19권6호
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    • pp.457-461
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    • 2004
  • 본 연구에서는 A. blazei의 DO-스탯 현탁 유가식 배양을 통하여 균사체 및 세포외 다당체 생산을 극대화하고자 하였다. 탄소원만을 포함하는 기질 공급액을 사용하는 경우보다 질소원이 적절히 첨가된 혼합 기질 공급액을 사용하는 것이 균사체 및 세포외 다당체 생산에 보다 효과적이었다. 기질공급액 중의 탄소원 조성을 달리하여 실험을 수행한 결과, 덱스트린을 배제하고 포도당만을 탄소원으로 사용하였을 때 가장 높은 균사체 및 세포외 다당체 생산성을 얻을 수 있었다. 이 때의 균사체 농도 및 생산성은 각각 36.5 g/l, 0.37g/l-h이었으며, 세포외 다당체 농도 및 생산성은 각각 10.9 g/l, 0.11 g/l-h이었다. 이는 회분식 배양 결과와 비교하여 균사체 농도 및 생산성 면에서는 각각 6배 및 2.2배, 세포외 다당체 농도 및 생산성 면에서는 각각 4.7배 및 1.8배 증가한 값이다. 이상의 결과들로부터 A. blazei의 고농도 균사체 배양을 위해 유가식 배양 방법이 매우 효과적임을 알 수 있었다.

The role of p21/CIP1/WAF1 (p21) in the negative regulation of the growth hormone/growth hormone receptor and epidermal growth factor/epidermal growth factor receptor pathways, in growth hormone transduction defect

  • Kostopoulou, Eirini;Gil, Andrea Paola Rojas;Spiliotis, Bessie E.
    • Annals of Pediatric Endocrinology and Metabolism
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    • 제23권4호
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    • pp.204-209
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    • 2018
  • Purpose: Growth hormone transduction defect (GHTD) is characterized by severe short stature, impaired STAT3 (signal transducer and activator of transcription-3) phosphorylation and overexpression of the cytokine inducible SH2 containing protein (CIS) and p21/CIP1/WAF1. To investigate the role of p21/CIP1/WAF1 in the negative regulation of the growth hormone (GH)/GH receptor and Epidermal Growth Factor (EGF)/EGF Receptor pathways in GHTD. Methods: Fibroblast cultures were developed from gingival biopsies of 1 GHTD patient and 1 control. The protein expression and the cellular localization of p21/CIP1/WAF1 was studied by Western immunoblotting and immunofluorescence, respectively: at the basal state and after induction with $200-{\mu}g/L$ human GH (hGH) (GH200), either with or without siRNA CIS (siCIS); at the basal state and after inductions with $200-{\mu}g/L$ hGH (GH200), $1,000-{\mu}g/L$ hGH (GH1000) or 50-ng/mL EGF. Results: After GH200/siCIS, the protein expression and nuclear localization of p21 were reduced in the patient. After successful induction of GH signaling (control, GH200; patient, GH1000), the protein expression and nuclear localization of p21 were reduced. After induction with EGF, p21 translocated to the cytoplasm in the control, whereas in the GHTD patient it remained located in the nucleus. Conclusion: In the GHTD fibroblasts, when CIS is reduced, either after siCIS or after a higher dose of hGH (GH1000), p21's antiproliferative effect (nuclear localization) is also reduced and GH signaling is activated. There also appears to be a positive relationship between the 2 inhibitors of GH signaling, CIS and p21. Finally, in GHTD, p21 seems to participate in the regulation of both the GH and EGF/EGFR pathways, depending upon its cellular location.

MicroRNA-296-5p Promotes Invasiveness through Downregulation of Nerve Growth Factor Receptor and Caspase-8

  • Lee, Hong;Shin, Chang Hoon;Kim, Hye Ree;Choi, Kyung Hee;Kim, Hyeon Ho
    • Molecules and Cells
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    • 제40권4호
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    • pp.254-261
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    • 2017
  • Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs post-transcriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells. It was observed that miR-296-5p potentiated the invasion of various GBM cells including LN229, T98G, and U87MG. Through bioinformatics approaches, two genes were identified as miR-296-5p targets: caspase-8 (CASP8) and nerve growth factor receptor (NGFR). From results obtained from Ago2 immunoprecipitation and luciferase assays, we found that miR-296-5p downregulates CASP8 and NGFR through direct interaction between seed sequence of the miRNA and 3'UTR of the target mRNA. Knockdown of CASP8 or NGFR also increased the invasive ability of GBM cells, indicating that CASP8 and NGFR are involved in potentiation of invasiveness by miR-296-5p. Consistent with our findings, CASP8 was downregulated in brain metastatic lung cancer cells, which have a high level of miR-296-5p, compared to parental cells, suggesting that miR-296-5p may be generally associated with the acquisition of invasiveness. Collectively, our results implicate miR-296-5p as a potential cause of invasiveness in cancer and suggest it as a promising therapeutic target for GBM.

인체미의 이상형에 따른 패션 일러스트레이션의 변화 (A Change of fashin IIIustration by the Ideal Type of Human Body Beauty)

  • 전경숙
    • 복식
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    • 제28권
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    • pp.65-84
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    • 1996
  • The purpose of this study is to analyze the relation between the beauty of human body and the fashion illustration in each period And I attained my object through the investigation of features and changes of illustration which is given a vivid description of the features and development of ideal humam body beauty. By various methods I studied this subject. Frist I refered to sundry records Secondly I investiated the fashion illustrations which are included in Vogue. On the basis of this data I grasped the ideal types of human body beauty which is founded during the social change in each 10 years. And I analyzed the relation be-tween the ideal type and fashion illustration which show the change of fashion. The summary of result is as follows. 1. In the early part of the 20th century the beauty of human body is represented with the figure of large-sized beauty which emphasize shoulder and bust. And fashion ikllustration show 9 life-size broad shoulder full bust lim waist and hourglass silhouette. 2, In the 1910s the swell of strength vanishes gradually and shoulder and sleeve are straight type. And fashion illustration show 7 life-size high waist line. And that is tublar sil-houette of high waist and streamline shape in which bust and hip are not emphasized. 3. In the 1920s the ideal type of human body beauty is straight type which shows flat bust and unexaggerate hip. And fashion illus-tration is about 8 life-size tublar silhouette of low waist and lunger and slimmer and young style in which bust and hip are not emph-asized. 4. In the 1930s the ideal is womamly slim and long style. Fashion illustration is about 8 life-size and slim & long silhouette in which waist line is emphasized and bust and hip line come out. 5. In the 1940s the ideal type is womamly style which has narrow shoulder rich bast and slim waist. And fashion illustration is about 7 life-size and hourglass silhouette which has unartificial shoulder slim waist and empha-sized bust. 6. In the 1950s the ideal type is that of ro-bust health which emphasize build and muscu-lar system. And fashion illustration is 8.5 life-size and show full bust and made waist slimmer. That is sheath silhouette. 7. In the child who has full face with large eyeball slender and long leg: narrow and immatured body comparatively big head. And fashion illus-tration is 7 life-size and show slim and long neck flat bust long and slim limbs and big head. That is H type silhouette. 8. In the 1970s the ideal type is high stat-ure flat breast small hip and wide shoulders. And fashion illustration is wide shoulders and slim waist as 11 life-size and straight sil-houete. 9. In the 1980s the ideal type is extremely emphasized breadth of shoulder because healthy body and muscle are recognized as the symbol of ideal attractiveness. And fashion il-lustration is about 8.5 life-size and show mus-cular slim type that is slim silhouette. 10 At the present time the ideal type is slim and tall type which is empasized healthy beauty. And fashion illustration is 12 life-size which has healthy body and skin So that is slim and long type.

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