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.

CAD/CAM 으로 제작된 Ceramic Inlay의 변연누출에 관한 비교연구

조병훈,이명종,임미경,이광원,손호현 大韓齒科保存學會 1997 Restorative Dentistry & Endodontics Vol.22 No.2

To compare the marginal leakage of CAD/CAM-fabricated ceramic inlay, gold inlay and amalgam, forty extracted caries-free premolars were prepared with Class Ⅱ MO cavity design. The teeth were divided into four groups of ten samples each. Group 1 was restored with CAD/CAM-fabricated ceramic inlays cemented with Scotchbond Resin Cement / Scotchbond Multi-purpose plus. Group 2 was restored with gold inlays cemented with Scotchbond Resin Cement / Scotchbond Multi-purpose plus. Group 3 was restored with gold inlays cemented with zinc phosphate cement. And, Group 4 was restored with amalgam. All samples were thermocycled, and stored in 1% methylene blue. Marginal leakage was examined at four margins, that is, occlusal distal, priximal gingival, occlsal facial and occlusal lingual margins from sectioned samples under steeomicroscope(x15). The results were as follows: 1. Group 1 and 2 showed no statistically significant difference among marginal leakage at all four examined margins(p>0.05). 2. Group 3 and 4 showed significant marginal leakage at proximal gingival margin compared with other margins(p<0.05). 3. Significantly increased marginal leakage at priximal gingival, occlusal facial and occlusal lingual margins in group 3 were observed compared with other groups(p<0.05).

심실중격결손증-치험 1예-

조광현,우종수,황윤호,이양행,박철호,김종성,김철호,이경순,조영일,박태인 인제대학교 1985 仁濟醫學 Vol.6 No.4

A successful treatment of infants and children with congenital heart defects depends upon several factors: diagnosis must be accurate, the operative technique, including techniques of perfusion and myocardial preservation, must be suited to the needs of patients and intensive cares, including accurate anesthesia, must be applied through all stages of investigation and treatment, i.e. before, during and after the operation. Recently we performed a open heart surgery successfully for a six-years old girl who had suffered from frequent upper respiratory tract infection and mild to moderate exertional dyspnea with congenital heart defects (ventricular septal defect, Kirklin type II, with patent foramen ovale). The operation and postoperative course were very smooth. And now we report this with review of literatures.

silver-age의 web-interface에 관한 연구 : 한국의 silver-age를 중심으로

조은정,이광호 건국대학교 조형연구소 2001 조형연구 Vol.9 No.-

Times have changed. And come to the time one man, one computer. Our social environment, into the web. And don't five about one-day without computer, silver-age is the Informal An elderly person degeneration of body and change state of mind. From social develop, grow a matter of concern and interest about silver-age, and for welfare facilities about silver-age. Now recent universalization of the web, the design has change to satisfy the user's needs, breaking from the convention supply-oriented concept, as a result of which the concept of the interface has spreaded all over the society. This change been on the level to provide users with ease and convenience in use. Saying that creating a Web is design is not exaggeration. A huge new market is being born. Mastering digital technology can be said to be a new requirrment for designers to survive in the profession. A method of study started for compose web-interface about silver-age, if they are use the web, he have to thinking. It is convenient. For welfare measures is as follows about silver-age. first, health-home and the spirit of filial piety and respect, second, social security one's old age, third, the health system for silver-age, last, social-activity. For that reason a necessary and sufficient condition use the web, with silver-age. So, this thesis's goal is research web site for silver-age, and offer convenience use computer.

Helicobacter pylori와 대장균의 Shuttle Vector 개발

조명제,이우곤,이상룡,김경희,안영숙,김성희,김현주,류복덕,최여정,윤영혜,백승철,전영석,이광호 경상대학교 유전공학연구소 1997 遺傳工學硏究所報 Vol.16 No.-

In this study, a vehicle vector using cryptic plasmids was constructed for gene transfer in Helicobacter pylori. pHP51(3.9 kb) and pHP489(1.2 kb) were selected for constructing vectors from cryptic plasmid of H. pylori isolates in Korea. The HindⅢ-digestedDNA fragment(1.2kb) of pHP489 and 1.6kb DNA fragment of pHP51 were ligated with a kanamycin resistance gene(aph3'-Ⅲ) from C. jejuni to produce the recombinant plasmids pHP489K and pHP51K, respectively. Transformation frequency of pHP51K by electroporation was low. But pHP489K could be effectively transformed into various H. pylori strains. In order to design an intermdiate vehicle vector for gene transfer into H. pylori, pBlueHP489K was prepared by recloning pHP489K DNA into pBluescript and pTZ19R vector. This vector permitted the DNA fragment containing pHP489 sequence, aph3'-Ⅲ, and cloned DNA to be cut and self-ligated in the SacⅠ site after cloning. ureA and ureB gene were inserted into pBlueHP489K, resulting in pBlueHP489K/AB. The DNA fragment containing pHP489, kanamycin resistance gene(aph3'-Ⅲ), and urease structural gene was cut away from pBlueHP489K/AB and self-ligated to generate pBlueHP489K/AB. pBlueHP489K/AB made urease-negative H. pylori strains restore their urease activity. By this experiment, pBlueHP489K was confirmed to be the vehicle system for transferring H. pylori genes.

신원방우황청심원의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

Abstract-In order to investigate the phamacological properties of New Wonbang Woohwangchungsimwon Pill (NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10^-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not aftect significantly the relaxing effects of NSCH and SCH, NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs). NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA). V_max and resting membrane potential (RMP) at low doses, whereas inhibited the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

I-Muscone의 심혈관계에 관한 약리연구

조태순,김낙두,허인회,권광일,박석기,심상호,신대희,박대규 충남대학교 약학대학 의약품개발연구소 1997 藥學論文集 Vol.13 No.-

In order to investigate the pharmacological properties of l-muscone, effects of l-muscone and musk were studied on the cardiovascular system with various experimental models. In isolated rat aorta, l-muscone and musk made the relaxation of blood vessels in maximum contractile response to phenylephrin (10^-6M) in endothelium-containing rings of the rat aorta, but not in endothelium-denuded rings. However, l-muscone and musk in the presence of the inhibitor of NO synthase and guanylate cyclase did not make the relaxation of blood vessel. In spontaneously hypertensive rats (SHRs), l-muscone and musk slightly reduced blood pressure but significantly decreased heart rate. In the isolated perfused rat hearts. l-muscone and musk did not affect significantly on LVDP, contractile force, coronary flow and (-dp/dt)/(+dp/dt). These results suggest that l-muscone and musk have weak cardiovascular effects with relaxation of blood vessel and decrease of heart rate, but without significant cardiac functions.

중국의 양돈산업과 교역 전망에 관한 연구

조광호 한국농업정책학회, 한국축산경영학회 2001 농업경영정책연구 Vol.28 No.3

This paper gives a comprehensive view on China's hog industry and examines the trend of production and consumption, export and import, production pattern, production cost and price, distribution channel of hog and pork, government policy and the trade possibility between Korea and China. Though the importation of pork from China is prohibited by the outbreak of foot and mouth disease in China, the importation of low priced bacon belly and rib is quite within the bounds of possibility in the future. In parallel, we will have a good possibility in the exportation of high quality meat such as tenderloin and loin. There will be a fair chance to make inroads into the Chinese market for feed industry, breeding industry.