In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

Lee, Sunghun,Lee, Dong Hun,Park, Bong-Woo,Kim, Riyoun,Hoang, Anh Duc,Woo, Sang-Keun,Xiong, Wenjun,Lee, Yong Jin,Ban, Kiwon,Park, Hun-Jun Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Vascular regeneration in ischemic hearts has been considered a target for new therapeutic strategies. It has been reported that ETV2 is essential for vascular development, injury-induced neovascularization and direct cell reprogramming of non-endothelial cells into endothelial cells. Thus, the objective of this study was to explore the therapeutic potential of ETV2 in murine models of myocardial infarction in vivo. Direct myocardial delivery of lentiviral ETV2 into rodents undergoing myocardial infarction dramatically upregulated the expression of markers for angiogenesis as well as anti-fibrosis and anti-inflammatory factors in vivo. Consistent with these findings, echocardiography showed significantly improved cardiac function in hearts with induced myocardial infarction upon ETV2 injection compared to that in the control virus-injected group as determined by enhanced ejection fraction and fractional shortening. In addition, ETV2-injected hearts were protected against massive fibrosis with a remarkable increase in capillary density. Interestingly, major fractions of capillaries were stained positive for ETV2. In addition, ECs infected with ETV2 showed enhanced proliferation, suggesting a direct role of ETV2 in vascular regeneration in diseased hearts. Furthermore, culture media from ETV2-overexpressing cardiac fibroblasts promoted endothelial cell migration based on scratch assay. Importantly, intramyocardial injection of the adeno-associated virus form of ETV2 into rat hearts with induced myocardial infarction designed for clinical applicability consistently resulted in significant augmentation of cardiac function. We provide compelling evidence that ETV2 has a robust effect on vascular regeneration and enhanced cardiac repair after myocardial infarction, highlighting a potential therapeutic function of ETV2 as an efficient means to treat failing hearts.</P></▼1><▼2><P><B>Cardiovascular disease: New hope for healing the heart</B></P><P>A gene therapy strategy that stimulates cardiovascular repair could improve recovery for heart attack patients. Heart attacks inflict severe damage on the heart and blood vessels, tissues with limited capacity for self-repair. Researchers led by Kiwon Ban of the City University of Hong Kong and Hun-Jun Park of the Catholic University of Korea, Seoul, have now demonstrated that a gene responsible for cardiovascular development can also efficiently stimulate heart repair. They used viruses to deliver the gene into a mouse model of heart attack, and showed that treated heart tissues exhibited strong recovery relative to untreated controls. The treatment reduced scar tissue formation and promoted proliferation of the cells lining blood vessels and blood vessel formation, measurably improving heart function. This approach could lay the groundwork for treating a common potentially fatal event.</P></▼2>

가상공간의 가공 공정과 상태 구현에 관한 연구

이수훈,김봉석,홍민성,김종민,JUN NI,박상호,송준엽,이창우,하태호 한국공작기계학회 2005 한국공작기계학회 춘계학술대회논문집 Vol.2005 No.-

This paper presents virtual machining system in order to realize turning process in virtual space. A reliable virtual turning process simulation was developed based on the surface shaping system which is capable of considering geometric model, thermal error model, and vibration model. Accuracy of surface shape resulting from proposed machining simulator was verified experimentally. This paper also developed the watchdog agent that continuously assessed, diagnosed, and predicted performance of products and machines in machining. The Watchdog agent extracted feature signal using time-frequency analysis among various signals from multi-sensor and evaluated machining condition using performance confidence value.

휴대폰 카메라용 자동초점 구동기의 충격해석

이성민,김봉석,송준호,이수훈,이혜진,이문구,송준엽,이창우 한국공작기계학회 2008 한국공작기계학회 춘계학술대회논문집 Vol.2008 No.-

Recently, the robustness against daily impact is important according to portablization and downsizing of mobile electronics. Especially, almost parts of cellular phone should undergo drop test when they fall 1.5 m above ground. This test simulates the case when cellular phone slips through user's fingers while he is talking on the phone. This paper studies a drop test of auto focusing (AF) actuator for camera module in cellular phone. This component is composed of voice coil motor (VCM) as an actuator and leaf spring as a guide and suspension. The leaf spring's deformation is essential for the test because its permanent distortion disables the focusing, and then, a high quality photograph cannot be obtained. Up to now the drop test has been carried out after fabricating real AF actuator. We propose a dropt test model which simulates the drop test based on finite element analysis. This model makes us enable investigate the stress acting on the clamping and curved parts of leaf spring. Stress over Von Mises criterion lets the spring deformed permanently, and then AF actuator malfunctioned, It helps us to design and modify AF actuator without manufacturing the real product. And also, it saves the time and cost for the development of new products.

전통시장 시설현대화사업이 전통시장 활성화에 미치는 영향 분석

이준호(Lee, Jun-Ho),김영(Kim, Yeong),김경훈(Kim, Kyoung-hun) 한국지역개발학회 2013 韓國地域開發學會誌 Vol.25 No.1

After full opening of distribution market in 1996, its competitiveness was lost and declined due to the emergence of a variety of distribution types, change of customers consumption habits, and purchase patterns. Therefore, Korean government began to support the modernization projects of traditional markets through the establishment of law for the activation of existing traditional markets. In this regard, this study attempts to diagnose the problems of facility modernization projects through substantial and concrete effect analysis on facility modernization projects to provide the activation methods effectively. To achieve this goal, we analyzed the overall satisfaction and substantial effect of facility modernization projects for traditional markes by carrying out questionnaire surveys on merchants at Jun-gang Yudeung Market in Jinju. As a result of questionnaire survey, customers were generally satisfied with the facility modernization project, the market environment was improved and the customer numbers and sales amount which show the actual improvement also increased after implementing the projects. Also, it was proved that customer numbers and the sales amount after the facility modernization project of traditional markets increased and the degree in the increase was low level of 5~20%. Therefore, it was analyzed that sub-project items of the facility modernization project, which have a significant effect on the activation of traditional markets, had a low level of influence.

매크로/마이크로 레벨 볼트 결합 구조물에서의 실험적/해석적 방법을 통한 시스템 특성 비교

김봉석,이성민,이문구,이수훈,Jun Ni,송준엽,이창우,하태호 한국공작기계학회 2006 한국공작기계학회 추계학술대회논문집 Vol.2006 No.-

As the micro technology and miniaturization of a structure and component in the last couple of decades have been concretely realized, the understanding of structural and dynamic characteristics and prediction of dynamic behavior are indispensable to the miniaturized structures and micro machines. This paper shows the effect of dynamic characteristics in bolt-jointed structures by comparing natural frequencies and mode shapes between macro and micro-scale beams through experimental modal analysis and finite element analysis with a1 8 test models by materials, by size, and by joining condition; that is, SS41 and A16061-T651, micro and macro, and monolithic beam and bolt-jointed beam.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

Pretreatment with Lycopene Attenuates Oxidative Stress-Induced Apoptosis in Human Mesenchymal Stem Cells

Kim, Ji Yong,Lee, Jai-Sung,Han, Yong-Seok,Lee, Jun Hee,Bae, Inhyu,Yoon, Yeo Min,Kwon, Sang Mo,Lee, Sang Hun The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although $H_2O_2$ ($200{\mu}M$) increased intracellular ROS levels in human MSCs, lycopene ($10{\mu}M$) pretreatment suppressed $H_2O_2$-induced ROS generation and increased survival. $H_2O_2$-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by $H_2O_2$ treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.

관동맥질환에서 저밀도 지단백 입자 크기의 분포

임효영,김인숙,승기배,강동헌,전두수,장기육,박준철,이수영,홍순조,최규보 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.8

Pretreatment with Lycopene Attenuates Oxidative Stress-Induced Apoptosis in Human Mesenchymal Stem Cells

( Ji Yong Kim ),( Jai Sung Lee ),( Yong Seok Han ),( Jun Hee Lee ),( Inhyu Bae ),( Yeo Min Yoon ),( Sang Mo Kwon ),( Sang Hun Lee ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although H2O2 (200 mM) increased intracellular ROS levels in human MSCs, lycopene (10 μmM) pretreatment suppressed H2O2-induced ROS generation and increased survival. H2O2-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by H2O2 treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.

국내에서 분리된 Aujeszky's Disease Virus의 면역원성 : Ⅰ. Aluminum Hydroxide겔 흡착 불활화 Aujeszky's Disease Virus항원의 면역원성 Ⅰ. Immunogenicity of the Inactivated Aujeszky's Disease Virus with Aluminum Hydroxide Gel Adjuvant

전무형,이헌준,박정우,안수환 충남대학교부설 생명공학연구소 1992 생물공학연구지 Vol.2 No.-

Aujeszky's disease virus(ADV), NYJ-1 strain, isolated from the diseased piglets in Korea was inactivated with binary ethyleneimine or formalin and absorbed in aluminum hydroxide gel. Safety and humoral and cellular immunogenicity of the antigens were investigated in mouse, guinea pig and piglets. In mouse inoculation test, the antigens showed 100% of safety and induced a significant level of ADV antibody. The protective potency following intracerebral challenge with the virulent ADV at 10^7.5TCID_50/0.2㎖ were 60% to 64.3%. In guinea pig inoculation test, it was found that the antigens were quite safe, inducing 63.2 to 124.9 of virus neutralization(VN) titers at the 5th week post inoculation(pi). The protectivity of the antigens against the challenge of the virulent ADV were 62.5% to 75.0%. In piglet inoculation test, the antigens were quite safe after the primary and booster injections, and induced 28.7 to 39.1 of VN titers at the 5th week pi. The high levels of ADV antibodies were also recognized by agar gel precipitation test, latex agglutination test and immunoenzyme assays. Leucocyte adherence inhibition(LAI) test for the piglets revealed 22.3±3.8% to 32.8±6.9% of LAI index at the 4th week pi, and the evident reactions of delayed type hypersensitivity was observed in subcutaneous inoculation of the antigen to the immunized piglets. Following the challenge, the immunized piglets showed none of specific clinical signs of AD and revealed the higher gain of body weight, and the lower secretion of ADV from the nasal cavity as compared with the control group.