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>

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.

Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen

Woo, Je Moon,Shin, Da-Yong,Lee, Sung Ju,Joe, Yeonsoo,Zheng, Min,Yim, Jin Ho,Callaway, Zak,Chung, Hun Taeg Molecular Vision 2012 Molecular vision Vol.18 No.-

<P><B>Purpose</B></P><P>To determine whether curcumin induces expression of the defensive enzyme heme oxygenase-1 (HO-1) and protects cells against oxidative stress in cultured human retinal pigment epithelial cells.</P><P><B>Methods</B></P><P>Effective concentrations and toxicities of curcumin were determined after 3 h of curcumin treatment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Confluent human retinal pigment epithelium cell lines (ARPE-19) were preincubated with curcumin and oxidatively challenged with H<SUB>2</SUB>O<SUB>2</SUB>. HO-1 expression was determined with western blot analysis. To confirm the protective role of HO-1 in oxidative stress, small interfering RNA (siRNA) against HO-1 or inhibitor of HO-1 was treated with curcumin in retinal pigment epithelium cells. Intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry and confocal microscopy. Apoptosis was evaluated with Annexin V-fluoroscein isothiocyanate staining.</P><P><B>Results</B></P><P>Curcumin had little cytotoxicity at concentrations less than 30 μM, and HO-1 expression was the highest at the 15 μM concentration. At this concentration, curcumin also increased the cytoprotective effect against the oxidative stress of H<SUB>2</SUB>O<SUB>2</SUB> through the reduction of ROS levels in human retinal pigment epithelial cells. Curcumin’s effect on the reduction of ROS was mediated by the increase in HO-1 expression.</P><P><B>Conclusions</B></P><P>Curcumin upregulated the oxidative stress defense enzyme HO-1 and may protect human retinal pigment epithelial cells against oxidative stress by reducing ROS levels.</P>

태안 마도 앞바다 출수 중국 도자기의 성격

진호신(Jin, Ho-Shin) 동북아시아문화학회 2021 동북아시아문화학회 국제학술대회 발표자료집 Vol.2021 No.07

Many Chinese ceramics have been excavated from the underwater off Mado Island in Taean since 2009. Since ancient times, the sea has been called ‘Nanhangnyang’ meaning that is hard to cross. These Chinese ceramics are interpreted as a result of the Goryeo Dynasty’s Yeosong Trading. Most of these ceramics, which are believed to have been left behind by merchants and envoys of Song-Wien era were made in Fuzen China and reached the Korean Peninsula through the old Chinese city of Puzou and Chonzou. The Chinese pottery, which was excavated coast of Mado-Island is made from the Five Dynasties to Jin-Song-Wien era and is mostly exported from the Min-river of Fuzen Province. It is also a proof that the trade between the Koryo and Song Dynasty was so active. Since 2009, when underwater excavations began off the coast of Taean Mado, Chinese ceramics have presented many challenges tj Korean and Chinese researchers. In the future traffic studies on historic cities and old kiln site, including surveys on the Min River in Fuzen Provice will be needed.

Ciprofloxacin 제제의 생물학적 동등성에 관한 연구

최철희,신재국,신완균,유호진,이경훈,정원석,장인진,신상구 대한화학요법학회 1991 대한화학요법학회지 Vol.9 No.1

국내 시판중인 ciprofloxacin 제제인 Citopcin®(250㎎ tablet)의 동등성을 검토하기 위해 제조원인 Bayer사의 Citopcin®(250㎎ tablet)를 기준제제로 하여 18명의 건강한 남성 피험자를 대상으로 500㎎ 1회 교차 경구 투여후 약동학적 성상을 분석비교한 결과는 다음과 같다. 시험제제의 생체 이용율의 지표인 AUC, C_(mao), T_(max) 및 MRT들의 평균치는 백분율차이에 있어 모든 기준제제 지표의 ± 20% 이내였으며, 이들 생체 이용율 지표들은 분산분석 검정에서 차이를 인지할 수 없었다.생체 이용율 지표들의 기준제제에 대한 백분율 90% 대칭 신뢰구간 검토시 모든 경수들에서 ± 20% 이내의 조건을 만족하였으며 AUC의 경우에는 대칭형 신뢰구간으로 변환시 95% 신뢰구간에서도 동등성의 조건을 만족하였다, 이상의 시험결과로 시험제제인 Citopcin®은 기준제제인 Ciprobay®와 생물학적 동등한 제제로 판단되었다. The pharmacokinetics of ciprofloxacin was studied for the evaluation of the bioequivalence of the generic ciproflocacin products. Two single doses of 500㎎ each of ciprofloxacin(Ciprobay® 250㎎ tablet as a reference compound and Citopcin® 250㎎ tablet s a test compound) were administered orally to ighteen male volunteers in a balanced, randomized crossover design. Pek plasma levels of ciprofloxacin were observed about 1 hour after the doses and the peak concentrations of both products were similar(Ciprobay®, 3.18㎍/㎖; Citopcin®, 2.89㎍/㎖). The values of other pharmacokinetic parameter of ciprofloxacin computed for Ciprobay® are presented in that order: AUC=13.53:12.47㎍·h/㎖, T_(max)=1.28:1.14 hours; MRT=5.30:5.08 hours; t_(1/2)β=3.65:3.47 hours. No satistically significant, differences were detected when AUC and the other parameters were compared with the method of ANOVA. Using the criteria of 90% confidence interval for the assessment of bioequivalence al the parameters were acceptable. The products were found to be equivalent on the premise that no significant difference was detected when the relevant pharmacokinetic parameters were compared, and the confidence limit analysis showed acceptable results.

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.

Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells

Joo Heon Kim,김경민,Jin Uk Jeong,Jong-Ho Shin,신재민,방기태 대한신장학회 2019 Kidney Research and Clinical Practice Vol.38 No.3

Background: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. Methods: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. Results: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. Conclusion: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

조혈모세포이식 후 발생한 주폐포자층 폐렴에 대한 고찰

주지현,최정현,이동건,백지연,고윤호,이혜정,김세희,신호진,박윤희,박지영,김유진,신완식,김춘추 대한감염학회 2001 감염 Vol.33 No.4

Background : Pneumocytitis cainii pneumonia (PCP) can occur in immunocompromised hosts especially such as AIDS or cancer patients. Although recent research had focused on PCP in AIDS patients, few studies have described the clinical presentations of PCP in recipients of stem cell transplantation (SCT). We evaluated the clinical manifestations of PCP in SCT patients admitted at St. Mary's hospital, Seoul, Korea. Methods : The medical records of 17 PCP patients undergoing SCT between Feb. 1998 and Feb. 2000 were reviewed. The diagnosis of PCP was confirmed through the demonstration of Pneumocytitis cainii via either cytology of brochoalveolar lavage (BAL) or histological technique of lung biopsy. CMV disease and CMV infection were confirmed by BAL culture and antigenemia respectively . Results : Seventeen patients were all recipients of allogeneic SCT and 7 of 17 patients were performed non-sibling SCT. Patients presented with symptoms including brief period (4 ∼23 days) of fever (76%), dyspnea (70%), cough (64%), and signs such as rare(58.8%), Sixteen patients (94%) had been receiving immunosuppressive agent such as cyclosporine A (64%) or Fk506 (35%) without PCP prophylaxis. Eleven patients (64%) were treated with corticosteroid with mean dose of 16 mg/day prednisolone and mean duration of 4.6 months after post-SCT period. Twelve patients were co-infected with CMV. Another co-infected miCroorganisms were Pseudomonas aeruginosa, Mycobacterium tuberculosis, herpes simplex virus, parainfluenza virus, Average duration of treatment with trimethoprim-sulfamethoxazole (TMP/SMX) was 21 ±9 days. Four patients died, and three of them were related with PCP. Conclusion : PCP developed frequently in patients who were taking immunosuppressive drug due to graft versus host disease or were not taking TMP/SMX prophylaxis. High risk patients showing fever, cough, or dyspnea should be considered to take early bronchoscopic intervention for detection of PCP. When treat for PCP, it also be considered to the possibility of coinfection such as CMV. (Korean J Infect Dis 33:273∼279, 2001)

우수방사성의약품 생산시설 개발

신병철,정원명,박상현,이규일,박경배,박진호 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.2

Manufacturing facilities of the pharmaceuticals must meet certain level of the cleanness required so that foreign substances such as dust, moisture, heat, microorganism, or virus do not contaminate the product. In case of radiopharmaceuticals for medical treatment and diagnosis, not only should the operators and environment be protected from radiation but also need to be isolated from the foreign contaminant. Therefore, manufacturing facilities for radiopharmaceuticals must satisfy the design standards of both hot cell and clean room which are specified by GNP. However, standards of maintaining negative pressure for preventing spread of radioactive contaminant in isolated facilities conflict with the standards of maintaining positive pressure for keeping cleanness. To solve this problem, are pressure of hot cell was designed lower than in the adjacent area to meet standards of the radiation safety. To keep higher cleanness in certain part of the hot cell for filling, minimal relative positive pressure allows. In order to effectively maintain the cleanness that is required for production of Tc-99m generator, which takes 70% of whole demand of radiopharmaceuticals, the rooms placed in each side of production room are used as a buffer area and three lead hot cells are installed in production room. In this research, we established the appropriate engineered design concept for Tc-99m generator manufacturing facility, which satisfies both GMP cleanness standard for preventing particles, bacteria, other contaminants and the regulations of radiation safety for supervising and controlling the amount of radiation exposure and exhausted radioactivity. And the concept of multi-buffer zones is introduced to apply negative air pressure for hot cell with first priority and to continue relative positive air pressure for clean room.

구동기 성능 저하를 가진 불확실한 비선형 로봇 시스템에 대한 신경 적응 제어기의 설계

신진호,김원호 동의대학교 산업기술개발연구소 2006 産業技術硏究誌 Vol.20 No.-

It is more practicable that actuator torque coefficients applied at each joint are bounded nonlinear time-varying on time, rather than normally unity all the time. The bounded nonlinear time-varying actuator torque coefficients as well as uncertainties may cause the performance degradation of the robot or the actuators in a robotic system. This work presents a design methodology of a neuro-adaptive controller to overcome the performance degradation for uncertain nonlinear robotic systems with actuator failures. The proposed control scheme uses a RBFN(radial basis function network) approximating a nonlinear dynamic terms. An adaptive control input is added to overcome not only the uncertainties such as the approximation error, parameter variations and external disturbances, but also actuator failures. The proposed controller can improve the performance degradation and achieve task completion despite actuator failures and uncertainties. Simulation results are shown to verify the validity of the proposed control scheme.