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.

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.

정지궤도 위성과 지구국간 광통신 링크의 전송속도 해석

한종석,정진호,김영권,Han, Jong-Seok,Jung, Jin-Ho,Kim, Yung-Kwon 한국전기전자학회 1997 전기전자학회논문지 Vol.1 No.1

정지궤도 위성과 지구국간 광통신을 대기상태와 앙각의 함수로써 해석할 수 있는 한모델(Han's model)을 제시하였다. 한모델에서는 대기상태를 맑은날, 구름낀 날, 안개, 헤이즈, 비, 눈의 여섯가지 전형적인 상태로 구분한다. 비트오류을 $10^{-7}$을 만족하는 데이터 전송속도를 한모델을 이용하여 상향링크와 하향링크에 대해 해석하였다. 상향링크시의 포인팅손실이 하향링크시의 대기에 의한 공간 가간섭 저하보다 크기 때문에 데이터 전송속도는 하향링크 보다 오히려 상향링크시에 제한됨을 알 수 있었다. Han's model, which is able to analyze optical communication between earth station and geo-satellite as a function of atmospheric conditions and elevation angles. is presented. In Han's model, atmospheric conditions are roughly classified into six basic types; clear sky, cloud, haze, fog, rain and snow. Data rate satisfying for the BER below $10^{-7}$ is analyzed by Han's model in case of up-link and down-link, respectively. Data rate is more limited by up-link than by down-link because the pointing loss caused by atmosphere on the up-link is greater than the spatial coherence degradation caused by atmosphere on the down-link.

Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

Jung Kyung Hee,Kim Sang Eun,Go Han Gyeol,Lee Yun Ji,Park Min Seok,Ko Soyeon,Han Beom Seok,Yoon Young-Chan,Cho Ye Jin,Lee Pureunchowon,Lee Sang-Ho,Kim Kipyo,Hong Soon-Sun 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.6

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

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.

TNF-α로 유도된 혈관내피세포의 혈관염증에 미치는 오적산(五積散)의 억제 효과

한병혁 ( Byung Hyuk Han ),윤정주 ( Jung Joo Yoon ),김혜윰 ( Hye Yoom Kim ),안유미 ( You Mee Ahn ),홍미현 ( Mi Hyeon Hong ),손찬옥 ( Chan Ok Son ),나세원 ( Se Won Na ),이윤정 ( Yun Jung Lee ),강대길 ( Ho Sub Lee ),이호섭 대한본초학회 2018 大韓本草學會誌 Vol.33 No.4

Objectives : Ojeoksan, originally recorded in an ancient Korean medicinal book named “Donguibogam” and has been used for the treatment of circulation disorder of blood which was called blood accumulation (血積) in Korean medicine. Therefore, this study was carried out to investigate the beneficial effect of OJS on vascular inflammation in HUVECs. Methods : We evaluated the effect of OJS on the expression of cell adhesion molecules and protective role in HUVEC stimulated by TNF-α by using Western blot. Results : Pretreatment with OJS decreased the adhesion of HL-60 cells to TNF-α-induced HUVEC. OJS suppressed TNF-α-induced expression level of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and endothelial cell selectin (E-selectin). Moreover, OJS significantly decreased TNF-α-induced production of intracellular reactive oxygen species (ROS); and inhibited the phosphorylation of IκB-α in the cytoplasm compared to the experimental group. Pretreatment with OJS inhibited the trans-location of NF-κB p65 to the nucleus. OJS also inhibited phosphorylation of MAPKs compared to the experimental group. OJS significantly increased the protein expression of Nrf2 and HO-1. Conclusions : Ojeoksan has a protective effect on vascular inflammation, and might be a potential therapeutic agent for early atherosclerosis.

Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

Choi, Eun Sik,Lee, Yun Jung,Seo, Chang Seob,Yoon, Jung Joo,Han, Byung Hyuk,Park, Min Cheol,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2016 Evidence-based Complementary and Alternative Medic Vol.2016 No.-

<P>Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-<I>κ</I>B) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-<I>κ</I>B and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-<I>κ</I>B was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-<I>κ</I>B translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-<I>α</I> in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.</P>

혈액투석 환자의 가성 고칼륨혈증

최창렬,조형도,강태영,이준수,한호,정청일,이동규,유준호,한상웅,김호중 대한신장학회 2001 대한신장학회잡지 Vol.20 No.5

Fe-(6∼12wt. %)Al 압분체의 소결거동 및 고온내산화성

한정호,이동희 연세대학교 대학원 1981 延世論叢 Vol.18 No.1

본 연구는 고온내산화 재료인 Fe-Al계합금을 분말야금법으로 개발하기 위한 기초연구로서 Al함량이 비교적 높은 Fe-(6∼12wt.%)Al 압분체의 소결거동과 이들의 고온에서의 산화거동을 조사하는데 그 목적이 있다. 본 연구에서의 압분체는 순천분말과 50%Fe-50%Al 합금분말을 혼합하여 Al의 최종 조성이 6, 8, 10 및 12wt.%가 되게끔 하여 성형시킨 것이며, 이것을 여러가지 조건(소결온도 : 1,100℃, 1,200℃, 1,300℃ :소결시간 : 10분∼300분)하에서 소결하여, 각 단계에서의 밀도, 기공도, 치밀화변수의 측정 및 미세조직을 관찰하여 소결거동을 조사하였다. 또한 이들 소결압분체를 공기중, 900℃, 1,000℃ 및 1,100℃의 고온에서 최단 1분으로 부터 최장 15시간에 걸쳐서 산화처리를 험하여 이에 따른 중량증가의 측정과 미세조직 관찰을 병행하여 산화거동을 분석하였다. 본 연구의 결과에 의하면, 1,100℃의 고상소결에서는 합금화에 기인한 계속적인 팽창으로 말미암아치밀화가 이루어지지 않음을 알았다. 반면 액상소결의 경우 부분적인 wetting만이 이루어져 소결초기에서는, 팽창현상이 소결촉진효과 보다 크게 작용하여 치밀화에 역행하지만, 이 단계가 지나면 점차 치밀화가 이루어짐을 알 수 있었다. 그리고 소결압분체들의 산화는 기공을 중심으로 하여 진행됨을 볼 수 있었다. 한편 산화온도 1,000℃이하에서는 이들 소결체의 표면산화물이 보호피막으로 작용됨을 알았고, 1,100℃ 이상에서는 보호피막으로서 유효하지 못함을 알았다. This study is a powder metallurgy of Fe-Al alloy which is used for oxidation resistance at high temperature. The material used in this investigation was Fe-(6~l2wt.%) Al powder compacts, and sintering and oxidation behavior of the material at high temperature have been examined. The compacts were comported of pure iron powder and Fe-50% Al alloy powder so as to the final Al contents of the compact to be 6, 8, 10 and 12wt.%. The compacts were premised under 7ton/cm2 and sintered at various conditions (sintering temperature; 1,100℃, 1,200℃ and 1,300℃: sintering time; 10 to 300min.). The analysis of sintering behavior has been undertaken by the methods of porosity measurements, metallographic examinations and the calculated densification parameters. Also the sintered compacts were oxidized in air at various temperatures(900℃, 1,000℃, and 1,100℃) from 1min. to 15hr., and the oxidation behavior was analyzed by the weight gain measurements and metallographic examinations. The results obtained in these experiments can be summarized as fellows: 1) It was found that the solid state sintering at 1,100℃ did not bring about the densification, because of the continuous expansion by alloying at contact point. 2) The liquid phase sintering at 1300℃ resulted in only partial wetting, and the densification was diminished by the predominant expansion rather than the shrinkage at the initial stage. Thereafter the densification began due to the formation of homogeneous phase when the liquid phase was disappeared. 3) The oxidation of the sintered compacts was found to be proceeded at pore sites and was affected by sintering conditions as well as Al contents. 4) The oxidation below 1,000℃ is obeyed the parabolic rate law. Meanwhi1e the oxidation at 1,100℃ is facilitated linearly and the oxide layer is not likely to be effective as a protective layer above this temperature.

鹿茸藥鍼液의 DNA chip을 利用한 遺傳子 發顯 分析

한상원,서정철,이윤호,최제용 大韓鍼灸學會 2003 대한침구의학회지 Vol.20 No.3

Objective : Bone homeostasis is maintained by balance of bone formation and resorption. Therefore, bone related diseases arose by disturbance of this balance between osteoblast and osteoclast activities. To develop a successful screening system the therapeutic components based on oriental medicine is essential to set up systematic approach for that purpose. The purpose of this study is to the know the gene expression using cDNA microarray assay. Methods : Cervi Pantotricuhum Cornu Herbal-acupuncture extract was prepared by boiling. human osteosarcoma cells(HOS) were treated with Cervi Pantotricuhum Cornu Herbal-acupuncture solution. Then mRNA was extracted and cDNA microarray assay was performed. Results : Human osteosarcoma cells(HOS) treated with Cervi Pantotricuhum Cornu Herbal-acupuncture solution(500㎍/㎖) showed that thioredoxin, TAFII31 and two novel genes were increased. However many genes decreased their expression by Cervi Pantotricuhum Cornu Herbal-acupuncture. Conclusions : This type of approach will give a good chance to explore the favorable effects of Cervi Pantotricuhum Cornu Herbal-acupuncture. Futher study is needed for investigating the effect of Cervi Pantotricuhum Cornu Herbal-acupuncture.