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>

최근 국내외에서 육성된 무궁화 127 품종 중 조경적 활용가치가 높은 유망품종 선발

김광호 ( Kim Kwang-ho ),이춘석 ( Lee Chun-suk ),강호철 ( Kang Ho-chul ) 한국전통조경학회(구 한국정원학회) 2016 한국전통조경학회지 Vol.34 No.3

본 연구는 조경수용 무궁화 우수품종 보급을 위한 유전자원 수집과 특성을 평가하기 위해 최근 국내외에서 육성된 127품종의 1년생 접목묘를 이용하여 2014년부터 2015년까지 2년 동안 생육 및 형태적 특성조사를 실시하였다. 수집된 품종 중 화색 및 꽃이특이한 품종을 조사하여 무궁화를 조경수로 활용도를 높이는데 기여하고자 하였으며 얻어진 결과는 다음과 같다. 최근 국내외에서 육성된 품종들의 화색별 분류로는 크게 분홍색 단심(pink color with red eye spot), 흰색 단심(white color withred eye spot), 붉은 자주색 단심(purplish red color with red eye spot), 분홍보라색 단심(violet pink color with red eye spot), 심홍색단심(crimson color with red eye spot), 흰색 바탕에 붉은색 무늬의 이중색(asadal), 흰색(white color), 푸른색(blue color) 등 총 8종류로 분류되었다. 화색이 붉은 자주색으로서 적색이 강한 꽃으로 국내에서 육성된 품종으로 ‘광명’, ‘난파’, ‘노스페이스’, ‘불새’, ‘비단’,‘송암’, ‘영창’, ‘적퍼소’, ‘키호’, ‘탐라’, ‘화수레드’, ‘환희’ 등이 있었으며, 국외에서 육성되어 국내에 도입된 품종으로는 ‘Aphrodite’,‘Dr. Uemoto’, ‘Freedom’, ‘Pink Cup’, ‘PS 80-1’, ‘Purpureus Variegatus’, ‘Red Giant’, ‘Woodbridge’ 등이 있었다. 화색이 분홍보라색으로서 특이한 품종으로는 ‘꼬마’, ‘도투락’, ‘명미’, ‘병화’, ‘산처녀’, ‘태화’, ‘Hikari-hanagasa’, ‘Little Kim Violet’ 등이 있었다. 화색이 심홍색으로 기존의 꽃에서는 볼 수 없는 특이한 품종으로 ‘종무’와 ‘Ruffled Satin’ 등이 있었다. 최근 국내외에서 육성된 품종중 조경수용 소재로 보급할 수 있는 품종중 기존 품종에 비해 꽃의 크기가 큰 품종으로 무궁화 종간교잡종인 Hibiscus hybrid ‘Daewangchun’, ‘Daeil’,‘Jina’ 등이 있었다. 반면 꽃이 작고 조경적 가치가 높은 품종으로 ‘꼬마’, ‘미백’, ‘안동’, ‘릴킴’, ‘은하수’ 등이 있었다. 백단심계 무궁화‘꼬마’ 품종은 수고가 작은 왜성형으로 꽃의 크기가 5.2cm로 작은 소형화 품종으로 나타났다. 기존 품종에 비해 단심의 길이가 긴품종으로 ‘훈장’과 ‘하이리레드’가 있었다. 홍단심계 무궁화 ‘훈장’은 꽃의 크기는 12.0cm로 중간크기이나 단심길이는 4.8cm로 지금까지육성된 품종중 가장 긴 품종이었다. 또한 홍단심계 무궁화 ‘하이리레드’의 단심길이 역시 4.2cm로 꽃잎 길이에 비해 단심의 길이가 길어 조경적 가치가 높은 것으로 판단되었다. This study was carried out to characterize 127 recently developed cultivars of Rose of Sharon (Hibiscus spp.) in Korea and foreign Countries for landscape uses. The examined factors were growth characteristics such as tree height of a 1-year grafted plant(cm), plant type, growth habit, leaf characteristics such as shape and size, flower characteristics such as color, shape, size, and red eye during 2014 and 2015 for landscape uses. The results are obtained as follows; In the results of flower color of the 127 recently developed cultivars, pink color with red eye spot, white color with red eye spot, purplish red color with red eye spot, violet purple color with red eye spot, crimson color with red eye spot, asadal, blue color with red eye spot, and white color were distributed. In the flower characteristics, Hibiscus hybrid ‘Daewangchun’ had the largest flower size of 16.0cm out of the 127 cultivars. H. syriacus ‘Antong’, ‘Lil Kim’, and ‘Ggoma’ were cultivars with smaller flowers than other cultivars. H. syriacus ‘Hunjang’ had largest red eye, of 5.2cm of length compared to the other cultivars. The cultivars with unique flower color for landscape uses are H. syriacus ‘Kwangmyung’, ‘Nanpa’, ‘North face’, ‘Bulsae’, ‘Bidan’, ‘Songam’, ‘Youngchang’, ‘Jukpeoso’, ‘Kiho’, ‘Tamla’, ‘Hwasoored’ and ‘Hwanhee’. These flowers had a purplish red color and were developed in Korea. H. syriacus ‘Aphrodite’, ‘Dr. Uemoto’, ‘Freedom’, ‘Pink Cup’, ‘PS 80-1’, ‘Purpureus Variegatus’, ‘Red Giant’, ‘Woodbridge’ also had unique flowers with a purplish red color and were introduced from foreign countries. In addition, cultivars with violet pink flowers were H. syriacus ‘Ggoma’, ‘Doturak’, ‘Myungmi’, ‘Byunghwa’, ‘Sancheonyu’, ‘Taehwa’, ‘Hikari-hanagasa’, and ‘Little Kim Violet’. ‘Jongmoo’ and ‘Ruffled Satin’ had flowers with crimson color. Therefore, the new cultivars with unique flower colors were a promising cultivars to a woody landscape plant. Cultivars with large flower sizes were Hibiscus hybrid ‘Daewangchun’, Hibiscus hybrid ‘Daemang’, and Hibiscus hybrid ‘Jina’. H. syriacus ‘Ggoma’, ‘Mibeak’, ‘Antong’, ‘Lil Kim’, and ‘Eunhasu’ had small flower sizes. Cultivars with long red eye were H. syriacus ‘Hunjang’ and H. syriacus ‘Hi Lea Red’. Therefore, the new cultivars, Hibiscus hybrid ‘Daewangchun’, Hibiscus hybrid ‘Daemang’, Hibiscus hybrid ‘Jina’ with large flower sizes, H. syriacus ‘Ggoma’, ‘Mibeak’, ‘Antong’, ‘Lil Kim’, and ‘Eunhasu’ with small flower sizes, H. syriacus ‘Hunjang’ and H. syriacus ‘Hi Lea Red’ with long red eye, were promising cultivars to a woody landscape plant.

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.

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>

HDPE 개질 아스팔트 혼합물의 강도 및 변형특성

김광우,이기호,권오선,고태영 강원대학교 부설 석재복합신소재 제품연구센터 2004 석재연 논문집 Vol.9 No.-

본 연구는 폐비닐 펠렛을 도로포장재료로 재활용하여 자원절약 및 아스팔트 혼합물의 품질향상을 위한 연구이다. 이를 위하여 폐비닐의 첨가량별 배합설계를 수행하여 적정 폐비닐 첨가량과 최적 아스팔트 함량으로 편마암과 화강암 2가지 골재와 폐비닐인 RHDPE의 함량을 4가지로 혼합물을 제작하여 8종류의 재질 혼합물과 2종류의 무개질 혼합물을 제작하였다. 그리고 이 공시체에 대하여 마샬안정도, 간접인장강도 및 Kim test와 반복주행시험 등 실내시험을 통하여 혼합물의 특성을 분석하였다. 폐비닐 첨가량은 RHDPE가 8%일 때 안정도와 간접인장강도 모두 가장 우수한 것으로 나타났고 취성도 나타나지 않았다. RHDPE를 첨가한 혼합물에 대하여 Kim test를 수행한 결과 DR과 DS 모두 높은 상관성을 보였다. 그리고 반복주행시험에서는 RHDPE를 첨가한 혼합물이 일반 혼합물보다 우수하였다. 향후 많은 실험을 통해 RHDPE의 우수성을 입증한다면 소성변형 저항성에 우수한 재료로 이용될 수 있을 것이다. This study is a fundamental research for recycled high-density polyethylene (RHDPE) in asphalt mixture for improving roadway pavement. Marshall mix design was conducted and optimum asphalt content(OAC) was determined for dense-graded surface course mixture by RHDPE content. Marshall stability test, indirect tensile strength (ITS) test, wheel tracking trest and Kim-test were carried out to measure the characteristics of RHDPE-added asphalt concretes. From the results of this study, RHDPE in asphalt mixture if possible. It could be considered that adding too much RHDPE in asphalt mixture is not proper. The optimum content of RHDPE was appeared to be 8%. In Kim-test, statistical analysis was performed for each loading head and aggregate to find out correlation between S_(D) values and each rut parameter. The analysis result showed that S_(D) had very high coefficient of determination with rut parameters on the average.

배전 자동화 시스템을 위한 관계 데이타베이스 설계

김상욱,김진호,김광호,이헌길 강원대학교 정보통신연구소 1998 정보통신논문지 Vol.2 No.-

This paper discusses the database design process for the automatic distribution system. Database design is a complex process for specifying the structure of information. In this paper, we first collect and analyze the requriements for the automatic distribution system. Next, we perform conceptual database design reflecting these requirements by using the E-R model. Finally, we perform logical database design reflecting the result of the previous step by using the relational model. Our results would be helpful in developing efficient automatic distribution systems.

簡易精神診斷檢査(SCL-90)의 韓國版 標準化 硏究Ⅰ : 正常人의 反應特性

金光日,元鎬澤,李正浩,金光潤 大韓神經精神醫學會 1978 신경정신의학 Vol.17 No.4

In recent years, community mental health and medical welfare programs have been gradually emphasized. Accordingly shortage of man power in psychiatric profession becomes an important issue. As an effort for resolution of it, psychiatric rating scales have been developed to provide the time saving device for psychiatric practice. Symptom Checklist-90, a self-report psychiatric rating scale, has been proved to be not only an efficient but also reliable and valid diagnostic tool in psychiatric practice. This scale, developed by Derogatis and his colleagues, consists of 90 symptomatic items which reflect 9 symptom dimensions; somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism dimension. The purposes of this study are to provide Korean version of the SCL-90 and investigate normal response characteristics for it's standardization in Korea. The scales were administered to 199 urban subjects from Seoul and 221 rural subjects from 2 villages of Kyung-Buk and Chun-Buk provinces. Data of 420 subjects were divided into dichotomous subgroups in respect to sex, age (30year and over, and under 30 years), education (6th grade and under, 12th grade and upper), and residency(Seoul and rural) respectively. Each pair of dichotomous subgroups was compared for scale scores by analysis of variance. The results were as follows; 1. Considering sex difference, female subjects revealed significantly higher scores on all scales except hostility scale. 2. In subgroup, dichotomized by education, signjficant differences are seen 6 scales as somatization, obsessive compulsive, interpersonal sensitivity, depression, hostility and paranoid ideation. Somatization score is higher in lower educated group, whereas 5 other scales scores are higher in high educated group. 3. There were no significant difference between age subgroups except somatization scale, in that older group obtained higher scores than the younger. 4. In regional comparison, Seoul subjects obtained significantly higher scores on 7 scales except anxiety phobia and psychoticism scales. The results have been discussed and the authors suggest to separate sex norms for standardization of SCL-90. Further detailed research for preperation of several norms differred by educational and regional backgrounds is recommended.

서로 다른 CNC 환경을 갖는 공작기계의 인터넷 기반 점검

김동훈,김선호,김경돈,김찬봉,고광식 한국공작기계학회 2004 한국공작기계학회 춘계학술대회논문집 Vol.2004 No.-

This paper proposes Internet-based checking scheme for machine-tools with a variant CNC. Checking points defined in this research are classified into two categories such as structured point and operational point. The formal includes the vibration of bearing, temperature of spindle unit and another periodical management. And the latter includes oil checking, clamp locking/unlocking and machining on/off status. Through this research, for the global management of variant CNC machines interspersed with CAC and OAC in manufacturing system, the suitable environment for Internet-based checking of variant CNC machines was designed and the checking methods for CAC and OAC machines were compared with each other.

트레드밀 걷기 운동 시 무게부하의 차이가 호흡순환기능 및 대사기능에 미치는 영향

김용규,이채산,김자영,박미숙,김광중,이광호 한국스포츠리서치 2003 한국 스포츠 리서치 Vol.20 No.1

The purpose of this study was to compare on cadiopulmonary and metabolism function of 10㎏ weight loading group(10 females) and W university students with non weight loading group(10 females. Each group did treadmill walking exercise for twenty minutes by the modified balke protocol. Heart rate(HR), systolic(SBP), MVO₂, and VO₂max were analyzed using 2×2(groups×during) repeated measures analysis of variance (MANOVA). And peak blood velocity(PBV) and MBV were analyzed by using 2×2(groups×during) repeated measures analysis of variance (MANOVA). Lactate and glucose were amalyed by separate 2×2 (groupxduring) analysis of variance(ANOVA). Results of this study suggest that: The change of HR, SBP and MVO₂ in experience and control group showed the significant(p<.05) increase during walking exercise. Variables between experience and control group showed not significant level. But VO₂ in each group showed the significant(p<.001) increase during walking exercise. Differenc among each group showed significant(p<.001) level. Lactate and glucose level in each group showed significant(p<.001, p<.05) increase during walking exercise. Differences among each group showed not significant level. PBV and MBV in each group significant(p<.001) increase during walking exercise. Difference among each group showed significant(p<.05) level. According to these results, weight loading walking exercise considering safety promotes to cardiovascular function and it is expected to be an effective exercise methods able to improve the physical inefficiency of long time walking type.

Azithromycin으로 치료한 임신 중 쓰쓰가무시병 1예

김광석,최진욱,서호종,김기훈,박성호,서광섭,고성만,김순혜,김호정 대한감염학회 2001 감염 Vol.33 No.5

We report a case of tsutsugamushi disease in a 26 year-old pregnant woman who was treated with azithromycin. Her gestation period was 27 weeks and she admitted with fever, rash, and eschar on the right shoulder. Currently recommended medications for the treatment of scrub typhus are doxycycline or chloramphenicol. But, these drugs are class D drugs according to the U.S. Food and Drug Administration (FDA) Fetal Risk Summary, so they couldn't be used to treat pregnant women. Recently, a few case reports suggested that azithromycin, a relatively new macrolide antibiotic, was effective and safe for the treatment of scrub typhus in pregnant women. And, there is no evidence that azithromycin causes harmful effects to the developing fetus or to children. On the basis of current in vivo test that confirms the effectiveness of azithromycin, it may be the drug of choice for the treatment of scrub typhus in pregnant women and children. (Korean J Infect Dis 33:380-382, 2001)