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      • Silibinin Inhibits Tumor Growth through Downregulation of Extracellular Signal-Regulated Kinase and Akt <i>in Vitro</i> and <i>in Vivo</i> in Human Ovarian Cancer Cells

        Cho, Hyun Jin,Suh, Dong Soo,Moon, Soo Hyeon,Song, Yong Jung,Yoon, Man Soo,Park, Do Yoon,Choi, Kyung Un,Kim, Yong Keun,Kim, Ki Hyung American Chemical Society 2013 Journal of agricultural and food chemistry Vol.61 No.17

        <P>Anticancer activity of silibinin, a flavonoid, has been demonstrated in various cancer cell types. However, the underlying mechanisms were not elucidated in human ovarian cancer cells. The present study was undertaken to examine the effect of silibinin <I>in vitro</I> and <I>in vivo</I> on tumor growth in human ovarian cancer cells. Silibinin decreased cell viability in a dose- and time-dependent manner. Silibinin caused an increase in reactive oxygen species (ROS) generation, and the silibinin-induced cell death was prevented by the antioxidant <I>N</I>-acetylcysteine (NAC). Western blot analysis showed silibinin-induced downregulation of extracellular signal-regulated kinase (ERK) and Akt. Transfection of constitutively active forms of MEK and Akt prevented the silibinin-induced cell death. Oral administration of silibinin in animals with subcutaneous A2780 cells reduced tumor volume. Subsequent tumor tissue analysis showed that silibinin treatment induced a decrease in Ki-67-positive cells, an increase in transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, activation of caspase-3, and inhibition of p-ERK and p-Akt. These results indicate that silibinin reduces tumor growth through inhibition of ERK and Akt in human ovarian cancer cells. These data suggest that silibinin may serve as a potential therapeutic agent for human ovarian cancers.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2013/jafcau.2013.61.issue-17/jf400192v/production/images/medium/jf-2013-00192v_0008.gif'></P>

      • KCI등재

        주의력결핍-과잉행동장애를 동반한 알코올 의존환자들의 특성 : 임상적/유전학적 자료분석

        김붕년,손기현,전지현,곽욱환,유희정,조수철,박철수 大韓神經精神醫學會 2003 신경정신의학 Vol.42 No.3

        Objectives : This study was conducted to estimate the comorbidity rate of ADHD in a group of patients with alcohol dependency and to find out the characteristics of alcoholic patients with ADHD using the diverse clinical and genetic variables. Methods : Eighty five patients with alcohol dependency were recruited from 4 mental hospitals in Kyoung-Nam and Kyoung-Ki province. For the evaluation of ADHD symptoms in both childhood and adulthood, the highly structured Diagnostic Interview Schedule for Children-IV (DISC-FV)-ADHD module was used. The various standardized scales and questionnaires were also applied to evaluate the comorbid conditions and psychopathological status. All the subjects' blood was collected and genetic study for the polymorphism of DRD2, TH, 5-HTTLPR, COMT, ALDH2 was performed. Results : 1) The comorbid rate of definite ADHD in alcoholic patients was 38% (28/85). 2) The frequency of unmarried status was significantly higher in ADHD group compared non-ADHD group. 3) The onset of pathologic drinking and auditory hallucination was significantly earlier in ADHD group than non-ADHD alcholic group. 4) In ADHD alcoholic group, antisocial behavior was more frequently reported, and the score of co-dependency scale, depression/anxiety, aggression and obsessive compulsive drinking scales were significantly higher compared to non-ADHD alcoholic group. 5) No signficant difference was found in the frequency of polymorphic alleles in COMT, DRD2, 5-HTTLPR, ALDH2, TH between ADHD and non-ADHD alcoholic group. Conclusion : In alcoholic patients, the rate of adult type ADHD was higher than expected rate in general population. The alcoholic patients with ADHD suffered from more sever degree of alcohol dependency and earlier alcohol related problems. ADHD-alcoholic group showed higher diverse comorbid psychopathology and lower marital status compared to non-ADHD-alcoholic group. No difference, however, was found in genetic data between two groups.

      • Effects of Cu,Zn-superoxide dismutase on cell proliferation and neuroblast differentiation in the mouse dentate gyrus.

        Yoo, Dae Young,Shin, Bich Na,Kim, In Hye,Kim, Woosuk,Kim, Dae Won,Yoo, Ki-Yeon,Choi, Jung Hoon,Lee, Choong Hyun,Yoon, Yeo Sung,Choi, Soo Young,Won, Moo-Ho,Hwang, In Koo Kluwer Academic/Plenum Publishers 2012 Neurochem Res Vol.37 No.2

        <P>Oxidative stress is one of the most important factors in reducing adult hippocampal neurogenesis in the adult brain. In this study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) on lipid peroxidation, cell proliferation, and neuroblast differentiation in the mouse dentate gyrus using malondialdehyde (MDA), Ki67, and doublecortin (DCX), respectively. We constructed an expression vector, PEP-1, fused PEP-1 with SOD1, and generated PEP-1-SOD1 fusion protein. We administered PEP-1 and 100 or 500 관g PEP-1-SOD1 intraperitoneally once a day for 3 weeks and sacrificed at 30 min after the last administrations. PEP-1 administration did not change the MDA levels compared to those in the vehicle-treated group, while PEP-1-SOD1 treatment significantly reduced MDA levels compared to the vehicle-treated group. In the PEP-1-treated group, the number of Ki67-positive nuclei was similar to that in the vehicle-treated group. In the 100 관g PEP-1-SOD1-treated group, the number of Ki67-positive nuclei was slightly decreased; however, in the 500 관g PEP-1-SOD1-treated group, Ki67-positive nuclei were decreased to 78.5% of the vehicle-treated group. The number of DCX-positive neuroblasts in the PEP-1-treated group was similar to that in the vehicle-treated group. However, the arborization of DCX-positive neuroblasts was significantly decreased in both the 100 and 500 관g PEP-1-SOD1-treated groups compared to that in the vehicle-treated group. The number of DCX-positive neuroblasts with tertiary dendrites was markedly decreased in the 500 관g PEP-1-SOD1-treated group. These results suggest that a SOD1 supplement to healthy mice may not be necessary to modulate cell proliferation and neuroblast differentiation in the dentate gyrus.</P>

      • 濟大 學生生活指導의 改善方向 探索

        玄惠慶,姜志勇,許鐵洙,梁奇千 濟州大學校 學生生活硏究所 1982 學生生活硏究 Vol.5 No.-

        A. The necessity and purpose of the study Since 1960s the number of university and college students has increased due to the rapid industrial development which requires more technical and intellectual persons. Also the upward spreading effects of education with generalization of secondary education have increased the social demands of liberal education, which expedite university students' diversity and heterogeneity. Therefore, the problems of students are no longer those of school authorities, but expand into social and national problems. Recently most of university in Korea have put more emphasis on the rearrangement and reinforcement of Student Guidance System. Especially, in case of Jeju National University, taking into considerations the special geographical conditions far away from the Korean mainland, and transitional stage on which JNU was promoted to national full-university status, along with the unification of campuses, the more careful interests and efforts are required for student guidance. This study was conducted with a view to providing the opportunities of educational and social specialization of student guidance. The following are the purpose of this study: 1) To set up directions for student guidance which can carry out the role and function of the university. 2) To consider, in the aspect of education, the main factors which influence the problems of university students. 3) To find out the difference between the problems of students' demand and abilty and realities of guidance, by comparing and analyzing present guidance realities between universities. 4) To offer improvement directions for efficient student guidances. B. The scope and contents of the study 1) The problem of student guidance in view of the purpose and function of a university. 2) The fundamental viewpoint of guidance in university 3) A theoretical investigation for efficient student guidance 4) A root cause of student problems 5) The present condition and problems of student guidance 6) Improvement directions for guidance C. The method of the study 1) To analyze the domestic data as well as foreign data 2) To analyze the questionnaire 3) To analyze the results of guidance through the actual result reports of student guidance 4) To analyze various data of student guidance 5) To represent by percentage(%) the realities and problems of student guidance D. The problematic factors of student guidance in the light of purpose and function of a university 1) The original purpose and functions of university are the acquisition of knowledge the transmission of knowledge, and application of knowledge. They are based on the wholemen community of intellectuals in which research, education, and service are determined to be prime mission, but hasn't well been fulfilled because of the present special situations of Korea. 2) In the expectations of university's roles, it is becoming important to harmonize the real desire of administrative officials, intellectual desire of professors, and idealistic of students with each other. 3) A university's research function of creating academic atmosphere is very unsatisfactory. 4) The relationship between professors and students, and even among students hasn't well progressed because of excessive solicitude of omission by graduation quota system as well as full classes. And cultural education is not conducting effectively because it is very fragmentary and formal. 5) The chaos is being produced about the establishment of concept of community service given to university education, the ways and limitations of participation in society and actual world. E. The viewpoint of student guidance The contents and methods of student guidance are decided according to the view of students to be the subject of guidance. In the reformative viewpoint of student guidance by educative instruction methods, main method of guidance are authority, blind obediance, cramming, subjectivity, control, rectification. From the educative viewpoint of student guidance, self-direction can be possible by means of students' interest, desire and ability. Future student guidance must be conducted to develop their potentiality and natural ability of growth without external force or blind gramming. F. Following theoretical investigation were enforced in order to establish effective directions for student guidance. 1) The concept and purpose of the orientation for freshmen and its basic policy and contents 2) The necessity and contents of department arrangement guidance 3) The practice of alloted academic adviser system 4) The educational functions, necessity, and meaning of campus extracurricular activity 5) The role and function of student government(SNDC) 6) The welfare and scholarship system for students G. As a result of a selection of root causes of student problems from the introspection, the following were important order of immediate and expected problems 1405 freshmen; 1. Studies Problem(40.3%) 2. Course problem(36.4%) 3. Economic life problem(36.9%) 4. Social fitness Problem(26.7%) 5. Health Problem(16.0%) The investigation consequence for sophomore and junior are following; 1. A course Problem(35.2%) 2. Economic life problem(35.4%) 3. Human relation problem between professor and student(35.2%), and a good use problem of spare time(35.2%) 4. Studies problem(26.4%) H. The problems were revealed by a statistics which were investigated and analyzed realities of student guidance as follows, respectively: 1. In the orientation for fresh, it is emphatic to give only a information, the program of a important purpose in an orientation that are helpful to initiation of university life with a safety emotionally by withdrawing from strain from strange environment is making light of. 2. In the guidance of a department choice, department allocation by a record is making without giving a chance searching for self-characteristic like aptitude or hobbies, the guidance plan and materials of objectivity are not prepared, and the chance choosing carefully comes very short of. 3. In the management of partial charge professors system, the relation position between professor and student is very formal because, as a matter of fact, it is meaningfulness to guide students from a professor is responsible for guidance of so many students, director of professors are in want of the whole recognition about guidance contents. 4. Though the circle activities are very important as an educational function, a director professors of a circle has charge of guidance for so many students, the activities without purpose consciousness are unfolding, the activities with interest and recreation mainly are rich in, and the activities for enlightenment sound activity model which gets a value experience are situation insufficiency itself. 5. In the activities and management of Student Body, he is not accomplishing plan and function by nature, the activities and management individual and new are very lack owing to emphasis of events centre and actual results centre. And the appearance of making heteronomy now that he is not also chose relation to the circles in SNDC is more and more deepening. 6. The lower organization taking charge of students guidance specially in managent of the students guidance institute are in need, the number of specialists are for want of, it is just so formal to run the students guidance institute because the institute's finance is in very poverty, its originally functions are not accomplishing due to the consultation mood in consultation room is stiff. 7. Our university lacks in research facilities and mental incentive with regard to student welfare function. I. I am directing the way of student guidance for withdrawing from and getting rid of the problems revealing, concerning the students guidance to the best of his ability by the realities of students problems as follows; First, the investigation and research activities and assistance understanding and helping students have to provide in the side of prevention of problems by understanding university students' nature consciousness and characteristic regularly. Second, students' spontaneous participation, the development of interesting and useful programmes, and faculty members' active supports & guidance should be given to obtain effective result of fresh's orientation. Third, school authorities should provide freshmen with opportunity to judge their aptitudes from the time of entrance by holding orientation several times, and by offering detailed informations on the department selection. Fourth, The academic & human relations between professors and students should be maintained through proper enforcement of alloted academic professor system. Fifth, every circle and club should established proper and patent objectivities of activity, and try, to create and introduce useful and interesting programmes in order to promote an educational function of each circle and club. Sixth, in order to eleminate the gap between students and Students Government, students should take deep interests in Student Body's activity, while Student Body should develop academic and literary activity to promote students research activities. Seventh, in order to promote the function of Student Guidance Institute, there should be secured expert staff for smooth counselling, investigation and employment guide as well as financial and administrative support of school authorities. Finally, university authorities should organize several institute such as student welfare committee(institute) so that they might grasp what student opinions & desire are and make students lead comfortable campus lives.

      • Mycophenolic Acid와 Rapamycin이 흰쥐 사구체 혈관간세포증식과 세포외기질 생성에 미치는 영향

        김명수,박제현,하헌주,허규하,서지연,김유선,김혜진,박기일 이화여자대학교 약학연구소 2004 藥學硏究論文集 Vol.- No.14

        Background: Excess proliferation and extracellular matrix (ECM) accumulation of mesenchymal cells such as vascular smooth muscle cells (VSMC) and glomerular mesangial cells cause chronic allograft nephropathy showing transplant vascular sclerosis and glomerulosclerosis. Mycophenolic acid (MPA) and rapamycin (RPM) are well known as strong inhibitors of VSMC proliferation, but their effects on the glomerular mesangial cells are not yet clearly understood. This study examined the effects of MPA or RPM on PDGF-induced proliferation and ECM accumulation in rat glomerular mesangial cells. Methods: Mesangial cells isolated from the glomeruli of Sprague-Dawley rats were cultured with DMEM containing 20% fetal bovine serum. Growth arrested and synchronized cells were administered with test drugs (MPA10 nM-10μM, RPM 0.1 nM-1μM) before the addition of PDGF 10 ng/mL. Cell proliferation was assessed by [³H]thymidine incorporation, collagen by [³H]proline incorporation, and fibronectin, ERK, and p38 MAPK by Western blot analysis. Results: PDGF increased mesangial cell proliferation by 4.64-fold. Compared to stimulated control, MPA above 500 nM and RPM above 10nM showed a significant inhibitory effect in a dose-dependent manner. The IC_(50) of MPA and RPM against PDGF-induced mesangial cell proliferation were around 500 nM and 100 nM, respectively. The collagen synthesis was also inhibited by MPA and RPM, but the fibronectin secretion was inhibited by MPA alone. The proliferation of mesangial cell correlated with activation of ERK and. p38 MAPK. MPA, but not RPM, inhibited ERK and p38 MAPK activation. Conclusion: This study demonstrated that MPA and RPM significantly inhibited PDGF-induced proliferation and ECM production in rat glomerular mesangial cells. The inhibitory effects of MPA, but not RPM, are correlated with ERK and p38 MAPK.

      • Bacillus sp. GM44가 생산하는 Chitosanase의 동력학적 연구

        이기선,임현수,김승모 여수대학교 1999 論文集 Vol.14 No.2

        Optimal conditions for the production of chitosanoligosaccharide were studied with chitosanase produced by Bacillus sp. GM44.Enzyme stability was maintained above 90% after 6 days at pH 5.0 and optimum initial reaction rate was appeared maximum in 1.0% of chitosan solution. The effect of PH on the production of chitosansaccharides was not significantly affected between pH 5.0 and 5.5.In case of temperature, the maximum activity of chitosanase was shown at 50℃. However, the maximum production yield of chitosanoligosaccharide was appeared at 40℃. The production yield of chitosanoligosaccharide was appeared above 90% at 0.4%~2.0% of chitosan solution and about 64.6% at 4.0% of chitosan solution. The final concentration of chitosanoligosaccharide appeared 3.438mg/ml at 1.0% of chitosan solution and 10.52mg/ml at 4.0% of chitosan solution. By TLC analysis, the composition of chitosanoligosaccharides was mainly 3-5mer. The optimum condition of pH and temperature for the production of chitosanoligosaccharides were pH 5.0 and 40℃, respectively.

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