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>

FK506이 T 림프구 사멸에서 활성산소 생성에 미치는 영향

이호균(Ho Kyun Lee),정상영(Sang Young Chung),최수진나(Soo Jin Na Choi) 대한외과학회 2009 Annals of Surgical Treatment and Research(ASRT) Vol.77 No.5

Purpose: Tacrolimus (FK506) has been widely used as an immunosuppressant in organ transplanted recipients to suppress organ rejection phenomenon. We investigated the role of oxidative stress and heme oxygense-1 by FK506 on human Jurkat T cells. Methods: The cells viability was examined by DAPI stain, enzyme activity of caspase family proteins, and western blotting for Baks, PUMA, iNOS, HO-1. Cells were cultured in the absence or presence of CoPPIX or ZnPPIX and the fluorescence intensity was analyzed using a flow cytometry. Results: Treatment with FK506 increased the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, and NO in Jurkat cells in a dose-dependent manner. Immunohistochemistry and Western blot analysis data revealed the hemoxygenase-1 (HO-1) was induced by the addition of FK506 in Jurkat cells. Induction of CoPP, HO-1 inducer, resulted in decreased intracellular H₂O₂ and NO concentrations. Instead ZnPP, an HO-1 competitive inhibitor did it reversely. In addition, ZnPP regulates iNOS protein synthesis by inhibition of HO-1. Conclusion: Increase of HO-1 expression would induce to decrease the intracellular H₂O₂ and NO concentrations. Also, HO-1 would regulate iNOS protein synthesis. Consequently, we can expect the regulation of HO-1 expression with concomitants use of FK506 to suppress organ rejection phenomenon by enhancing apoptosis.

Ameliorative effect of <i>Alnus japonica</i> ethanol extract on colitis through the inhibition of inflammatory responses and attenuation of intestinal barrier disruption <i>in vivo</i> and <i>in vitro</i>

Chi, Jin Hua,Kim, Young Ho,Sohn, Dong Hwan,Seo, Geom Seog,Lee, Sung Hee Elsevier 2018 BIOMEDICINE AND PHARMACOTHERAPY Vol.108 No.-

<P><B>Abstract</B></P> <P>Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract caused by high levels of pro-inflammatory cytokines and epithelial barrier dysfunction. <I>Alnus japonica</I> Steud. (Betulaceae) has been used in traditional Asian medicine. However, the potential of <I>A. japonica</I> for the treatment of intestinal inflammation has not been investigated. This study investigated the effects of ethanol extract from <I>A. japonica</I> bark (AJE) on colonic mucosa injury in mice with dextran sodium sulfate (DSS)-induced colitis. Treatment with AJE ameliorated pathological damage and the histopathologic features of DSS-induced colitis. The administration of AJE also inhibits DSS-induced pro-inflammatory cytokines expression, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2. Notably, AJE administration attenuated the reduction of tight junction proteins, zonula occludens (ZO)-1 and occludin, in DSS-induced colitis. In addition, AJE increased heme oxygenase (HO)-1 expression and prevented DSS-induced apoptosis in colonic epithelial cells. Furthermore, <I>in vitro</I> studies demonstrated that AJE inhibits TNF-α-induced IL-8, IL-1β, and COX-2 expression in human intestinal epithelial HT-29 cells and <I>tert</I>-butyl hydroperoxide-induced reduction of ZO-1 and occludin expression in human intestinal epithelial Caco-2 cells. AJE-induced HO-1 protein expression was also found in both HT-29 and Caco-2 cells. Taken together, our findings demonstrated that AJE inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis <I>in vivo</I> and human intestinal epithelial cells <I>in vitro</I>. These results suggest that AJE might have beneficial effects for the treatment of IBD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> AJE attenuates the severity of DSS-induced colitis mice. </LI> <LI> AJE suppresses expression of pro-inflammatory mediators in DSS-induced colitis mice. </LI> <LI> AJE protects intestinal barrier integrity in DSS-induced colitis mice. </LI> <LI> AJE increases HO-1 expression in mouse colonic epithelial cells. </LI> <LI> AJE inhibits inflammation and protects loss of TJ proteins of human IEC cells. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

제주도 지하수 질산염 농도의 시·공간적 변화 특성: 장기(1993-2015) 모니터링 자료의 평가

김호림(Ho-Rim Kim),오준섭(Junseop Oh),도현권(Hyun-Kwon Do),이경진(Kyung-Jin Lee),현익현(Ik-Hyun Hyun),오상실(Sang-Sil Oh),감상규(Sang-Kyu Kam),윤성택(Seong-Taek Yun) 대한자원환경지질학회 2018 자원환경지질 Vol.51 No.1

1993년부터 2015년까지 관측된 제주도 지하수 장기모니터링 관측정(N = 4,835)에서 수집된 지하수 수질자료(N = 21,568)를 기반으로 질산성질소의 시공간적 변동 특성을 평가하였다. 제주도 지하수의 질산성질소 농도의 중앙값은 2.5 mg/L로서 다른 국가나 대륙의 조사 결과에 비해 다소 높거나 유사한 것으로 나타났다. 또한 지하수 용도, 행정구역 및 고도 별로 유의한 차이를 보였다. 특히, 산간 지역에 비해 저지대 해안가에 위치한 농업 및 주거지역에서 농도가 높음을 확인하였다. Mann-Kendall 및 Sen’s slope 분석을 활용한 질산성질소 농도의 추세 분석 결과, 하류 저지 대에 비해 중산간지역에서의 질산성질소 농도 증가 경향이 뚜렷하였다. 제주도 내 토지 피복의 시계열 변화 특성과 결부 지어 보면, 중산간지역의 오염 증가 추세는 농업지역의 확장 등 인위적 활동 증가에 기인한 결과로 판단된다. 반면,기지정된 지하수자원특별관리구역에서는 전반적으로 질산성질소 농도의 감소 경향이 나타났는데, 이는 지하수 관리 측면에서 수질관리를 위한 적극적인 정책이 유효함을 시사한다. 본 연구에서는 제주도 지하수의 질산성질소 오염관리를 위한 적정 방안을 제안한다. The spatio-temporal variations of nitrate concentrations in groundwater of Jeju Island were evaluated by an analysis of time series groundwater quality data (N = 21,568) that were collected from regional groundwater monitoring (number of wells = 4,835) for up to 20 years between 1993 and 2015. The median concentration of NO 3 -N is 2.5 mg/L, which is slightly higher than those reported from regional surveys in other countries. Nitrate concentrations of groundwater in wells tend to significantly vary according to different water usage (of the well), administrative districts, and topographic elevations: nitrate level is higher in low-lying agricultural and residential areas than those in high mountainous areas. The Mann-Kendall trend test and Sen’s slope analysis show that nitrate concentration in mid-mountainous areas tends to increase, possibly due to the expansion of agricultural areas toward highland. On the other hand, nitrate concentrations in the Specially Designated Groundwater Quality Protection Zones show the temporally decreasing trend, which implies the efficiency of groundwater management actions in Jeju. Proper measures for sustainable groundwater quality management are suggested in this study.

정밀 Positioning를 이용한 망막세포 치료 및 담석 제거

최상훈(Sang-hoon Choi),김진수(Jin-녀 Kim),이호(Ho Lee) 한국레이저가공학회 2008 한국레이저가공학회 학술대회 논문집 Vol.2008 No.-

Among many medical application of lasers, the pulsed laser induced surgery is one of the most popular fields. In the current study, we demonstrated the laser-induced selective cell targeting using the precision positioning stage. Furthermore, we compared laser induced ablation of human urinary calculi using two different lasers (Ho:YAG : 2.9㎛, Er:YAG : 2.1㎛).

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

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.

Protective Effect of Baicalin Against Carbon Tetrachloride–Induced Acute Hepatic Injury in Mice

Park, Sang-Won,Lee, Chan-Ho,Kim, Yeong Shik,Kang, Sam Sik,Jeon, Su Jin,Son, Kun Ho,Lee, Sun-Mee The Japanese Pharmacological Society 2008 JOURNAL OF PHARMACOLOGICAL SCIENCES Vol.106 No.1

<P>This study examined the effects of baicalin, a bioactive flavonoid isolated from <I>Scutellariae Radix</I>, on carbon tetrachloride (CCl<SUB>4</SUB>)-induced liver injury. Mice were treated intraperitoneally with 0.5 ml/kg CCl<SUB>4</SUB> and different groups of animals received 25, 50, 100, and 200 mg/kg baicalin. At 24 h after the CCl<SUB>4</SUB> treatment, the level of serum aminotransferases and lipid peroxidation was significantly elevated, whereas the hepatic glutathione content was decreased. These changes were attenuated by baicalin. The histological studies showed that baicalin inhibited the portal inflammation, centrizonal necrosis, and Kupffer cell hyperplasia, which are the three most common characteristics of CCl<SUB>4</SUB>-induced liver damage. The serum level and mRNA expression of tumor necrosis factor-α were markedly increased by the CCl<SUB>4</SUB> treatment but suppressed by baicalin. The mRNA and protein expression levels of inducible nitric oxide synthase and heme oxygenase-1 increased significantly at 24 h after the CCl<SUB>4</SUB> treatment. Baicalin attenuated the increase in the protein and gene expression of inducible nitric oxide synthase but augmented the increase in those of heme oxygenase-1. These findings suggest that baicalin protects hepatocytes from the oxidative damage caused by CCl<SUB>4</SUB>, and this protection is likely due to the induction of HO-1 expression and the inhibition of the proinflammatory mediators.</P>

고속선 및 기존선에서 한국형 고속열차의 집전특성 분석 : 판토그라프-가선 간 접촉력 경향을 중심으로

목진용(Jin-Yong Mok),김영국(Young-Guk Kim),박춘수(Choon-Soo Park),김기환(Ki-Hwan Kim),이성호(Sung-Ho Lee) 한국철도학회 2004 한국철도학회 학술발표대회논문집 Vol.- No.-

The pantograph for Korean High Speed Train was developed and had been evaluating by through "G7-R&D project" for home grown high speed train technology. In this paper, from the point of view in mechanical aspect, comparison study on the current collection characteristics between the KHST pantograph and contact wire in catenary system on the High-Speed Line and Ho-Nam/Kyoung-Bu conventional lines is conducted. A measuring system for the performance and mechanical characteristics of the KHST pantograph is used for this study, which was developed and installed on the Proto-type Korean High Speed Train, and physical characteristics were measured while the KHST runs on the High-Speed Line and conventional lines. Through this study, remarkable variations of characteristics which can affect to a current collection quality of high-speed train are found and analyzed from measured mean contact forces in both tracks.

Intracavitary Radiation Therapy for Recurrent Cystic Brain Tumors with Holmium-166-Chico : A Pilot Study

Ha, Eun Jin,Gwak, Ho-Shin,Rhee, Chang Hun,Youn, Sang Min,Choi, Chang-Woon,Cheon, Gi Jeong The Korean Neurosurgical Society 2013 Journal of Korean neurosurgical society Vol.54 No.3

Objective : Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. Methods : Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. Results : There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. Conclusion : Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.