Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

Lee, Moon Hee,Han, Min Ho,Lee, Dae-Sung,Park, Cheol,Hong, Su-Hyun,Kim, Gi-Young,Hong, Sang Hoon,Song, Kyoung Seob,Choi, Il-Whan,Cha, Hee-Jae,Choi, Yung Hyun UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.39 No.2

<P>In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and gamma H2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keapl) expression. Notably, these events were eliminated by transient transfection with Nrf2-specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal-regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO-1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2,-induced oxidative cytotoxicity.</P>

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

Lee, Yoo-hwan,Kim, Jung-hee,Song, Choon-ho,Jang, Kyung-jeon,kim, Cheol-hong,Kang, Ji-Sook,Choi, Yung-hyun,Yoon, Hyun-Min KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.1

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

부산·울산·경남지역 직업병 감시체계

김정일,김병권,김정원,채창호,이철호,강동묵,김지홍,김진하,김영욱,이영하,이지호,김정호,윤형렬,유철인,정백근,장태원,김운규,윤동영,강진욱,김종은,안진홍,이동준,장준호,이광영,송혜란,최영희,이용환,조병만,최홍렬,고상백,김은아,이유진,홍영습,정갑열,김정만,김준연 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.1

Objective: Occupational medicine specialists in the Busan, Ulsan and Kyung-Nam areas established an area-based occupational disease surveillance system and used this system to collected case information for the purpose of preventing occupational diseases Methods: l l hospital participated in this system. The authors selected five main diseases, which were hand-arm vibration syndrome (HAVS), work-related musculoskeletal disorder (WRMSD), occupational asthma, occupational skin disease and occupational and occupational lung cancer and established their case definitions. All cases were reported on the web, and real time analysis was conducted. Results: Between April 2001 and April 2003, 192 cases of HAVS, 118 cases of WRMSD, 33 cases of occupational asthma, 17 cases of occupational skin disease and 17 cases of occupational lung cancer (for a total of 377 cases of these five main diseases) were reported. most of the HAVS cases came from shipbuilding, and 172 of them (92.7%) were associated with grinding. Of the four main types of WRMSD, carpal tunnel syndrome (CTS) was the most prevalent with 46 cases and shipbuilding was also the main industry involved (83.9%). The ergonomic risk factors involved mainly associated with the hand. In 19 (57.6%) and 4 (12.1%) cases of occupational asthma, the agents involved. The causative agents of occupational lung cancer included Cr, welding fume, PAH, Ni, etc. 10(58.8%) of the cases were diagnosed as squamous cell carcinoma and 5(29.4%) as adenoma. Conclusion: This result showed that an area-based occupational disease surveillance system might provide an effective method of evaluating the prevalence of such diseases, however the Busan, Ulsan and Kyung-Nam provinces are too large to be treated as individual areas. Therefore, the authors suggest that each province should establish its own surveillance system.

진피 메탄올 추출물의 활성산소종 생성을 통한 인체 백혈병 세포의 apoptosis 유발

김가희(Ga Hee Kim),이문희(Moon Hee Lee),한민호(Min Ho Han),박철(Cheol Park),홍수현(Su Hyun Hong),최영현(Yung Hyun Choi) 한국생명과학회 2013 생명과학회지 Vol.23 No.8

진피(Citri Pericarpium)의 항암작용 기전 해석을 위하여 U937 백혈병 세포의 apoptosis 유발에 미치는 메탄올추출물(EMCP)의 영향을 조사하였으며, apoptosis 조절에 중요한 몇 가지 유전자들의 발현 및 활성 변화, ROS의 생성 변화를 조사하였다. EMCP 처리에 의한 U937 세포의 증식 억제는 apoptosis 유도와 연관성이 있음을 DAPI 염색을 통한 apoptotic body 출현의 증가 및 Flow cytometry 분석에 의한 Sub-G1기 세포 빈도의 증가로 확인하였다. EMCP 처리에 의한 apoptosis 유도에서 Bax 발현 증가, caspases의 활성 및 PARP의 단편화 등이 동반되었으며, ROS 생성의 증가와 연관성이 있었다. 산화적 손상에 대해 세포나 조직을 보호하는 역할을 하는 것으로 알려진 세포 내 항산화 효소인 HO-1의 발현이 EMCP의 처리에 의해 증가되었으나 ROS 생성 억제제인 NAC의 전처리에 의해 감소된 HO-1의 발현은 전사인자인 Nrf2의 핵으로의 이동 억제와 관련되어 있었다. 이상의 결과에서 EMCP 처리에 의한 U937 세포의 apoptosis 유발에는 ROS 생성의 증가와 pNrf2에 의해 조절되는 HO-1의 발현 증가가 중요한 기전으로 작용한다는 것을 알 수 있었다. 이러한 자료는 진피의 항암기전 해석을 이해하는데 중요한 기초자료로서 활용될 수 있을 것으로 생각된다. Citri Pericarpium is one of the most commonly used traditional herbal medicines in Korea, China, and Japan. Its extracts have many properties including the treatment of indigestion and inflammatory respiratory syndromes such as bronchitis and asthma. However, the underlying molecular mechanisms of anti-cancer activity and molecular targets are not fully understood. In this work, we investigated the anti-proliferative activity of Citri Pericapium (EMCP) methanol extract on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death using U937 human leukemia cells in vitro. EMCP treatment decreased cell proliferation in a dose-dependent manner following an increase of the sub-G1 phase, the down-regulation of Bax proteins, the activation of caspases, the degradation of poly (ADP-ribose) polymerase proteins (PARP), and the induction of ROS generation. However, the quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the EMCP-induced apoptosis effects. In addition, heme oxygenase-1 expression also recovered by inhibiting the nuclear translocation of phosphorylated NF-E2-related factor 2. Taken together, our data indicate that ROS are involved as key mediators in the early molecular events in the EMCP-induced apoptotic pathway.

Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts

Lee, Moon Hee,Cha, Hee-Jae,Choi, Eun Ok,Han, Min Ho,Kim, Sung Ok,Kim, Gi-Young,Hong, Su Hyun,Park, Cheol,Moon, Sung-Kwon,Jeong, Soon-Jeong,Jeong, Moon-Jin,Kim, Wun-Jae,Choi, Yung Hyun Spandidos Publications 2017 International journal of molecular medicine Vol.39 No.3

<P>Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)-like activity and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical scavenging activity were determined. We also investigated the cytoprotective effects of morin against hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in V79-4 Chinese hamster lung fibroblasts. Our results demonstrated that morin had strong scavenging effects against ABTS' radicals with enhanced SOD activity, which varied in a dose-dependent manner. Morin was found to reduce H2O2-induced intracellular reactive oxygen species generation and nuclear DNA damage, and it recovered cell viability damaged by H2O2 via inhibition of mitochondrial dysfunction-mediated apoptosis. Notably, the treatment of V79-4 cells with morin markedly enhanced the expression of heme oxygenase-1 (HO-1) but not quinone oxidoreductase-1, which was associated with the increased expression and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the downregulation of Kelch-like ECH-associated protein 1 expression. Based on our findings, we conclude that morin effectively ameliorated oxidative stress-induced DNA damage through intrinsic free radical scavenging activity and activation of the Nrf2/HO-1 pathway.</P>

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

8×8 bit 직병렬 플러쉬 승산기의 설계 및 구현

홍경호,김철우,서희돈 嶺南大學校工業技術硏究所 1992 연구보고 Vol.20 No.2

Multiplier is a very important arithmetic component which performs an essential function in many digital computing systems. In this paper, the flush multiplier is proposed, which each data bit is come in serially is multiplied by coefficient bits, and is capable of k-bits production in k clocks. The proposed multipliers are able to perform the parallel multiplication fast and area-efficiently, and they are faster then the parallel multiplier using some algorithm which has been known as very fast algorithm.

구리 지역에서 조사한 고혈압의 인지도, 치료률 및 관리률

홍철호,김순길,홍택원,이제,신진호,이재웅,김경수,김정현,임헌길,이방헌 대한간질학회 2003 대한간질학회지 Vol.9 No.1

치간 삭제 후 불소 또는 수산화인회석 도포 시 재광화 및 탈회억제에 관한 연구

홍현실,김호영,성지영,조진형,김상철 대한치과교정학회 2010 대한치과교정학회지 Vol.40 No.4

치간 삭제 후 재광화 및 치아우식 예방법을 찾기 위한 노력의 일환으로 1.23% 인산화불소 젤 또는 5%, 10% 수산화인회석함유 페이스트를 치간 삭제된 법랑질 표면에 도포하였고, 그 후 젖산탈회용액으로 처리하였다. 법랑질 표면의 재광화 및 탈회 후 결정구조 변화를 주사전자현미경으로 관찰하고 칼숨, 인, 불소 함량 등의 변화를 energy dispersive X-ray spectroscopy 로 분석해서 비교하였다. 치간 삭제 후 5%, 10% 수산화인회석함유 페이스트를 도포한 군에서 칼숨과 인 합량이 증가하였고, 1.23% 인산화불소 젤 도포 군에서는 불소 함량이 증가하였다. 또한 모든 재광화 제제에서 법랑질 표면이 매끄럽고 부드러워졌으며 결정구조가 작고 치밀해짐을 관찰할 수 있었다. 10% 수산화인회석합유 페이스트로 재광화한 군은 탈회 후에도 칼슐과 인 함량이 증가된 채로 유지되었고, 5% 수산화인회석합유 페이스트로 재광화한 군은 탈회 후 인 함량이 증가된 채로 유지되었다. 치간 삭제 후 탈회 처리 시 대조군의 법랑질은 파괴양상이 심해 거친 굴곡으로 이루어진 불규칙한 표면 상태를 나타내었으나 불소 및 수산화인회석으로 재광화한 군에서는 법랑질의 파괴양상이 적어 작은 결정입자들과 미세공극이 유지되었다. Objective: The aim of this study was to evaluate the effect of remineralization and inhibition to demineralization after fluoride gel (acidulated phosphate fluoride, APF) or hydroxyapatite (HAp) paste application on interdentally stripped teeth. Methods: After interdental stripping, 1.23% APF or 5%, 10% HAp paste were applied for 7 days for remineralization. Afterwards, teeth were exposed to lactate carbopol buffer solution for demineralization. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) were used to compare change in surface contents and crystal structures after remineralization, and then after demineralization. Results: EDS analysis indicated that calcium (p < 0.001) and phosphate (p < 0.01) contents were increased after 10% HAp paste application on stripped enamel, calcium (p < 0.05) and phosphate (p < 0.01) contents were increased after 5% HAp paste application, and fluoride (p < 0.01) contents were increased after 1.23% APF application. SEM image showed that enamel surfaces became smoother and crystal structures became small and compact after APF or HAp application. After demineralization, calcium (p < 0.05) and phosphate (p < 0.05) contents remained increased on the enamel remineralized with 10% HAp paste, and phosphate (p < 0.05) contents remained increased on the enamel remineralized with 5% HAp paste. After demineralization, surfaces looked less destroyed in the enamel remineralized beforehand than those of the control, and small pores between crystal structures, formed by remineralization were remained. Conclusions: Hydroxyapatite paste and fluoride gel were helpful to remineralize and inhibit deminerlization on stripped enamel.

한우에서 인공유발된 제2위내 이물의 초음파상

김명철,변홍섭,박명호,박종오,김종만 충남대학교 수의과대학 동물의과학연구소 1997 動物醫科學硏究誌 Vol.5 No.-

This study was performed to determine the ultrasonographic appearance of the reticulum in the cattle according to the intake of foreign body. Metal balls, magnets, gravels and rubber were administered to a 13 months old female Korean native cattle. After foreign bodies in the reticulum were ascertained, foreign bodies were observed by ultrasonography. The ultrasonographic values in this study can be used as reference for the diagnosis of foreign body of the reculum in cattle.