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>

이광수와 나쓰메 소세키의 문학교육론이 지닌 근대성 비교연구

권혁건(Kwon,Hyuk-Gun),이호규(Lee,Ho-Gyoo),김주현(Kim,Ju-Hyun) 동북아시아문화학회 2011 동북아 문화연구 Vol.1 No.28

Soseki is representative novelist and theorists of Japanese modern literature, and Lee Gwangsoo (Lee) is known as person who opened doors to Korean modern literature. They are representing not only Korean and Japanese modern literature, but also Oriental modern literature. We focused on the early stages of their literary theories. As well, looked into their arguments based on their ideas of literary education in relation between literature and society. Although Soseki and Lee are both representatives of Korean and Japanese modern literature, we have found their literary theories to have contrasts, as well as undertoned ideal substance. Their findings show identical recognition in defining the workings of human mind as intellect, emotion and volition. Also, their thoughts on the realm of emotion is the characteristic of literature, and explained modern literature by drawing the concepts of rationality and truth. Soseki insisted literary art is not a simple skill; a literary artist could influence others due to their ideals that a literary artist is someone who has the biggest and highest ideals. Lee’s argument resembles Soseki’s argument. Lee contended literary art can be made simply with skill and endeavor. Only highly gifted artist can take charge of a growing self-regulating person who could lead society through literature. Soseki and Lee both, therefore, conclude the Occidental natural science (in other words, education that is logical and substantiate) is modern education, and upcoming Oriental new education need to take after. We found Soseki and Lee have contended education through literature that could produce self-regulating and liberal individuals based on the mentioned Occidental new education.

Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen

Woo, Je Moon,Shin, Da-Yong,Lee, Sung Ju,Joe, Yeonsoo,Zheng, Min,Yim, Jin Ho,Callaway, Zak,Chung, Hun Taeg Molecular Vision 2012 Molecular vision Vol.18 No.-

<P><B>Purpose</B></P><P>To determine whether curcumin induces expression of the defensive enzyme heme oxygenase-1 (HO-1) and protects cells against oxidative stress in cultured human retinal pigment epithelial cells.</P><P><B>Methods</B></P><P>Effective concentrations and toxicities of curcumin were determined after 3 h of curcumin treatment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Confluent human retinal pigment epithelium cell lines (ARPE-19) were preincubated with curcumin and oxidatively challenged with H<SUB>2</SUB>O<SUB>2</SUB>. HO-1 expression was determined with western blot analysis. To confirm the protective role of HO-1 in oxidative stress, small interfering RNA (siRNA) against HO-1 or inhibitor of HO-1 was treated with curcumin in retinal pigment epithelium cells. Intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry and confocal microscopy. Apoptosis was evaluated with Annexin V-fluoroscein isothiocyanate staining.</P><P><B>Results</B></P><P>Curcumin had little cytotoxicity at concentrations less than 30 μM, and HO-1 expression was the highest at the 15 μM concentration. At this concentration, curcumin also increased the cytoprotective effect against the oxidative stress of H<SUB>2</SUB>O<SUB>2</SUB> through the reduction of ROS levels in human retinal pigment epithelial cells. Curcumin’s effect on the reduction of ROS was mediated by the increase in HO-1 expression.</P><P><B>Conclusions</B></P><P>Curcumin upregulated the oxidative stress defense enzyme HO-1 and may protect human retinal pigment epithelial cells against oxidative stress by reducing ROS levels.</P>

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.

한국형출혈열 병원체 Hantaan virus에 대한 뇨의 살균작용

이호왕,백낙주,양상기 대한감염학회 1981 감염 Vol.13 No.1

Korean hemorrhagic fever(KHF) reported for the first time in Korea in 1951, althought it had previously been known from both Manchuria and Russia. Since that time it has been known as Korean hemorrhagic fever and has remained endemic near the Demilitarized Zone between North and South Korea. In 1976 and 1978, Lee et al reported the isolation of Hantaan virus, the etiologic agent of KHF, from the patients and Apodemus agrarius coreae collected in the endemic areas of KHF and developed Lee's method of serological diagnosis of KHF. Very recently, Lee et al demonstrated virus excretion in the urine of infected Apodemus agrarius for a long time. The urine from both Apodemus agrarius and susceptible human were examined its effect on the infectivity of Hantaan virus to Apodemus mice. The results are summarized as follows: 1) The urine from Apodemus agrarius rodent, the natural reservoir of Hantaan virus, had higher activity to inactivate the infectivity of Hantaan virus than that of human. 2) The urine from Apodemus agrarius just after sampling was pH 8.3 and it had stronger antiviral activity than the urine adjusted to pH 7.2. 3) pH of human urine just after sampling was 6.1 and this urine decreased 10~100 10? of the virus after 3 hours in room temperature, but the urine with pH 7.2 had no change to infectivity of the virus.

ORiginal Article : Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

( Yoon Jeong Choi ),( Nayoung Kim ),( Ju Yup Lee ),( Ryoung Hee Nam ),( Ji Hyung Seo ),( Seonmin Lee ),( Hee Jin Kim ),( Yoon Jin Choi ),( Hye Seung Lee ),( Dong Ho Lee ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-Lcysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods: Sprague- Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanolonly group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor a, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results: PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMKS005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions: These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. (Gut Liver 2016;10:348- 355)

Safety of subtotal or total colectomy with primary anastomosis compared to Hartmann procedure for left-sided colon cancer obstruction or perforation

Eun-Do Kim,Jin-Kwon Lee,Jin-Kyu Cho,Jae-Myung Kim,Ji-Ho Park,Ju-Yeon Kim,Sang-Ho Jeong,Young-Tae Ju,Chi-Young Jeong,Eun-Jung Jung,Young-Joon Lee1,Soon-Chan Hong,곽승진 대한종양외과학회 2019 Korean Journal of Clinical Oncology Vol.15 No.2

Purpose: Whether subtotal or total colectomy with primary anastomosis (PA) is safer than Hartmann procedure (HP) for left-sided colon cancer obstruction or perforation remains controversial. The purpose of this study was to compare postoperative morbidity, mortality, and defecation frequency between PA and HP for left-sided colon cancer obstruction or perforation. Methods: This retrospective study enrolled 54 patients from January 2014 to February 2018 who underwent emergency surgery due to left-sided colon cancer obstruction or perforation. Results: PA was carried out in 20 patients while HP was performed for 34 patients. Thirty-day mortality did not show significant difference between the two groups (15.0% vs. 14.7%, P=1.000). No anastomotic leakage occurred in PA group while three (8.8%) cases of stump leakage occurred in HP group. Stoma repair was performed for 13 cases (44.8%) and stoma reformation was performed for one case in HP group (7.7%). Stoma related complications occurred in five cases (17.24%). For patients after stoma repair, defecation frequency at 3 months after operation was 2.91±2.88 times per day in PA group and 2.86±2.63 times per day in HP group. At 1 year after operation, defecation frequency was changed to 1.40±1.12 times per day in PA group and 1.17±0.39 times per day in HP group. Conclusion: Primary ileosigmoid or ileorectal anastomosis for left-sided colon cancer obstruction or perforation is safe, and shows similar outcome of defecation frequency compared to H

The Identification of Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, Using Macroscopic, Microscopic and Physicochemical Methods

Jee-Hyun Yoon,Ha-Yeong Park,Tae-Ju Kim,Seung-Ho Lee,Jung-Hoon Kim,Guem-San Lee,Hong-Jun Kim,Young-Sung Ju 대한한의학회 2014 대한한의학회지 Vol.35 No.4

The Identification of Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, Using Macroscopic, Microscopic and Physicochemical Methods

Yoon, Jee-Hyun,Park, Ha-Yeong,Kim, Tae-Ju,Lee, Seung-Ho,Kim, Jung-Hoon,Lee, Guem-San,Kim, Hong-Jun,Ju, Young-Sung The Society of Korean Medicine 2014 대한한의학회지 Vol.35 No.4

Objectives: This study aimed for establishing the discriminative criteria for Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, which can be confused as 'Mokhyang', because of similar appearances and synonyms. Methods: Morphological characteristics of dried herbal medicines were compared by macroscopic observation. To examine microscopic features of 'Mokhyang', paraffin embedding and the staining by using Ju's method were conducted. Physicochemical experiments were performed using HPLC analysis and antioxidant assay. Results: The types of stem, phyllotaxy and leaf shape were chosen as macroscopic criteria and the size, oil spots, color and root top as well as phloem and central cylinder were compared using microscopic features. The HPLC results showed different amounts of costunolide and dehydrocostuslactone among Aucklandiae Radix, Inulae Radix and Vladimiriae Radix. However, Aristolochiae Radix only contained aristolochic acid. The antioxidant assays also showed that Vladimiriae Radix exhibited strongest antioxidant activity followed by Aucklandiae Radix, Inulae Radix and Aristolochiae Radix. Conclusions: These results demonstrate that macroscopic, microscopic and physicochemical methods would be useful tools for the discrimination of 4 kinds of 'Mokhyang'.

타타늄의 열처리 조건에 따른 동전위 양극분극특성 및 표면 미세구조 변화

주동현,이용렬,정영화,양홍서,박상원,이도재,송호준,박영준 大韓齒科器材學會 2002 대한치과재료학회지 Vol.29 No.2

The corrosion resistance of metallic implants is essential for successful implant osseointegration. Moreover, the implant surface should have appropriate surface roughness for the attachment of the osteoblast and collagen fibrils. When titanium is exposed to air a thermodynamically very stable oxide film is formed at once. This oxide is very thin and yet it protects the metal from corrosion instantaneously. However, the oxide would not be ideal, and it would be supposed that the state of oxide film would be various by the different conditions when it is formed. The objective of this study was to evaluate the electrochemical properties and surface microstructural changes of titanium after passivation treatment or exposure to high heat (in vacuum or in air). ASTM grade 2 commercially pure titanium (Ti) disks of 10㎜ diameter were wet ground and polished with 240 and 600 grit SiC, and then ultrasonically cleaned with distilled water and ethanol. Cleansed as-received samples (As-R group) were passivated with 30% nitric acid solution at 50℃ for 15 minutes to make the Pas group. The Std-V samples were made by treating the Ti disks in vacuum quartz tube (10^-8 Torr) at 530℃ for 40 min for stress relieving, followed by annealing at 700℃ for 90 min, and then slow cooling to room temperature. The Std-A samples undergo identical procedure as the Std-V group except that it is done in air. For 530℃-V samples, Ti disks were heated at 530℃ for 40 minutes and slow cooled to room temperature. The 1000℃-V samples were produced by heating Std-V specimens again at 1000℃ for 2 hr, followed by cooling to room temperature. 530℃-A and 1000℃-A samples were also prepared. Potentiodynamic anodic polarization measurement, SEM, AFM and XRD analysis were performed to evaluate the effects of the various treatments. The difference in the mean values of E_corr between groups showed statistically significant difference (P<0.05), but that of I_corr did not show significance (P>0.05). When Ti surface was passivated there was a shift of corrosion potential (E_corr) in the noble direction and a lower corrosion current density (I_corr) value. Std-A samples showed most noble E_corr value among the tested groups. 530℃-V samples showed more noble E-corr than other tested groups except Std-A group. 1000℃-V samples showed more noble E-corr than those of Std-V sample. In the case of Std-, 530℃- and 1000℃-groups, -A sub-groups showed better corrosion resistant characteristics than -V sub-groups in regard to E-corr and I_corr values. In the SEM observations, the surfaces of the As-R samples showed only scratch line on smooth surface. In Pas samples, thick oxide layer covered the surface under high magnification observation. 530℃-A samples were covered by oxide granules, and Std-A samples had 25~50 nm-thick acicular oxides. The 1000℃-A samples were covered by coarse oxide crystals with a granule diameter of 0.1~0.6 μm having a gross appearance of milky white color, which was identified by XRD as a rutile. On the other hand, 1000℃-V samples showed an Widmansta¨tten structrue of which the orientation of the lattice is formed along crystallographic planes of the parent crystals. On the AFM observation, 530℃-A samples showed RMS roughness of 79.38 nm which is 5 times rougher than those of the As-R samples. Std-A sample had a roughness of 330.47 nm which is about 20-times rougher than that of the As-R sample. 1000℃-A samples were covered by coarse granular oxides and the roughness were about 0.56 μm. Vacuum sub-group samples showed a more smooth surface than air sub-group samples, and the oxide film was more dense. Due to variability of the surface treatment and heat treatment conditions, the process of the oxide formation seems to be affected thereby making the corrosion properties and surface micro-morphology different. However, more various electrochemical analysis together with surface analysis, and an investigation for the effects of those on the osteoblast cell adhesion and calcium phosphate apposition are needed for the improvement of the osseointegration rates of the titanium implants.