Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

사과 추출물과 phloretin에 의한 항염증 활성

김근호(Geun-Ho Kim),이은주(Eun-Joo Lee),류승민(Seung-Min Ryu),손호용(Ho-Yong Sohn),김종식(Jong-Sik Kim) 한국생명과학회 2021 생명과학회지 Vol.31 No.2

본 연구에서는 풋사과의 열수추출물(GAHW)과 에탄올추출물(GAE), 그리고 애사과 열수추출물(UAHW)을 제조하고 LPS로 활성화된 RAW264.7세포주를 이용하여 이들의 항염증 활성을 연구하였다. 모든 추출물이 세포생존율에는 영향을 미치지 않고 nitric oxide (NO) 생산을 저해하였으며, iNOS의 발현도 감소시켰다. 반면, UAHW만이 COX-2의 발현을 저해하였다. 또한 모든 추출물이 모든 MAPKs의 인산화를 감소시켰다. 모든 추출물이 ROS의 생산을 농도의존적으로 감소시켰으며, GAHW와 GAE에 의해 HO-1의 발현이 증가됨을 확인하였다. 또한, 사과 flavonoid인 phloretin과 phloridzin의 항염증 활성을 연구하였다. Phloretin은 농도의존적으로 NO의 생산을 저해하였으나, phloridzin은 NO 생산에 아무 영향이 없었다. 또한, phloretin은 iNOS와 COX-2 단백질의 발현을 감소시킨 반면, phloridzin은 두 단백질 발현에 영향을 주지 못하였다. 따라서, 이러한 연구결과는 사과 추출물은 MAPK 경로와 HO-1 경로를 조절함으로써 항염증 활성을 가지며, phloretin이 사과의 항염증 활성을 담당하는 파이토케미칼의 하나가 될 수 있음을 제시한다. In the present study, we prepared hot water extracts of green apple (GAHW) and unripe apple (UAHW), and ethanol extract of green apple (GAE), and investigated their anti-inflammatory activities in LPS-activated RAW264.7 cells. All extracts dramatically suppressed nitric oxide (NO) production in a dose-dependent manner in LPS-stimulated RAW264.7 cells without affecting cell viability. In addition, all extracts decreased the expression of iNOS, whereas UAHW only reduced the expression of COX-2. All extracts suppressed the phosphorylation of MAPKs (p38, ERK, and JNK) indicating all extracts show their anti-inflammatory activities via regulating MAPK pathway. Furthermore, all extracts reduced the production of reactive oxygen species in a dose-dependent manner and they increased the expression of heme oxygenase-I (HO-I) whereas UAHW could not. We also investigated whether apple flavonoids phloretin and phloridzin can have their anti-inflammatory activities in same in vitro model. Phloretin dramatically decreased NO production in a dose dependent manner without affecting cell viability, whereas phloridzin have no effects. Phloretin also reduced the expression of iNOS as well as COX-2, whereas phloridzin could not. Overall, these results suggest that apple extracts have their anti-inflammatory activities via regulating MAPKs and HO-1 pathways, and apple flavonoid phloretin can be one of phytochemicals responsible for anti-inflammatory effect of apple.

Ho-166 부착풍선도자를 이용한 방사선 조사의 돼지 관상동맥 스텐트 재협착 예방 효과

김원 ( Kim Won ),정명호 ( Jeong Myeong Ho ),박옥영 ( Park Og Yeong ),정우곤 ( Jeong U Gon ),박우석 ( Park U Seog ),김주한 ( Kim Ju Han ),안영근 ( An Yeong Geun ),조정관 ( Jo Jeong Gwan ),박종춘 ( Park Jong Chun ),강정채 ( Kang Je 한국지질동맥경화학회 ( 구 한국지질학회 ) 2002 韓國脂質學會誌 Vol.12 No.1

배경 : 국내에서 개발된 방사선 동위원소 Holmium-166 (166Ho)은 주로 베타선을 방출하며, 166Ho을 부착한 풍선도자를 이용하여 돼지 관상동맥 재협착 모형에서 풍선확장술 후 신생내막 증식을 전신적 부작용 없이 안전하고 효과적으로 억제하였음을 보고한 바 있다. 본 연구에서는 돼지 관상동맥 스텐트 재협착 모형에서 스텐트 시술 후 신생내막 증식에 의한 재협착 병변을 166Ho 부착 풍선도자를 이용하여 치료하여 그 효과를 관찰하고자 하였다. 방법

Mg₂SiO₄ : La, Ho 열형광선량계에서 활성제 농도가 글로우 커브에 미치는 영향 La, Ho TLD on Activation Concentration

김영국,손인호,채건식,노경석,오재근,이은숙 경남대학교 신소재연구소 1996 論文集 Vol.6 No.-

본 연구에서는 Mg₂SiO₄에 활성화 물질로 La, Ho를 첨가하여 열형광체를 제작하였고 불순물의 농도를 1wt.% ∼5 wt.%까지 변화시키면서 열평광강도의 glow curve를 측정하였다. 도한 열형광체의 glow curve를 peak shape법으로 분석해서 TL특성에 대한 포획 매개변수와 활성화 에너지, 발광차수, 선량의존성등을 조사하였으며, 그 물리적 특성을 조사하고 선량계로서 타당성과 실용성을 확인하였다. The Mg₂SiO₄: La, Ho thermoluminescent phospher has been prepared by sintring Mg₂SiO₄after doping the transition elements La and Ho. The heating rate is 10℃/sec at this thermoluminescent phospher are heated. The maximum peaks are found in the measured Mg₂SiO₄: La and Ho. TL glow curve at 229℃ and 345 C when the 1 wt.%-5 wt.%. The glow curve of TLD increased TL intensity and temperature of peak appears to the high temperature when the heating rate is l0℃/sec-25℃/sec. The activation energy of the main peak has been estimated by the peak shape method. The estimated activation energies are 1.77 eV. 1.52 eV respectively. The thermoluminescence process in Mg₂SiO₄: La and Ho are found to the 2nd order when the main peak of the glow curve is analyzed by peak shape method. The dose responses of Mg₂SiO₄: La and Ho TLD are linear up to intensity of X-ray.

다중흐름모형에서 정책기업가의 역할 시론적 연구 : 공무원 범죄에 관한 몰수 특례법(전두환 추징금 사례 1997~2013)의 개정 논의를 중심으로

Dong Kyu Lee,Dong Geun Yum,Jun Ho Lee,Kyoung Rok Kim 위기관리 이론과 실천 2014 Crisisonomy Vol.10 No.11

This study examines the preceding researches on the policy entrepreneurs at home and abroad and after discussing the policy entrepreneurs, analyzes the flow of the revision process of the partial revised bill(hereinafter referred to as Chun Doo-hwan Collection Law) of the confiscation special law about public official crime by administration using the multiple streams framework model, and this researcher attempts to analyze the activities of how the policy entrepreneur among diverse policy actors who plays an important role in opening policy window influenced the revision process in the process of enacting the partial revised bill of the confiscation special law about public official crime. And how the policy window of the partial revised bill of the confiscation special law about public official crime that was not opened in the previous administrations came to be opened in the Park Geun-hye administration is analyzed. The results of this study confirmed that in the previous administrations the policy entrepreneur to open the policy window did not appear but in the Park Geun-hye administration President Park Geun-hye played the role of the policy entrepreneur, producing Chun Doo-hwan 본 연구는 정책기업가 대한 국내외 선행연구를 검토하고, 정책 기업가에 대한 심도있는 논의를 하고자 하였다. 또한 공무원 범죄에 관한 몰수 특례법 일부 개정안(이하 전두환 추징법)의 정책과정을 다중흐름모형을 이용하여 각 정권별로 흐름을 분석하였다. 공무원 범죄에 관한 몰수 특례법 일부 개정안의 정책결정 과정에서, 정책기업가 (policy entrepreneur)가 어떻게 중요한 영향을 미칠 수 있는 활동을 할 수 있었는지에 대한 분석을 시도하고자 한다. 그리고 이전 정권에서는 열리지 않던 ‘공무원 범죄에 관한 몰수 특례법’ 일부 개정안에 대한 정책의 창이 현재 박근혜 정부에 와서는 어떻게 열리게 되었는지에 대한 분석을 한다. 연구결과, 이전의 정권들에서는 정책의 창을 여는 정책기업가가 나타나지 않았고, 박근혜 정부에서는 박근혜 대통령이 정책기업가의 역할을 하여 전두환 추징법이 산출되었다는 것을 확인하였다.

인삼 선발계통의 지역적응성 검정

Bong Jae Seong,Sun Ick Kim,Ka Soon Lee,Moo Geun Jee,Su Dong Kim,A Reum Kwon,Hyun Ho Kim1,Young Chang Kim 한국약용작물학회 2017 한국약용작물학술대회 발표집 Vol.2017 No.05

Background : For cultivation of varieties of ginseng, the pure line selection method, which is to select the best among those cultivated in farms for pedigree breeding, replicated yield trials and regional adaptation trials before registering as a new variety, is widely used. Although there are 25 registered varieties of ginseng in Korea, the quality of ginseng is declining together with the amount of harvest being decreased by 15 - 20% due to the heat injuries and diseases from the warming & abnormal climate. Thus, the needs for development of disaster-resistant varieties with better chances of surviving through high temperature, salts and disease are increasing. Therefore, this study is to cultivate disaster-resistant varieties among those selected for their disaster tolerance and salt tolerance through regional adaptation trials. Methods and Results : As a result of examining the growth characteristics of the selected 2 - 5 year old varieties used in the study, among the 5-year old crops, Goryeo 4 and Eumseong 5 showed superior growth in both above and below aerial parts, and among the 4-year old crops, Eumseong 11 and Cheonryang showed superior growth while the growth in the below aerial parts were satisfactory in the order of Cheonryang > Eumseong 10 > Eumseong 11 > Eumseong 9. Among the 3-year old crops, the most superior growth in both above and below aerial parts was observed in Eumseong 14 with the weight of the below aerial part, root diameter and taproot length at 13.8 g, 11.8 ㎝ and 6.2 ㎝ respectively. Among the 2-year old crops, Eumseong 10 showed the most superior growth in both above and below aerial parts. Conclusion : Based on the above results, Goryeo 4 and Eumseong 5 among the 5-year old crops, Eumseong 11 among the 4-year old crops, Eumseong 14 among the 3-year old crops and Eumseon 10 among the 2-year old crops showed the most superior growth among the selected varieties. The growth characteristics of both above and below aerial parts in each year will continuously be monitored.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Shin, Tae-Kyeong,Kang, Mi-Sun,Lee, Ho-Youn,Seo, Moo-Sang,Kim, Si-Geun,Kim, Chi-Dae,Lee, Won-Suk The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Tae Kyeong Shin,Mi Sun Kang,Ho Youn Lee,Moo Sang Seo,Si Geun Kim,Chi Dae Kim,Won Suk Lee 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1Ձ (HIF-1Ձ) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1Ձ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

척수 손상으로 발생된 신경인성 방광 환자의 요역동학 검사상 고위험 인자 분석

김형지,송인호,이근호 단국대학교 1998 論文集 Vol.32 No.-

Purpose : Spinal cord injury is one of the most devastating states of infirmity encountered by today's health care professional. Historically, urologic complication have been the major source of morbidity and mortality among spinal cord injury patients. The main objective in management of neuropathic bladder is the preservation of renal function because the renal deterioration is the most serious problem of neuropathic bladder. We investigated risk factors for renal dysfunction in neuropathic bladder from spinal cord injury. Materials and methods : A total 36 spinal cord injury patients of neuropathic bladder with voiding dysfunction was evaluated by urodynamic study and we analyzed the risk factors associated with upper urinary tract deterioration. Results : In cases of spinal cord injury, detrusor external sphincter dyssynergia and high detrusor pressure were risk factors of upper tract deterioration. Conclusions : In management of neuropathic bladder, the abnormalities of individual lesion-specific urodynamic parameters(detrusor sphincter dyssynergia, low compliance, high detrusor pressure) should be factored into the assessment of upper urinary tract deterioration.