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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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    • v.49 no.9
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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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    • v.11 no.4
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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.

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

  • Kang Ji-Hyun;Kwon Kae Kyoung;Kim Sang-Jin
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.7 no.3
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    • pp.146-151
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    • 2004
  • Cyclodextrin compounds including 2-hydroxypropyl-β-cyclodextrin(β-HPCD) though to be accelerate the biodegradation of PAHs molecule by increasing solubility of PAHs through detaining PAHs in their's cavity. However, only this mechanism is not sufficient to explain the enhancement of PAHs biodegradation by β-HPCD. To find out possible additional role of β-HPCD in the enhancement of PAHs biodegradation, biodegradation rates of pyrene and benzo[a]pyrene (B[a]P) by a PAHs degrading Novosphingobium pentaromtivorans US6-1 strain were compared between with and without addition of β-HPCD. Changes of bacterial biomass were also measured simultaneously. In addition catechol 1,2-dioxygenase activity was determined depending on pre-incubation conditions. As a result, β-HPCD accelerate the degradation rate of pyrene by strain US6-1 and especially the β-HPCD amendment was obligatory for the degradation of B[a]p. Bacterial biomass was responsible for β-HPCD, however, PAHs compounds such as pyrene and B[a]P did not contribute to the bacterial biomass. Catechol 1,2-dioxygenase specific activity of US6-l cells pre-cultured in MM2 medium containing l% β-HPCD was higher than that of cells pre-cultured in ZoBell medium. The former case also showed similar activity compared to that of cells serially starved in MM2 medium after grown in ZoBell medium. These results imply that the presence of β-HPCD accelerate the degradation of PAHs by increasing the bacterial biomass as well as by increasing the water solubility of PAHs.

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

  • Jeong, Yu-Rim;Han, Sam-Sung
    • Journal of muscle and joint health
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    • v.30 no.3
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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.

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

  • Jae Im Kwon;Yung Hyun Choi;Hyun Hwangbo
    • Journal of Life Science
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    • v.34 no.2
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    • pp.94-104
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    • 2024
  • β-Lapachone is a natural quinone compound originally obtained from the bark of the lapacho tree (Tabebuia vellanedae), which has been used in traditional medicine in several South and Central American countries for treating various diseases. Although β-lapachone has been reported to have potent anticancer activity in many types of cancer cells, its effect on the proliferation of hepatocellular carcinoma (HCC) cells is still unclear. Therefore, in this study, we investigated the effect of β-lapachone on the proliferation of human HCC Hep3B cells. According to our results, the decrease in cell viability of Hep3B cells caused by β-lapachone was closely related to the induction of apoptosis, which was confirmed through changes in nuclear morphology and flow cytometry. In addition, in Hep3B cells treated with β-lapachone, the expression of Bcl-2, an anti-apoptotic factor, was decreased, while the expression of Bax, an apoptosis inducer, was increased, and the activity of the caspase cascade was also increased. However, in the presence of a pan-caspase inhibitor, β-lapachone-induced apoptosis was weakened, indicating that the induction of apoptosis by β-lapachone was caspase-dependent. Moreover, β-lapachone treatment activated extracellular-regulated kinase (ERK) signaling while inhibiting activation of the phosphoinositide 3 kinase (PI3K)/Akt pathway. Furthermore, the effect of the ERK inhibitor on suppressing the induction of apoptosis by β-lapachone was minimal, and the PI3K inhibitor significantly increased β-lapachone-induced apoptosis. The findings from this study will contribute to a better understanding of the anticancer activity of β-lapachone in HCC cells.

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

  • Kim, Eunl-Hwi;Ha, Young-Sun;Park, Young-Kyung
    • Journal of Digital Convergence
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    • v.19 no.1
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    • pp.239-248
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    • 2021
  • This study was aimed to investigate the factors influencing teacher efficacy of depression, anxiety, stress among school teachers in COVID- 19 special disaster area. The data were collected from May 9 to 16, 2020 for 123 high school teachers in D city. As a result of the study, the influential factor of teacher efficacy was satisfaction with duty (β=0.27, p=.002), economic level (β=0.18, p=.022), education (β=0.18, p=.022), subjective health state (β=0.16, p=.047), stress (β=-0.16, p=.044), gender(β=0.16, p=.042). These factors accounted for 35% in teacher efficacy. It was found that depression(β=-0.09, p=.468) and anxiety(β=-0.12, p=.320) had no significant effect on teacher efficacy. When developing a program to improve teacher efficacy, it is required to prepare measures not only to manage stress but also to improve job satisfaction.

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

  • Ha, Young-Sun;Park, Yong-Kyung
    • Journal of the Korea Convergence Society
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    • v.11 no.11
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    • pp.393-403
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    • 2020
  • This study was aimed to investigate the factors influencing particulate matter behavior of particulate matter knowledge, particulate matter attitude among adolescents. A descriptive study design was used. Participants were 218 high school students in D city. The data were collected from May 13 to 24 2019. Collected data were analyzed by t-test, one-way ANOVA, Pearson's correlation coefficient, multiple regression using SPSS WIN 18.0 program. Results: The influential factor for particulate matter behavior was particulate matter attitude (β=0.52, p<.001). It was found that particulate matter education experience (β=0.08, p=.157), academic background of father (β=0.08, p=.288), academic background of mother (β=0.05, p=.463), particulate matter knowledge (β=-0.05, p=.415), residence with (β=-0.09, p=.126), school record (β=-0.02, p=.710) had no significant effect on teacher efficacy. In order to develop a program to increase the particulate matter behavior for youth, it is necessary to prepare a plan to improve the attitude of particulate matter.

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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    • v.33 no.9
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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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    • v.18 no.4
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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.

Factors Influencing Health-related Quality of Life of the Elderly by the Types of Households (가구 유형에 따른 노인의 건강 관련 삶의 질에 미치는 영향요인)

  • Yun, Mi-Soon;Choi, Eun-Hi;Kim, Yoo-Jin;Kang, Yuri;Choi, Si-Eun
    • Journal of muscle and joint health
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    • v.28 no.2
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    • pp.174-182
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    • 2021
  • Purpose: This study is a secondary data analysis study to identify factors related to the quality of life of people aged 65 y or older, according household type. Methods: In 2019, the study extracted the data from the elderly participants (65 y of age or older) from G province Community Health Survey. The data were compiled and analyzed in a composite sample. Results: The quality of life was lowest among single people, grandparents-grandchildren (F=39.88, p<.001). Variables that significantly influenced quality of life in single-person households were basic security(β=-.03, p=.002), high-risk drinking (β=.04, p=.002), number of day to walk (β=.01, p<.001), diabetes mellitus (β=-.03, p<.001), depression (β=-.02, p<.001), and contact frequency (β=.00, p<.001). Variables that significantly influenced grandparents-grandchildren households were basic security (β=.03, p<.001), smoking(β=-.02, p<.001), number of day to walk (β=.00, p<.001), hypertension (β=-.01, p=.009), diabetes mellitus (β=-.04, p<.001), cognitive impairment (β=-.02, p<.001), depression(β=-.02, p<.001), contact frequency (β=.01, p<.001), and neighborhood trust (β=.02, p<.001). Conclusion: In this study, there were differences in health-related quality of life for each type of household, and various support systems are needed in their social networks to suit their characteristics.