Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus <i>Aspergillus</i> sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines

Kim, Dong-Cheol,Cho, Kwang-Ho,Ko, Wonmin,Yoon, Chi-Su,Sohn, Jae Hak,Yim, Joung Han,Kim, Youn-Chul,Oh, Hyuncheol MDPI AG 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.4

<P>In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus <I>Aspergillus</I> sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS) as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS) generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO)-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.</P>

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

한국 정신장애의 역학 조사 연구[I] : 각 정신장애의 유병률

조맹제,함봉진,김장규,박강규,정은기,서동우,김선욱,조성진,이준영,홍진표,최용성,박종익,이동우,이기철,배재남,신정호,정인원,박종한,배안,이충경 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.4

Objectives : This study aims to estimate the prevalence of the DSM-IV psychiatric disorders in Korean population using the Korean version of Composite International Diagnostic Interview (K-CIDI). Methods : Subjects were selected by taking multi-stage, cluster samples of 7,867 adult household residents, 18 to 64 years of age, in ten catchment areas. Total 78 trained interviewers administered the K-CIDI to the selected respondents, from June 1 to November30,2001. Results : Total 6,275 respondents completed the interview. Some 33.5% of respondents reported at least one lifetime disorder, 20.6% reported at least one-year disorder, and 16.7% reported at least one-month disorder. The most common lifetime disorders were alcohol abuse/dependence (17.24%), nicotine dependence/withdrawal (11.19%), specific phobia (5.16%), and major de-pressive disorder (4.25%). The lifetime prevalence of substance abuse/dependence (0.25%) and schizophrenia (0.16%) was very low. Nicotine and alcohol use disorder showed very high male/female ratio. Mood disorder and anxiety disorder were more prevalent among female than male. Conclusion : The prevalence of psychiatric disorders was high. In comparison with other studies, remarkable differences in distributions of psychiatric disorders across the areas and times were observed.

SOL-GEL법을 이용한 강유전체 BaTiO₃박막 및 Ceramics 제조

조채룡,이수재,장민수,김호종,정세영,노동택,김성철 동의대학교 기초과학연구소 1993 基礎科學硏究論文集 Vol.3 No.1

Concentrated solution was prepared for a sol-gel process of BaTiO₃. Barium hydroxide and Ti-isopropoxide were used as the raw materials with methanol and isopropanol as solvents. Dense ferroelectric polycrystalline BaTiO₃thin films with the perovskite structure were fabricated by spin coating of the prepared concentrated solution on a few substrates. From XRD investigation, it was confirmed that tetragonal phase of polycrystalline BaTiO₃powders are formed after heat treatment above 550℃ in air and grain-oriented BaTiO₃thin films are obtained by coating of 0.06M concentrated solution on the substrates. It was observed that surfaces of thin films deposited on the substrates by our methods were formed crack-free and uniformly. The thickness of thin film which depends the concentration of the solution was 400∼900Å for 1 time coating, which was confirmed by SEM analysis. Ceramics and thin films show dielectric constant of 4600 (at 1㎑) and capacitance 300∼800㎊ (at 1㎑) at room temperature, respectively.

시클러 캡슐(세파클러 250㎎)에 대한 경보세파클러 캡슐의 생물학적동등성

조혜영,강현아,김세미,박찬호,오인준,임동구,문재동,이용복 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.1

The purpose of the present study was to evaluate the bioequivalence of two cefaclor capsules, Ceclor (Lilly Korea Co., Ltd.) and Kyongbocefaclor (Kyongbo Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of cefaclor from the two cefaclor formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2. 4.0. 6.8 buffer solution and water). Twenty four healthy male subjects. 22.96±1.52 years in age and 67.03±7.90 kg in body weight, were divided into two groups and a randomized 2x2 cross-over study was employed. After one capsule containing 250 mg of cefaclor was orally administered, blood was taken at pre-determined time intervals and the concentrations of cefaclor in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition. the pharmacokinetic parameters such as AUC_(t), C_(max) and T _(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC_(t). C_(max) and untransformed Tmaa. The results showed that the differences between two formulations based on the reference drug, Ceclor. were -1.90%, 2.68% and -7.60% for AUCt, C_(max) and T_(max), respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.91-log 1.06 and log 0.92-log 1.18 for AU', and C_(max), respectively). Thus. the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kyongbocefaclor capsule was bioequivalent to Ceclor capsule.

시분할 방식 고주파 공진 인버터의 특성해석

조규판,원재선,김동희,노채균,배영호 영남대학교 공업기술연구소 2000 工業技術硏究所論文集 Vol.28 No.1

In this paper, we propose the high frequency resonant inverter of the time sharing type which has the effects that the duty cycle of each elements and the thermal loss can be reduce. The analysis of the proposed circuit is described generally by using the normalized parameters. Also, the principle of basic operation and the characteristics of drive were estimated by the switching frequency and the load parameters. And we got the data for designing by the characteristic values obtained at the estimate of characteristic. At the same time, the example of the design's method was proposed and the waveforms of simulation were compared with theoretical waveforms. It is certain that the proposed circuit will be used and expanded in the high frequency power supplies like induction heating systems.

정신재활 치료가 정신분열병 환자의 재발율, 입원횟수, 입원일수 그리고 치료 경비에 미치는 효과 : 2년 추적조사 연구

조진석,공지현,김진원,심경순,하준선,김철권,강동호,장정희,변원탄 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.5

목 적 : 사회기술훈련, 환자교육, 가족교육, 집단치료, 예술치료, 작업치료와 같은 포괄적인 정신재활 치료를 약물치료와 병행할 경우 약물치료만 시행할 때에 비해 정신분열병 환자의 재발율, 입원횟수, 입원일수, 직접 치료경비 등에 어떤 효과가 있는 지를 알아보기 위함이다. 연구방법 : 1993년 9월부터 1995년 2월까지 양산 신경정신병원의 폐쇄병동에서 퇴원한 20∼35세 사이의 정신분열병 환자 173명을 대상으로 46명에게는 6개월동안 정신재활 치료를 시행하였고 127명에게는 통상적인 외래치료만 시행한 후 연구시작 시점을 포함하여 2년동안 양군에 속한 환자들을 대상으로 재발율, 입원횟수, 입원일수, 직접 치료경비 등을 1년 단위로 추적 조사하였으며, 연구시작 시점을 기준으로 전과 후의 매년 평균 입원횟수, 입원일수, 직접 치료경비도 서로 비교하였다. 결 과 : 정신재활 치료를 약물치료와 병행할 경우 약물치료만 시행할 때에 비해 재발율, 입원횟수, 입원일수, 직접 치료비용이 현저히 감소되었다. 그리고 정신재활 치료를 받은 군에서는 치료 전에 비해 치료 후에 재발율, 입원횟수, 입원일수, 직접 치료비용이 유의하게 감소하였지만 통상적인 외래치료만 받은 군에서는 치료 전과 후간에 유의한 변화를 보이지 않았다. 결 론 : 정신분열병 환자들에게 정신재활 치료를 약물치료와 병행할 경우 약물치료만 시행할 때에 비해 환자의 임상적 경과를 호전시킬 뿐 아니라 가족의 경제적 부담도 줄일 수 있다. Objective : We evaluated the clinical efficacy of a comprehensive psychiatric rehabilitation of schizophrenia, including family psychoeducation, patient education, social skills training, group psychotherapy, art therapy, and occupational therapy. Method : From September 1993 to February 1995, 173 chronic schizophrenics who met DSM-IV criteria and were discharged from a locked ward were assigned into the psychiatric rehabilitation service group(psychiatric rehabilitation group, n=46) or the customary out-patient service group(out-patient group, n=127) prospectively, but not randomly. Assignment was based on preferences of patients and their relatives, Each subject included in the psychiatric rehabilitation group received twice weekly patient education, social skills training, family psychoeducation, group psychotherapy, art therapy, occupational therapy and maintenance chemotherapy during a 6-month period. Those in the out-patient group received individual supportive psychotherapy and maintenance chemotherapy according to their clinical needs for 10-20 minutes once per week. After entry into the study, all subjects were assessed for the number of readmission, days of hospitalization, and the direct treatment costs through the first and second year of follow-ups. These outcome variables were also compared pre-and post-2 years at the time point of entry into the study. Aftercare chemotherapy on a weekly to monthly basis continued for the remainder of the two year follow-up period. Results : With regard to the mean number of hospital admissions per year, the mean days of hospitalization per year, and the direct treatment costs per year, the psychiatric rehabilitation group had significantly decreased all clinical outcomes 2 years after compared with before receiving psychiatric rehabilitation. But there were no significant differences in the all clinical outcomes between before and after study intake in the out-patient group. For the number of relapse regardless of drug compliance, 4 patients(9%) during first year and 14 patients(30%) during second year were relapsed in the 46 subjects of the psychiatric rehabilitation group. In contrast, 75 patients(59%) during first year and 90 patients (71%) during second year relapsed in the out-patient group. When considering the effect of drug noncompliance to relapse, 4(9%) and 14 patients(30%) were relapsed while on medication respectively during the first and second year in the 46 of the psychiatric rehabilitation group, vs. 27(34%) of 79 patients on medication during the first year and 31(46%) of 68 patients on medication during the second year were relapsed in the out-patient group. Conclusions : These results indicate that the comprehensive psychiatric rehabilitation can be useful therapeutic intervention both to improve the clinical outcomes of schizophrenic patients and to reduce the economical burden of their relatives.

個人用 컴퓨터를 위한 標準 그래픽 시스템의 設計

趙東燮,李相縞 梨花女子大學校 韓國生活科學硏究院 1986 韓國生活科學硏究院 論叢 Vol.37 No.-

이 논문에서는 BASIC 언어를 대상으로 컴퓨터 그래픽 분야에 있어서의 표준화에 관하여 연구하였다. 사용 언어는 Apple Ⅱ 개인용 켬퓨터의 호환 기종에서 실행되는 Apple-BASIC이며 표준화 기법으로 입력된 프로그램이 컴퓨터에 의하여 처리되기 전에 먼저 전처리(pre-processing)되는 방법을 제시하였고, 전처리를 수행하는 그래픽 표준화 처리 프로그램을 설계하였다. 또한 그래픽 표준화 처리 프로그램을 사용한 예를 통하여 그래픽 표준화 처리를 위한 명령의 실행 과정을 설명하였으며, 아울러 프로그램의 구성상의 특징인 구조화 BASIC에 관하여 연구하였다. One of the major issues in computer graphics is the standardization of graphics primitives. This paper describes the graphics primitives and proposes the design and implementation of graphics systems for personal computers. Our primary objective is to design the programming language used as a graphics language. The second is to implement such language by using personal computers. Graphics primitives are preprocessed to obtain the hardware dependent routines. All of the graphics primitives are so large. Thus, the model we have developed on personal computers ignores the 3D primitives. Several examples show the preprocessing of the given graphics primitives and their validities.

청년기 여자펜싱선수들의 경기 종목별 심상훈련연습 특성

최태석,이동범,천영호,이근배 한국스포츠리서치 2003 한국 스포츠 리서치 Vol.14 No.4

Open-ended questionnaire was asked 135 girls senior high school fencing athletics. According to these collected and analyzed open-ended questionnaires, they give the following conclusions. Mostly, open-ended questionnaires showed girls senior high school fencing players practiced many images such as self-confidence, patience, tenacity, competition and a practice, and in an image frequency aspect, epee players showed more images than foil players. However, in image content, while epee players had a tendency of defense, foil players, in contrast, showed attack-oriented images. As our worldwide predominant fencing athletics train formally the deficient imagery discipline, it is very important to make the applicable program of imagery discipline.