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>

Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells

Yang, Ha-Na,Lee, Seung-Eun,Jeong, Seong-Il,Park, Cheung-Seog,Jin, Young-Ho,Park, Yong-Seek The Korean Society of Ginseng 2011 Journal of Ginseng Research Vol.35 No.3

Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on $H_2O_2$-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2-mediated HO-1 induction in human endothelial cell by inhibition of cell death.

Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells

Hana Yang,Seung Eun Lee,Seong Il Jeong,Cheung-Seog Park,Young-Ho Jin,Yong Seek Park 고려인삼학회 2011 Journal of Ginseng Research Vol.35 No.3

Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on H₂O₂-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2-mediated HO-1 induction in human endothelial cell by inhibition of cell death.

Crotonaldehyde-exposed macrophages induce heme oxygenase-1 expression as an adaptive mechanism

Seung Eun Lee,Hana Yang,Gun Woo Son,Hye Rim Park,Young-Ho Jin,Cheung-Seog Park,Yong Seek Park 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.2

Cigarette smoke represents one of the most significant risk factors for the progression of vascular disease. Exposure to cigarette smoke induces oxidative stress in the vascular system and results in vascular dysfunction. Crotonaldehyde, a highly reactive α,β-unsaturated aldehyde, is a foremost compound of cigarette smoke and a product of endogenous lipid peroxidation. Heme oxygenase-1 (HO-1) expression plays an essential role in cellular defense against environmental insults and represents an adaptive response. Here, we showed the effects of crotonaldehyde on the induction of HO-1 expression in RAW 264.7 macrophages. Crotonaldehyde treatment resulted in significantly increased phosphorylation of p38 mitogenactivated protein kinase (MAPK) and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, treatment with zinc protoporphyrin (ZnPP; the specific HO-1 inhibitor) markedly augmented the death of crotonaldehyde-treated macrophages. In summary, these results highlight the role of the HO-1 upregulation through p38 MAPK-Nrf2 activation in the adaptive response to crotonaldehyde in macrophages.

Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression

Lee, Seung Eun,Yang, Hana,Son, Gun Woo,Park, Hye Rim,Park, Cheung-Seog,Jin, Young-Ho,Park, Yong Seek MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.7

<P>The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease.</P>

키넥트 센서를 이용한 고령자 대상의 선자세 균형능력 평가

양승태(Seung-Tae Yang),강동원(Dong-Won Kang),서정우(Jeong-Woo Seo),김대혁(Dae-Hyeok Kim),김태호(Tae-Ho Kim),최진승(Jin-Seung Choi),탁계래(Gye-Rae Tack) 대한전기학회 2017 전기학회논문지 Vol.66 No.2

Portable low-cost Kinect sensor was used to analyze standing balance ability of the elderly. Eighty subjects who can walk alone and have a normal cognitive level participated in this experiment. Based on Berg Balance scale (BBS) test with 52 points, subjects were divided into Healthy older (HO: 46 persons, BBS: 53.80 ± 1.19) and Impaired older (IO: 34 persons, BBS: 49.06 ± 2.03) group. Each subject performed 30 seconds four different standing balance tests (EO: Eyes Open, EC: Eyes Close, EOf: Eyes Open on foam, ECf: Eyes Close on foam). Five variables (Mean distance, Range of distance, Root mean square, Mean velocity, 95% ellipse area) were calculated from the hip joint center movement of Kinect sensor. Results showed that there were significant differences between groups for four different standing tests. Calculated variables from kinect sensor showed significant correlation with BBS score. Especially, mediolateral mean distance, mediolateral root mean square, mediolateral range of distance and 95% ellipse area showed discriminative ability for all tests. Mean values of variables of IO were higher than those of HO, which means the decreased balance ability in IO compared with HO. Therefore, it was possible to estimate simple balance assessment of the elderly using portable low-cost Kinect sensor.

8년간(1992~1999) 산업안전보건연구원에 의뢰된 직업병 심의 사례 분석

강성규,김규상,김양호,최정근,안연순,진영우,최병순,양정선,김은아,채창호,최용휴,김대성,박정선,정호근 대한산업의학회 2000 대한직업환경의학회지 Vol.12 No.2

Objectives : Pneumoconisis and noise-induced hearing loss (NIHL) have been reported as main occupational diseases by the Special Health Examination. The Industrial Accident Compensation Insurance has reported various work-related diseases, however, these two diseases occupied almost a half of compensated cases. Therefore, it was not well known about the status of occupational diseases other than pneumoconiosis, NIHL, and cardio-cerebrovascular accident (CVA). This study was conducted to analyze claimed cases as an occupational disease, that was requested to the Korea Industrial Safety and Health Agency (KOSHA). Methods : The local office of the Korea Labor Welfare Corporation (KLWC) has asked the KOSHA for confirmation of claimed cases as an occupational disease. We analyzed 379 cases requested from KLWC, the Ministry of Labor, employers, unions and occupational health agencies from 1992 to 1999. Results : Male was 80.7 % of the requested cases. Their mean age was 42 years old and 75.5 % of them were more than 35 years old. The requested cases were increased rapidly from 25 cases in 1992 to 108 cases in 1999 and the accept rate was 50.7 %. The majority of requested cases were respiratory diseases(22.4%), cancers(18.5%), Neuropsychiatric problems(14.5%), and musculoskeletal problems(13.5%). The accept rate was high in reproductive, respiratory, musculoskeletal and digestive disorders and low in neuropsychiatric, renal and otologic problems and occupational cancers. 73.6% of them were caused by chemical agents, especially 28.5 % were by organic solvents. 67% of them were clinically confirmed at university hospitals. A half of the cases were from KyongIn area, even the request came from the whole country. Conclusions : A claim was common in workers whose age was over 35 years old and exposure history was over 10 years. The respiratory diseases and neuropsychiatric disorders were still main problems in occupational health and occupational cancers was increasing even though its accept rate was not high yet.

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.

신장내 국소혈류량 조절에 대한 신교감신경의 영향

양훈모,민영기,김동진,송호연,송윤섭 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.2

Control of blood pressure is affected by regulation of intrarenal blood flow. Renal sympathetic nerve simulation inhibits pressure-depressor mechanism of kidney. This antidepressor mechanism was known as happening to due to a decrease the blood supply of renal medulla. It is not known whether renal sympathetic nerve innervation of renal medulla is and it affects regulation of medullary blood flow. We tried to measure total renal blood flow(TRBF), cortical blood flow(CBF), papillary blood flow(PBF) by ultrasonic and laser Doppler techniques in Wistar rats during 3 kinds of renal sympathetic nerves stimulation. The simulation orders are tried randomly and each stimulation period is 15 minute. TRBF and CBF decreased at 1 Hz by 2 and 2%, 3Hz by 18 and 15%, 5Hz by 49 and 44%, respectively as similar to each other. But PBF increased by 1% at 1 Hz and 4% at 3 Hz, while it decreased by 4% at 5 Hz. Therefore, it seems superficial renocortical and total renal blood flows are closely regulated by renal sympathetic nerves with increasing vasoconstriction at 5 Hz, onthe other hand while medullary blood flow seems to be under strong local control, tending to offset neurogenic flows restrictions.

경영판단원칙과 주주대표소송

양동석,박진호 조선대학교 통일문제연구소 2001 統一 問題 硏究 Vol.14 No.-