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.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Shin, Tae-Kyeong,Kang, Mi-Sun,Lee, Ho-Youn,Seo, Moo-Sang,Kim, Si-Geun,Kim, Chi-Dae,Lee, Won-Suk The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Analysis of Judicial Precedents Cases Regarding Skin Cancer from 1997 to 2017 in Republic of Korea

( Su Hwan Shin ),( Won Lee ),( So Yoon Kim ),( Gwanghyun Jo ),( Je-ho Mun ),( Soo Ick Cho ) 대한피부과학회 2019 Annals of Dermatology Vol.31 No.3

Background: Both medical disputes and the incidence of skin cancer are increasing in Korea. Objective: The aim of this study was to figure out the medical litigation related to skin cancer and propose a method to prevent the medical disputes. Methods: Skin cancer-related judgments were searched by The Supreme Court of Korea’s Written Judgment Management System based on the keywords for skin cancer. The search system included sentenced cases at the Lower Courts, the Appellate Courts, and the Supreme Court from 1997 to 2017. Results: Seven cases were selected as the litigation cases related to skin cancer. Four cases (57.1%) presented malignant melanoma, while the rest presented squamous cell carcinoma, metastatic skin cancer, and peripheral T cell lymphoma (1 case in each). Four cases resulted in death from cancer metastasis, and 3 cases presented as sequelae. The legal issues related to the medical disputes could be categorized as follows: misdiagnosis, delayed diagnosis, performance error, and lack of informed consent. Delayed diagnosis and lack of informed consent were the most common issues (n=4) in the precedents. Five cases (71.4%) were sentenced the awarded amounts to the plaintiff, including 2 cases of settlement decision. The average awarded amount was 42,553,644±27,567,455 Korean won. Conclusion: Physicians should pay attention to the cases of the skin cancer to prevent medical malpractice and disputes. The practices pertaining to proper diagnosis, treatment plans, and obtaining an informed consent should be followed during the course of treating skin cancer. (Ann Dermatol 31(3) 300∼306, 2019)

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Tae Kyeong Shin,Mi Sun Kang,Ho Youn Lee,Moo Sang Seo,Si Geun Kim,Chi Dae Kim,Won Suk Lee 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1Ձ (HIF-1Ձ) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1Ձ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

과학기술정보콘텐츠 통합관리시스템 구축을 위한 데이터 마이그레이션 모델 수립 및 적용 사례

신성호(Sung-Ho Shin),이민호(Min-Ho Lee),이원구(Won-Goo Lee),윤화묵(Hwa-Mook Yoon),성원경(Won-Kyung Sung),김광영(Kwang-Young Kim) 한국컴퓨터정보학회 2011 韓國컴퓨터情報學會論文誌 Vol.16 No.11

국내 데이터베이스 구축 시장은 작년 기준으로 3조 6,633억원 규모로 추정된다. 데이터베이스 산업의 지속적인 성장과 맞물려, 데이터 마이그레이션의 중요성도 날로 높아지고 있다. 고객 위치를 찾아주는 g-CRM이나 고객에게 상품을 추천하는 맞춤 설계 기능 등은 모두 고객 데이터베이스, 상품 데이터베이스, 지리정보 데이터베이스 등이 결합되어야 구현 가능한 서비스들이다. 스마트 비즈니스의 핵심 인프라도 통합되고 완전하며 신뢰할 수 있는 데이터베이스라고 할 수 있다. 이러한 데이터베이스의 중요성에도 불구하고, 데이터 마이그레이션 및 통합 과정의 효율적인 수행 방안이나 데이터 검증 방법에 대하여는 구체적인 연구가 부족한 실정이다. 본 연구에서는 다양한 타입으로 존재하는 과학기술분야 콘텐츠들을 대상으로 데이터 마이그레이션을 위한 모델을 설계하였고, 모델을 기반으로 실제 데이터 마이그레이션 작업을 수행한 결과를 제시하였다. 아울러 데이터 마이그레이션 결과에 대한 검증을 위해 데이터베이스의 완전성, 데이터값의 일관성, 관계의 일관성을 검증하였고, ANSI/ASQ Z1.4-2003에서 제시된 샘플링 검사 기법도 적용하였다. 결과적으로 모델 수립에 의한 체계적인 데이터 마이그레이션 수행은 데이터베이스 정합성 및 데이터값의 정확성에 영향을 미치고, 고품질의 데이터베이스를 유지하기 위한 필수 요소라 할 수 있다. The domestic market of database in Korea is estimated to be over 3.663 trillion won. The data migration is getting to be more important along with the continuous growth of the database industry. g-CRM and private recommending function are examples of the service that can be given through coupling among customer database, product database, geographic information database, and others. The core infrastructure is also the database which is integrated, perfect, and reliable. There are not enough researches on efficient way of data migration and integrating process and investigation of migrated data though trends of database in IT environment as above. In connection with this issue, we have made a model for data migration on scientific and technological contents and suggest the result of data migration process adapting that model. In addition, we verified migration's exhaustiveness, migration's consistency, and migration's coherence for investigation of migrated data and database. From the result, we conclude data migration based on proper model has a significant influence on the database consistency and the data values correctness and is essential to maintain high qualified database.

Analysis of judicial precedents cases regarding skin cancer from 1997 to 2017 in Republic of Korea

( Gwanghyun Jo ),( Su Hwan Shin ),( Won Lee ),( So Yoon Kim ),( Je-ho Mun ),( Soo Ick Cho ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Both medical disputes and the incidence of skin cancer are increasing in Korea. Objectives: To figure out the medical litigation related to skin cancer and propose a method to prevent the medical disputes Methods: Skin cancer-related judgments were searched by The Supreme Court of Korea’s Written Judgment Management System based on the keywords for skin cancer. The search system included sentenced cases at the Lower Courts, the Appellate Courts, and the Supreme Court from 1997 to 2017 Results: Seven cases were selected as the litigation cases related to skin cancer. Four cases (57.1%) presented malignant melanoma, while the rest presented squamous cell carcinoma, metastatic skin cancer, and peripheral T cell lymphoma (1 case in each). Four cases resulted in death from cancer metastasis, and 3 cases presented as sequelae. The legal issues related to the medical disputes could be categorized as follows: misdiagnosis, delayed diagnosis, performance error, and lack of informed consent. Delayed diagnosis and lack of informed consent were the most common issues (n=4) in the precedents. Five cases (71.4%) were sentenced the awarded amounts to the plaintiff, including 2 cases of settlement decision. The average awarded amount was 42,553,644±27,567,455 Korean Won. Conclusion: Physicians should pay attention to the cases of the skin cancer to prevent medical malpractice and disputes.

H₂O₂로 산화적 스트레스가 유도된 각질 형성 세포에서 흑삼 추출물의 항노화 효과

안소희(So Hee Ahn),이계원(Gye Won Lee),권득상(Deuk Sang Kwon),신현중(Hyun Joong Shin),조영호(Young Ho Cho) 한국식품영양과학회 2021 한국식품영양과학회지 Vol.50 No.10

본 연구에서는 95°C에서 6번 증숙하여 제조한 흑삼 추출물의 항산화 활성과 피부세포에서 산화적 스트레스로부터 보호 효과를 확인하고, 항산화 효소 발현, 주름개선 및 보습관련 단백질 발현에 미치는 영향을 측정하였다. 흑삼 추출물(BGE-A6)의 항산화 활성을 평가하기 위하여 DPPH, ABTS, superoxide anion 라디칼 소거 활성 및 환원력을 측정하였다. 그 결과 증숙 후 흑삼 추출물이 증숙 전에 비하여 DPPH 라디칼 소거 활성은 4배, ABTS 라디칼 소거 활성은 5배 정도 항산화 활성이 증가하는 것으로 나타났다. 피부 각질 형성 세포에서 산화적 스트레스로부터 BGE-A6의 세포보호 효과를 측정하기 위하여 BGE-A6를 1시간 전처리하고 0.5 mM H₂O₂를 6시간 동안 처리하여 분석한 결과, H₂O₂ 처리로 증가된 ROS 생성이 BGE-A6를 100 μg/mL 농도로 처리한 경우 약 40% 정도 감소되는 것으로 나타났다. 또한, BGE-A6의 ROS 소거 효과를 규명하기 위하여 세포 내 존재하는 항산화 효소의 발현량을 western blot으로 평가한 결과 H₂O₂에 의해 유도된 산화 스트레스로부터 감소된 항산화 효소(HO-1, CAT, SOD)의 발현을 농도 의존적으로 회복시켰다. 또한, BGE-A6의 주름 개선 효과를 확인하기 위하여 콜라겐 발현 및 MMP-1 발현 억제 정도를 ELISA와 western blot으로 측정한 결과 0.5 mM H₂O₂를 처리하였을 때 감소된 콜라겐 생성량이 BGE-A6를 100 μg/mL 농도로 처리할 경우 H₂O₂ 처리에 의해 감소된 콜라겐 생성량을 약 20% 정도 회복시키는 것으로 확인되었다(P<0.05). 0.5 mM H₂O₂를 처리하였을 때 증가된 MMP-1의 생성이 BGE-A6 처리 시 농도 의존적으로 억제되는 것으로 나타났다. BGE-A6의 피부보습 관련 단백질 발현에 미치는 영향을 western blot으로 측정한 결과 HAS2와 AQP3 발현량 및 EGFR의 인산화를 처리 시 농도 의존적으로 증가시키는 것으로 나타났다. 결론적으로 피부세포에 H₂O₂를 처리하여 산화적 스트레스를 유도하였을 때 BGE-A6는 항산화 효소의 발현을 통해 세포보호 효과를 나타내고, AQP3, HAS2 및 콜라겐 단백질의 발현은 증가시키고 MMP-1의 발현을 감소시켜 피부보습 및 피부장벽 기능을 유지하는 것으로 사료된다. 또한, AQP3의 증가는 피부조직 및 피부세포막에 발현되는 EGF 수용체의 인산화를 증가시킴으로써 피부 건조에 대한 보호 효과도 있는 것으로 판단된다. 따라서 흑삼 추출물은 항산화 효과, 피부보습 및 장벽기능 유지를 통한 항노화 화장품 소재로 활용이 가능할 것으로 기대된다. In this study, black ginseng extract steamed six times at 95°C (BGE-A6) was evaluated for its antioxidant, anti-wrinkle, and skin moisturizing effects in human keratinocytes. When steamed six times at 95°C, the content of total ginsenosides including minor ginsenosides (Rg3, Rh4, Rk1, and Rg5) was the highest at 14.97 mg/g. The antioxidant properties of BGE-A6 were measured by using different in vitro antioxidant assays such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid, ABTS), and superoxide anion radical scavenging activity. The antioxidant activity of BGE-A6 was increased in a dose-dependent manner. A 2′,7′-dichlorofluorescin diacetate (DCFDA) assay and a western blot assay were performed to verify the reactive oxygen species (ROS) scavenging activity of BGE-A6 in H₂O₂-induced human keratinocytes. Pretreatment with 100 μg/mL of BGE-A6 inhibited intracellular ROS production by about 40%. Also, the expression of heme oxygenase-1 (HO-1), catalase (CAT), and superoxide dismutase-1 (SOD-1), very well-known as antioxidant enzymes, was increased by BGE-A6 in a dose-dependent manner. BGE-A6 was shown to significantly inhibit the expression of matrix metalloproteinase-1 and increase the production of type I collagen, thus confirming its anti-wrinkle activity (P<0.05). Furthermore, BGE-A6 significantly increased the phosphorylation of the epidermal growth factor receptors (EGFR) and the expression of moisturizing proteins, such as hyaluronic acid synthase 2 (HAS2) and aquaporin 3 (AQP3), indicating that it is effective in enhancing skin hydration. The results of this study suggest that BGE-A6 has potential for use as an effective compound in anti-aging cosmetics to address wrinkle formation and skin hydration.

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.

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.

산업장 근로자의 스트레스에 대한 한의계 연구경향

차윤엽 ( Yun Yeop Cha ),고연석 ( Youn Seok Ko ),이정한 ( Jung Han Lee ),정원석 ( Won Suk Chung ),신병철 ( Byung Cheul Shin ),전찬용 ( Chan Yong Jeon ),고호연 ( Ho Yeon Go ),선승호 ( Seong Ho Sun ),장보형 ( Bo Hyoung Jang ),송윤경 한방재활의학과학회 2013 한방재활의학과학회지 Vol.23 No.2

Objectives : The purpose of this study is to explore the trends of Korean medical study on stress in the industrial worker. Methods : We received numbers of the studies about stress in the industrial worker from 6 Korean web databases, using key words such as ‘Industry AND Stress’, ‘Oriental medicine AND Stress’, ‘Worker AND Stress’, ‘Workplace AND Stress’. We received 12 research papers and they were analyzed and the journals, the authors, the contents of 3 classification of those research papers. Results : Among them, we had 6 reviews of Dept. of preventive medicine and Dept. of third medicine, college of Korean Medicine, Won-kwang University, and the rest of them were 6 reviews. We had 4 reviews of Korean Journal of Oriental Preventive Medical Society, 2 reviews of the Journal of Traditional Korean Medicine, 2 reviews of Journal of Oriental Neuropsychiatry and so on. According to the contents of reviews, we had 7 reviews of correlation of industrial worker and stress, 4 reviews of cause on the industrial worker’s stress and 1 case report. Conclusions : We reviewed the trends of Korean medical study on stress in the industrial worker. The stress in the industrial workers were related with the type of occupation, social psychology, drinking, smoking, the satisfaction of job, the harmony of organization.And we knew that the musculoskeletal pain was related to the industrial worker’s stress. In the future, abundant case studies, follow-up trials and RCTs should be done about the industrial worker’s stress.