• Title/Summary/Keyword: Nrf1/2

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Antioxidant effect of ergothioneine on in vitro maturation of porcine oocytes

  • Ji-Young Jeong;Lian Cai;Mirae Kim;Hyerin Choi;Dongjin, Oh;Ali Jawad;Sohee Kim;Haomiao Zheng;Eunsong Lee;Joohyeong Lee;Sang-Hwan, Hyun
    • Journal of Veterinary Science
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    • v.24 no.2
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    • pp.24.1-24.13
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    • 2023
  • Background: Ergothioneine (EGT) is a natural amino acid derivative in various animal organs and is a bioactive compound recognized as a food and medicine. Objectives: This study examined the effects of EGT supplementation during the in vitro maturation (IVM) period on porcine oocyte maturation and subsequent embryonic development competence after in vitro fertilization (IVF). Methods: Each EGT concentration (0, 10, 50, and 100 μM) was supplemented in the maturation medium during IVM. After IVM, nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels of oocytes were investigated. In addition, the genes related to cumulus function and antioxidant pathways in oocytes or cumulus cells were investigated. Finally, this study examined whether EGT could affect embryonic development after IVF. Results: After IVM, the EGT supplementation group showed significantly higher intracellular GSH levels and significantly lower intracellular ROS levels than the control group. Moreover, the expression levels of hyaluronan synthase 2 and Connexin 43 were significantly higher in the 10 μM EGT group than in the control group. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (NQO1) were significantly higher in the oocytes of the 10 μM EGT group than in the control group. In the assessment of subsequent embryonic development after IVF, the 10 μM EGT treatment group improved the cleavage and blastocyst rate significantly than the control group. Conclusions: Supplementation of EGT improved oocyte maturation and embryonic development by reducing oxidative stress in IVM oocytes.

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

  • Hong Kyu Lee;Yun-Jung Na;Su-Min Seong;Dohee Ahn;Kyung-Chul Choi
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.368-378
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    • 2024
  • Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

Effects of hot water extracts of roasted radish against renal oxidative stress induced by high-fat diet (고지방식사로 유도된 신장 산화스트레스를 개선하는 가압볶음 무말랭이 열수추출물 효과)

  • Jeon, Yeonhui;Kim, Mijeong;Han, Seongkyung;Song, Yeong-Bok;Song, Yeong Ok
    • Korean Journal of Food Science and Technology
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    • v.49 no.2
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    • pp.203-208
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    • 2017
  • The antioxidant and anti-inflammatory effects of roasted dried radish (RDR) against renal oxidative stress were examined in high-fat diet (HFD)-fed mice. The HFD was prepared by adding lard to chow diet to provide 50% of the calories from fat. Hot water extracts of dried radish (DR) or RDR were administered orally to mice at 237 mg/kg bw/day, whereas distilled water was administered as a vehicle for 12 weeks. Compared to the control group, renal reactive oxygen species, peroxynitrite, and thiobarbituric acid reactive substance level in the DR or RDR group were significantly decreased, whereas the glutathione level was increased (p<0.05). Protein expressions of antioxidant factors such as nuclear factor erythroid 2-related factor-2, heme oxygenase-1, glutathione S-transferase, superoxide dismutase, catalase, and glutathione peroxidase were significantly increased in the DR and RDR groups; however, nuclear factor-kappa B expression was suppressed (p<0.05). These antioxidant and anti-inflammatory effects of RDR were found to be significantly greater than those of DR.

In Silico Analysis of Gene Function and Transcriptional Regulators Associated with Endoplasmic Recticulum (ER) Stress (Endoplasmic recticulum stress와 관련된 유전자기능과 전사조절인자의 In silico 분석)

  • Kim, Tae-Min;Yeo, Ji-Young;Park, Chan-Sun;Rhee, Moon-Soo;Jung, Myeong-Ho
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1159-1163
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    • 2009
  • It has been postulated that endoplasmic (ER) stress is involved in the development of several diseases. However, the detailed molecular mechanisms have not been fully understood. Therefore, we characterized a genetic network of genes induced by ER stress using cDNA microarray and gene set expression coherence analysis (GSECA), and identified gene function as well as several transcription regulators associated with ER stress. We analyzed time-dependent gene expression profiles in thapsigargin-treated Sk-Hep1 using an oligonucleotide expression chip, and then selected functional gene sets with significantly high expression coherence which was processed into functional clusters according to the expression similarities. The functions related to sugar binding, lysosome, ribosomal protein, ER lumen, and ER to golgi transport increased, whereas the functions with mRNA processing, DNA replication, DNA repair, cell cycle, electron transport chain and helicase activity decreased. Furthermore, functional clusters were investigated for the enrichment of regulatory motifs using GSECA, and several transcriptional regulators associated with regulation of ER-induced gene expression were found.

Inhibitory Effects of Ojeoksan on TNF-α-induced Vascular Inflammation in Human Umbilical Vein Endothelial Cells (TNF-α로 유도된 혈관내피세포의 혈관염증에 미치는 오적산(五積散)의 억제 효과)

  • Han, Byung Hyuk;Yoon, Jung Joo;Kim, Hye Yoom;Ahn, You Mee;Hong, Mi Hyeon;Son, Chan Ok;Na, Se Won;Lee, Yun Jung;Gang, Dae-Gil;Lee, Ho Sub
    • The Korea Journal of Herbology
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    • v.33 no.4
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    • pp.59-67
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    • 2018
  • Objectives : Ojeoksan, originally recorded in an ancient Korean medicinal book named "Donguibogam" and has been used for the treatment of circulation disorder of blood which was called blood accumulation (血積) in Korean medicine. Therefore, this study was carried out to investigate the beneficial effect of OJS on vascular inflammation in HUVECs. Methods : We evaluated the effect of OJS on the expression of cell adhesion molecules and protective role in HUVEC stimulated by TNF-${\alpha}$ by using Western blot. Results : Pretreatment with OJS decreased the adhesion of HL-60 cells to TNF-${\alpha}$-induced HUVEC. OJS suppressed TNF-${\alpha}$-induced expression level of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and endothelial cell selectin (E-selectin). Moreover, OJS significantly decreased TNF-${\alpha}$-induced production of intracellular reactive oxygen species (ROS); and inhibited the phosphorylation of $I{\kappa}B-{\alpha}$ in the cytoplasm compared to the experimental group. Pretreatment with OJS inhibited the trans-location of NF-${\kappa}B$ p65 to the nucleus. OJS also inhibited phosphorylation of MAPKs compared to the experimental group. OJS significantly increased the protein expression of Nrf2 and HO-1. Conclusions : Ojeoksan has a protective effect on vascular inflammation, and might be a potential therapeutic agent for early atherosclerosis.

Cordycepin inhibits chondrocyte hypertrophy of mesenchymal stem cells through PI3K/Bapx1 and Notch signaling pathway

  • Cao, Zhen;Dou, Ce;Li, Jianmei;Tang, Xiangyu;Xiang, Junyu;Zhao, Chunrong;Zhu, Lingyu;Bai, Yun;Xiang, Qiang;Dong, Shiwu
    • BMB Reports
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    • v.49 no.10
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    • pp.548-553
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    • 2016
  • Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering to repair articular cartilage defects. However, hypertrophy of chondrocytes derived from MSCs might hinder the stabilization of hyaline cartilage. Thus, it is very important to find a suitable way to maintain the chondrogenic phenotype of chondrocytes. It has been reported that cordycepin has anti-inflammatory and anti-tumor functions. However, the role of cordycepin in chondrocyte hypertrophy remains unclear. Therefore, the objective of this study was to determine the effect of cordycepin on chondrogenesis and chondrocyte hypertrophy in MSCs and ATDC5 cells. Cordycepin upregulated chondrogenic markers including Sox9 and collagen type II while down-regulated hypertrophic markers including Runx2 and collagen type X. Further exploration showed that cordycepin promoted chondrogenesis through inhibiting Nrf2 while activating BMP signaling. Besides, cordycepin suppressed chondrocyte hypertrophy through PI3K/Bapx1 pathway and Notch signaling. Our results indicated cordycepin had the potential to maintain chondrocyte phenotype and reconstruct engineered cartilage.

Involvement of Endoplasmic Reticulum Stress Response in the Neuronal Differentiation

  • Cho, Yoon-Mi;Jang, Yoon-Seong;Jang, Young-Min;Seo, Jin-Young;Kim, Ho-Shik;Lee, Jeong-Hwa;Jeong, Seong-Whan;Kim, In-Kyung;Kwon, Oh-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.6
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    • pp.239-246
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    • 2007
  • Expressions of endoplasmic reticulum stress response (ERSR) genes were examined during the neuronal differentiation of rat fetal cortical precursor cells (rCPC) and rat pheochromocytoma PC12 cells. When rCPC were differentiated into neuronal cells for 7 days, early stem cell marker, nest in, expression was decreased from day 4, and neuronal markers such as neurofilament-L, -M and Tuj1 were increased after day 4. In this condition, expressions of BIP, ATF6, and phosphorylated PERK as well as their down stream signaling molecules such as CHOP, ATF4, XBP1, GADD34, Nrf2 and $p58^{IPK}$ were significantly increased, suggesting the induction of ERSR during neuronal differentiation of rCPC. ERSR was also induced during the differentiation of PC12 cells for 9 days with NGF. Neurofilament-L transcript was time-dependently increased. Both mRNA and protein levels of Tuj1 were increased after the induction, and the significant increase in NeuN was observed at day 9. Similar to the expression patterns of neuronal markers, BIP/GRP78 and CHOP mRNAs were highly increased at day 9, and ATF4 mRNA was also increased from day 7. These results strongly suggest the induction and possible role of ERSR in neuronal differentiation process. Further study to identify targets responsible for neuronal induction will be necessary.

Radix et Rhizoma Ginseng chemoprevents both initiation and promotion of cutaneous carcinoma by enhancing cell-mediated immunity and maintaining redox homeostasis

  • Yu, Suyun;Wang, Siliang;Huang, Shuai;Wang, Wei;Wei, Zhonghong;Ding, Yushi;Wang, Aiyun;Huang, Shile;Chen, Wenxing;Lu, Yin
    • Journal of Ginseng Research
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    • v.44 no.4
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    • pp.580-592
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    • 2020
  • Background: Radix et Rhizoma Ginseng (thereafter called ginseng) has been used as a medicinal herb for thousands of years to maintain people's physical vitality and is also a non-organ-specific cancer preventive and therapeutic traditional medicine in several epidemiologic and preclinical studies. Owing to few toxic side effects and strong enhancement on body immunity, ginseng has admirable application potential and value in cancer chemoprevention. The study aims at investigating the chemopreventive effects of ginseng on cutaneous carcinoma and the underlying mechanisms. Methods: The mouse skin cancer model was induced by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate. Ultraperformance liquid chromatography/mass spectrometry was used for identifying various ginsenosides, the main active ingredients of ginseng. Comprehensive approaches (including network pharmacology, bioinformatics, and experimental verification) were used to explore the potential targets of ginseng. Results: Ginseng treatment inhibited cutaneous carcinoma in terms of initiation and promotion. The content of Rb1, Rb2, Rc, and Rd ginsenosides was the highest in both mouse blood and skin tissues. Ginseng and its active components well maintained the redox homeostasis and modulated the immune response in the model. Specifically, ginseng treatment inhibited the initiation of skin cancer by enhancing T-cell-mediated immune response through upregulating HSP27 expression and inhibited the promotion of skin cancer by maintaining cellular redox homeostasis through promoting nuclear translocation of Nrf2. Conclusion: According to the study results, ginseng can be potentially used for cutaneous carcinoma as a chemopreventive agent by enhancing cell-mediated immunity and maintaining redox homeostasis with multiple components, targets, and links.

Proanthocyanidins Suppresses Lipopolysaccharide-stimulated Inflammatory Responses via Heme Oxygenase-1 Induction in RAW264.7 Macrophages (프로안토시아니딘의 항염증효과)

  • Cheon, Hye-Jin;Park, Sun Young;Jang, Hee-Ji;Cho, Da-Young;Jung, Jiwon;Park, Gimin;Jeong, Kyeong Mi;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.29 no.4
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    • pp.484-491
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    • 2019
  • Proanthocyanidins are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerous in vitro and in vivo studies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, immunomodulation, DNA repair, and antitumor activity. Among immune cells, macrophages are crucial players in a variety of inflammatory responses to environmental conditions. However, it has been widely reported that macrophages cause chronic inflammation and are involved in a variety of diseases, such as obesity, diabetes, metabolic syndrome, and cancer. In this study, we report the suppressive effect of proanthocyanidins via the heme oxygenase-1 (HO-1)-related system, on the immune response of the LPS-stimulated mouse macrophage cell line RAW264.7. Increased HO-1 expression at mRNA and protein levels were found in proanthocyanidins-treated RAW264.7 cells. Further, proanthocyanidins enhanced nuclear factor-erythroid 2-related factor 2 translocation into the nucleus. RAW264.7 cells were treated with lipopolysaccharide (LPS) with or without proanthocyanidins, and inflammatory mediator expression levels were assessed. Proanthocyanidins treatment resulted in the attenuation of nitric oxide production and inducible nitric oxide synthase expression in LPS-stimulated RAW264.7 cells. In addition, mRNA and protein expression of proinflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6, was inhibited by proanthocyanidins treatment in LPS-stimulated RAW264.7 cells. These findings support proanthocyanidins as a promising anti-inflammatory agent.

Analysis of Research Trends in Journal of Distribution Science (유통과학연구의 연구 동향 분석 : 창간호부터 제8권 제3호까지를 중심으로)

  • Kim, Young-Min;Kim, Young-Ei;Youn, Myoung-Kil
    • Journal of Distribution Science
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    • v.8 no.4
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    • pp.5-15
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    • 2010
  • This study investigated research trends of JDS that KODISA published and gave implications to elevate quality of scholarly journals. In other words, the study classified scientific system of distribution area to investigate research trends and to compare it with other scholarly journals of distribution and to give implications for higher level of JDS. KODISA published JDS Vol.1 No.1 for the first time in 1999 followed by Vol.8 No.3 in September 2010 to show 109 theses in total. KODISA investigated subjects, research institutions, number of participants, methodology, frequency of theses in both the Korean language and English, frequency of participation of not only the Koreans but also foreigners and use of references, etc. And, the study investigated JDR of KODIA, JKDM(The Journal of Korean Distribution & Management) and JDA that researched distribution, so that it found out development ways. To investigate research trends of JDS that KODISA publishes, main category was made based on the national science and technology standard classification system of MEST (Ministry Of Education, Science And Technology), table of classification of research areas of NRF(National Research Foundation of Korea), research classification system of both KOREADIMA and KLRA(Korea Logistics Research Association) and distribution science and others that KODISA is looking for, and distribution economy area was divided into general distribution, distribution economy, distribution, distribution information and others, and distribution management was divided into distribution management, marketing, MD and purchasing, consumer behavior and others. The findings were as follow: Firstly, main category occupied 47 theses (43.1%) of distribution economy and 62 theses (56.9%) of distribution management among 109 theses in total. Active research area of distribution economy consisted of 14 theses (12.8%) of distribution information and 9 theses (8.3%) of distribution economy to research distribution as well as distribution information positively every year. The distribution management consisted of 25 theses (22.9%) of distribution management and 20 theses (18.3%) of marketing, These days, research on distribution management, marketing, distribution, distribution information and others is increasing. Secondly, researchers published theses as follow: 55 theses (50.5%) by professor by himself or herself, 12 theses (11.0%) of joint research by professors and businesses, Professors/students published 9 theses (8.3%) followed by 5 theses (4.6%) of researchers, 5 theses (4.6%) of businesses, 4 theses (3.7%) of professors, researchers and businesses and 2 theses (1.8%) of students. Professors published theses less, while businesses, research institutions and graduate school students did more continuously. The number of researchers occupied single researcher (43 theses, 39.5%), two researchers (42 theses, 38.5%) and three researchers or more (24 theses, 22.0%). Thirdly, professors published theses the most at most of areas. Researchers of main category of distribution economy consisted of professors (25 theses, 53.2%), professors and businesses (7 theses, 14.9%), professors and businesses (7 theses, 14.9%), professors and researchers (6 theses, 12.8%) and professors and students (3 theses, 6.3%). And, researchers of main category of distribution management consisted of professors (30 theses, 48.4%), professors and businesses (10 theses, 16.1%), and professors and researchers as well as professors and students (6 theses, 9.7%). Researchers of distribution management consisted of professors, professors and businesses, professors and researchers, researchers and businesses, etc to have various types. Professors mainly researched marketing, MD and purchasing, and consumer behavior, etc to demand active participation of businesses and researchers. Fourthly, research methodology was: Literature research occupied 45 theses (41.3%) the most followed by empirical research based on questionnaire survey (44 theses, 40.4%). General distribution, distribution economy, distribution and distribution management, etc mostly adopted literature research, while marketing did empirical research based on questionnaire survey the most. Fifthly, theses in the Korean language occupied 92.7% (101 theses), while those in English did 7.3% (8 theses). No more than one thesis in English was published until 2006, and 7 theses (11.9%) were published after 2007 to increase. The theses in English were published more to be affirmative. Foreigner researcher published one thesis (0.9%) and both Korean researchers and foreigner researchers jointly published two theses (1.8%) to have very much low participation of foreigner researchers. Sixthly, one thesis of JDS had 27.5 references in average that consisted of 11.1 local references and 16.4 foreign references. And, cited times was 0.4 thesis in average to be low. The distribution economy cited 24.2 references in average (9.4 local references and 14.8 foreign references and JDS had 0.6 cited reference. The distribution management had 30.0 references in average (12.1 local references and 17.9 foreign references) and had 0.3 reference of JDS itself. Seventhly, similar type of scholarly journal had theses in the Korean language and English: JDR( Journal of Distribution Research) of KODIA(Korea Distribution Association) published 92 theses in the Korean language (96.8%) and 3 theses in English (3.2%), that is to say, 95 theses in total. JKDM of KOREADIMA published 132 theses in total that consisted of 93 theses in the Korean language (70.5%) and 39 theses in English (29.5%). Since 2008, JKDM has published scholarly journal in English one time every year. JDS published 52 theses in the Korean language (88.1%) and 7 theses in English (11.9%), that is to say, 59 theses in total. Sixthly, similar type of scholarly journals and research methodology were: JDR's research methodology had 65 empirical researches based on questionnaire survey (68.4%), followed by 17 literature researches (17.9%) and 11 quantitative analyses (11.6%). JKDM made use of various kinds of research methodologies to have 60 questionnaire surveys (45.5%), followed by 40 literature researches (30.3%), 21 quantitative analyses (15.9%), 6 system analyses (4.5%) and 5 case studies (3.8%). And, JDS made use of 30 questionnaire surveys (50.8%), followed by 15 literature researches (25.4%), 7 case studies (11.9%) and 6 quantitative analyses (10.2%). Ninthly, similar types of scholarly journals and Korean researchers and foreigner researchers were: JDR published 93 theses (97.8%) by Korean researchers except for 1 thesis by foreigner researcher and 1 thesis by joint research of the Korean researchers and foreigner researchers. And, JKDM had no foreigner research and 13 theses (9.8%) by joint research of the Korean researchers and foreigner researchers to have more foreigner researchers as well as researchers in foreign countries than similar types of scholarly journals had. And, JDS published 56 theses (94.9%) of the Korean researchers, one thesis (1.7%) of foreigner researcher only, and 2 theses (3.4%) of joint research of both the Koreans and foreigners. Tenthly, similar type of scholarly journals and reference had citation: JDR had 42.5 literatures in average that consisted of 10.9 local literatures (25.7%) and 31.6 foreign literatures (74.3%), and cited times accounted for 1.1 thesis to decrease. JKDM cited 10.5 Korean literatures (36.3%) and 18.4 foreign literatures (63.7%), and number of self-cited literature was no more than 1.1. Number of cited times accounted for 2.9 literatures in 2008 and then decreased continuously since then. JDS cited 26,8 references in average that consisted of 10.9 local references (40.7%) and 15.9 foreign references (59.3%), and number of self-cited accounted for 0.2 reference until 2009, and it increased to be 2.1 references in 2010. The author gives implications based on JDS research trends and investigation on similar type of scholarly journals as follow: Firstly, JDS shall actively invite foreign contributors to prepare for SSCI. Secondly, ratio of theses in English shall increase greatly. Thirdly, various kinds of research methodology shall be accepted to elevate quality of scholarly journals. Fourthly, to increase cited times, Google and other web retrievals shall be reinforced to supply scholarly journals to foreign countries more. Local scholarly journals can be worldwide scholarly journal enough to be acknowledged even in foreign countries by improving the implications above.

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