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>

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.

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>

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>

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>

성인에서 발생한 설사 동반성 용혈성 요독 증후군 3례

김진호,장광열,김구,배성진,김성은,김기현,최필선 동아대학교의과대학 1997 동아의대학술지 Vol.9 No.2

초음파 가이드를 통한 맥락막상강출혈의 치료

이기헌,유재호,김태원,이상준,김신동 고신대학교 의과대학 2009 고신대학교 의과대학 학술지 Vol.24 No.1

Purpose : Intraoperative suprachoroidal hemorrhage is one of the most serious complications. We report a case of suprachoroidal hemorrhage during phacoemulsification surgery, was managed properly. Methods : Suprachoroidal hemorrhage occurred during phacoemulsificaiton in other hospital. The patient was referred to our department immediately after closing the surgical wound. On initial examination, iris and vitreous were prolapsed through surgical wound. Ciliary body was closely place to anterior chamber, and retina was not visible. Results : Prolapased ocular tissue were reduced by emergency operation. We controlled the patient’s intraocular pressure and inflammation. Ultrasonography was repeatedly performed to check the degree of liquefaction of suprachoroidal hemorrhage. After 9 days of suprachoroidal hemorrhage onset, vitrectomy and drainage through sclera was performed. Postoperative state was stable with successful removal of suprachoroidal hemorrhage. After 2 weeks of secondary operation, retinal detachment has occurred on nasal retinal area, so we performed scleral buckling and endolaser photocoagulation. After 6 months, retina was attached well and intraocular pressure was in normal range. Conclusion : In suprachoroidal hemorrhage, drainage of suprachoroidal hemorrhage after liquefaction of thrombi is effective. After successful drainage, postoperative complications may accompany such as retinal detachment or elevation of intraocular pressure. 목적 : 술중 발생하는 맥락막상 출혈은 매우 심각한 합병증이다. 저자는 수정체 유화술 중에 발생한 맥락막상 출혈을 적절히 대처한 증례를 보고하는 바이다. 대상과 방법 : 수정체 유화술 중 발생한 맥락막상강 출혈환자가 수술창을 봉합 후 즉시 본원으로 전원되었다. 초진시 홍채와 유리체가 수술창을 통해 탈출되어 있었으며, 전방을 통해 모양체가 확인되었으나, 망막은 보이지 않았다. 탈출된 안구내 조직을 응급수술을 통해 복원 후 환자의 안압과 염증을 조절하였다. 초음파를 반복적으로 실시하여 맥락막상 출혈의 액화 정도를 확인하였으며, 출혈 9일 후 유리체 절제술과 공막을 통한 배액술을 시행하였다. 결과 : 맥락막상 출혈이 성공적으로 제거되었으며 술 후 상태는 안정적이었다. 수술 2주 후 비측 망막 박리가 발생하여 공막돌륭술과 안구내 삽관 레이저술을 시행하였다. 6개월 후 망막은 잘 붙어있었으며, 안압은 정상 범위를 유지하였다. 결론 : 맥락막상 출혈의 경우 출혈의 배액 시기를 결정하는 것이 어렵지만, 규칙적인 초음파를 통해 배액술의 시기를 결정할 수 있다. 또한 맥락막상강 출혈의 성공적인 배액 이후에도 망막박리 및 안압상승과 같은 합병증의 동반에 대해 유념해야한다.

大形建物 放流水 再利用을 위한 濾過工程의 處理特性

김기태,김은호,김익성,성낙창,임경택,강헌찬 동아대학교 환경문제연구소 1996 硏究報告 Vol.19 No.1

To reuse discharge water in large building, pilot - plant study was conducted experimentally, and the results were as follows ; 1. pH in effluent was lower than it in influent, because organisms was decomposed by microorganisms in filtration tower. Since CO₂ gas was generated, dissolved in water, and then converted into carbonic acid, pH seemed to be influenced. 2. The initial concentrations of COD, BOD and SS were unstable but stable with time. If full - scale plant did unusually operate for a long time, when did pilot - plant, it was known that COD was somewhat influenced but BOD & SS were almost not influences. 3. The production cost of reuse was about 256won/ton. If this subject of study were compared with Pusan, water supply & sewage fee would be 500 - 890won/ton. Therefore, when discharge water is reused to a water closet, there would be no problem at all. 4. If about 50% of wastewater will be reused from daily average generated volume, average 700,000won will be saved monthly. On the other hand, economically a additional tax exemption could be expected there from, and it's more economical. In case of D. University, it's estimated that reuse will be accomodated.

천안/아산권역내 곡교천의 수질분석 및 지리정보체계를 이용한 유역 오염원 관리방안에 관한 연구

황병기,이상호 한국환경과학회 2000 한국환경과학회지 Vol.9 No.6

Chonan and Asan city have been a focal point due to rapid development as the first station for Express Railroad and key cities West Coast Development Region. Gokgyo stream adjacent to the cities plays an important role as a drainage channel for an agriculture and a discharger of urban storm water. Water quality of the stream has been deteriorating caused by pollution sources such as a untreated wastewater discharge and runoff from the watershed. In this study, we conducted 4 surveys in April, May, July, and September to understand the current state of water quality for the stream and to make it possibe to predict future water-quality variation for future development. The system runs on a personal computer under the windows enviroment and provides extensive graphics using graphic user interface(GUI) for user-friendly assessment. Using the pull-down menus provided by the GUI panel, the user is able to operate the system by pointing and clicking the icon to identify the state of water-quality at locations concerned. Furthermore, we developed an integrated watershed management system. The constructed system could be a useful tool as a decesion maker for pollution source control strategy.

관동맥 재개통 후 QTc간격분산의 감소 : 정량적으로 측정한 심근 허혈의 호전 정도와의 연관성 Relationships with the Quantitative Degree of Improvement in Myocardial Ischemia

박상선,최기준,남기병,이철환,홍멸기,박성욱,박승정,신중우,문대혁,김유호 대한순환기학회 2000 Korean Circulation Journal Vol.30 No.8