Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

일본산 배 SPS 수입금지 조치 해제의 사전분석

한석호(Suk-Ho Han),서홍석(Hong-Seok Seo),염정완(Jung-Won Youm) 한국산학기술학회 2017 한국산학기술학회논문지 Vol.18 No.1

본 논문은 국산 배와 일본산 배에 대한 국내소비자의 무차별 선호를 가정한 가격격차 방법론을 적용하여 일본산 배의 수입금지 조치 해제 시 경제적 · 정량적 영향을 사전에 분석하는 방법론을 소개한다. 방법론을 이용하여 2018년 일본산 배의 수입허용 가정 시 시뮬레이션을 수행한 결과, 연평균 5만 톤의 일본산 배가 국내시장에 유입될 것으로 추정된다. 이 수입량은 국내 배 가격하락 뿐만 아니라 국산 배 생산량 감소를 야기하여 국내 배 생산 감소효과를 초래하여, 연평균 930억원 수준의 직접적인 피해가 예상된다. 국내 배 재배면적과 생산량은 베이스라인 대비 0.7%, 1.4% 감소할 것으로 예측된다. 또한, 생산 · 소비 대체재를 포함한 다른 품목 부문에 미치는 간접적인 영향을 합한 전체 농업분야의 연평균 감소액은 약 2,090억 원 수준으로 베이스라인 대비 0.4% 감소할 것으로 전망된다. 본 연구에서 제안한 SPS 수입금지 조치 해제 시나리오 영향평가는 기존에 수행해오던 양허안 중심의 시나리오 분석과 병행하여, 메가 FTA 참여 시 농업분야 파급영향의 사전분석 방법론을 개선할 것으로 기대된다. This paper proposed a methodology to analyze the economic and quantitative effects of lifting the import ban on Japanese pears by applying a price gap approach in the absence of any preference for either type of pear. Assuming that Korea will allow Japanese pear imports in 2018, the simulation results show that an annual average of 50,000 tons will flow into the domestic market from Japan. These imports will cause a decrease in the price and production of domestic pears, which would have a direct effect on the domestic pear industry, leading to an annual average reduction of 93 billion won. The cultivation area and production quantity are projected to be decreased by 0.7% and 1.4%, respectively, compared to the baseline. Also, the annual average reduction in the overall agriculture sector is predicted to be about 209 billion won, which is a 0.4% reduction compared to the baseline. This research is expected to improve the methodologies available for proactive analysis, with the existing analysis focused on customs tariffs when Korea considers joining mega-FTAs.

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Sokho Kim,Myung-Hoon Oh,Bum-Seok Kim,Won-Il Kim,Ho-Seong Cho,Byoung-Yong Park,Chul Park,Gee-Wook Shin,Jungkee Kwon 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to 200mM) for 1 h before treatment with 1 mg/ mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Kim, Sokho,Oh, Myung-Hoon,Kim, Bum-Seok,Kim, Won-Il,Cho, Ho-Seong,Park, Byoung-Yong,Park, Chul,Shin, Gee-Wook,Kwon, Jungkee The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to $200{\mu}M$) for 1 h before treatment with 1 mg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

고속가공에서 2중 신경망을 이용한 표면거칠기 예측과 가공DB 구축 효율화 방안

원종률,남성호,유송민,이석우,최헌종 한국공작기계학회 2004 한국공작기계학회 추계학술대회논문집 Vol.2004 No.-

In this paper, a double artificial neural network (ANN) approach and the efficient machining database building scheme are presented for the prediction of surface roughness in high-speed machining. In this approach, 4 machining parameters and used for the prediction of cutting force components, and the combinations of 4 parameters and the predicted cutting force components are finally used for the prediction of surface roughness. The experimental results comparing the these results with the predicted values using simple 4 input nodes have been also investigated to verify the effectiveness of the proposed approach.

불안장애환자가 나타내는 사고내용의 특성

원호택,신현균,박현순,권석만 서울大學校 社會科學大學 心理科學硏究所 1996 心理科學 Vol.5 No.1

본 연구는 인지내용이 정서장애에 영향을 미친다는 인지적 내용-특수성 가설에 근거하여 불안장애환자의 사고내용을 조사하고자 했다. 사고내용에 있어서, 불안장애 환자들이 정상인 또는 비불안 정신장애환자와 어떤 차이점이 있는지를 조사했으며 나아가서 불안장애의 하위유형인 공황장애환자와 비공황 불안장애환자간에 어떤 차이점이 있는지를 탐색하고자 했다.이를 위해서 공황장애환자 34명, 비공황 불안장애환자 24명, 비불안 정신장애환자 34명을 포함한 92명의 정신장애 환자와 60명의 정상인을 대상으로 하여 그들의 사고내용을 측정하였다. 이들의 사고내용은 불안민감성 척도(ASI), 광장공포인지 질문지(ACQ), 신체감각 질문지(BSQ)를 사용하여 측정되었다. 각 집단별 사고내용을 정밀하게 비교하기 위하여 각 척도의 개별문항에 대해서 차이비교검증을 실시하였다.본 연구의 주된 결과는 다음과 같다. 첫째, 공황 장애를 비롯해 불안장애 환자집단은 정상인 집단에 비해 세 척도에서 측정된 불안유발 사고내용을 현저하게 많이 가지고 있었다. 둘째, 공황장애 환자집단은 비불안 정신장애 환자(우울증 및 신체화) 집단에 비해 신체적 증상에 대해서 더 예민하고 이를 위협적인 것으로 평가하는 경향성이 있었다. 셋째, 공황장애 환자들은 비공황 불안장애 환자나 비불안 정신장애환자에 비해 극단적이고 파국적인 위험과 관련된 사고내용을 많이 가지고 있었다. 특히 공황장애 환자들은 다양한 신체적 증상과 변화에 예민하고 이를 죽음이나 통제상실상태와 같이 극단적이고 파국적인 것으로 해석하는 사고경향이 있는 반면, 비공황 불안장애 환자들은 대인관계에서의 부적절한 대처나 능력에 대한 부정적 평가와 같이 일반적이며 비파국적인 위험이나 위협과 관련된 사고내용을 많이 갖는 경향이 있었다.ABSTRACT The aim of the present study is to investigate some characteristics of patients with anxiety disorders in their thought contents from the theoretical perspective of the cognitive content-specificify hypothesis that cognitive contents influence emotional disorders. For this, differences in thought contents between patients with panic and non-panic anxiety disorder as well as between patients with anxiety disorders and non-anxiety psychiatric patients or nomal controls were examined.The data were collected from 92 psychiatric patients (34 panics, 24 non-panics, 34 non-anxiety psychiatric patients) and 60 normal controls. Their thought contents were measured with the Anxiety Sensitivity Inventory, Agoraphobic Cognition Questionnaire, and Body Sensation Questionnaire. The difference between groups in the individual item of the three measures was tested using ANOVA and multiple comparison tests.The main findings in the present study are as follows: First, the patients with anxiety disorders reported significantly more thoughts with anxiety-provoking contents than normal controls. Second, the patients with panic disorders tended to be more sensitive to physical symptoms and to interpret these as being threatening than the non-anxiety psychiatric patients. Third, the patients with panic disorder had more thoughts with contents related to extreme and catastrophic danger than those with non-panic anxiety disorders. In particular, those with panic disorder had strong tendency to be senstive to physical symptoms or changes and to interpret these as suggesting extreme and catastrophic danger such as death or loss of control, whereas those with non-panic anxiety disorders tended to have thoughts with contents related to general and non-catastrophic danger or threats such as inadequate coping in interpersonal situations or negative evaluation about their ability.

한국형 우울장애 약물치료 알고리듬 2006 (Ⅰ)

서정석,민경준,김원,석정호,박원명,송해철,이상열,전덕인,전현태,홍진표,한국형 우울장애 약물치료 알고리듬 2006 연구그룹 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.5

Objectives : Since the publication of Korean Medication Algorithm Project for Major depressive Disorder (KMAP-MD) in 2002, there has been a substantial need for a revision due to rapid progress in the pharmacological management for depressive disorder. We revised KMAP-MD to Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2006. This paper is one of the following 4 papers consisting of Korean pharmacological algorithm for depressive disorder. Methods : The questionnaire consisted of 4 parts ; initial treatment of 1) non-psychotic depressive disorder, 2) psychotic depressive disorder, 3) treatment strategy for clinical subtypes and drug choice considering adverse effects, and 4) treatment for depressive disorder in women. It was composed of 22 questions, and each question had 54 sub-items. The questionnaire was completed by the review committee consisting of 101 experienced Korean psychiatrists. We classified the expert opinion to 3 categories (the first-line, the second-line, or the third-line). Results : For non-psychotic major depression, regardless ofthe severity of an episode, the antidepressant (AD) monotherapy was the optimal first-line treatment. SSRI, venlafaxine, and mirtazapine were the 1st-line AD. In case of a partial or no response to initial strategy, adding another AD was recommended. For psychotic major depression, combination of an AD and an atypical antipsychotic (AAP) was the treatment of choice. Among AAPs, quetiapine, rispendone, olanzapine were preferred. For non-responder to initial strategy, the next step was adding or changing AD before changing AAP. For women with premenstrual dysphoric syndrome or postpartum depression without psychotic features, AD monotherapty was a preferred strategy while for psychotic postpartum depression, combination of AD and AAP was recommended. Experts recommended various ADs according to adverse effect. Conclusion : These results suggest that the medication strategies for depressive disorder are rapidly changing and reflect the recent studies and clinical experiences.

전정기능검사에서 정상소견을 보이는 어지러운 환자들의 임상적 특징

정원호,방은국,홍성화,이치규,이현석 대한평형의학회 2002 Research in Vestibular Science Vol.1 No.2

여과사 표면처리에 의한 부식물질 흡착

延動錫,李元鎬 충주대 산업과학기술연구소 2001 産業科學論文集 Vol.9 No.-

Suspended and dissolved substance were included in water. Suspended substances can be relatively easily removed by sand filter, whereas, complete removal of dissolved substances in water was not possible at present. It is due to repulsion between negative charge of dissolved substances and sand filter previously used. Potential application of sand filters coated with Al and Fe in removing humid substances was evaluated in this experiment to improve removal efficiency of the dissolved substances in the water. In the adsorption experiment, the removal efficiency of humic substances was higher in the coated sand filter than In the uncoated one. More specifically, the higher removal efficiency of the humic substances in the Al-coating sand filter was obtained over the pH range randomly determined(4.2, 5.1, 7.6, and 10.0). Especially, the removal efficiency of the humic substance at the pH 10 was relatively constantly maintained at a level of about 95% during the maximum 8 hours. After then, it was sharply decreased. In the leaching experiment, the concentration of leachate in both coated and uncoated sand filters was all the highest at pH 9.95. It was relatively higher over the pH range of 7 to 10 than other pH range. Finally, the removal efficiency of the humic substances obtained in the readsorption experiment was rapidly declined, compared to that obtained in the adsorption experiment. Experiment results acquired in this research may be used to develop a promising technology for the removal of bacteria, algae, and colorful colloids, and a variety of dissolved substances in water.