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>

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.

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>

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.

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>

Gliotoxin ameliorates TNBS-induced colitis through regulation of NF-kB, and up-regulation of HO-1

김상욱 ( Kim Sang Ug ),( Jay Min Oh ),( Yeon Hwa Kim ),( Jung Moo Hur ),( Kyo Sang Yoo ),( Yong Sung Kim ),( Joo Jin Yeom ),( Tae Hyeon Kim ),( Suck Chei Choi ),( Chang Duk Jun ),( Yong Ho Nah ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-

<Background & aims> During inflammation in colon, cells of the gut mucosa produce or express various inflammatory mediators, including IL-8, TNF-a and IL-1b, and intercellular adhesion molecule 1 (ICAM-1). These cytokines and chemokines have recently been

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>