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>

HDPE 개질 아스팔트 혼합물의 강도 및 변형특성

김광우,이기호,권오선,고태영 강원대학교 부설 석재복합신소재 제품연구센터 2004 석재연 논문집 Vol.9 No.-

본 연구는 폐비닐 펠렛을 도로포장재료로 재활용하여 자원절약 및 아스팔트 혼합물의 품질향상을 위한 연구이다. 이를 위하여 폐비닐의 첨가량별 배합설계를 수행하여 적정 폐비닐 첨가량과 최적 아스팔트 함량으로 편마암과 화강암 2가지 골재와 폐비닐인 RHDPE의 함량을 4가지로 혼합물을 제작하여 8종류의 재질 혼합물과 2종류의 무개질 혼합물을 제작하였다. 그리고 이 공시체에 대하여 마샬안정도, 간접인장강도 및 Kim test와 반복주행시험 등 실내시험을 통하여 혼합물의 특성을 분석하였다. 폐비닐 첨가량은 RHDPE가 8%일 때 안정도와 간접인장강도 모두 가장 우수한 것으로 나타났고 취성도 나타나지 않았다. RHDPE를 첨가한 혼합물에 대하여 Kim test를 수행한 결과 DR과 DS 모두 높은 상관성을 보였다. 그리고 반복주행시험에서는 RHDPE를 첨가한 혼합물이 일반 혼합물보다 우수하였다. 향후 많은 실험을 통해 RHDPE의 우수성을 입증한다면 소성변형 저항성에 우수한 재료로 이용될 수 있을 것이다. This study is a fundamental research for recycled high-density polyethylene (RHDPE) in asphalt mixture for improving roadway pavement. Marshall mix design was conducted and optimum asphalt content(OAC) was determined for dense-graded surface course mixture by RHDPE content. Marshall stability test, indirect tensile strength (ITS) test, wheel tracking trest and Kim-test were carried out to measure the characteristics of RHDPE-added asphalt concretes. From the results of this study, RHDPE in asphalt mixture if possible. It could be considered that adding too much RHDPE in asphalt mixture is not proper. The optimum content of RHDPE was appeared to be 8%. In Kim-test, statistical analysis was performed for each loading head and aggregate to find out correlation between S_(D) values and each rut parameter. The analysis result showed that S_(D) had very high coefficient of determination with rut parameters on the average.

개질 아스팔트 혼합물의 변형강도 측정 연구

김광우,도영수,이기호,조문진,최선주 강원대학교 부설 석재복합신소재 제품연구센터 2004 석재연 논문집 Vol.9 No.-

본 논문은 아스팔트 혼합물의 소성변형 저항성과 상관성이 높은 특성치를 찾고자 Kim test를 개발하여 현재 적용성 연구결과를 다루고 있다. 이 논문은 새로운 강도특성치인 변형강도(S_(D))를 개발하는 Kim, test 연구의 4단계 연구 결과이다. 13 mm 골재(편마암, 화강암)와 입도(밀입도, 갭입도) 5가지 폴리머로 제조한 8가지 바인더로 두 가지 입도에서 소성변형 저항성이 다른 32가지 혼합물을 만들었다. 슬래브(305㎜×305㎜×62㎜)공시체를 제조하여 한쪽은 Kim, test를 수행하기 위하여 18 cm정도로 잘라서 코어를 3개 채취하고 다른 한쪽은 12cm크기로 하여 반복주행시험을 실시하였다. Kim, test는 하중봉 3(0.75), 4(1.0)을 사용하였다. W/T시험으로부터 최종 침하 깊이와 동적안정도의 두 가지 소성변형 계수를 각 혼합물별로 구했다. 각 하중봉과 골재별, 입도별로 S_(D)와 소성변형 계수간의 통계적 상관관계 분석을 수행한 결과 S_(D)와 소성변형 계수와의 결정계수가 매우 높게 (R²>0.95) 나타났다. 하중봉 4(1.0)이 3(0.75)보다 다소 높은 상관성을 보였다. 향후 Kim test실험에서 하중봉 4(1.0)을 사용하고 4단계 방법을 이용한다면 소성변형 특성치인 침하깊이(DR)와 동적안정도(DS)와의 상관성이 매우 큰 시험법이 될 것이다. 또한 변형강도의 파괴 메커니즘은 콘크리트의 펀칭파괴와 유사하여 콘크리트의 전단강도 추정식을 근거로 아스팔트 콘크리트의 재료 특성에 적합한 추정식 계수 ◁ 원문 수식 참조 ▷ 를 얻었다. 이 식을 이용한다면 아스팔트 콘크리트가 견딜 수 있는 임계하중을 변형강도에 근거하여 추정할 수 있을 것이다. This study shows predictability of rut parameters of modified and unmodified asphalt concretes based on the deformation strength (S_(D)) which is calculated from the maximum load, deformation and size variables of loading head under simple static loading. This paper is the result of latest studies, phase 4 which is a part of Kim, Test studies for developing a new strength property for asphalt concrete. Two aggregates, gneiss and granite, two gradations, dense-graded, gap-graded, with maximum, size of 13mm and eight binders using different contents of five polymers (RLDPE, RHDPE, LDPE, SBS, SBR) were used to produce 32 different mixtures. A slab (305㎜×305㎜×62㎜) was cut into two pieces(18cm and 12cm width) and three 10cm cores were taken for S_(D) test from the larger piece and wheel tracking test was performed on the smaller piece. Kim test was performed using loading head 4(1.0), 3(0.75). Two rut parameters, depth of rut and dynamic stability, from the rut depth-cycle curve from a WT test were obtained for each mixture. Statistical analysis were performed for each loading head, aggregate, and gradation to find out correlation between S_(D) values and each rut parameter. The analysis results showed that S_(D) had high R² (over 0.95) on the average with rut parameters. The loading head 4(1.0) showed R² better than 3(0.75). It is concluded that S_(D) is the property that has excellent predictability for rut parameter of asphalt concretes. An equation, ◁ 원문 수식 참조 ▷ was obtained based on the equation of concrete shear load creating punching failure and current test data, because the failure mechanism of S_(D) is similar to punching failure of concrete. In the equation, P is shearing force creating punching effect, b is length of perimeter of punching area and d is depth of specimen. If this formula is used, a critical load for deformation failure will be predicted based on the S_(D).

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes

Kim, Se-Jin,Ho Hur, Joon,Park, Channy,Kim, Hyung-Jin,Oh, Gi-Su,Lee, Joon No,Yoo, Su-Jin,Choe, Seong-Kyu,So, Hong-Seob,Lim, David J,Moon, Sung K,Park, Raekil Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.2

<P>Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine <I>in vivo</I>. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.</P>

HDPE 폐비닐 개질 아스팔트 혼합물의 강도 및 공용 특성 연구

김광우 ( Kim Kwang Woo ),이기호 ( Lee Gi Ho ),권오선 ( Kwon Oh Sun ),조문진 ( Cho Mun Jin ) 한국농공학회 2004 한국농공학회 학술대회초록집 Vol.2004 No.-

본 연구는 폐비닐 펠렛을 도로포장재료로 재활용하여 자원절약 및 아스팔트 혼합물의 품질향상을 위한 연구이다. 이를 위하여 폐비닐의 첨가량별 배합설계를 수행하여 적정 폐비닐 첨가량과 최적 아스팔트 함량으로 편마암과 화강암 2가지 골재와 폐비닐인 RHDPE의 함량을 4가지로 혼합물을 제작하여 8종류의 개질 혼합물과 2종류의 무개질 혼합물을 제작하였다. 그리고 이 공시체에 대하여 마살안정도, 간접인장강도 및 Kim test와 반복주행시험 등 실내시험을 통하여 혼합물의 특성을 분석하였다. 폐비닐 첨가량은 RHDPE가 8%일 때 안정도와 간접인장강도 모두 가장 우수한 것으로 나타났고 취성도 나타나지 않았다. RHDPE를 첨가한 혼합물에 대하여 Kim test를 수행한 결과 DR과 DS 모두 높은 상관성을 보였다. 그리고 반복주행시험에서는 RHDPE를 첨가한 혼합물이 일반 혼합물보다 우수하였다. 향후 많은 실험을 통해 RHDPE의 우수성을 입증한다면 소성변형 저항성에 우수한 재료로 이용될 수 있을 것이다. This study is a fundamental research for recycled high-density polyethylene (RHDPE) in asphalt mixture for improving roadway pavement. Mix design was conducted by RHDPE content and optimum asphalt content (OAC) was determined for dense-graded surface course mixture. Marshall stability test, indirect tensile strength (ITS) test, wheel tracking test and Kim-test were carried out to measure the characteristics of RHDPE-added asphalt concretes. From the results of this study, RHDPE in asphalt mixture is possible. It could be considered that adding too much RHDPE in asphalt mixture is not proper. The optimum content of RHDPE was appeared to be 8%. In Kim-test, Statistical analysis were performed for each loading head and aggregate to find out correlation between SD values and each rut parameter. The analysis result showed that SD had very high coefficient of determination on the average with rut parameters.

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>

Schisandrae semen essential oil attenuates oxidative stress-induced cell damage in C2C12 murine skeletal muscle cells through Nrf2-mediated upregulation of HO-1

KANG, JI SOOK,HAN, MIN HO,KIM, GI-YOUNG,KIM, CHEOL MIN,CHUNG, HAE YOUNG,HWANG, HYE JIN,KIM, BYUNG WOO,CHOI, YUNG HYUN Spandidos Publications 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.35 No.2

정신분열병 및 정신분열형 장애에 대한 올란자핀의 효과와 안전성

안용민,강대엽,권준수,김창윤,김철응,반건호,신영민,이기철,이동우,이중서,조현상,채정호,김용식 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.4

연구목적 : 본 다기관 공동임상연구는 국내 환자를 대상으로 새로운 항정신병약물인 올라자핀의 치료 효과와 안전성을 확인하고자 시행되었다. 방 법 : 1999년 7월부터 2000년 3월까지 국내 10개 병원에 방문한 정신분열병 및 정신분열형 장애 105명을 대상으로 비대조 개방 임상연구를 시행하였다. 중등도 이상의 정신병 증상을 지니거나, 부작용으로 약물교체가 필요한 경우 또는 기분장애 증상의 치료가 필요한 환자를 대상으로 하였다. 2∼7일간의 약물 배설기간 후에 1일 10mg의 올란자핀을 투여하였고, 이후로 3∼7일 간격으로 용량을 조절하여 총 8주간 투여하였다. 치료 효과는 PANSS(Positive and Negative Syndrome Scale), BPRS(Brief Psychiatric Rating Scale), CGI(Clinical Global Impression-Severity), MADRS(Montgomery-Asberg Depression Rating Scale), HAM-A(Hamilton Rating Scale for Anxiety)로 판정하였다. 안전성 평가는 자발적인 이상반응 보고, 활력징후와 혈액 검사 및 SAS(Simpson-Angus Scale), BARS(Barnes Akathisia Rating Scale), AIMS(Abnormal Involuntary Movement Scale)척도를 이용하였다. 결 과 : 105명중에서 85.7%인 90명이 8주간의 치료를 완료하였다. 평균 최빈 용량은 일일 16.1(±4.7)mg이었고, 종료시점에서의 BPRS전체 점수가 기저 상태에 비해 40%이상 감소된 반응군은 69.5%이었다. PANSS의 양성 증후군과 일반정신병리 뿐만 아니라 음성 증후군 소척도에서도 유의한 감소를 보였으며, 이 감소들은 치료 초기부터 나타나서 8주간 지속되었다. 43.8%의 피험자가 중등도 이상의 우울증상을 같이 지니고 있었으며, 올란자핀에 의해 MADRS와 HAM-A가 유의하게 감소하였다. 치료 기간 동안에 활력징후에는 뚜렷한 변화가 없었으나 체중은 8주간 지속적으로 증가하였다. SAS와 AIMS는 감소하였으며, 정좌불능증을 제외한 나머지 추체외로 증상의 발생비율도 낮았다. 임상적인 증상이나 징후를 동반하지 않는 ALT/SGPT의 상승을 보였지만 프로락틴을 포함하는 대부분의 혈액 검사상 뚜렷한 이상 변화는 없었다. 결 론 ; 비록 본 임상연구가 비대조 개방 임상연구로서 많은 제한점을 가지고 있지만, 올란자핀이 기존 약물에 내약성을 보이거나 기분증상을 동반하는 정신병에 치료 효과가 있었다. 그리고 기존 항정신병약물 치료시에 문제가 되었던 추체외로 증상과 고프르로락틴 혈증을 포함하는 대부분의 부작용면에서 안전성을 보여 주었다. Objective : This multicenter clinical trial was carried out to investigate the efficacy and the safety of olanzpine for the treatment of Korean patients. Mothod : 105 patients with schizophrenia and schizophreniform disorder, visited at 10 mental or university hospitals, had received an open and non-comparative treatment with olanzapine for 8 weeks. Patients had psychotic or depressive symptoms with the severity above moderate degree or intolerable side effects to previous antipsychotics. After a wash-out period of 2-7 days, 10mg olanzapine was prescribed initially to all the patients, and then the dosage could be adjusted within the range of 5-20mg/day of olanzapine by 3-7 days. Results : 90(85.7%) of 105 patients completed the 8-weeks trial and the mean modal dose of olanzapine was 16.1(±4.7%)mg/day. At the end of the trial, 73 patients(69.5%) were classified as responder, which was defined as 40% or more improvement in BPRS(Brief Psychiatric Rating Scale) score comparing to baseline. There was a significant reduction in the scores of PANSS(Positive and Negative Syndrome Scale)and subscales including negative symptom scores and CGI. Also weekly analysis showed that the reductions in scores were kept on for the whole period of the trial. 43.8% of all the patients had depressive symptoms at the baseline and total scores of MADRS(Montgomery-Asberg Depression Rating Scale) and HAM-A(Hamilton Rating Scale for Anxiety) were also reduced after the trials. Vital signs revealed no clinically significant changes but continuous weight gain was observed during the treatment with olanzapine. The scores of SAS(Simpson-Angus Scale) and AIMS(Abnormal Involuntary Movement Scale) for assessing the EPS(extrapyramidal symptoms)and tardive dyskinesia respectively were significantly decreased and only a few patients reported EPS as adverse events. Although mild and clinically non-significant of ALT/SGPT was observed, most laboratory parameters including plasma prolactin level showed to significant changes during the trial. Conclusions : Although this trial had many limitations because it was a non-comparative and open study, olanzapine showed high efficacy on the positive, negative and depressive symptoms in schizophrenia and schizophreniform disorder.In addition to that, olanzapine showed a substantially favorable safety profile, such as low incidence of EPS and hyperprolactinemia.

Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts

Lee, Moon Hee,Cha, Hee-Jae,Choi, Eun Ok,Han, Min Ho,Kim, Sung Ok,Kim, Gi-Young,Hong, Su Hyun,Park, Cheol,Moon, Sung-Kwon,Jeong, Soon-Jeong,Jeong, Moon-Jin,Kim, Wun-Jae,Choi, Yung Hyun Spandidos Publications 2017 International journal of molecular medicine Vol.39 No.3

<P>Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)-like activity and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical scavenging activity were determined. We also investigated the cytoprotective effects of morin against hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in V79-4 Chinese hamster lung fibroblasts. Our results demonstrated that morin had strong scavenging effects against ABTS' radicals with enhanced SOD activity, which varied in a dose-dependent manner. Morin was found to reduce H2O2-induced intracellular reactive oxygen species generation and nuclear DNA damage, and it recovered cell viability damaged by H2O2 via inhibition of mitochondrial dysfunction-mediated apoptosis. Notably, the treatment of V79-4 cells with morin markedly enhanced the expression of heme oxygenase-1 (HO-1) but not quinone oxidoreductase-1, which was associated with the increased expression and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the downregulation of Kelch-like ECH-associated protein 1 expression. Based on our findings, we conclude that morin effectively ameliorated oxidative stress-induced DNA damage through intrinsic free radical scavenging activity and activation of the Nrf2/HO-1 pathway.</P>

도시열섬현상 저감을 위한 그린네트워크 구축 방안에 관한 연구 : 대구광역시 달서구를 대상으로

김기호,김수봉,정응호 한국환경과학회 2004 한국환경과학회지 Vol.13 No.6

As urbanization has been expanded in Korea, open spaces, such as urban parks and public sites, have been utilized for other uses, and then this bring out environmental changes for the worse. It is expected that these changes become more serious problems due to overpopulation, increasing individualism, and development of transportation. This research base on the consideration of connecting between decreasing urban green spaces and distributed green sites so as to build the substantial plan for the Green Network construction for urban heat island mitigation in Dalseo district, Daegu Metropolitan City. The result were as follow; 1) Connecting existing natural sites to the remained parks green zone made an Ideal form of Green-Network system. 2) Some school sites were selected for usable open spaces in order to build Green-Network system, and the plan connecting together with exist natural sites was suggested. 3) Moreover, the scheme of planting on the road spaces for connecting green spaces was proposed. 4) The devices of planting on the urban riverside for enhancing the role of urban stream to form green network was conceived.