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>

Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

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.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

Conceptual Study for Tissue-Regenerative Biodegradable Magnesium Implant Integrated with Nitric Oxide-Releasing Nanofi bers

Jin‑Kyung Jeon,Hyunseon Seo,Jimin Park,Soo Ji Son,Yeong Rim Kim,Eun Shil Kim,Jong Woong Park,Woong‑Gyo Jung,Hojeong Jeon,Yu‑Chan Kim,Hyun‑Kwang Seok,Jae Ho Shin,Myoung‑Ryul Ok 대한금속·재료학회 2019 METALS AND MATERIALS International Vol.25 No.4

The excessive initial corrosion rate of Mg is a critical limitation in the clinical application of biodegradable Mg implantsbecause the device loses its fi xation strength before the fractured bone heals. This study suggests a new approach to overcomethis hurdle by accelerating tissue regeneration instead of delaying the implant biodegradation. As angiogenesis is anessential process in early bone regeneration, a Mg implant coated with electrospun nanofi bers containing nitric oxide (NO),which physiologically promotes angiogenesis, is designed. The integrated device enables adjustable amounts of NO to bestored on the NO donor-conjugated nanofi ber coating, stably delivered, and released to the fractured bone tissue near theimplanted sites. An in vitro corrosion test reveals no adverse eff ect of the released NO on the corrosion behavior of the Mgimplant. Simultaneously, the optimal concentration level of NO released from the implant signifi cantly enhances tube networkformation of human umbilical vein endothelial cells without any cytotoxicity problem. This indicates that angiogenesis canbe accelerated by combining NO-releasing nanofi bers with a Mg implant. With its proven feasibility, the proposed approachcould be a novel solution for the initial stability problem of biodegradable Mg implants, leading to successful bone fi xation.

An Improved Speech Processing Strategy for Cochlear Implants Based on an Active Nonlinear Filterbank Model of the Biological Cochlea

Kim $^$, Kyung Hwan,Choi, Sung Jin,Kim, Jin Ho,Kim, Doo Hee IEEE 2009 IEEE Transactions on Biomedical Engineering Vol.56 No.3

<P>The purpose of this study was to improve the speech processing strategy for cochlear implants (CIs) based on a nonlinear time-varying filter model of a biological cochlea. The level-dependent frequency response characteristic of the basilar membrane is known to produce robust formant representation and speech perception in noise. A dual resonance nonlinear (DRNL) model was adopted because it is simpler than other adaptive nonlinear models of the basilar membrane and can be readily incorporated into the CI speech processor. Spectral analysis showed that formant information is more saliently represented at the output of the proposed CI speech processor compared to the conventional strategy in noisy conditions. Acoustic simulation and hearing experiments showed that the DRNL-based nonlinear strategy improves speech performance in a speech-spectrum-shaped noise.</P>

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>

양궁 선수의 마음챙김 능력 향상을 위한 심리훈련 프로그램 적용

김진호(Kim, Jin-Ho),오원석(Oh, Won-Seok) 한국사회체육학회 2017 한국사회체육학회지 Vol.0 No.67

The purpose of this study is to investigate the effects of mindfulness training with psychological techniques in a professional archery team in South Korea. First of all, it is conducted to find the changes in mindfulness through the KIMS during the mindfulness training, and to analyze the changes in both mindfulness and psychological technique factors. After ten times of meditation (1h-1h30m/1d), ACT and MAC based on the mindfulness training program, there were significant positive influences of psychological factors such as techniques, acceptance, concentration behavior and attention behavior on an intervention group compared to a control group, resulting in KIMS. Although there were no significant differences in confidence and teamwork in the intervention group after the psychological techniques, there were positive effects on willpower, goal setting , concentration, anxiety control and imagery statistically in the intervention group. In conclusion, mindfulness training has positive effects on the mindfulness in Korean archers. This training also has a positive influence on psychological technique factors such as attention, imagery, concentration and anxiety control. According to previous literatures, it is proved that there were positive effects on the psychological technique factors with the changes in mindfulness. Therefore, it is required to develop tools which can measure the mindfulness and to apply the correlation of mindfulness and psychological techniques to the field.

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.

초음파 C-scan을 이용한 터빈 블레이드 열차폐코팅의 등온열화에 의한 박리 평가 기법

이호걸(Ho-Girl Lee),김학준(Hak-Joon Kim),송성진(Sung-Jin Song),석창성(Chang-Sung Seok) 한국비파괴검사학회 2016 한국비파괴검사학회지 Vol.36 No.5

가스터빈 블레이드는 고온 고압의 환경 아래 장시간 가동하기 위하여 초합금 모재에 세라믹 코팅으로 이루어진 열차폐코팅(thermal barrier coating, TBC)은 필수요소이다. 하지만 TBC 또한 가스터빈 가동 중 일정 열화온도 및 가동시간에서 top coat의 박리현상이 일어난다. TBC의 박리는 블레이드의 손상과 직결되므로 가스터빈의 안정적인 가동을 위해서 TBC의 박리 평가가 선행되어야 한다. 기존 비파괴평가 기법 연구는 산화알루미늄층(thermally grown oxide, TGO)의 생성 유무 또는 완전 박리의 정성적 평가가 이루어져 왔다. 본 연구에서는 TBC 박리를 정량적으로 평가하기 위해 초음파검사의 C-scan기법을 이용한 TBC의 부분박리손상 map을 구현하였다. 시편들은 1,100˚C로 등온열화하여 각각 열화시간을 변화시킨 시편들을 사용하였다. 단일 탐촉자를 이용한 펄스-에코법으로 C-scan을 수행하였고 TBC 내 부분박리를 검출하기 위해 초음파를 수침법으로 시편에 수직탐상하였다. 그리고 Rogers-Van Buren과 Kim의 이론 반사식을 이용하여 부분박리영역 지름이 1 mm부터 6 mm까지 부분박리지수를 도출했다. 이를 적용하여 각 부분박리지수에 따른 부분박리 손상 map을 영상화하였다. TBC는 열화시간이 증가할수록 부분박리지수에 관계없이 부분박리영역이 모두 증가함을 확인할 수 있었다. 또한 단일 시편 내에서 부분박리지수가 증가할수록 부분박리영역이 감소하는 것을 확인하였다. 부분박리손상 map의 부분박리영역에 따른 분포를 이용하여 TBC의 완전박리 기준과 잔여 수명을 또한 도출할 수 있었다. Thermal barrier coating (TBC) is an essential element consisting of a super-alloy base and ceramic coating designed to achieve long operational time under a high temperature and pressure environment. However, the top coat of TBC can be delaminated at certain temperatures with long operation time. As the delamination of TBC is directly related to the blade damage, the coupling status of the TBC should be assured for reliable operation. Conventional studies of nondestructive evaluation have been made for detecting generation of thermally grown oxide (TGO) or qualitatively evaluating delamination in TBC. In this study, the ultrasonic C-scan method was developed to obtain the damage map inside TBC by estimating the delamination in a quantitative way. All specimens were isothermally degraded at 1,100˚C with different time, having different partial delamination area. To detect partial delamination in TBC, the C-scan was performed by a single transducer using pulse-echo method with normal incidence. Partial delamination coefficients of 1 mm to 6 mm were derived by the proportion of the surface reflection signal and flaw signal which were theoretical signals using Rogers-Van Buren and Kim"s equations. Using the partial delamination coefficients, the partial delamination maps were obtained. Regardless of the partial delamination coefficient, partial delamination area was increased when degradation time was increased in TBC. In addition, a decrease in partial delamination area in each TBC specimen was observed when the partial delamination coefficient was increased. From the portion of the partial delamination maps, the criterion for delamination was derived.