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.

Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

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.

Sauchinone Suppresses Pro-inflammatory Mediators by Inducing Heme Oxygenase-1 in RAW264.7 Macrophages

Li, Bin,Lee, Dong-Sung,Choi, Hyun-Gyu,Kim, Kyoung-Su,Kang, Dae-Gil,Lee, Ho-Sub,Jeong, Gil-Saeng,Kim, Youn-Chul Pharmaceutical Society of Japan 2011 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.34 No.10

<P>Sauchinone, a biologically active lignan isolated from the roots of <I>Saururus chinensis</I> (L<SMALL>OUR</SMALL>.) B<SMALL>AILL</SMALL>. (Saururaceae), is reported to exert a variety of biological activities, such as hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone in suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to a reduction in COX-2-derived prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) and iNOS-derived nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. Present study also demonstrates the effects of sauchinone in inducing heme oxygenase-1 (HO-1) expression and an increase in heme oxygenase (HO) activity in RAW264.7 macrophages. The effects of sauchinone on LPS-induced PGE<SUB>2</SUB>, NO, tumor necrosis factor-α (TNF-α) and interlukine-1β (IL-1β) production were partially reversed by the HO-1 inhibitor Tin protoporphyrin was also seen in this study. In addition, we found that treatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) reduced sauchinone-induced HO-1 expression. Sauchinone also increased ERK phosphorylation. These results suggest that sauchinone inhibits pro-inflammatory mediators through expression of anti-inflammatory HO-1 <I>via</I> ERK pathway.</P>

족과관절염좌 환자에 대한 동씨침법과 일반침법의 효과에 대한 비교 연구

안호진,정동화,황규선,윤기붕,김태우,문장혁,백종엽,이상무,Ahn, Ho-jin,Jeong, Dong-hwa,Hwang, Kyu-seon,Yoon, Ki-bung,Kim, Tae-woo,Moon, Jang-huyk,Baek, Jong-yeob,Lee, Sang-moo 대한침구의학회 2003 대한침구의학회지 Vol.20 No.1

Objective: The purpose of this study is to compare the effects of Dong-si acupuncture therapy and General acupuncture therapy for the patients with acute ankle sprain. Methods : This study has been carried out for 60 cases of ankle sprain patients who have visited Dong-Seo Oriental medical Hospital from May 1, 2002 to September 30, 2002. We have treated 30 cases of them by Dong-si acupuncture therapy and the other 30 cases by General acupuncture therapy. And we have compared those two group. Results : 1. There was no significant difference at the treatment period and the number of treatment times in comparing two groups. 2. The number of treatment times for good effect is that : Dong-si took $1.57{\pm}0.85$ times and General acupuncture therapy took $2.15{\pm}0.96$ times. And we have found that the effect of Dong-si acupuncture therapy is faster than the other.

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

뇌졸중 후 중추성 통증 환자에 대한 동서협진이 진통과 재활에 미치는 영향

이현종,김수영,이상훈,서동민,이두익,김건식,이재동,이윤호,양형인,박재경,최도영 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Purpose : In order to study the effectiveness of East-West pain treatment on central poststroke pain(CPSP), we evaluated its effect on alleviation of pain and rehabilitation of CPSP Patients who were treated with electroacupuncture and west pain treatment for four weeks. Methods : Twenty four patients diagnosed by their pain characteristics of central pain from stroke were treated with sympathetic nerve block, gabapentin, amitriptyline, and electroacupuncture for four weeks. Pain intensity through the visual analogue scale(VAS), and improvements of mobility and rehabilitation through the modified Barthel index(MBI) and Rankin scale(RS), respectively, before and after pain treatment were also assessed. Results : VAS pain scores were significantly improved from 7.7±1.7 to 4.4±2.0 with pain treatment(p<0.05). In accordance with improvement of pain scores, RS and MBI scores were also improved from 2.88±0.95 to 2.13± 1.01 and from 83.0± 16.9 to 94.7±9.5(p<0.05), respectively, with pain treatment(p<0.05). Conclusions : It was suggested that the active pain treatment was contributed to the rehabilitation of CPSP patients, resulting in improvement of quality of life of CPSP patients. Futhermore, East pain treatment in combination with West pain treatment may be useful modality to alleviate CPSP.

Validation of the oxford classification of iga nephropathy: A Single-Center Study in Korean Adults

( Ho Young Lee ),( Sul Hee Yi ),( Mi Seon Seo ),( Jin Nam Hyun ),( Jin Seok Jeon ),( Hyunjin Noh ),( Dong Cheol Han ),( Seung Duk Hwang ),( So Young Jin ),( Soon Hyo Kwon ) 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.3

Background/Aims: The recently published Oxford classification of IgA nephropathy (IgAN) proposed a split system for histological grading, based on prognostic pathological features. This new classification system must be validated in a variety of cohorts. We investigated whether these pathological features were applicable to an adult Korean population. Methods: In total, 69 adult Korean patients with IgAN were analyzed using the Oxford classification system at Soonchunhyang University Hospital, Seoul, Korea. All cases were categorized according to Lee`s classification. Renal biopsies from all patients were scored by a pathologist who was blinded to the clinical data for pathological variables. Inclusion criteria were age greater than 18 years and at least 36 months of follow-up. We excluded cases with secondary IgAN, diabetic nephropathy combined other glomerulopathies, less than 36 months of follow-up, and those that progressed rapidly. Results: The median age of the patients was 34 years (range, 27 to 45). Mean arterial blood pressure was 97 ± 10 mmHg at the time of biopsy. The median follow-up period was 85 months (range, 60 to 114). Kaplan-Meier analysis showed significant prognostic predictions for M, E, and T lesions. A Cox proportional hazard regression analysis also revealed prognostic predictions for E and T lesions. Conclusions: Using the Oxford classification in IgAN, E, and T lesions predicted renal outcome in Korean adults after taking clinical variables into account.

NGS_SNPAnalyzer: a desktop software supporting genome projects by identifying and visualizing sequence variations from next-generation sequencing data

Dong‑Jun Lee,Taesoo Kwon,Chang‑Kug Kim,Young‑Joo Seol,Dong‑Suk Park,Tae‑Ho Lee,Byung‑Ohg Ahn 한국유전학회 2020 Genes & Genomics Vol.42 No.11

Background Sequence variations such as single nucleotide polymorphisms are markers for genetic diseases and breeding. Therefore, identifying sequence variations is one of the main objectives of several genome projects. Although most genomeproject consortiums provide standard operation procedures for sequence variation detection methods, there may be differencesin the results because of human selection or error. Objective To standardize the procedure for sequence variation detection and help researchers who are not formally trainedin bioinformatics, we developed the NGS_SNPAnalyzer, a desktop software and fully automated graphical pipeline. Methods The NGS_SNPAnalyzer is implemented using JavaFX (version 1.8); therefore, it is not limited to any operatingsystem (OS). The tools employed in the NGS_SNPAnalyzer were compiled on Microsoft Windows (version 7, 10) andUbuntu Linux (version 16.04, 17.0.4). Results The NGS_SNPAnalyzer not only includes the functionalities for variant calling and annotation but also providesquality control, mapping, and filtering details to support all procedures from next-generation sequencing (NGS) data to variantvisualization. It can be executed using pre-set pipelines and options and customized via user-specified options. Additionally,the NGS_SNPAnalyzer provides a user-friendly graphical interface and can be installed on any OS that supports JAVA. Conclusions Although there are several pipelines and visualization tools available for NGS data analysis, we developedthe NGS_SNPAnalyzer to provide the user with an easy-to-use interface. The benchmark test results indicate that theNGS_SNPAnayzer achieves better performance than other open source tools.