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Implication of High Mobility Group Box 1 (HMGB1) in Multicellular Tumor Spheroid (MTS) Culture-induced Epithelial-mesenchymal Transition (Multicellular tumor spheroid (MTS) 배양에 의한 EMT에서 HMGB1의 역할)

  • Lee, Su Yeon;Ju, Min Kyung;Jeon, Hyun Min;Kim, Cho Hee;Park, Hye Gyeong;Kang, Ho Sung
    • Journal of Life Science
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    • v.29 no.1
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    • pp.9-17
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    • 2019
  • As tumors develop, they encounter microenvironmental stress, such as hypoxia and glucose depletion, due to poor vascular function, thereby leading to necrosis, which is observed in solid tumors. Necrotic cells are known to release cellular cytoplasmic contents, such as high mobility group box 1 (HMGB1), into the extracellular space. The release of HMGB1, a proinflammatory and tumor-promoting cytokine, plays an important role in promoting inflammation and metabolism during tumor development. Recently, HMGB1 was shown to induce the epithelial-mesenchymal transition (EMT) and metastasis. However, the underlying mechanism of the HMGB1-induced EMT, invasion, and metastasis is unclear. In this study, we showed that noninvasive breast cancer cells MCF-7 formed tightly packed, rounded spheroids and that the cells in the inner regions of a multicellular tumor spheroid (MTS), an in vitro model of a solid tumor, led to necrosis due to an insufficient supply of O2 and glucose. In addition, after 7 d of MTS culture, the EMT was induced via the transcription factor Snail. We also showed that HMGB1 receptors, including RAGE, TLR2, and TLR4, were induced by MTS culture. RAGE, TLR2, and TLR4 shRNA inhibited MTS growth, supporting the idea that RAGE/TLR2/TLR4 play critical roles in MTS growth. They also prevented MTS culture-induced Snail expression, pointing to RAGE/TLR2/TLR4-dependent Snail expression. RAGE, TLR2, and TLR4 shRNA suppressed the MTS-induced EMT. In human cancer tissues, high levels of RAGE, TLR2, and TLR4 were detected. These findings demonstrated that the HMGB-RAGE/TLR2/TLR4-Snail axis played a crucial role in the growth of the MTS and MTS culture-induced EMT.

Single Dose Oral Toxicity Test of Water Extract of Corni Fructus in ICR Mice (ICR 마우스를 이용한 산수유 건피 추출물의 단회 경구투여 독성시험)

  • Hwang-Bo, Hyun;Kwon, Da Hye;Kim, Min Young;Ji, Seon Yeong;Choi, Eun Ok;Kim, Sung Ok;Jeong, Ji-Suk;Hong, Su Hyun;Choi, Sung Hyun;Park, Cheol;Choi, Yung Hyun
    • Journal of Life Science
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    • v.29 no.1
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    • pp.112-117
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    • 2019
  • Herbal medicines are widely used as therapeutic products in many countries. Corni fructus (CF), the dried ripe sarcocarp of Cornus officinalis Sieb. et Zucc (Cornaceae), has been used for thousands of years in traditional medicine and has been reported to be effective for the prevention and treatment of various diseases, such as kidney diseases and diabetes. Recent research on CF has documented a wide spectrum of therapeutic properties, which include anti-inflammatory, ant-oxidative, immunomodulatory, and anti-cancer effects. However, there is no information on its safety. Therefore, in this study, the toxicity of water extract of CF to ICR mice was investigated. The mice received a single dose of water extract of CF (1,000, 2,000, and 5,000 mg/kg of body weight) via the oral route. Mortality, clinical signs, body weight changes, gross findings, and weights of the principal organs after 14 d were then assessed. The results revealed no adverse effects of CF as determined by clinical signs, body weights, or organ weights and no gross pathological findings in any of the treatment groups. These results suggest that the 50% lethal dose and approximated lethal dose of CF extract is over 5,000 mg/kg. The findings provide scientific evidence for the safety of CFs.

Anti-Cancer Effect of Ursolic Acid in Melanoma Cell A375SM and A375P (Ursolic acid의 악성 흑색종 세포주 A375SM과 A375P에서의 항암효능)

  • Woo, Joong-Seok;Kim, Na-Won;Lee, Jin-Gyu;Kim, Jae-Hyuk;Lim, Da-Young;Kang, Shin-Woo;Kim, Sung-Hyun;Yoo, Eun-Seon;Lee, Jae-Han;Han, So-Hee;Park, Young-Seok;Kim, Byeong-Soo;Kim, Sang-Ki;Park, Byung-Kwon;Jung, Ji-Youn
    • Journal of Food Hygiene and Safety
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    • v.34 no.2
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    • pp.183-190
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    • 2019
  • Ursolic acid is recognized for various effects such as anti-cancer, antioxidant, and anti-inflammatory activity. In this study, we confirmed the anti-cancer effect of ursolic acid on human melanoma cancer cells, A375SM and A375P. Survival rate of the melanoma cells was confirmed by MTT assay and the proliferation rate was confirmed by wound healing assay. The rate of apoptotic bodies was confirmed by DAPI staining, and apoptosis rate was confirmed by flow cytometry. The induction of apoptosis protein was examined by western blotting according to the concentration of ursolic acid in melanoma cells. The survival and proliferation rates of melanoma cells were decreased according to the treatment concentrations of ursolic acid. DAPI staining showed that chromosomal condensation of melanoma cells was increased with increasing concentrations of ursolic acid, and increased apoptosis rate of melanoma cells by ursolic acid was confirmed by flow cytometry. We also confirmed by western blotting that cleaved-PARP and Bax were increased and Bcl-2 was decreased at $12{\mu}M$ concentration of uricolic acid in melanoma cells. This study was carried out at low concentrations of ursolic acid, 0 to $20{\mu}M$, and analyzed 24 h after treatment. As a result of this study, it is thought that ursolic acid has the anti-cancer effect through the regulation of apoptosis-related proteins in melanoma cells A375SM and A375P.

Exploring the Objectives and Contents of Global Citizenship Education in the NSFCS 3.0: Focusing on the View of the 'World' and the Keywords (미국 국가 기준 가정과교육과정에 포함된 세계시민교육 관련 목표와 내용 탐색: '세계'관점과 핵심어를 중심으로)

  • Heo, Young-Sun;Kim, Nam-Eun;Chae, Jung Hyun
    • Journal of Korean Home Economics Education Association
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    • v.33 no.3
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    • pp.107-127
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    • 2021
  • The purpose of this study is to examine the relationship between the content areas and competencies of the Family & Consumer Sciences National Standards(NSFCS 3.0) of the U. S. and UNESCO Global Citizenship Education(GCED). For this purpose, the global perspective, content areas and competencies in NSFCS 3.0 and the keywords related to the three areas of content areas of UNESCO GCED were analyzed. Specifically, the content standards and competencies related to the words 'world' or 'global' were extracted and their relationship to the GCED topics and keywords were analyzed. The results of the study are as follows. First, NSFCS 3.0 described the direct correlation between individuals and the world by recognizing individuals as global citizens in 14 areas except for 'interpersonal relations' and 'parenting', specifically using the keyword of 'world' in content standards and competencies. Second, in the content standards and competencies of NSFCS 3.0, the keywords related to the topics of GCED areas were presented evenly in the three areas of FCS, dietary habits, family life, and human development. The social and emotional areas were not presented in clothing, housing, and consumer life. On the other hand, the behavioral area, which is emphasized most in the GCED, is presented in all the FCS content areas. From this, it is apparent that the learning field for GCED may be considered as the area of life pursued by the home economics curriculum. The results of this study provide foundational bases for understanding the relationship between NSFCS 3.0 and the GCED, and implications as to how to implement the content of the GCED in the next revision of the national home economics curriculum of Korea.

Evaluation of Perceived Naturalness of Urban Parks Using Hemeroby Index (헤메로비 등급(Hemeroby Index)을 활용한 도시공원의 인지된 자연성 평가)

  • Kim, Do-Eun;Son, Yong-Hoon
    • Journal of the Korean Institute of Landscape Architecture
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    • v.49 no.2
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    • pp.89-100
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    • 2021
  • This study evaluated the degree of interaction between the people and the environment using perceived naturalness measure. The seventh-grade index of Hemeroby was divided into subclasses of land cover according to degrees of human influence. The grade was standardized for each indicator to evaluate the current state of urban parks in Seoul by applying probability density function and weight. User evaluation was conducted on six distinctive parks selected. In the results, three implications were found between spatial evaluation according to the perceived naturalness. First, park users evaluated highly for the spaces such as broad-leaved forest, coniferous forest and mixed forest evaluated highly in the Hemeroby grade index. Park users generally recognized that various types of trees in the area had high naturalness. The density of trees is one of the factors in perceived naturalness. Second, water spaces were highly evaluated for naturalness in the Hemeroby grade index. However, the perceived naturalness of water spaces such as inland wetlands, pond and reservoir evaluated in various ways depending on environmental conditions around the park. Third, perceived naturalness is easily evaluated through vertical landscape elements such as trees rather than horizontal landscapes such as grassland. The perceived naturalness is similar to the naturalness evaluation using land cover. However the study found the perceived naturalness for a specific space was different from the Hemeroby index. Perceived naturalness by the user includes the content that the individual sees, hears, and experiences. Park users are usually structuring naturalness through evaluating the value of urban green spaces based on personal perception. Therefore there is no absolute standard criterion for evaluating the naturalness of urban green spaces. A deeper study is needed that considers user bundles or user groups with conflicting interests on the perceived naturalness in urban parks. These studies will be essential data on the direction of naturalness urban park service should provide.

Designing and Fabricating of the High-visibility Smart Safety Clothing (고시인성 스마트 안전의류의 설계 및 제작)

  • Park, Soon-Ja;Kim, Sun-Woong
    • Science of Emotion and Sensibility
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    • v.23 no.4
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    • pp.105-116
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    • 2020
  • The purpose of this study is to progress the limitations and disadvantages of existing safety clothing by applying high technology to current safety clothing that is produced and distributed only with fluorescent fabrics and retroreflective materials. Therefore, the industrial suspender-type safety belt and engineering technology are introduced, designed, and fabricated to help save a life in an emergency. First, the suspender-type safety belt to be developed is designed to emit light by LED attached to the film, and the body of the belt-wearer is recognized from a distance through retroreflection from the flashing LED. It aims to support people's safety by preventing accidents during roadside work, rescue activities, and sports activities at night. Second, with the development of advanced devices when the user is in an unconscious state due to distress or falls into an unconscious state due to distress or accident, the tilt sensor of the control unit attached to the belt automatically detects the angle of the human body and generates light and sound. It is intended to further enhance the utilization by mounting a sensing and signaling device that generates a distress signal and shaping it in the form of a belt attached to a vest that can be easily detached from the outside of the garment. When the wearer falls due to an accident, the tilt sensor of this belt detects the angle change and then the controller generates a high-frequency sound and repeated LED blinking signals at the same time. In the case of conventional safety vests, it is almost impossible to detect that the person is wearing a vest when there is no ambient light, but in case of the safety belts in this study, the sound and light signals of the safety belt enable us to find the wearer within 100 meters even when there is no ambient light.

Understanding the Access and Benefit-Sharing of Genetic Resources for Environmental Ecology Researchers (나고야의정서 이행에 따른 ABS 체계의 이해와 환경생태분야 연구자의 대응방안)

  • Lee, Jonghyun;An, Minho;Chang, YounHyo
    • Korean Journal of Environment and Ecology
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    • v.35 no.4
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    • pp.336-346
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    • 2021
  • The enforcement of the Nagoya Protocol, which regulates the acquisition and use of genetic sources, an essential material for biotechnology R&D, has imposed a burden for additional documentation works to researchers. In the past, countries regarded genetic resources as a common human heritage and thus allowed researchers to use them freely. However, they can no longer afford the luxury of such freedom now since many countries are introducing new laws and regulations on the acquisition and use of the resources as the Nagoya Protocol recognizes the exclusive ownership of genetic resources. Therefore, Korea, which is highly dependent on foreign genetic resources, needs a more systematic response. This paper aims to review the key contents of the Nagoya Protocol to raise awareness among domestic and foreign genetic resource users, including researchers of environment and ecology and present the overall structure, and flow of acquisition, access, and benefit sharing (ABS) for the use of foreign genetic resources to help them respond appropriately to the new landscape. The researchers' efforts and support at the national level are necessary at the same time to appropriately respond to the Nagoya Protocol. First, the researchers must understand the overall framework and the specific response in each stage under the Nagoya Protocol scheme. It is necessary to respond to the ABS procedure of the resource provider country from accessing genetic resources to sharing benefits resulting from it. In that regard, the Nagoya Protocol has imposed more restrictions on research activities and raised the burden outside of research. The current trend of recognizing the country's sovereign rights over genetic resources is likely to continue and widespread worldwide as resource-rich countries are expected to continue protecting their resources. Therefore, our study will help environmental ecology researchers understand ABS and conduct research under the Nagoya Protocol and legal obligations of resource provider countries step by step, from access to benefit sharing.

Alteration of MicroRNAs Targeted Integrins by PD-MSCs Transplantation Is Involved in Hepatic Regeneration in a Rat Model with BDL (담관결찰 쥐 모델에서 태반유래중간엽줄기세포 이식에 의한 miRNA 표적 인테그린 변화의 간재생 효과)

  • Park, Sohae
    • Journal of Life Science
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    • v.31 no.8
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    • pp.710-718
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    • 2021
  • Placenta-derived mesenchymal stem cells (PD-MSCs) are promising candidates for cell-based therapy in regenerative medicine. The migration and homing potential of PD-MSCs to injured sites is a critical property of MSC engraftment. MicroRNAs (miRNAs) have recently been shown to regulate the critical functions of MSCs, such as proliferation, survival, and migration. The objective of the present study was to identify the miRNA and target genes involved in PD-MSCs homing in a bile duct ligation (BDL) rat model. We selected candidate miRNAs targeting genes for PD-MSCs homing based on microarray analysis. PD-MSC engraftment in BDL-injured rat liver was identified by immunofluorescence assay and human-specific Alu gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) one week after transplantation. Compared with migrated naïve PD-MSCs under hypoxic and normoxic conditions (Hyp/Nor), the transplanted group with PD-MSCs (Tx) showed distinct differences in miRNA expressions in BDL-injured rat liver. We also validated the miRNAs and their target genes for PD-MSCs homing. The expressions of integrin α4 (ITGA4) and integrin α5 (ITGA5) target genes for miR-199a-5p and miR-148a-3p were significantly upregulated in the Tx group (p<0.05). In addition, integrin β1 (ITGB1) and integrin β8 (ITGB8) were upregulated by suppressing miR-183-5p and miR-145-5p, respectively. These results demonstrated that PD-MSCs regulate miRNA expression related to the integrin family for their homing effects on the BDL-injured rat liver. The findings further suggest that miRNA-mediated regulation of the integrin family contributes to the therapeutic efficacy of PD-MSCs in the rat hepatic fibrosis model by BDL.

Effect of Scytosiphon lomentaria Ethanol Extracts on Myostatin Activity and Zebrafish Obesity Induced by High Feeding (고리매(Scytosiphon lomentaria) 에탄올 추출물이 마이오스타틴 활성과 고 급식으로 유도된 비만 제브라피쉬에 미치는 영향)

  • Jung, Jun Gyo;Kim, Jae Hong;Kim, Jeong Hwan;Kim, Yong Soo;Jin, Deuk-Hee;Jin, Hyung-Joo
    • Journal of Life Science
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    • v.31 no.8
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    • pp.699-709
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    • 2021
  • Muscle mass improvement through lifestyle modification has been shown to reduce the risk of metabolic syndrome. This study examined the capacity of ethanol extracts of Scytosiphon lomentaria (SLE) to suppress the bioactivity of myostatin, a potent negative regulator of skeletal muscle mass, as well as the effect of SLE treatment on metabolic homeostasis in obese zebrafish induced by high feeding. A total of 10 ㎍/ml SLE completely blocked myostatin (1 nM/ml) signaling in the pGL3-(CAGA)12 luciferase assay and suppressed myostatin-induced Smad2 phosphorylation in the Western blot analysis. In the zebrafish larvae analysis, the whole body glucose concentration of the high feeding control (HFC) group was significantly higher than that of the normal feeding control (NFC) group. However, the glucose levels of the high feeding group treated with 12.5 ug SLE and of the high feeding group treated with 18.75 ug SLE were similar to those of the NFC group. The mRNA expression level of the GLUT2 gene of the HFC group was significantly lower than that of the NFC group. SLE treatment restored the expression of the GLUT2 gene to a level that was close to that of the NFC group, indicating that SLE is capable of regulating glucose levels in zebrafish larvae. The current results highlight the potential of SLE as a natural MSTN inhibitor and supplement that can be used to facilitate the treatment of metabolic syndrome.

Cross-cultural Adaptation and Psychometric Evaluation of the Korean Version of the A-ONE (한국판 일상생활활동중심 작업기반 신경행동평가(A-ONE)의 개발 및 평가)

  • Kang, Jaewon;Park, Hae Yean;Kim, Jung-Ran;Park, Ji-Hyuk
    • Therapeutic Science for Rehabilitation
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    • v.10 no.2
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    • pp.109-128
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    • 2021
  • Objective : The purpose of this study was to develop a Korean version of the Activities of Daily Living (ADL)-focused Occupation-Based Neurobehavioral Evaluation (A-ONE) through cross-cultural adaptation and examine its validity and reliability. Methods : This study translated the A-ONE into Korean and performed cross-cultural adaptation for the Korean population. After the development of the Korean version of the A-ONE, cross-cultural and concurrent validities were analyzed. Internal consistency, test-retest reliability, and inter-rater reliability were also evaluated. Results : We adapted three items to the Korean culture. The Korean version of the A-ONE showed high cross-cultural validity with a content validity index (I-CVI) >0.9. It correlated with the Functional Independence Measure (FIM) (r=0.52-0.77, p<0.001), except for communication. Cronbach's α was 0.58-0.93 for the functional independence scale (FI) and 0.42-0.93 for the neurobehavioral specific impairment subscale (NBSIS). Intraclass correlation coefficients (ICCs) indicated high test-retest and inter-rater reliability for FI (ICC=0.79-1.00 and 0.75-1.00, respectively) and NBSIS (ICC=0.74-1.00 and 0.72-1.00, respectively). Conclusion : The Korean version of the A-ONE is well adapted to the Korean culture and has good validity and reliability. It is recommended to evaluate ADL performance skills and neurobehavioral impairments simultaneously in Korea.