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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.

Comparative analysis of inundation flow patterns and flood risk assessment methods within subway stations (지하철 역사 내 침수 흐름 분석 및 침수 위험도 평가 방법 비교)

  • Shin, Jaehyun;Kim, Minjeong;Cho, Inhwan;Park, Inhwan
    • Journal of Korea Water Resources Association
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    • v.56 no.10
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    • pp.667-678
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    • 2023
  • In this study, quasi-3D inundation flow simulations were conducted for a simplified subway station configuration. The effects of variations in rainwater inflow locations and discharge were investigated, analyzing the resulting inundation flow patterns and flood risk. The inundation simulation results calculated the incipient velocities for slipping and toppling accidents to assess pedestrian safety. The results indicated that velocities exceeding the incipient velocity for slipping accidents mainly occurred on the flooded staircase. Meanwhile, velocities surpassing the incipient toppling accidents were observed around the staircase and the corridor near the staircase leading to B2F. This observation is consistent with the results from the specific force distribution analysis. To provide detailed flood risk assessments, the Flood Hazard Degree (FD) was applied with four levels of criteria, along with the Flood Intensity Factor (FIF). The results demonstrated that FD identified a broader area at risk of flood-induced consequences compared to FIF. When comparing the different inundation risk assessment methods, the specific force method tended to overestimate the risk area, whereas FIF tended to underestimate it. Furthermore, among all assessment methods, the influence of rainwater discharge was found to have a more dominant effect on flood risk assessment compared to the number of rainwater inflow locations. Additionally, the direction of inundation flow influenced the assessed risk, with collision-induced flow patterns leading to higher flood risk than those with identical flow directions.

Purple perilla frutescens extracts containing α-asarone inhibit inflammatory atheroma formation and promote hepatic HDL cholesterol uptake in dyslipidemic apoE-deficient mice

  • Sin-Hye Park;Young Eun Sim;Min-Kyung Kang;Dong Yeon Kim;Il-Jun Kang;Soon Sung Lim;Young-Hee Kang
    • Nutrition Research and Practice
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    • v.17 no.6
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    • pp.1099-1112
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    • 2023
  • BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

Investigating the Performance of Bayesian-based Feature Selection and Classification Approach to Social Media Sentiment Analysis (소셜미디어 감성분석을 위한 베이지안 속성 선택과 분류에 대한 연구)

  • Chang Min Kang;Kyun Sun Eo;Kun Chang Lee
    • Information Systems Review
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    • v.24 no.1
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    • pp.1-19
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    • 2022
  • Social media-based communication has become crucial part of our personal and official lives. Therefore, it is no surprise that social media sentiment analysis has emerged an important way of detecting potential customers' sentiment trends for all kinds of companies. However, social media sentiment analysis suffers from huge number of sentiment features obtained in the process of conducting the sentiment analysis. In this sense, this study proposes a novel method by using Bayesian Network. In this model MBFS (Markov Blanket-based Feature Selection) is used to reduce the number of sentiment features. To show the validity of our proposed model, we utilized online review data from Yelp, a famous social media about restaurant, bars, beauty salons evaluation and recommendation. We used a number of benchmarking feature selection methods like correlation-based feature selection, information gain, and gain ratio. A number of machine learning classifiers were also used for our validation tasks, like TAN, NBN, Sons & Spouses BN (Bayesian Network), Augmented Markov Blanket. Furthermore, we conducted Bayesian Network-based what-if analysis to see how the knowledge map between target node and related explanatory nodes could yield meaningful glimpse into what is going on in sentiments underlying the target dataset.

Factors Affecting End-of-life Care Performance of Nurses in Hospice and Palliative Nursing Institutions (호스피스 완화의료 전문기관 간호사의 임종간호수행 영향요인)

  • Min-Gi Jun;Myoung-Jin Kwon
    • Journal of Industrial Convergence
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    • v.22 no.5
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    • pp.107-116
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    • 2024
  • This study is a descriptive research study to determine the extent to which end-of-life care stress, death awareness, and prior decision-making attitudes of nurses at a hospice and palliative nursing institution have an impact on end-of-life care performance. The subjects of this study were 200 nurses working at a hospice and palliative nursing institution. Data collection for this study was conducted from August 9 to September 30, 2021, using two methods: written questionnaire and internet survey. The data analysis method used Pearson's correlation coefficient to analyze the relationship between the subjects' end-of-life care stress, death awareness, prior decision-making attitude, and end-of-life care performance. Hierarchical Regression was used to identify factors affecting the subject's end-of-life care performance. The results of this study showed a significant correlation between end-of-life care performance and death awareness (r=.22, p=.002), and end-of-life care performance and prior decision-making attitude (r=.20, p=.004). And prior decision-making attitude and death awareness had a significant impact on end-of-life care performance. As death awareness and prior decision-making attitudes increased, end-of-life care performance increased, and end-of-life care stress did not appear to be a statistically significant factor influencing end-of-life care performance. In order to improve hospice nurses' ability to provide end-of-life care, intervention that takes into account the influencing factors is required.

Along and across-wind vibration control of shear wall-frame buildings with flexible base by using passive dynamic absorbers

  • Ivan F. Huergo;Hugo Hernandez-Barrios;Roberto Gomez-Martinez
    • Wind and Structures
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    • v.38 no.1
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    • pp.15-42
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    • 2024
  • A flexible-base coupled-two-beam (CTB) discrete model with equivalent tuned mass dampers is used to assess the effect of soil-structure interaction (SSI) and different types of lateral resisting systems on the design of passive dynamic absorbers (PDAs) under the action of along-wind and across-wind loads due to vortex shedding. A total of five different PDAs are considered in this study: (1) tuned mass damper (TMD), (2) circular tuned sloshing damper (C-TSD), (3) rectangular tuned sloshing damper (R-TSD), (4) two-way liquid damper (TWLD) and (5) pendulum tuned mass damper (PTMD). By modifying the non-dimensional lateral stiffness ratio, the CTB model can consider lateral deformations varying from those of a flexural cantilever beam to those of a shear cantilever beam. The Monte Carlo simulation method was used to generate along-wind and across-wind loads correlated along the height of a real shear wall-frame building, which has similar fundamental periods of vibration and different modes of lateral deformation in the xz and yz planes, respectively. Ambient vibration tests were conducted on the building to identify its real lateral behavior and thus choose the most suitable parameters for the CTB model. Both alongwind and across-wind responses of the 144-meter-tall building were computed considering four soil types (hard rock, dense soil, stiff soil and soft soil) and a single PDA on its top, that is, 96 time-history analyses were carried out to assess the effect of SSI and lateral resisting system on the PDAs design. Based on the parametric analyses, the response significantly increases as the soil flexibility increases for both type of lateral wind loads, particularly for flexural-type deformations. The results show a great effectiveness of PDAs in controlling across-wind peak displacements and both along-wind and across-wind RMS accelerations, on the contrary, PDAs were ineffective in controlling along-wind peak displacements on all soil types and different kind of lateral deformation. Generally speaking, the maximum possible value of the PDA mass efficiency index increases as the soil flexibility increases, on the contrary, it decreases as the non-dimensional lateral stiffness ratio of the building increases; therefore, there is a significant increase of the vibration control effectiveness of PDAs for lateral flexural-type deformations on soft soils.

Development and Validation of MRI-Based Radiomics Models for Diagnosing Juvenile Myoclonic Epilepsy

  • Kyung Min Kim;Heewon Hwang;Beomseok Sohn;Kisung Park;Kyunghwa Han;Sung Soo Ahn;Wonwoo Lee;Min Kyung Chu;Kyoung Heo;Seung-Koo Lee
    • Korean Journal of Radiology
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    • v.23 no.12
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    • pp.1281-1289
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    • 2022
  • Objective: Radiomic modeling using multiple regions of interest in MRI of the brain to diagnose juvenile myoclonic epilepsy (JME) has not yet been investigated. This study aimed to develop and validate radiomics prediction models to distinguish patients with JME from healthy controls (HCs), and to evaluate the feasibility of a radiomics approach using MRI for diagnosing JME. Materials and Methods: A total of 97 JME patients (25.6 ± 8.5 years; female, 45.5%) and 32 HCs (28.9 ± 11.4 years; female, 50.0%) were randomly split (7:3 ratio) into a training (n = 90) and a test set (n = 39) group. Radiomic features were extracted from 22 regions of interest in the brain using the T1-weighted MRI based on clinical evidence. Predictive models were trained using seven modeling methods, including a light gradient boosting machine, support vector classifier, random forest, logistic regression, extreme gradient boosting, gradient boosting machine, and decision tree, with radiomics features in the training set. The performance of the models was validated and compared to the test set. The model with the highest area under the receiver operating curve (AUROC) was chosen, and important features in the model were identified. Results: The seven tested radiomics models, including light gradient boosting machine, support vector classifier, random forest, logistic regression, extreme gradient boosting, gradient boosting machine, and decision tree, showed AUROC values of 0.817, 0.807, 0.783, 0.779, 0.767, 0.762, and 0.672, respectively. The light gradient boosting machine with the highest AUROC, albeit without statistically significant differences from the other models in pairwise comparisons, had accuracy, precision, recall, and F1 scores of 0.795, 0.818, 0.931, and 0.871, respectively. Radiomic features, including the putamen and ventral diencephalon, were ranked as the most important for suggesting JME. Conclusion: Radiomic models using MRI were able to differentiate JME from HCs.

Analysis of factors affecting the employment of people with developmental disabilities (발달장애인 취업의 성공 및 저해 요인 연구)

  • Jinhyeok Choi;Byeolhae Shin
    • Journal of Intellectual Disabilities
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    • v.20 no.2
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    • pp.67-90
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    • 2018
  • This study aims to provide base data and suggestions to develop a system which considers both improvement of personal competency and national and societal dimensions for employment of people with developmental disabilities. The raw data of '1st Panel Survey of Employment for the Disabled from 2nd wave' was analyzed by cross analysis and logistic regression in order to examine factors which have potential to affect employment of people with developmental disabilities. The results are as follows: 'Gender', 'Level of education', health status', 'communication skills', 'possess a license or certification', 'actual skills and qualification of area of expertise', 'family support level for employment', 'satisfaction level of daily life', 'job hunting through public agency' and 'job hunting through acquaintance' showed positive effect on employment of developmental disabilities population. On the other hand, 'need level of assistance in daily life' and 'national basic livelihood security' showed negative effect on employment of developmental disabilities population. The improvement of personal competency should be focus on the lacking skills such as communication skills and health. In addition, educational and occupational support need to be diversified. A need of solution for low-income issue and modification of national basic livelihood security policy was suggested to increase motivation to do job-hunting and maintenance of employment.

Extraordinary Response of Metastatic Pancreatic Cancer to Chemotherapy (항암 치료에 좋은 반응을 보였던 전이성 췌장암 증례)

  • Shin, Dong Woo;Kim, Jinkook;Lee, Jong-chan;Kim, Jaihwan;Hwang, Jin-Hyeok
    • Journal of Digestive Cancer Research
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    • v.7 no.1
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    • pp.22-25
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    • 2019
  • A 58-year-old woman presented with right flank and back pain for one month. After undergoing an abdominal computed tomography (CT), she was referred to our hospital. The abdominal CT showed a hypodense pancreatic tail mass with multiple retroperitoneal lymph node metastases. Positron emission tomography-computed tomography (PET-CT) scan showed high 18F-FDG uptake in pancreatic tumor and enlarged lymph nodes. Endoscopic ultrasound fine needle aspiration (EUS-FNA) revealed adenocarcinoma, which stained strongly in hENT1 (human equilibrative nucleoside transporter 1) on immunohistochemistry. She received gemcitabine 1,000 mg/m2 + nanoparticle albumin-bound paclitaxel 125 mg/m2 as a palliative chemotherapy. Follow-up abdominal CT and PET-CT after 4 cycles of chemotherapy showed that both pancreatic mass and the metastatic retroperitoneal lymph nodes were nearly disappeared. We report a case of 58-year-old female with metastatic pancreatic cancer who had a dramatic response to palliative chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel).

Potential Mechanism and Involvement of p120-Catenin in the Malignant Biology of Glioma

  • Leilei Wang;Jianshen Liang;Suzhen Ji;Chunlou Wang;Qiang Huang
    • Journal of Korean Neurosurgical Society
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    • v.67 no.6
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    • pp.609-621
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    • 2024
  • Objective : This study analyzed the influence of p120-catenin (catenin [cadherin-associated protein], delta 1 [CTNND1]) on the malignant characteristics of glioma and elucidated the potential underlying mechanism. Methods : The p120 expression level was assessed in the brain tissues of 42 glioma patients and 10 patients with epilepsy by using the immunohistochemical method. Meanwhile, quantitative polymerase chain reaction (QT-PCR) technology was employed to assess the expression of p120 in the brain tissues of 71 glioma patients and 13 epilepsy patients. LN229, U251, and U87 glioma cells were used for in vitro analysis and categorized into four treatment groups : siRNA-blank control (BC) group (no RNA sequence was transfected), siRNA-negative control (NC) group (transfected control RNA sequences with no effect), and siRNA-1 and siRNA-2 groups (two p120-specific interfering RNA transfection). p120 expression in these treatment groups was quantified by western blotting assay. The migratory and invasive capabilities of glioma cells were studied by wound healing assay and Transwell invasion assay, respectively, under different treatment conditions. MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide) assay and cell cycle and apoptosis assay were used to determine glioma cell proliferation and apoptosis, respectively. Enzyme-labeled assay was performed to measure intracellular calcium ion concentration. Immunofluorescence assay was performed for determining microtubule formation and glioma cell distribution. Results : Brain tissues of the glioma group exhibited a remarkable increase in the p120 expression level as compared to brain tissues of the nontumor group (p<0.05). Furthermore, a strong positive correlation was noted between the malignancy degree in glioma brain tissues and p120 expression in Western blotting (r=0.906, p<0.0001) and QT-PCR (F=830.6, p<0.01). Compared to the BC and NC groups, the siRNA transfection groups showed a significant suppression in p120 expression in glioma cells (p<0.05), with a marked attenuation in the invasive, migratory, and proliferative capabilities of glioma cells as well as an increase in apoptotic potential (p<0.05). Enzyme-labeled assay showed a remarkable increase in calcium concentration in glioma cells after siRNA treatment. Immunofluorescence assay revealed that the microtubule formation ability of glioma cells reduced after siRNA treatment. Conclusion : p120 has a pivotal involvement in facilitating glioma cell invasion and proliferation by potentially modulating these processes through its involvement in microtubule formation and regulation of intracellular calcium ion levels.