Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration

Bae, Gi-Sang,Kim, Dong-Goo,Jo, Il-Joo,Choi, Sun-Bok,Kim, Myoung-Jin,Shin, Joon Yeon,Kim, Dong-Uk,Song, Ho-Joon,Joo, Myungsoo,Park, Sung-Joo ELSEVIER 2019 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.69 No.-

<P><B>Abstract</B></P> <P>Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Desoxo-narchinol-A (DN) is a natural compound of HO-1 inducer in pancreas. </LI> <LI> Mechanism of DN-induced HO-1 is mediated by MAPK/Activator Protein-1/HO-1 signaling. </LI> <LI> DN-induced HO-1 blocks neutrophil infiltration into pancreas via inhibition of CXCL2. </LI> <LI> DN inhibits cerulein-induced acute pancreatitis (AP) and AP-associated lung injury. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Genetic Diversity of Korean Rice Breeding Parents as Measured by DNA Fingerprinting with Simple Sequence Repeat (SSR) Markers

Song,Moon-Tae,Lee,Jeom-Ho,Lee,Sang-Bok,Cho,Youn-Sang,Ku,Ja-hwan,Seo,Kyoung-In,Choi,Seong-ho,Hwang,Heung-Goo 한국자원식물학회 2003 Plant Resources Vol.6 No.1

Molecular markers are useful tools for evaluating genetic diversity and determining cultivar identity. Present study was conducted to evaluate the genetic diversity within a diverse collection of rice accessions used for Korean breeding programs. Two hundred eighty-seven rice cultivars, composed of temperate japonica, tropical japonica, indica, and Tongil-type of Korean crossing parents were evaluated by means of 15 simple sequence repeat (SSR) markers. A total of 99 alleles were detected, and the number of alleles per marker ranged from 4 to 11, with an average of 6.6 per locus. Polymorphism information content (PIC) for each of the SSR markers ranged from 0.2924 to 0.8102 with an average of 0.5785. These results, with the result that use of only 15 SSR markers made all rice cultivars examined could be uniquely distinguished, imply the efficiency of SSR markers for analysis of genetic diversity in rice. Cluster analysis was performed on similar coefficient matrics calculated from SSR markers to generate a dendogram in which two major groups corresponding to japonica (Group I) and indica and Tongil type rice (group II) with additional subclasses within both major groups. The narrowness of the Korean breeding germplasm was revealed by the fact that most of the Korean-bred and Japan-bred temperate japonica cultivars were concentrated into only 2 of the sub-group I-1 (143 cultivars) and I-2 (58 cultivars) among six sub-groups in major group of japonica. This is because of the japonica accessions used in this study was a very closely related ones because of frequent sharing of the crossing parents with similar genetic background with synergy effect of the inherited genetic difference between indica and japonica. A rice breeding strategy with the use of molecular markers was discussed for overcoming of genetic vulnerability owing to this genetic narrowness.

경부고속철도건설사업 성과평가

송성태(Sung Tae Song),최문규(Moon Kyu Choi),박상구(Sang Gu Park),장호환(Ho Hwan Jang),차효정(Hyo Jung Cha) 한국철도학회 2012 한국철도학회 학술발표대회논문집 Vol.2012 No.5

1992년 첫 삽을 뜨면서 시작한 경부고속철도건설사업이 2004년 4월, 1단계 개통을 한데 이어 지난 2010년 11월 완전 개통하였다. 경부고속철도 개통으로 경부축 지역의 2시간대 서비스 제공을 통한 국토의 균형발전 촉진 및 여가·관광사업 활성화, 기술발전, 환경비용 및 에너지 절감 등 긍정적인 효과를 이룬 반면, 잦은 기본계획 변경으로 인한 사업비 및 사업기간의 증가, 현실과 맞지 않은 설치기준으로 인한 과잉설계 문제 등 부정적 효과도 초래했다. 본 연구를 통해 사업추진 단계별 주요 이슈에 대해 객관적인 시각으로 문제점을 분석하고 시사점을 도출함으로써, 현재 추진하고 있는 호남고속철도와 수도권고속철도 사업에서는 시행착오를 줄이고 사업을 효율적으로 추진하는데 활용하고자 한다. Launched in 1992, the Gyeung-Bu High Speed Railway (HSR) was fully opened in November 2010 following the partial opening of the first phase in April 2004. Since the opening it has made tremendous achievements, including but not limited to, technical innovation, balanced regional development, growth of leisure and tourism industries, and savings of environmental costs and energy. On the other hand, it has brought negative effects such as increase in project time and cost by frequent changes of the basic plan and over-design based on unrealistic criteria. In this study we will analyze major issues that occurred at each stage of the Gyeong-Bu HSR project and draw implications. Thus, this study will enhance to efficiently implement the Ho-Nam and Seoul Metropolitan HSR project through minimizing possible trials and errors.

Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

Lee, Moon Hee,Han, Min Ho,Lee, Dae-Sung,Park, Cheol,Hong, Su-Hyun,Kim, Gi-Young,Hong, Sang Hoon,Song, Kyoung Seob,Choi, Il-Whan,Cha, Hee-Jae,Choi, Yung Hyun UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.39 No.2

<P>In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and gamma H2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keapl) expression. Notably, these events were eliminated by transient transfection with Nrf2-specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal-regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO-1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2,-induced oxidative cytotoxicity.</P>

Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

대전 기존도심의 보행자 공간 기본 구상

宋容浩,李相이 忠南大學校 地域開發硏究所 1998 地域開發論叢 Vol.10 No.-

This research aims to propose the pedestrian space at old downtown in order to activate the existing CBD in Taejon. The first part reviews the urban problems happened in modern metropolitan and meaning of pedestrian space as an effective & economic method renovating urban environment. The second part reviews the traffics & activities, the traffic control system, and the renovation scheme of the pedestrian space. The conclusions are as follows; 1) To be successful pedestrian space bases on the control of traffics and the resolution of district traffic at the old downtown. 2) The old downtown area needs to be made as a pedestrian zone so that urban activities will be strengthen with new added functions 3) The concept of pedestrian zone based on human life must be adopted to the whole city in the future.

농구 선수의 만성 슬개건염

서경호,서경묵,김성원,김백곤,송인섭 大韓再活醫學會 1998 Annals of Rehabilitation Medicine Vol.22 No.6

애국계몽기의 정치소설론 연구

송현호,김상대 亞洲大學校 1988 論文集 Vol.11 No.-

This dessertation has dealt with the formation process of modern novels and its developing patterns in order to make the history of criticism in modern Korea straight. The following is an outline of the discussion. The theories of patriotic, enlightening novels can be devided into two parts: the reformation of novels and making the then ideology into a logic system. Those who participated in the reformation of novels insisted upon creating historical novels which should be realistic in order to overcome the situation of those days. The movement could be said to be a sort of methodology of creative writing. Through the above discussion of the theories of patriotic, enlightening novels the fact is revealed that the previous studies about the history of Korean criticism was a prejudice.

말기 신부전 환자에서 투여 경로에 따른 유전자 재조합 인 Erythropoietin(Epokine^(�))의 효과와 안정성에 대한 연구 : 제 4상 연구 A Phase 4 Single Center Study

송현용,윤향숙,강신욱,최규헌,하성규,이호영,한대석 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

목 적 : 국내 독자적 기술로 첫 개발된 유전자 재조합 인 에리트로포에틴(Epokineⓡ)의 투여방법에 따른 유효성과 안정성을 알아보고자 하였다. 방 법 : Epokineⓡ을 주당 100-150 U/kg, 주 2회, 12주간 피하 주사하여 목표 또는 안정된 혈색소치 유지 후 무작위로 피하 및 정맥 주사군으로 나누어 12주간 혈액투석 및 복막투석 환자13명, 28명에서 유효성, 안정성을 분석하였다. 결 과 : 양군에서 혈색소치와 헤마토크릿은 Epokineⓡ 투여 2주 후부터 증가, 혈색소치가 혈액투석 환자는 투여 전 7.3 g/dL, 투여 12주 9.5 g/dL, 24주 10.6 g/dL로, 복막투석 환자는 6.8g/dL에서 12주 10.2 g/dL, 24주 10.8 g/dL로 증가하였다. 양군에서 교정 망상적혈구수(%)는투여 1주 후부터 전 기간동안 증가하였다. 혈청 내 철분, ferritin치는 양군에서 투여 2주 후부터감소, 총 철분 결합능은 투여 2주 후부터 증가하였다. 12주째 혈액투석 환자에서 많은 Epokineⓡ용량이 필요했으나(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001) 24주 후 양군의 용량차이는 없었다(123.6±41.5 vs 99.2±49.3 U/kg/wk, p>0.05). 혈액투석 환자에서 피하 주사가Epokineⓡ 투여용량이 더 적었으나(97.4±15.4 vs 145.4±2.9 U/kg/wk, p<0.002) 복막투석 환자는 차이가 없었다(93.0±60.2 vs 105.4±9.7 U/kg/wk, p>0.05) 연구기간 중 9명(18.8%)에서혈압강하제 추가가 필요한 혈압상승, 근육통 동반 상기도 감염 유사증상 및 두통 등의 부작용이 있었다. 대부분 자연소실 혹은 대증요법으로 치유되었고 2명이 부작용으로 탈락하였다. 결 론 : 말기 신부전 환자의 빈혈 개선에 사용하는 Epokineⓡ의 효과는 복막투석 환자에서 더 좋았으며 투여 경로는 정맥주사보다 피하주사가 높음을 알 수 있었다. Background : We evaluated the clinical efficacy and safety of recombinant human erythropoietin(Epokine^(ⓡ)). Methods : A comparative prospective study of intravenously and subcutaneously administrated Epokine^(ⓡ) conducted 13 patients performing hemodialysis and 28 patients performing continuous ambulatory peritoneal dialysis with end-stage renal disease. Epokine^(ⓡ) was given initially at a dosage of 100 unit/kg, subcutaneously, two times a week. The patients had achieved stable or more than 10 g/dL of hemoglobin level for 12 weeks and then we randomized switching intravenously or subcutaneously administrated Epokine^(ⓡ) for another 12 weeks. Results : Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine^(ⓡ) administration. In HD patients, hemoglobin increased significantly from 7.3 to 9.5 after 12 weeks and to 10.6 after 24 weeks. In CAPD patients, hemoglobin increased significantly from 6.8 to 10.2 after 12 weeks and then 10.8 after 24 weeks(p<0.05). Corrected reticulocyte count(%) was significantly increased from baseline levels beginning from 1 week after Epokine^(ⓡ) administration and continuously increased during study period in both group. Serum ferritin and serum iron decreased significantly and total iron binding capacity increased significantly after 2 weeks. At 12 weeks, HD patients were significantly needed more dosage of Epokine^(ⓡ) than CAPD patients(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001), but at 24 weeks, the dosage was not different(123.6±41.5 vs 99.2±49.3 U/kg/wk, p> 0.05). In HD patients, intravenously administrated Epokine^(ⓡ) group was more dosage than subcutaneously group(97.4±15.4 vs 145.4±2.9 U/kg/wk, p< 0.002), but CAPD patients were not different by administration method(93.0±60.2 vs 105.4±9.7 U/kg/ wk, p>0.05). The 9 cases(18.8%) were suffered from headache and flu-like syndrome, but these side effects were not severe and disappeared from conventional therapy. Conclusion : Epokine^(ⓡ) administration is safe and effective in treating anemia of ESRD patients and subcutaneously administration is significantly more effective than intravenously. (Korean J Nephrol 2002;21(2):190-198)