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>

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.

Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

운동강도의 차이가 대장에서의 Heme oxygenase-1 발현에 미치는 영향: Oligonucleotide chip microarray analysis

최은주 ( Eun Ju Choi ),류호영 ( Ho Young Ryu ),차광석 ( Kwang Suk Cha ) 한국운동생리학회(구-한국운동과학회) 2012 운동과학 Vol.21 No.1

이 연구의 목적은 운동강도 차이에 의한 대장조직이 Heme oxygenase-1(HO-1)의 mRNA 발현에 어떠한 영향을 미치는지 규명하기 위해, Sprage-Dawley계 흰쥐를 대상으로 통제그룹(CON)과 저강도 운동그룹(LIE), 고강도 운동그룹(HIE)으로 구분하여 4주 동안 트레드밀운동 후 48시간 이후에 High through-put microarray analysis방법으로 다음과 같은 실험을 실시하였다. 본 실험은 Rat ABI oligo chip 26,857 개의 유전자 중 filtering을 통하여 12.079개 유전지를 선택하였고, 이 중 유의성 있는(p<.05) 유전자 12,072개를 선별하였으며, clustering분석 방법과 면역조직화학염색법에서도 HO-l이 운동강도에 따라 유의하게 발현하였다(p<.05). Microarray분석 후 RT-PCR로 확인한 결과 HO-I의 유전자 발현양상이 일치하는 결과를 얻었다. 이 실험의 결과로서 운동이 대장에서 HO-1 발현에 영향을 주는 것을 알 수 있었다. 운동이 대장에서의 mRNA 발현이 저강도 운동그룹(LIE)보다 고강도 운동그룹(HIE)에서 더 많이 발현되어지는 것으로 보아 고강도 운동에 의해 발생되는 산소라디칼을 HO-l의 유도를 통하여 적절히 제거함으로써 스스로 항상성을 유지하고 있는 것으로 생각되어진다. The purpose of this study is to identify how large intestine tissue effects to mRNA expression in Heme oxygenase-l (HO-1) due to differences in exercise intensity. To perform this experiment we divided Sprage-Dawley rats into 3 groups (control group (CON). low-intensity exercise group (LIE) and high-intensity exercise group (HIE)), and in 48 hours after 4 weeks treadmill exercise. the following experiment was performed with "High through-put micro array analysis methods" . 12,079 genes were chosen by filtering of the Rat ASI oligo chip 26.857 genes in this experiment Among 12.079 genes, we selected significant genes (p<.05) that were also expressed in the ways of clustering analysis and immunohistochemistry. With results of RT-PCR confirming and microarray analyzing, we derived that gene expression profiles of HO-l had been consistent. As a result of this experiment, we certainly identified that exercise effects to HQ-l expression in large intestine. mRNA expression was more expressed in high-intensity exercise group CHIE) than low-intensity exercise group (LIE), it seems that homeostasis maintains itself by properly removing oxygen radical. caused by high intensity exercise. through reduction of HO-l.

15d-PGJ2 inhibits NF-kB and AP-1-mediated MMP-9 expression and invasion of breast cancer cell by means of a heme oxygenase-1-dependent mechanism

장혜연,On-Yu Hong,Hyun Jo Youn,김민걸,Cheorl-Ho Kim,정성후,Jong-Suk Kim 생화학분자생물학회 2020 BMB Reports Vol.53 No.4

Activation of peroxisome proliferator-activated receptor  (PPAR) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and overexpressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPAR. In this study, we investigated the effects of induction of HO-1 by PPAR on TPAinduced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-B /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ2, a natural PPAR ligand. 15d-PGJ2 induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ2. These results suggest that 15d-PGJ2 inhibits TPA-induced MMP- 9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPAR/HO-1 signaling- pathway inhibition may be beneficial for prevention and treatment of breast cancer.

난치성 만성정신분열증 환자의 생활의 질에 미치는 정신사회치료 프로그램의 효과에 대한 예비연구

송동호,배민진,이종호,이홍식,김선경,서호석,김찬형,전지용 大韓神經精神醫學會 1995 신경정신의학 Vol.34 No.4

Objects : Recent studies of psychosocial adjustment after hospitalization have found that the combination of maintenance antipsychotic drug treatment and psychosocial treatment including psychoeducational program are highly predictive of social rehabilitation and reduction of subsequent relapse. Two groups of patients with refractory chronic schizophrenia were preliminarily compared to determine the effect of a psychosocial treatment program on the quality of life in refractory chronic schizophrenics in an open comparative trial. Methods : One group(N=11) was assigned to approximately six months of the psychosocial treatment program(including psychoeducation program and activity program such as interpersonal relationship program, social skill training, self management program, outings, etc), in a group format, twice a week and a fixed maintenance dosage of clozapine ; while scale(QLS) was used to provide an objective measure of changes in patient's psychosocial functioning and a general assessment of psychopathology was made using the Brief Psychiatric Rating Scale(BPRS). Results : Both BPRS total positive score and the QLS total score, especially in the intrapsychic foundation factor of the scale showed a statistically significant improvement in the psychosocial treatment group. But there was no significant change in both BPRS and QLS scores over a 6-month period in the non-psychosocial treatment group. A significant negative correlation was found between the negative symptom and changes of QLS total, instrumental role and common object and activities scores respectively after receiving a 6-month of the psychosocial treatment program. Conclusion : These results suggest that a psychosocial treatment program including the integration of psychoeducation and a skill training oriented activity program serve as an outpatient treatment modality to improve the quality of the life in refractory chronic schizophrenia. To further clarify the effect of psychosocial treatment in chronic schizophrenia, a randomized trial should be done.

공기 싸이클론 분리 장치의 분체 분리 효율

姜錫浩,朴永孝,金珠浩,朱星浩 嶺南大學校 工業技術硏究所 1985 연구보고 Vol.13 No.1

The collection efficiency of the Lapple's standard-type cyclone separator was determined in order to investigate the effects of the particle size of the dust samples, the dust loading, and the air inlet velocity to the cyclone under the ambient conditions. The experimental conditions are in the following ranges; the air inlet velocity; 5 to 14.7 m/s, the particle sizes of the mono-dispersed system; 14 to 280 ㎛, the dust loading; 17.8 to 58.6 g/㎥, respectively. The collection efficiencies determined were compared with those predicted by the semi-empirical equations proposed earlier by Strauss (³) and by Licht et al, (⁴) and those are shown to be increased, as the particle size of the sample dusts and the air inlet velocity increase, respectively. However, the effect of the dust loading in the air could not be recognized, but slightly increased. For the poly-dispersed particulate samples, having a wide particle size distribution, the grade or separation efficiency curve was experimentally determined to specify more exactly the cyclone separation performance, and the result was discussed with the statistical analysis previously worked by Herrmann.(??)

110 m 허들경기의 제 1허들에 대한 우수선수와 비우수선수의 운동역학적 요인 비교

길호종 ( Ho Jong Gil ),윤석훈 ( Suk Hoon Yoon ) 한국운동역학회 2013 한국운동역학회지 Vol.23 No.1

본 연구는 남자 110 m 허들경기의 제 1허들의 허들링 기술에 대한 중요성을 인지하고 최근 1년간 국내 허들경기 입상경력이 있는 14초 대의 우수선수 5명(SG)과 입상 경력이 없으며 출전 경험이 적은 15초대 비우수 선수 5명(LSG)을 대상으로 출발로부터 제 1 허들링이 완료되는 순간까지를 운동역학적으로 분석하였다. 이러한 목적을 수행하기 위하여 선수들의 허들링시 시간요인, 거리요인, 각도 요인, 각속도 요인, 그리고 지면반력 요인을 분석하였다. 본 연구결과 두 그룹 사이에 각 국면별에서는 소요시간의 차이가 나타나지 않았으나, 전체 허들링 시간에서는 통계적으로 유의하게 SG가 LSG에 비하여 빠른 결과를 나타내었다( p<.05). 이러한 결과는 Yoon(1999)의 연구에서 SG가 LSG에 비해 빠른 소요시간을 보인다는 연구와 유사한 결과를 나타내고 있으며, 스타트 후 15 m에서 발생하는 균형성, 리듬, 운동량이 기록에 가장 크게 영향을 미친다는 연구(Goss, 1991)를 뒷받침 해주고 있다. 또한 각 국면별 그룹간의 통계적인 시간 차이는 보이지 않으나, 전체 허들링 시간의 통계적인 차이를 보인 결과는 본 연구의 실험대상자의 수에 기인한다고 보인다. 즉, 본 연구의 결과에서는 제시되지 않았으나 통계적인 검증값인 t 값은 구간별로 -1.119∼-1.912의 범위에 있었고 p 값도 .6∼.8 사이의 결과를 나타내고 있어 보다 많은 연구대상자를 확보하였다면 구간별로 통계적인 차이를 발견할 수 있었을 것으로 생각된다. 또한 <Figure 4>에서 제시된바와 같이 SG는 허들링 기술의 시작(P1)보다는 마무리단계(P3)에서 LSG와 더 큰 시간 차이를 보였다. 이러한 패턴은 SG와 LSG를 구분 할 수 있는 좋은 근거라고 할 수 있다. 즉 <Table 1>에서 제시된 것처럼 SG가 LSG에 비하여 높은 COM 위치를 가지고 있음에도 불구하고 짧은 구간시간(P3)을 보여주고 있다는 점은 SG가 P3에서 큰 전진 낙하 속도를 생성하고 이러한 결과는 다음번 허들을 넘기 위한 빠른 3보 4스텝의 만드는 도움을 주고 있다는 방증이라 할 수 있다. 두 번째, 제 1허들을 넘는 과정에서 나타나는 보폭과 신체중심의 위치의 경우 보폭에서 SG가 약 10 cm 짧게, 신체중심의 최대 높이에서 SG가 LSG보다 약 5 cm가량 높게 나타나면서 소요시간이 빨랐다는 것은, 동작의 변화가 SG가 매우 빠르다는 것을 나타내고 있다. 그러나 허들을 넘기 위한 최적의 신체중심의 최대 높이가 120 cm라는 (Park, 1996) 연구 결과와는 현저한 차이가 나타나면서 효과적인 허들링을 구사하기 위해선 좀 더 낮은 자세로 신체중심을 유지해야 한다는 것을 알 수 있었다. 이것은 훈련상황에서 의도적으로 낮게 유지하여 지속해야 한다는 점을 시사해주고 있다. 세 번째, 착지구간의 전경각도에서 SG와 LSG가 유의한 차이를 보이면서 SG가 상대적으로 작은 각도를 유지하며 허들링을 구사하는 것을 볼 수 있었다. 이 결과는 Lee(2008)의 연구에서 보고된 우수선수일수록 도약과 착지구 간에서 낮은 자세로 유지하며 넘는 기술적 차이가 존재한다는 것을 뒷바침 해주고 있다. 한편, 허들링구간인 공중에서는 LSG가 SG에 비해 상체 전경각도의 각속도가 높게 나타나면서 유의한 차이를 보였다. 이것은 LSG가 상하의 움직임에 큰 변화를 시도하는 것으로 보여지며, 이는 Goss(1991)가 주장한 신체중심의 상하 이동을 최소화해야 한다는 연구결과에 비효과적 동작을 취하고 있다는 것을 나타낸다. 이 결과에 따르면 효과적인 허들링을 구사하기 위해선 전경각의 크기보다 신체중심에 대해 최소한의 변화를 주는 전경각 속도의 변화훈련을 적극 도입해야 할 것으로 추측된다. 본 연구는 제 1허들을 기술력 차이를 규명하기 위한 방법으로 운동학적 분석과 함께 직접적으로 신체중심의 제동력과 추진력에 영향을 주는 3차원 지면반력을 분석하여 비교하였다. 이 결과에 따르면 LSG의 경우 신체중심의 높이에 직접적으로 영향을 미치는 최대 수직반력에서 SG보다 약 1.4 N/Bw 높은 수치를 기록하면서 통계적으로 유의한 차이가 나타났다. 또한 통계적인 유의차이가 나타나지 않았으나, 지면 반력의 제동력을 나타내는 전-후 지면반력에서 SG가 약 0.5 N/Bw의 힘으로 제동이 발생하는 것을 알 수 있다. 이를 통해 SG가 LSG에 비해 도약구간에서 수평속도를 잃지 않고 이동 한다는 것을 짐작할 수 있다. 110 m 허들경기의 제 1허들에 대한 운동역학적 기술차 이를 분석한 결과를 종합해 보면, 제 1허들을 넘기 위한 도약구간부터 착지 순간까지 전반적으로 우수 선수가 비 우수선수에 비해 동작의 변화를 최소화 한다는 것을 관찰할 수 있었으며, 특히 허들을 넘기 위한 수평속도에 영향을 미치는 지면반력에서 우수선수가 추진력을 감소시키지 않으며 넘는 것으로 나타났다. 따라서 제 1허들의 성공적인 수행을 위해서는 무엇보다도 허들 도입구간에서 추진력을 발생시키는 발구름과 동시에 최소의 동작 변화를 실시하는 훈련이 필요할 것으로 판단된다. The purpose of this study was to provide a fundamental information for enhancing 110m hurdlers` performance through conducting comparative biomechanical analysis between Skilled Group(SG) and Less- Skilled Group(LSG) those who are not in the first section of 110m hurdles. To persue the purpose of this study, total of 10 hurdlers participated. Then they were divided into two groups; SG: five hurdlers who have won awards with 14-second range at 2010 national track and field event, and LSG: five hudlers who did not win any awards with 15-second range. Three-dimensional motion analysis with 12 infrared cameras(Oqus 300, Qualisys) and 1 force plate(Type 9286AA, Kistler) was performed. From this study following conclusions were obtained. 1) For the overall runtime, SG revealed faster elapsed time than that of LSG. 2) At E4, LSG showed greater trunk angle than that of SG. 3) At E3 LSG revealed higher angular velocities than that of SG. 4) No significant differences was found for AP GRF between groups but LSG showed greater VGRF than that of SG.

Anti-Inflammatory Effect of By-Products from<i>Haliotis discus hannai</i>in RAW 264.7 Cells

Rho, Ho-Seok,Kim, Hyang,Kim, Jung-Ae,Karadeniz, Fatih,Ahn, Byul-Nim,Nam, Ki-Ho,Seo, Youngwan,Kong, Chang-Suk Hindawi Limited 2015 Journal of chemistry Vol.2015 No.-

<P>Several reports promoted the potential of shellfish due to their ability to act as antioxidant, anti-inflammatory, and antimicrobial agents. Pacific abalone,<I>Haliotis discus hannai</I>viscera is, reported to possess bioactivities such as antioxidative stress and anti-inflammatory. In this study, anti-inflammatory potential of mucus-secreting glands from shell-shucking waste of<I>H. discus hannai</I>was evaluated using RAW 264.7 mouse macrophage cell model. Results indicated that presence of<I>H. discus hannai</I>mucosubstance by-products (AM) significantly lowered the nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-<I>α</I>, IL-1<I>β</I>, and IL-6 and enzymes iNOS and COX-2. Also, AM was shown to increase expression of anti-inflammatory response mediator HO-1. Presence of AM also scavenged the free radicals<I>in vitro</I>. In conclusion, by-products of<I>H. discus hannai</I>are suggested to possess notable anti-inflammatory potential which promotes the possibility of utilization as functional food ingredient.</P>

Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-kB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1

( Jae Ho Choi ),( Sun Woo Jin ),( Eun Hee Han ),( Bong Hwan Park ),( Hyung Gyun Kim ),( Tilak Khanal ),( Yong Pil Hwang ),( Minh Truong Do ),( Hyun Sun Lee ),( Young Chul Chung ),( Hee Suk Kim ),( Tae 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Purpose: The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells. Methods: Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism. Results: CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells. Conclusion: We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.ⓒ2014 Elsevler Gmbh. All rights reserved.