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Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity

  • Chih-Hsin Lin;Yu-Shao Hsieh;Ying-Chieh Sun;Wun-Han Huang;Shu-Ling Chen;Zheng-Kui Weng;Te-Hsien Lin;Yih-Ru Wu;Kuo-Hsuan Chang;Hei-Jen Huang;Guan-Chiun Lee;Hsiu Mei Hsieh-Li;Guey-Jen Lee-Chen
    • Biomolecules & Therapeutics
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    • v.31 no.1
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    • pp.127-138
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    • 2023
  • Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer's disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine's screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

Analysis of a Compound-Target Network of Oryeong-san (오령산 구성성분-타겟 네트워크 분석)

  • Kim, Sang-Kyun
    • Journal of the Korea Knowledge Information Technology Society
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    • v.13 no.5
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    • pp.607-614
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    • 2018
  • Oryeong-san is a prescription widely used for diseases where water is stagnant because it has the effect of circulating the water in the body and releasing it into the urine. In order to investigate the mechanisms of oryeong-san, we in this paper construct and analysis the compound-target network of medicinal materials constituting oryeong-san based on a systems pharmacology approach. First, the targets related to the 475 chemical compounds of oryeong-san were searched in the STITCH database, and the search results for the interactions between compounds and targets were downloaded as XML files. The compound-target network of oryeong-san is visualized and explored using Gephi 0.8.2, which is an open-source software for graphs and networks. In the network, nodes are compounds and targets, and edges are interactions between the nodes. The edge is weighted according to the reliability of the interaction. In order to analysis the compound-target network, it is clustered using MCL algorithm, which is able to cluster the weighted network. A total of 130 clusters were created, and the number of nodes in the cluster with the largest number of nodes was 32. In the clustered network, it was revealed that the active compounds of medicinal materials were associated with the targets for regulating the blood pressure in the kidney. In the future, we will clarify the mechanisms of oryeong-san by linking the information on disease databases and the network of this research.

Trends of Dental Caries Prevalence in Children Under 14-Year-Old Using a Health Insurance Database (건강보험 데이터를 이용한 14세 이하 소아청소년의 치아 우식 유병률 경향성)

  • Seongeun Mo;Jaegon Kim;Daewoo Lee;Yeonmi Yang
    • Journal of the korean academy of Pediatric Dentistry
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    • v.50 no.4
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    • pp.409-420
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    • 2023
  • The purpose of this study is to analyze trends in the prevalence of dental caries and demand for dental caries treatment among children under 14 years old using Health Insurance Review and Assessment data. The analysis was conducted using treatment records from a random sample of approximately 1 million pediatric patients from a population that included all children and adolescents for each year from 2011 to 2020. In this study, the number of children diagnosed with K02 dental caries and the number of children receiving dental caries treatment across all ages have increased. However, the number of children aged 10 to 14 who received pulp treatment or extraction has decreased. In the National Survey of Children's Oral Health, the decay-missing-filled teeth index for 5- and 12-year-olds has stagnated or increased slightly, but the percentage of the population with active dental caries has decreased. Accessibility and local environments for dental caries treatment have generally improved compared to the past, but preventive dental care has stagnated over the past decade. Therefore, it is necessary to evaluate the effectiveness of oral health programs implemented in Korea to promote and prevent dental caries among children.

Active Phytochemicals of Indian Spices Target Leading Proteins Involved in Breast Cancer: An in Silico Study

  • Ashok Kumar Krishnakumar;Jayanthi Malaiyandi;Pavatharani Muralidharan;Arvind Rehalia;Anami Ahuja;Vidhya Duraisamy;Usha Agrawal;Anjani Kumar Singh;Himanshu Narayan, Singh;Vishnu Swarup
    • Journal of the Korean Chemical Society
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    • v.68 no.3
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    • pp.151-159
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    • 2024
  • Indian spices are well known for their numerous health benefits, flavour, taste, and colour. Recent Advancements in chemical technology have led to better extraction and identification of bioactive molecules (phytochemicals) from spices. The therapeutic effects of spices against diabetes, cardiac problems, and various cancers has been well established. The present in silico study aims to investigate the binding affinity of 29 phytochemicals from 11 Indian spices with two prominent proteins, BCL3 and CXCL10 involved in invasiveness and bone metastasis of breast cancer. The three-dimensional structures of 29 phytochemicals were extracted from PubChem database. Protein Data Bank was used to retrieve the 3D structures of BCL3 and CXCL10 proteins. The drug-likeness and other properties of compounds were analysed by ADME and Lipinski rule of five (RO5). All computational simulations were carried out using Autodock 4.0 on Windows platform. The proteins were set to be rigid and compounds were kept free to rotate. In-silico study demonstrated a strong complex formation (positive binding constants and negative binding energy ΔG) between all phytochemicals and target proteins. However, piperine and sesamolin demonstrated high binding constants with BCL3 (50.681 × 103 mol-1, 137.76 × 103 mol-1) and CXCL10 (98.71 × 103 mol-1, 861.7 × 103 mol-1), respectively. The potential of these two phytochemicals as a drug candidate was highlighted by their binding energy of -6.5 kcal mol-1, -7.1 kcal mol-1 with BCL3 and -6.9 kcal mol-1, -8.2 kcal mol-1 with CXCL10, respectively coupled with their favourable drug likeliness and pharmacokinetics properties. These findings underscore the potential of piperine and sesamolin as drug candidates for inhibiting invasiveness and regulating breast cancer metastasis. However, further validation through in vitro and in vivo studies is necessary to confirm the in silico results and evaluate their clinical potential.

A Comparative Study on Mapping and Filtering Radii of Local Climate Zone in Changwon city using WUDAPT Protocol (WUDAPT 절차를 활용한 창원시의 국지기후대 제작과 필터링 반경에 따른 비교 연구)

  • Tae-Gyeong KIM;Kyung-Hun PARK;Bong-Geun SONG;Seoung-Hyeon KIM;Da-Eun JEONG;Geon-Ung PARK
    • Journal of the Korean Association of Geographic Information Studies
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    • v.27 no.2
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    • pp.78-95
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    • 2024
  • For the establishment and comparison of environmental plans across various domains, considering climate change and urban issues, it is crucial to build spatial data at the regional scale classified with consistent criteria. This study mapping the Local Climate Zone (LCZ) of Changwon City, where active climate and environmental research is being conducted, using the protocol suggested by the World Urban Database and Access Portal Tools (WUDAPT). Additionally, to address the fragmentation issue where some grids are classified with different climate characteristics despite being in regions with homogeneous climate traits, a filtering technique was applied, and the LCZ classification characteristics were compared according to the filtering radius. Using satellite images, ground reference data, and the supervised classification machine learning technique Random Forest, classification maps without filtering and with filtering radii of 1, 2, and 3 were produced, and their accuracies were compared. Furthermore, to compare the LCZ classification characteristics according to building types in urban areas, an urban form index used in GIS-based classification methodology was created and compared with the ranges suggested in previous studies. As a result, the overall accuracy was highest when the filtering radius was 1. When comparing the urban form index, the differences between LCZ types were minimal, and most satisfied the ranges of previous studies. However, the study identified a limitation in reflecting the height information of buildings, and it is believed that adding data to complement this would yield results with higher accuracy. The findings of this study can be used as reference material for creating fundamental spatial data for environmental research related to urban climates in South Korea.

NEAR-INFRARED VARIABILITY OF OPTICALLY BRIGHT TYPE 1 AGN (가시광에서 밝은 1형 활동은하핵의 근적외선 변광)

  • JEON, WOOYEOL;SHIM, HYUNJIN;KIM, MINJIN
    • Publications of The Korean Astronomical Society
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    • v.36 no.3
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    • pp.47-63
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    • 2021
  • Variability is one of the major characteristics of Active Galactic Nuclei (AGN), and it is used for understanding the energy generation mechanism in the center of AGN and/or related physical phenomena. It it known that there exists a time lag between AGN light curves simultaneously observed at different wavelengths, which can be used as a tool to estimate the size of the area that produce the radiation. In this paper, We present long term near-infrared variability of optically bright type 1 AGN using the Wide-field Infrared Survey Explorer data. From the Milliquas catalogue v6.4, 73 type 1 QSOs/AGN and 140 quasar candidates are selected that are brighter than 18 mag in optical and located within 5 degree around the ecliptic poles. Light curves in the W1 band (3.4 ㎛) and W2 band (4.6 ㎛) during the period of 2010-2019 were constructed for these objects by extracting multi-epoch photometry data from WISE and NEOWISE all sky survey database. Variability was analyzed based on the excess variance and the probability Pvar. Applying both criteria, the numbers of variable objects are 19 (i.e., 26%) for confirmed AGN and 12 (i.e., 9%) for AGN candidates. The characteristic time scale of the variability (τ) and the variability amplitude (σ) were derived by fitting the DRW model to W1 and W2 light curves. No significant correlation is found between the W1/W2 magnitude and the derived variability parameters. Based on the subsample that are identified in the X-ray source catalog, there exists little correlation between the X-ray luminosity and the variability parameters. We also found four AGN with changing W1-W2 color.

Policies for Improving Thermal Environment Using Vulnerability Assessment - A Case Study of Daegu, Korea - (열취약성 평가를 통한 열환경 개선 정책 제시 - 대구광역시를 사례로 -)

  • KIM, Kwon;EUM, Jeong-Hee
    • Journal of the Korean Association of Geographic Information Studies
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    • v.21 no.2
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    • pp.1-23
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    • 2018
  • This study aims to propose a way for evaluating thermal environment vulnerability associated with policy to improve thermal environment. For this purpose, a variety of indices concerning thermal vulnerability assessment and adaptation policies for climate change applied to 17 Korean cities were reviewed and examined. Finally, 15 indices associated with policies for improving thermal environment were selected. The selected indices for thermal vulnerability assessment were applied to Daegu Metropolitan City of South Korea as a case study. As results, 15 vulnerability maps based on the standardized indices were established, and a comprehensive map with four grades of thermal vulnerability were established for Daegu Metropolitan City. As results, the area with the highest rated area in the first-grade(most vulnerable to heat) was Dong-gu, followed by Dalseo-gu and Buk-gu, and the highest area ratio of the first-grade regions was Ansim-1-dong in Dong-gu. Based on the standardized indices, the causes of the thermal environment vulnerability of Ansim-1-dong were accounted for the number of basic livelihood security recipients, the number of cardiovascular disease deaths, heat index, and Earth's surface temperature. To improve the thermal environment vulnerability of Ansim-1-dong, active policy implementation is required in expansion and maintenance of heat wave shelters, establishment of database for the population with diseases susceptible to high temperature environments, expansion of shade areas and so on. This study shows the applicability of the vulnerability assessment method linked with the policies and is expected to contribute to the strategic and effective establishment of thermal environment policies in urban master district plans.

Advanced Improvement for Frequent Pattern Mining using Bit-Clustering (비트 클러스터링을 이용한 빈발 패턴 탐사의 성능 개선 방안)

  • Kim, Eui-Chan;Kim, Kye-Hyun;Lee, Chul-Yong;Park, Eun-Ji
    • Journal of Korea Spatial Information System Society
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    • v.9 no.1
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    • pp.105-115
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    • 2007
  • Data mining extracts interesting knowledge from a large database. Among numerous data mining techniques, research work is primarily concentrated on clustering and association rules. The clustering technique of the active research topics mainly deals with analyzing spatial and attribute data. And, the technique of association rules deals with identifying frequent patterns. There was an advanced apriori algorithm using an existing bit-clustering algorithm. In an effort to identify an alternative algorithm to improve apriori, we investigated FP-Growth and discussed the possibility of adopting bit-clustering as the alternative method to solve the problems with FP-Growth. FP-Growth using bit-clustering demonstrated better performance than the existing method. We used chess data in our experiments. Chess data were used in the pattern mining evaluation. We made a creation of FP-Tree with different minimum support values. In the case of high minimum support values, similar results that the existing techniques demonstrated were obtained. In other cases, however, the performance of the technique proposed in this paper showed better results in comparison with the existing technique. As a result, the technique proposed in this paper was considered to lead to higher performance. In addition, the method to apply bit-clustering to GML data was proposed.

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A Study of Domain Name Disputes Resolution with the Korea-U.S. FTA Agreement (한미자유무역협정(FTA)에 따른 도메인이름 분쟁해결의 개선방안에 관한 연구)

  • Park, Yu-Sun
    • Journal of Arbitration Studies
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    • v.17 no.2
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    • pp.167-187
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    • 2007
  • As Korea has reached a free trade agreement with the United States of America, it is required to provide an appropriate procedure to ".kr" domain name disputes based on the principles established in the Uniform Domain Name Dispute Resolution Policy(UDRP). Currently, Internet address Dispute Resolution Committee(IDRC) established under Article 16 of the Act on Internet Address Resources provides the dispute resolution proceedings to resolve ".kr" domain name disputes. While the IDRC's proceeding is similar to the UDRP administrative proceeding in procedural aspects, the Domain Name Dispute Mediation Policy that is established by the IDRC and that applies to disputes involving ".kr" domain names is very different from the UDRP for generic Top Level Domain (gTLD) in substantial aspects. Under the Korea-U.S. Free Trade Agreement(KORUS FTA), it is expected that either the Domain Name Dispute Mediation Policy to be amended to adopt the UDRP or the IDRC to examine the Domain Name Dispute Mediation Policy in order to harmonize it with the principles established in the UDRP. It is a common practice of cybersquatters to warehouse a number of domain names without any active use of these domain names after their registration. The Domain Name Dispute Mediation Policy provides that the complainant may request to transfer or delete the registration of the disputed domain name if the registrant registered, holds or uses the disputed domain name in bad faith. This provision lifts the complainant's burden of proof to show the respondent's bad faith because the complainant is only required to prove one of the three bad faiths which are registration in bad faith, holding in bad faith, or use in bad faith. The aforementioned resolution procedure is different from the UDRP regime which requires the complainant, in compliance with paragraph 4(b) of the UDRP, to prove that the disputed domain name has been registered in bad faith and is being used in bad faith. Therefore, the complainant carries heavy burden of proof under the UDRP. The IDRC should deny the complaint if the respondent has legitimate rights or interests in the domain names. Under the UDRP, the complainant must show that the respondent has no rights or legitimate interests in the disputed domain name. The UDRP sets out three illustrative circumstances, any one of which if proved by the respondent, shall be evidence of the respondent's rights to or legitimate interests in the domain name. As the Domain Name Dispute Mediation Policy provides only a general provision regarding the respondent's legitimate rights or interests, the respondent can be placed in a very week foundation to be protected under the Policy. It is therefore recommended for the IDRC to adopt the three UDRP circumstances to guide how the respondent can demonstrate his/her legitimate rights or interests in the disputed domain name. In accordance with the KORUS FTA, the Korean Government is required to provide online publication to a reliable and accurate database of contact information concerning domain name registrants. Cybersquatters often provide inaccurate contact information or willfully conceal their identity to avoid objection by trademark owners. It may cause unnecessary and unwarranted delay of the administrative proceedings. The respondent may loss the opportunity to assert his/her rights or legitimate interests in the domain name due to inability to submit the response effectively and timely. The respondent could breach a registration agreement with a registrar which requires the registrant to submit and update accurate contact information. The respondent who is reluctant to disclose his/her contact information on the Internet citing for privacy rights and protection. This is however debatable as the respondent may use the proxy registration service provided by the registrar to protect the respondent's privacy.

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A Study on Contents of Vitamin K1 in Local Agricultural Products (지역농산물의 비타민 K1 함량 조사)

  • Lee, A Reum;Kim, Joo Hee;Park, Jae-Ho;Kim, Youngho;Hong, Eui Yon;Kim, Haeng-Ran;Choi, Youngmin;Lee, Junsoo;Eom, Hyun-Ju
    • The Korean Journal of Food And Nutrition
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    • v.29 no.3
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    • pp.301-306
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    • 2016
  • Vitamin K (phylloquinone) is an essential cofactor in the synthesis of active blood-clotting factors II, VII, IX and X. Deficiency of vitamin K leads to inadequate activity of these factors, resulting in bleeding. In this study, we investigated vitamin $K_1$ content of agricultural products that are widely and specifically grown in Korea including 9 leaves and vegetables, 16 fruits, and 11 cereals and specialty crops. Vitamin $K_1$ analysis of the agro-samples was by a validated, modified, reversed phase-HPLC method with fluorescence detection after post-column derivatization. The vitamin $K_1$ content ranged from 1.83 to $682.73{\mu}g$/100 g in leaves and vegetables, 0.17 to $28.22{\mu}g$/100 g in fruits, and ND to $279{\mu}g$/100 g in cereals and specialty crops. Among the 36 samples, high content of vitamin $K_1$ were found in Gugija (Lycium chinense Miller) leaves (average $682.73{\mu}g$/100 g) and Hansan ramie leaves (average $423.12{\mu}g$/100 g); however, mushroom, amaranth and Chinese artichoke showed no detectable levels. The results of ourstudy provide reliable vitamin $K_1$ content of Korean grown agricultural products that expand nutritional information and food composition database.