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.

Mycophenolic Acid에 의해 유도된 Jurkat 세포주 세포자멸사에서 Heme Oxygenase-1의 발현이 미치는 영향

이호균(Ho Kyun Lee),최수진나(Soo Jin Na Choi) 대한외과학회 2010 Annals of Surgical Treatment and Research(ASRT) Vol.78 No.6

Purpose: This study demonstrates that pharmacologic induction of heme oygenase-1 (HO-1) along with catalytic activation significantly modulated apoptosis of Jurkat cells induced by mycophenolic acid (MPA). Methods: Cells were cultured with the presence or absence of MPA. Flow cytometric analysis was performed after propidium iodide staining. Western blotting of HO-1, Bcl, and Bax was also performed. Cells were stained 4’-6-Diamidino-2-phenylindole (DAPI) and measured by flow cytometry in the absence or presence of CoPPIX. Results: Treatment of MPA decreased cell viability in a dose- and time-dependent manner. MPA-induced cell death was confirmed as apoptosis characterized by sub G0/G1 phase arrest. Expression of HO-1 assumes a pattern of decline after rising at the initial phase. CoPPIX, HO-1 inducer, significantly inhibited the cisplatin-induced apoptosis. Treatment of MPA resulted in reactive oxygen species (ROS) generation in Jurkat cells. CoPPIX attenuated ROS production in MPA-treated cells. Conclusion: This result suggests that the protective mechanism of HO-1 on MPA-induced cytotoxicity is associated with direct inhibition of ROS generation and mitochondrial permeability transition.

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.

한의진단명과 진단요건의 표준화 연구 III : 3차년도 연구결과 보고

최선미,양기상,최승훈,박경모,박종현,심범상,김성우,노석선,이인선,정진홍,이진용,김달래,임형호,김윤범,박성식,송태원,김종우,이승기,최윤정,신순식 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the third year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows : - analyzing and differentiating of epidemic febrile disease - analyzing and differentiating in accordance with the Sasang constitution medicine based on four-type recognition - differentiation of disease according to pathological changes of Chong and Ren channels - standards for diagnosis of women's disease - standards for diagnosis of children's disease - standards for diagnosis of motor and sensor disturbance (-muscle. born, joint, etc.) - standards for diagnosis of neuropsychiatric disease - standards for diagnosis of five sense organ disease - standards for diagnosis of external disease The indivisual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name, notion of diagnosis pattern, index of differentiation of symptoms and signs, the main point of diagnosis, analysis of diagnosis pattern, discrimination of diagnosis pattern, prognosis, a way of curing a disease, prescription, herbs in common use, disease appearing the diagnosis pattern, documents. The standards for diagnosis of each disease was arranged by the diagnostic requirements in the following order : another name, notion of disease, the main point of diagnosis, analyzing and differentiating of disease, analysis of disease, discrimination of disease, prognosis, a way of curing and prescription of disease, disease in western medicine appearing the disease in oriental medicine, documents.

7두의 개에서 배설성 요로조영술을 통한 신장 기능 평가

최윤정,이기자,최형준,이용진,박성준,송근호,정성목,최호정,이영원 忠南大學校 獸醫科大學 動物醫科學硏究所 2005 動物醫科學硏究誌 Vol.13 No.-

Excretory urography is a type of contrast study used to verify and localize upper urinary tract disease. It is an inexpensive and easy way to visualize of anatomic and functional status of the kidney and has been used as a primary imaging modality for the evaluation of urinary tract abnormalities. We describe urological signs of 7 dogs who examined with excretory urography and ultrasonography. Six cases were referred to veterinary medical teaching hospital. Chungnam national university (VMTH, CNU) to evaluate renal function after the treatment for renal failure and one case was referred showing hematuria. In case 1, 2 and 4, blood test and urinalysis was normal and the results of excretory urography presented that renal function were normal range. In case 3, the results of urinalysis, ultrasonography, and excretory urography except blood test presented abnormal kidney and hydronephrosis was diagnosed. In case 5 and 6, blood test, urinalysis, ultrasonography and excretory urography indicated renal failure. In case 7, blood test, urinalysis and ultrasonography presented partially abnormal signs, however, the results of excretory urography was normal range.

유치와 영구치에서 치과용 접착제의 전단결합강도

최진영,최남기,박영준,최충호,양규호 大韓小兒齒科學會 2007 大韓小兒齒科學會誌 Vol.34 No.4

The objective of this study was to compare the shear bond strengths of five adhesive systems to the enamel and dentin of primary and permanent teeth. Fifty noncarious primary and fifty permanent teeth were collected and stored in an 0.1% thymol solution at room temperature after extraction. The tested adhesives were: Adper Scotchbond Multi-purpose Plus Adhesive (SM) Adper Single bond 2 (SB), Clearfil SE Bond (SE), Adper Prompt L-Pop (PL), G-Bond (GB). For the shear bonding test, the labial and lingual surfaces of primary and permanent teeth were used. To obtain a flat surface, the labial and lingual surfaces of the teeth were sanded on SiO₂with number 600 grit and then divided into 20 groups of 10 surfaces each. All samples were theromocycled in water 5℃ and 55℃ for 1000 cycles. The results were as follows: 1. For primary enamel, shear bond strengths of SM and SB were significantly higher than that of SE and also SM, SB, and PL were higher than GB(p<0.05). 2. For primary dentin, there were no significant differences among the shear bond strengths of any other bonding systems except differnece between SE and GB. 3. For permanent enamel, SB showed significantly higher mean shear bond strength than those of any other bonding systems(p<0.05). 4. For permanent dentin, SM showed significantly higher mean shear bond strength than that of PL and GB(p<0.05). 5. Between the primary enamel and dentin, there were significant differences in SM, SB, and GB, whereas there was statistically significant difference in PL between the permanent enamel and dentin(p<0.05). 6. Between the primary and permanent teeth on enamel, there were no significant differences among all bonding systems, whereas there were statistically significant differences in SM and SB between the primary and permanent teeth on dentin(p<0.05). 본 연구에서는 최근에 개발된 치과용 접착제를 대상으로 유치와 영구치의 법랑질과 상아질에 대한 결합력을 비교 평가하여 입상에서 상아질 접착제를 적절하게 선택하는데 도움을 주고자 시행하였다. 실험재료로 Adper Scotchbond Multi-purpose Plus Adhesive (SM; 3M ESPE,USA),Adper Single bond 2 (SB; 3M ESPE,USA),Clearfil SE Bond (SE; Kuraray Medical Inc.,Japan),Adper Prompt L-Pop (PL; 3M ESPE,USA),G-Bond (GB:GC Cooperation Toyko,Japan)를 이용하여 전단결합강도를 평가하여 다음과 같은 결과를 얻었다. 1. 유치 법랑질에서 전단결합강도는 SM이 28.47±7.93 MPa로 가장 높았고 SB (28.18±6.84),PL (24.02± 6.14),SE (21.70±6.56),GB (17.70±6.68) 순이었다. SM과 SB는 SE보다 통계적으로 유의하게 높은 결합 강도를 보였으며,SM,SB,PL은 GB보다 높았다(p<0.05). 2. 유치 상아질에서 전단결합강도는 SE가 28.72±14.44MPa로 가장 높았고,PL (20.10±6.13),SM 07.72± 10.65),SB (15.48±2.66),GB (10.10±5.45) 순이었으며 SE와 GB간 에는 유의한 차이가 있었으나,다른 군 들 간에는 유의한 차이가 없었다. 3. 영구치 법랑질에서의 전단결합강도는 SB가 28.36±5.68 MPa로 가장 높았고 SM (22.77±4.63), PL(22.05 士6.57),SE (21.74±4.62),GB (15.60±6.75)순이었다. SB는 다른 접착제보다 통계적으로 유의하게 높은 결합력을 나타냈으며,GB는 가장 낮은 결합력을 보였다(p(0.05). 4. 영구치 상아질에서의 전단결합강도는 SM이 28.22±5.56 MPa로 가장 높았고,SB (21.68±7.44),SE (20.13 ±9.88),GB (14.30±6.81),PL (14.18±5.88)순이었으며,SM은 PL,GB와 유의한 차이가 있었다(p<0.05). 5. 유치의 법랑질과 상아질 간에는 SM,SB,GB에서 유의한 차이가 있었고,영구치 법랑질과 상아질 간에는 PL에서 유의한 차이가 있었다(p<0.05). 6. 유치 법랑질과 영구치 법랑질 간에는 모든 접착제에서 유의한 차이가 없었으나,유치 상아질과 영구치 상아질 간에는 SM과 SB에서 유의한 차이가 있었다(p<0.05).

Polyphosphate가 Porphyromonas endodontalis의 성장에 미치는 영향에 관한 연구

최성백,최호영,민병순,박상진,이진용,최기운 大韓齒科保存學會 1998 Restorative Dentistry & Endodontics Vol.23 No.1

Polyphosphate has been used to prevent decomposition of foods and has been shown to have inhibitory effect on the growth of gram positive bacteria. The purpose of this study was to evaluate the effect of polyphosphate on the growth of Porphyromonas endodontalis, a gram negative endodontopathic bacterium. Porphyromonas endodontalis ATCC 35406 was grown in the presence of polyphosphates with different chain lengths. Inhibitory effect of each polyphosphate which was added at the beginnig or during the culture, was determined by measuring the optical density of the bacterial cell at 540nm and by viable cell count. The results from this study were as follows : 1. Polyphosphates were shown the growth inhibition of the Porphyromonas endodontalis. 2. The minimal inhibitory concentration(MIC) of polyphosphate was observed to be 0.04%. 3. Polyphosphates with chain lengths of 25 and 75 demonstrated the greatest inhibitory effect on the growth of Porphyromonas endodontalis. 4. Polyphosphates are bactericidal to Porphyromonas endodontalis, demonstrating the growth inhibition of the bacterium. The overall results suggest that use of polyphosphate may affect the growth of Porphyromonas endodontalis. Further studies will be needed to confirm the effect of Polyphosphate.

감마선과 Methyl Bromide 처리가 사과의 생리화학적 품질에 미치는 영향

강호진,정헌식,조덕조,변명우,최성진,최종욱,권중호 한국식품저장유통학회 ( 구 한국농산물저장유통학회 ) 2003 한국식품저장유통학회지 Vol.10 No.3

감마선(0, 0.5, 1, 2, 3 kGy) 조사와 methyl bromide(MeBr, 26 g/㎏, 4hr) 훈증 및 이들의 처리시기가 사과의 생리화학적 품질특성에 영향을 비교하여, 검역처리를 위한 ◁그림 삽입▷ (원문을 참조하세요) 감마선 조사의 응용성을 검토하였다. 감마선과 MeBr 처리에 따른 사과의 생리화학적 품질평가에서 2kGy 이상의 감마선 조사와 MeBr 훈증은 사과의 일부 생리화학적 품질특성의 변화를 촉진시키는 것으로 나타났다. 감마선과 MeBr의 처리시기별로는 수확 직후보다는 저온(0℃)에서 40일 정도 보관 후 처리한 대체적으로 품질손상이 적은 것으로 나타났다. 따라서 1kGy 이하의 감마선 조사와 지연조사는 사과 과실의 품질을 비교적 양호한 상태로 유지할 수 있어 검역처리 기술로 활용성이 있는 것으로 생각된다. 'Fuji' apples were treated by gamma irradiation (0∼3 kGy) or methyl bromide fumigation at commercial conditions (MeBr, 25 g/㎏, 4 hr) for quarantine purpose at two different treatment timing after harvest and stored under air a 0℃ for 4 months. Associated with the treatment timing of irradiation or fumigation, after 40 days of storage at 0℃ following harvest was more adequate than immediately after harvest in keeping qualities of stored apples. However, more than 2 kGy irradiation and MeBr fumigation were detrimental to physiological and chemical qualities of the fruits. These results show that less than 1 kGy irradiation at the delayed timing has a possibility to be applied as a quarantine procedure without significant changes in the quality of apples.

혁명적 낭만주의로 본 임화의 시관

최호진 ( Ho Jin Choi ) 현대문학이론학회 2013 現代文學理論硏究 Vol.0 No.55

본 연구는 1930년대 중·후반 임화의 시론과 그의 시, 그가 비평의 대상으로 삼은 작품을 비교 분석하는 작업을 통해 임화가 창조하고 체현하고자 한 시관과 특성이 무엇인지 역추적하는 작업이다. 임화는 서정주의 「서풍부」와 안용만의 「강동의 품」, 윤곤강의 「희망」을 각각 현실이 고매한 상태에 도달한 시, 민족성과 향토에 대한 사랑이 잘 드러난 시, 아이러니와 패러독스로 시정신을 담보한 시라고 극찬한다. 이를 통해 임화가 경향시에서 사상성과 계급성뿐 아니라 내용과 형식의 통일을 중요시하고 경향시를 역사적인 의미의 전체적인 시로 발전시키기 위해 노력했다는 것을 알 수 있다. 임화가 비판한 정지용의 「고향」과 신석정의 「밤이여, 그것은 단조(單調)한 비극(悲劇)이 아니다」의 작품 분석을 통해서는 그가 시인의 대상적 실천과 관계된 부분을 매우 중요하게 생각한다는 것을 역추적할 수 있다. 임화가 중요하게 생각하는 혁명적 낭만주의와 주체의 실천적 모습을 이들 시에서 찾을 수 없는데 이것으로서 임화 시론의 중심 줄기는 시대 정신을 반영할 뿐만 아니라 실천이 전제된 생활이 담보돼야 한다는 것을 알 수 있다. 또한 방언을 시어로 선택한 백석의 시를 거론하지 않은 것을 통해 방언은 시가 담당해야 할 사회적 기능을 수행할 수 없으며, 임화에게 민족어로서의 시어는 역사성과 계급의식을 드러내는 현실 반영의 수단이자 혁명적 교화기능까지 수행하는 도구여야 함을 알 수 있다. 이러한 분석을 토대로 1930년대 중·후반 임화의 이데올로기는 시론의 추진력을 부여했으며. 그의 시관은 현실과 생활, 그에 따른 시대정신의 중요성을 강조하면서도 시의 속성으로서 혁명적 낭만주의, 감정, 고매한 시정신과 수단으로서 언어를 중시했다는 것을 알 수 있다. This study tries to understand what Mr. Im Hwa tries to create and realize with his works by analyzing and comparing his works on his views on the poem and his critical view on the other`s works. Im Hwa has highly praised the “Seopungbu” of Suh, Jeong-ju, “Dream of Gangdong” of Ahn, Yong-man and “Hope” of Yoon, Gon-gang as the poems which put the reality to the ultimate state, well expressed the love of ethnic people and homeland and used the irony and paradox in a poetic way. Through the analysis of his criticisms on the poems, we can understand that Im Hwa has put priority on not only ideology and classes but also the uniformity in contents and style and that he had made effort to develop the trendy poems to the poem having the historical meaning and total meaning. The findings of the analysis of his criticism on “Home town” of Jung Ji-yong and “Night is not the monotonous tragedy” of Shin Seok-jeong, we can find out that he put great emphasis on the poet`s relation to the practices. The revolutionary romanticism and the subject`s practical appearance which Im Hwa put emphasis on cannot be found in these poems. This shows that the critical point of Im Ho`s view on the poem reflects not only the spirit of the time but also that the practice should be the basis for them. In addition, the fact that he did not take care of the poem of Baek Seok, who selected the dialect as the words for poem shows that the words for poem is not only the means for him to show the history and recognition of class but also the means for revolutionary educational functions. These analyses show that the ideology has granted the power to his views on poems and that his view on poem has put emphasis on not only the importance of reality, life and spirit of times but also language as means for revolutionary romanticism, emotion and highly esteemed poetic spirit.