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>

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>

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.

신원방우황청심원액의 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 pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10^-6 M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, 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 excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD_90 and V_max at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.

양돈농가의 정보이용과 S/W활용에 대한 조사 연구

조광호,서종석 한국농업정보과학회 2001 농업정보과학 Vol.3 No.1

This study was done to examine the problems and resolutions for the hog farms in the current and future direction of information utilization and hog management software. Based on the survey of 70 farms which possess computers in Honam area, the main object of purchasing computers was to use in day to day life such as childrens' education. The object of purchasing for business use or information collection was relatively minor. The sites most frequently visited by internet were in the field of childrens' education, followed by agricultural marketing. The fields hog farms concern in the near future are found to be the sites, by the order, in marketing, children's education, e-mail, agricultural technology, agricultural management, and weather forecast. Besides the contents development in these fields, development of agricultural software seem to be urgently needed. Since hog management softwares have contributed to raise the accuracy in decision making by 20%, to raise productivity and profitability, to reduce labor and cost, and to raise quality(10%, respectively).

한국기업의 국제경영전략으로서의 국제 M&A에 관한 연구

조희영,장광호 동국대학교 경제경영연구원 1997 經濟經營硏究 Vol.21 No.1

From the times of the mid-1980s, Foreign Direct Investment(FDI) of Korean Firms has begun to show high degree and diversification, that is due to the rapid economical and managerial changes both domestically and Internationally. with the vigorous evolvement of this phenomenon, Int'l M&A has put in an appearance as a vital instrument of International Business Strategy of Korean firms. The most important characteristics of Int'l M&A is that it is the strategic asset-seeking investment through the utilization of exterior managerial resources, and a large number of theoretical and empirical studies shows that International M&A is superior to other forms of Foreign Direcct Investment is its performances. The main or principal motives of Int'l M&A are 1) successive growth of firms 2) acquirement of raw materials and resources 3) procurement of advanced technological knwohow 4) ensurement of over-seas market 5) diversification of products and region and 5) upgrade of labour productivities etc, The important characteristics of Int'l M&A of korean firms is 1) preponderances to the advanced countries 2) large scale of an amount of investment 3) simplicity of money and 4) taking the initiative by large and major firms etc, The necessities of Int'l M&A in Korean firms is can be summarized as follows : enfeeblement of price competition in international market, unstable movement of foreign exchange, procurement of advanced technological knowhow and advent of the era of high wage. To cope with the above situation strategically, Korean firms have to lay out a scheme as follows - procurement of professional knowhow, reasonable valuation to target firms, complete controlling of foreign exchange risk and make provision to out-in styles on M&A. Effective and well-directer use of Int'l M&A, to Korean firms, can and will served as a vital instrument and reasonable alternatives of efficient strategy on Foreign Direct Investment.

MRI용 초전도 능동차폐 마그네트의 설계에 관한 연구

조윤현,이광호,김성도 東亞大學校 附設 情報通信硏究所 1996 情報通信硏究所論文誌 Vol.4 No.1

An optimal design approach is presented for the high homegeneity superconducting magnet with a superconducting active shield esperically for a magnetic resonance imaging system. This paper is investigated magnetic phenomena for a stray magnetic to get reduction technigues of the unwanted stray magnetic field from the superconducting magnet.

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.

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.

심장수술 2,450예와 심장이식

조광현,황윤호,이양행,류지윤 인제대학교 1999 仁濟醫學 Vol.20 No.1