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        GOLGA2 loss causes fibrosis with autophagy in the mouse lung and liver

        Park, Sungjin,Kim, Sanghwa,Kim, Min Jung,Hong, Youngeun,Lee, Ah Young,Lee, Hyunji,Tran, Quangdon,Kim, Minhee,Cho, Hyeonjeong,Park, Jisoo,Kim, Kwang Pyo,Park, Jongsun,Cho, Myung-Haing Elsevier 2018 Biochemical and biophysical research communication Vol.495 No.1

        <P><B>Abstract</B></P> <P>Autophagy is a biological recycling process via the self-digestion of organelles, proteins, and lipids for energy-consuming differentiation and homeostasis. The Golgi serves as a donor of the double-membraned phagophore for autophagosome assembly. In addition, recent studies have demonstrated that pulmonary and hepatic fibrosis is accompanied by autophagy. However, the relationships among Golgi function, autophagy, and fibrosis are unclear. Here, we show that the deletion of <I>GOLGA2</I>, encoding a cis-Golgi protein, induces autophagy with Golgi disruption. The induction of autophagy leads to fibrosis along with the reduction of subcellular lipid storage (lipid droplets and lamellar bodies) by autophagy in the lung and liver. <I>GOLGA2</I> knockout mice clearly demonstrated fibrosis features such as autophagy-activated cells, densely packed hepatocytes, increase of alveolar macrophages, and decrease of alveolar surfactant lipids (dipalmitoylphosphatidylcholine). Therefore, we confirmed the associations among Golgi function, fibrosis, and autophagy. Moreover, <I>GOLGA2</I> knockout mice may be a potentially valuable animal model for studying autophagy-induced fibrosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> GOLGA2/GM130 loss induces autophagy with Golgi disruption in liver cells and transgenic mice. </LI> <LI> GOLGA2/GM130 loss leads to degradation of lipid structures (LBs and LDs) by autophagy. </LI> <LI> GOLGA2/GM130 loss causes liver and lung fibrosis. </LI> </UL> </P>

      • Improving mobile accessibility based on characteristics and behavior of the visually impaired

        Hyunji Park,Sooyoung Kim,Yoonchan Won,Kyungrak Choi,Jiyoung Hong,Minhaeng Cho,Jinhae Choi 대한인간공학회 2016 대한인간공학회 학술대회논문집 Vol.2016 No.11

        Objective: The aim of this study is to investigate behavior of people with visual impairment (including blind and low vision) and analyze their characteristics to improve mobile accessibility. Background: Even with ongoing attempts to improve mobile accessibility and minimize the information gap for the visually impaired, such as creating and enforcing accessibility guide for mobile devices, they are still faced with difficulties when using mobile devices. Therefore it is crucial to realize specific characteristics of different types of visual impairment and approach the real needs of these users when designing smartphone UX. Method: Six visually impaired participants (three fully blind, three low vision) are observed in their daily life using Shadow Tracking. Various daily activities and events, such as travelling from area to another, checking location information, using other supporting devices, using smartphone and more, are observed to refresh and improve current understandings on their behavior patterns and spot the real critical needs. Results: It was commonly observed among participants that voice assistant was used tremendously and travelling from one area to another was the activity with most difficulty. However, resulting behaviors widely varied based on their level of impairment and the starting point of it. Conclusion: This study observed daily lives and mobile device usages of visually impaired, and analyzed the different characteristics of behaviors by different types of visual impairment. These findings will lead to future design researches on UX improvements for current accessibility features and also on building general UX principles for voice assistant. Application: This research will be used for improving and designing mobile accessibility UX for people with visual impairment.

      • SCOPUSKCI등재

        Recognition of Transmembrane Protein 39A as a Tumor-Specific Marker in Brain Tumor

        Park, Jisoo,Lee, Hyunji,Tran, Quangdon,Mun, Kisun,Kim, Dohoon,Hong, Youngeun,Kwon, So Hee,Brazil, Derek,Park, Jongsun,Kim, Seon-Hwan Korean Society of ToxicologyKorea Environmental Mu 2017 Toxicological Research Vol.33 No.1

        Transmembrane protein 39A (TMEM39A) belongs to the TMEM39 family. TMEM39A gene is a susceptibility locus for multiple sclerosis. In addition, TMEM39A seems to be implicated in systemic lupus erythematosus. However, any possible involvement of TMEM39A in cancer remains largely unknown. In the present report, we provide evidence that TMEM39A may play a role in brain tumors. Western blotting using an anti-TMEM39A antibody indicated that TMEM39A was overexpressed in glioblastoma cell lines, including U87-MG and U251-MG. Deep-sequencing transcriptomic profiling of U87-MG and U251-MG cells revealed that TMEM39A transcripts were upregulated in such cells compared with those of the cerebral cortex. Confocal microscopic analysis of U251-MG cells stained with anti-TMEM39A antibody showed that TMEM39A was located in dot-like structures lying close to the nucleus. TMEM39A probably located to mitochondria or to endosomes. Immunohistochemical analysis of glioma tissue specimens indicated that TMEM39A was markedly upregulated in such samples. Bioinformatic analysis of the Rembrandt knowledge base also supported upregulation of TMEM39A mRNA levels in glioma patients. Together, the results afford strong evidence that TMEM39A is upregulated in glioma cell lines and glioma tissue specimens. Therefore, TMEM39A may serve as a novel diagnostic marker of, and a therapeutic target for, gliomas and other cancers.

      • Analysis of Motor Performance in Normal Finger Force Capabilities

        Hyunji Park,Baekhee Lee,Kihyo Jung,Byunghwa Lee,Duk L. Na,Heecheon You 대한인간공학회 2013 대한인간공학회 학술대회논문집 Vol.2013 No.5

        Objective: The present study is to analyze motor performances by evaluating finger force control capabilities in normal controls by age and gender. Background: Four phases of the force control capabilities consist of initiation, development, maintenance, and termination; however, the existing studies with regards to motor performances have been primarily conducted on reaction time of the initiation phase. Method: The study measured initiation time (IT), development time (DT), maintenance error (ME), termination time (TT) of 360 normal controls (30 males and females from each of age group 20s to 70s) by force control phase using Finger Touch (FT) system. Three-factor mixed-subjects ANOVA was conducted to analyze effects of age (20s ~ 70s), gender (male, female), and hand (left hand, right hand) on finger force control capabilities (α = .001). Results: Age and gender were significant in all phases and maintenance phase, respectively. IT of 60s and 70s had 9% and 19% higher than that of 20s ~ 50s. DT of 60s and 70s had 9% and 24% higher than that of 20s ~ 50s. ME of 60s and 70s had 43% and 110% higher than that of 20s ~ 50s. TT of 60s and 70s had 22% and 42% higher than that of 20s ~ 50s. ME of female in 20 ~ 50s, 60s, and 70s had significantly 22%, 42%, and 67% higher than that of male. Aforementioned measures of patients with aMCI, svMCI, and SVaD had 1.1 ~ 3.4 times higher than those of normal controls. Application: The characteristics of normal force control capabilities can be applied to develop a diagnostic model which evaluates quantitatively the existence and severity for various patients with motor intentional disorders.

      • SCOPUSKCI등재

        Dietary zinc inhibits the formation of colonic preneoplastic lesion induced by azoxymethane and dextran sodium sulfate in mice

        Park, Hyunji,Kim, Dang Young,Kang, Bong Su,Yoon, Ja Seon,Jeong, Jae-Hwang,Nam, Sang Yoon,Yun, Young Won,Kim, Jong-Soo,Lee, Beom Jun The Korean Society of Veterinary Science 2012 大韓獸醫學會誌 Vol.52 No.2

        Colorectal cancer (CRC) is one of the leading causes of cancer death in western countries or in the developed countries. Zinc intake has been associated with decreased risk of CRC. We investigated the effect of zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane followed by dextran sodium sulfate in mice. Five-week old ICR mice were fed with the different zinc levels (0.01, 0.1, 1 ppm) for 12 weeks. The numbers of ACF were measured in the colonic mucosa. The ACF number of HZn group was significantly low compared with LZn group or MZn group. Cytosolic superoxide dismutase activity was the highest in HZn group, while thiobarbituric acid reactive substance level for lipid peroxidation was the highest in LZn group. There was no difference in number of PCNA-positive proliferative cells among the groups. TUNEL-positive apoptotic cells were increased in HZn group compared with LZn group. The HZn group exhibited a decrease of ${\beta}$-catenin immunostaining areas compared with the LZn or MZn group. These findings indicate that dietary zinc might exert a protecting effect against colon carcinogenesis by inhibiting the development of ACF in the mice.

      • KCI등재

        Suppressive Effect of Zinc on the Formation of Colonic Preneoplastic Lesions in the Mouse Fed High Levels of Dietary Iron

        Hyunji Park,Bong Su Kang,Dang Young Kim,Ja Seon Yoon,Jae-Hwang Jeong,Sang Yoon Nam,Young Won Yun,Jong-Soo Kim,Beom Jun Lee 한국독성학회 2012 Toxicological Research Vol.28 No.1

        We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of β-catenin was also performed on the mucous membrane of colon. The number of large ACF (≥ 4 AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice.

      • KCI등재

        Protective Effect of Selenium on Experimental Colon Carcinogenesis in Mice Fed a Low Iron Diet

        Hyunji Park,윤영원,Jun-hyeong Kim,Bong Su Kang,남상윤,김종수,정재황,Eun Young Kim,이범준 한국식품위생안전성학회 2011 한국식품위생안전성학회지 Vol.26 No.4

        Selenium (Se) is known to prevent from several cancers, while iron (Fe) is known to be associated with high risk of cancers. The role of Se on colon carcinogenesis was investigated in an animal model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in low Fe mice. Six-week old ICR mice fed on a low Fe diet (4.5 ppm Fe; generally 10 times lower than normal Fe) with three different Se (0.02, 0.1 or 0.5 ppm) levels for 24weeks. The animals received weekly three (0~2nd weeks) i.p. injections of AOM (10 mg/kg B.W), followed by 2%DSS with drinking water for 1 week to induce the colon cancer. There were five experimental groups including vehicle,positive control (normal Fe level, AOM/DSS), Low Fe (LFe) + AOM/DSS+Low Se (LSe), LFe + AOM/DSS + medium Se (MSe) and LFe + AOM/DSS + high Se (HSe) groups. HSe group showed a 66.7% colonic tumor incidence, MSe group showed a 69.2% tumor incidence, and LSe group showed a 80.0% tumor incidence. The tumor incidence was negatively associated with Se levels of diets. Tumor multiplicity in Hse group was significantly low compared to the other groups (p < 0.05). With increasing Se levels of diets, the primary anti-proliferating cell nuclear antigen (PCNA)-positive cells were decreased and apoptotic bodies were increased in a dose-dependent manner. Sedependent glutathione peroxidase activity and its protein level were dependent on the levels of Se of diets. Malondialdehyde level in liver was lowest in Hse group among experimental groups. These findings indicate that dietary Se is chemopreventive for colon cancer by increasing antioxidant activity and decreasing cell proliferation in Fe-deficient mice.

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