• 제목/요약/키워드: βA

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Simultaneous destabilization of β-catenin and Ras via targeting of the axin-RGS domain as a potential therapeutic strategy for colorectal cancer

  • Cha, Pu-Hyeon;Choi, Kang-Yell
    • BMB Reports
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    • 제49권9호
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    • pp.455-456
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    • 2016
  • Mutations of APC and KRAS are frequently observed in human colorectal cancers (CRCs) and the Wnt/β-catenin and Ras pathways are consequently activated in a significant proportion of CRC patients. Mutations in these two genes are also known to synergistically induce progression of CRCs. Through a series of studies, we have demonstrated that inhibition of the Wnt/β-catenin signaling pathway negatively regulates Ras stability, therefore, Ras abundance is increased together with β-catenin in both mice and human CRCs harboring adenomatous polyposis coli (APC) mutations. In a recent study, we identified KY1220, a small molecule that simultaneously degrades β-catenin and Ras by inhibition of the Wnt/β-catenin pathway, and obtained its derivative KYA1797K, which has improved activity and solubility. We found that KYA1797K binds the RGS domain of axin and enhances the binding affinity of β-catenin or Ras with the β-catenin destruction complex components, leading to simultaneous destabilization of β-catenin and Ras via GSK3β activation. By using both in vitro and in vivo studies, we showed that KYA1797K suppressed the growth of CRCs harboring APC and KRAS mutations through destabilization of β-catenin and Ras. Therefore, our findings indicate that the simultaneous destabilization of β-catenin and Ras via targeting axin may serve as an effective strategy for inhibition of CRCs.

Factors Influencing Physical Activity after Discharge from Hospital for Total Hip Arthroplasty Patients

  • Ju Young Kim;Mi Yang Jeon
    • Physical Therapy Rehabilitation Science
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    • 제11권4호
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    • pp.535-545
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    • 2022
  • Objective: This study was conducted to identify predictive factors of physical activity in total hip arthroplasty patients, and to provide basic data for the developing physical activity promotion program for total hip arthroplasty patients. Design: Descriptive correlational research. Methods: Data were collected from August 2017 to May 2018. Surveys were distributed to 60 patients in a G university hospital located at J city, Gyeongsangnam-do. Data were analyzed by frequency, mean, standard deviation, t-test, ANOVA, Pearson's correlation coefficient, multiple regression analysis using SPSS 24 Win program. Results: The variables affecting the 4-week physical activity after discharge were age (β=.07), residence after discharge (β=-.22), cerebrovascular disease (β=-.13), mental and behavioural disease (β=-.11), taking antibiotic (β=-.26), walking ability (β=.41), nutritional status (β=.25), depression (β=.05). The eight variables accounted for 39.4% in the 4-week physical activity (F=4.49 p=.001). The variables affecting the 8-week physical activity after discharge were age (β=.06), waking ability (β=.34), nutritional status (β=.20), exercise self-efficacy (β=.05), depression (β=-.05). The six variables accounted for 28.0% in the 8-week physical activity (F=4.58, p<.001). Conclusions: The walking ability in discharge important to improve the physical activity, there is a need to develop an program to improve walking ability before discharge, in total hip arthroplasty. There is a need to develop a physical activity program to consistently participate in a community.

Novosphingobium pentaromtivorans US6-1에 의한 고분자 방향족 탄화수소 생분해과정에서 2-hydroxypropyl-$\beta$-cyclodextrin의 영향 (Effect of 2-hydroxypropyl-$\beta$-cyclodextrin on Biodegradation of High-Molecular Weight Polycyclic Aromatic Hydrocarbons by Novosphingobium pentaromtivorans US6-1)

  • 강지현;권개경;김상진
    • 한국해양환경ㆍ에너지학회지
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    • 제7권3호
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    • pp.146-151
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    • 2004
  • 포접력을 지닌 2-hydroxypropyl-β-cyclodextrin(β-HPCD)을 비롯한 cyclodextrin계 화합물은 소수성 유기물질의 용해도를 증가시킴으로써 미생물에 의한 분해를 촉진시키나 그 외의 자세한 기작은 알려져 있지 않다. 본 실험에서는 β-HPCD 유무에 따라 고분자 PAHs 분해력을 지닌 Novosphingobium pentaromtivorans US6-1 균주의 pyrene라 benzo[a]pyrene(B[a]P)의 분해정도, 이때의 biomass 변화 및 dioxygenase활성을 측정함으로써 PAHs 생분해과정에서 β-HPCD의 역할을 규명하고자 하였다. 실험구는 균주와 PAHs, β-HPCD의 존재 유무에 따라 8개 조건으로 준비하였으며 각 실험구의 배양기간에 따른 PAHs 분해도와 생체량의 변화를 측정하였다. Pyrene의 경우 β-HPCD가 존재함에 따라 분해도가 증진되는 것이 확인되었으며, 특히 B[a]P의 분해에는 β-HPCD가 필수요소로 작용하였다. 생체량의 변화는 PAHs의 존재 유무에 영향을 받지 않았고 β-HPCD의 존재 유무에 따라 차이를 나타내었다. 또한 US6-1 균주는 β-HPCD가 포함된 MM2 무기영양배지에서 전배양 할 때에 ZoBell 배지에서 전배양하는 경우에 비해 catechol-1,2-dioxygenase 효소활성이 높은 것으로 나타났으나 그 값은 빈영양상태에서 배양한 세포의 효소환성과 큰 차이를 보이지는 않았다. 이상의 결과로 볼 때 β-HPCD는 PAHs의 이용성을 높여주는 동시에 탄소원으로 이용되어 균주의 생체량 증가에 기여함으로써 PAMs의 분해력을 증진시키지만 dioxygenase 효소활성에는 영향을 미치지 않는 것으로 사료된다.

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기혼남성과 여성의 건강행태 및 건강 관련 삶의 질에 관한 연구 (Health Behavior and Health Related Quality of Life of married Males and Females)

  • 정유림;한삼성
    • 근관절건강학회지
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    • 제30권3호
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    • pp.147-156
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    • 2023
  • Purpose: This study examines the health behavior and health-related quality of life (HRQOL) among married men and women, utilizing data from the Korean National Health and Nutritional Examination Survey, encompassing 4,217 subjects. Methods: A multiple regression model was employed to analyze the data. Results: Married men demonstrated a significantly good relationship between HRQOL and perceived health state (β=.32, p<.001), while married women showed a similar relationship with perceived health state (β=.38, p<.001). Additionally, married men demonstrated significantly neutral relationship between HRQOL and perceived health state (β=.30, p<.001), as did the married women (β=.38, p<.001). Both married men (β=-.11, p<.001) and married women (β=-.08, p<.001) were found to experience depression. oreover, the HRQOL in married men was positively associated with private health insurance (β=.08, p=.001), and the same trend was observed in married women (β=.10, p<.001). Married men with unmet medical needs showed a negative association with HRQOL (β=-.08, p<.001), and married women with unmet medical needs showed a similar negative association (β=-.12, p<.001). Furthermore, outpatient medical use(2 weeks) was negatively associated with HRQOL in both married men (β=-.07, p=.001) and married women (β=-.07, p<.001). Moreover, married women displayed a significant negative association between HRQOL and the prevalence of obesity(β=-.04, p=.048) and stress (β=-.05, p=.009) and a positive association with aerobic exercise (β=.04, p=.027). Conclusions: This study suggests that health behavior significantly influences the HRQOL among married men and women. The findings of this study can guide policymakers in developing strategies to improve health behavior and HRQOL within households.

Hep3B 인간 간암세포에서 caspase 의존적이며 PI3K/Akt 신호전달의 불활성화와 관련된 β-lapachone의 세포사멸 유도 (Induction of Apoptosis by β-Lapachone in Hep3B Human Hepatocellular Carcinoma Cells Is Caspase-Dependent and Associated with Inactivation of PI3K/Akt Signaling)

  • 권재임;최영현;황보현
    • 생명과학회지
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    • 제34권2호
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    • pp.94-104
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    • 2024
  • β-lapachone은 다양한 유형의 질병을 치료하기 위해 남미 및 중미 지역의 전통 의학에서 널리 사용되어 온 Tabebuia vellanedae의 껍질에서 분리된 천연 퀴논 화합물의 일종이다. β-lapachone은 여러 유형의 암세포에서 강력한 항암 활성을 갖는 것으로 보고되었지만, 간세포암종 세포의 증식에 대한 효과는 아직 불분명하다. 따라서 본 연구에서는 β-lapachone 인간 간세포암종 Hep3B 세포의 증식에 미치는 영향을 조사하였으며, 본 연구의 결과에 의하면, β-lapachone 처리에 의한 Hep3B 세포의 세포생존율 감소는 세포사멸 유도와 밀접한 관련이 있었다. 또한, β-lapachone이 처리된 Hep3B 세포에서는 항세포사멸 인자인 Bcl-2의 발현이 감소한 반면, 세포사멸 유도 인자인 Bax의 발현은 증가하였으며, 이는 caspase cascade의 활성 증가와 연관성이 있었다. 그러나 pan-caspase 억제제가 존재하는 경우 β-lapachone에 의해 유발된 세포사멸은 약화되었으며, 이는 β-lapachone에 의한 세포사멸 유도가 caspase 의존적인 현상임을 의미한다. 아울러, β-lapachone의 처리는 ERK 경로를 활성화시키면서 PI3K/Akt 경로의 활성을 억제하였으며, β-lapachone 유도 세포사멸에 ERK 억제제의 효과는 미미했지만, PI3K 억제제는 β-lapachone에 의해 유도된 세포사멸을 유의하게 증가시켰다. 비록 생체 내 동물 모델에서의 확인이 필요하지만, 본 연구의 결과는 간세포암종 세포에서 β-lapa-chone의 항암 활성을 이해하는 데 유용한 자료로 활용될 것이다.

코로나바이러스감염증-19 특별재난 일개 지역 교사의 교사 효능감에 영향을 미치는 요인 융합 연구 (A Convergence Study on the Factors Affecting Teacher Efficacy among School Teachers in COVID- 19 Special Disaster Area)

  • 김은휘;하영선;박용경
    • 디지털융복합연구
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    • 제19권1호
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    • pp.239-248
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    • 2021
  • 본 연구는 코로나바이러스감염증-19 특별재난지역에 근무하는 중등학교 교사의 우울, 불안과 스트레스가 교사효능감에 미치는 영향을 파악하고자 시도되었다. 자료수집은 2020년 5월 9일부터 16일까지 D시 중등학교 교사 123명을 대상으로 하였다. 연구결과 직무 만족도(β=0.27, p=.002), 경제 수준(β=0.18, p=.022), 학력(β=0.18, p=.022), 주관적 건강상태(β=0.16, p=.047), 스트레스(β=-0.16, p=.044), 성별(β=0.16, p=.042)이 교사 효능감에 유의한 영향을 나타내었으며, 설명력은 35%이었다(F=11.80, p<.001). 우울(β=-0.09, p=.468)과 불안(β=-0.12, p=.320)은 교사 효능감에 유의한 영향을 미치지 않았다. 교사 효능감 증진을 위한 프로그램 개발 시 스트레스 관리뿐만 아니라 직무 만족도 증진을 위한 방안 마련이 요구된다.

청소년의 미세먼지 행위에 영향을 미치는 요인 (A study on the Factors Affecting Behavior for Particulate Matter among Adolescents)

  • 하영선;박용경
    • 한국융합학회논문지
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    • 제11권11호
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    • pp.393-403
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    • 2020
  • 본 연구는 청소년을 대상으로 미세먼지에 대한 지식, 태도 및 행위의 수준을 파악하고 미세먼지 행위에 영향을 미치는 요인을 검증하여 미세먼지 대응에 효과적으로 대처하기 위한 전략 개발의 기초자료로 활용하고자 수행되었다. 서술적 조사연구이며, 연구 대상은 D시 일개 고등학교 학생 218명이었으며, 연구 기간은 2019년 5월이며 2주간 실시되었다. 수집된 자료는 SPSS WIN 18.0 프로그램을 사용하여 t-test, one-way ANOVA, Pearson's correlation coefficient, multiple regression을 분석하였다. 미세먼지 태도(β=0.52, p<.001)가 미세먼지 행위에 유의한 영향을 나타내었으며, 설명력은 31%이었다(F=15.19, p<.001). 미세먼지 교육 경험(β=0.08, p=.157), 부의 학력(β=0.08, p=.288), 모의 학력(β=0.05, p=.463), 미세먼지 지식(β=-0.05, p=.415), 동거 가족(β=-0.09, p=.126), 학교 성적(β=-0.02, p=.710)은 미세먼지 행위에 유의한 영향을 미치지 않았다. 청소년을 위한 미세먼지 행위를 높이기 위한 프로그램 개발 시 미세먼지 태도를 증진시키기 위한 방안 마련이 필요하다.

Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • 제33권9호
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

Motional Properties in the Structure of GlcNAc(β1,3)Gal(β)OMe Studied by NMR Spectroscopy and Molecular Modeling

  • 심규창;이상원;김양미
    • Bulletin of the Korean Chemical Society
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    • 제18권4호
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    • pp.415-424
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    • 1997
  • Conformational flexibilities of the GlcNAc(β1,3)Gal(β)OMe are investigated through NMR spectroscopy and molecular modeling. Adiabatic energy map generated with a dielectric constant of 50 contains three local minima. All of the molecular dynamics simulations on three local minimum energy structures show fluctuations between two low energy structures, N2 at φ=80° and ψ=60° and N3 at φ=60° and ψ=-40°. We have presented adequate evidences to state that GlcNAc(β1,3)Gal(β)OMe exists in two conformationally discrete forms. Two state model of N2 and N3 conformers with a population ratio of 40:60 is used to calculate the effective cross relaxation rate and reproduces the experimental NOEs very well. Molecular dynamics simulation in conjunction with two state model proves successfully the dynamic equilibrium existed in GlcNAc(β1,3)Gal(β)OMe and can be considered as a powerful method to analyze the motional properties in the structure of carbohydrate. This observation also cautions against the indiscriminate use of a rigid model to analyze NMR data.

A red seaweed, Polysiphonia morrowii, extract promotes β-cell regeneration in zebrasfish (Danio rerio)

  • Thilini Ranasinghe;Seon-Heui Cha
    • Fisheries and Aquatic Sciences
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    • 제27권1호
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    • pp.17-22
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    • 2024
  • Diabetes Mellitus (DM) is a major health issue increasing worldwide. Currently, nearby half a billion people have diabetes. Two major types of DM that type 1 and type 2-DM have different etiologies but feature a crucial common pathological transition into dysfunction of pancreatic β-cells and consequently leading hyperglycemia and finally go into DM. Therefore, maintaining of β-cells such as preventing β-cells degeneration, and promoting β-cells regeneration and proliferation will be essential approaches in prevention and/or treatment of DM. There are many reports that various types of seaweed control metabolic diseases such as obesity, high blood pressure, and blood sugar control. However, no new drug candidates have been developed yet. Additionally, although seaweed has excellent blood sugar control effects, there is no evidence that it directly proliferates or regenerates beta cells. Therefore, we studied on the promotion of β-cell regeneration by a seaweed, Polysiponia morrowii extract (PME) which preserves β-cells and maintains its function. As a result, it was confirmed that PME directly promotes the proliferation of pancreatic islet β-cells with insulin secretion function in in vivo. Therefore, PME shows potential as a candidate for β-cell regeneration that may play a fundamental role in the treatment of diabetes.