Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

심근 허혈-재관류 백서 모델에서 mitogen-activated protein kinase 활성화에 대한 α-lipoic acid의 효과

김연경,박은미,최준호,윤경호,유남진,이은미,김남호,정진원,김민선,박병림,오석규 圓光大學校 醫科學硏究所 2006 圓光醫科學 Vol.21 No.1

다핵균 및 단핵균으로부터 고protease 생산균주의 Screening

송상호,임현수,최명락,유은정,김성영 여수대학교 1998 論文集 Vol.13 No.2

4 multinucleate and 7 mononuclear fungi were investigated for screening of high protease productive strains. The protease activity of mononuclear strains was generally greater than that of multinucleate strains. For acid proteinase, Aspergillus awamori AOK 1007 and Asp. oryzae shoyu 2 as mononuclear strains were selected in glucose-polypeptnoe medium. For acid carboxypeptidase, two mononuclear strains were screened as Asp. awamori AOK 1007 and Asp. usamii mut. shirousami AOK 1011 in glusose-sodium glutanate medium. In this result, mononuclear fungi appeared higher protease production than that of multinuclear fungi. So, mononuclear fungi may gave many merits to improve protease activity by using of mutation or cell fusion technology.

자궁암세포(HeLa)에 대한 사군자탕과 수종 항암제의 병용투여 효과

은재순,김현욱,소준노,오찬호,이송재 又石大學校 1993 論文集 Vol.15 No.-

The studies were conducted to investigate the combined effects of Sa Kunja Tang(SKT) and several anti-cancer drugs. The effects of SKT and several anti-cancer drugs on the proliferation of HeLa cells, human cervical cell line, was estimated by MTT colorimetric assays. The SKT extract inhibited the proliferation of HeLa cell at 10^-4g/ml. The inhibitory action of the mitomycin C(MMC), mercaptopurine(MCP) and 5-fluorouracil(5-Fu) treated group, respectively, on the proliferation of HeLa cell was increased by the SKT. When the mice were treated by the MMC, the number of leukocyte was decreased significantly at the 1st and 3rd day, but recovered at the 7th day. In the groups of the MMC treated with the SKT, the number of leukocytes was increased significantly than the group of the MMC treated only at the 3rd day. The SKT extract decreased the thymus weight of mice. The SKT extract increased the number of plaque forming cells(PFC), but the MMC treated group decreased the number of PFC. The combined treatment of MMC and the SKT increased the number of PFC significantly than the MMC treated group. The SKT extract increased the proliferation of T cells, but the MMC treated group decreased the proliferation of T cells. The combined treatment of MMC and the SKT increased T cell proliferation significantly than the MMC treated group. In conclusion, the results presented in this paper suggest that the SKT extract can decrease the dose of anti-cancer drugs on HeLa cell, and recover the side dffects of the MMC, such as leukopenia and immunosuppresion, without any intercalating the anti-proliferative action of the MMC in vivo.

Effects of 17β-estradiol on colorectal cancer development after azoxymethane/dextran sulfate sodium treatment of ovariectomized mice

Song, Chin-Hee,Kim, Nayoung,Lee, Sun Min,Nam, Ryoung Hee,Choi, Soo In,Kang, So Ra,Shin, Eun,Lee, Dong Ho,Lee, Ha-Na,Surh, Young-Joon Elsevier 2019 Biochemical pharmacology Vol.164 No.-

<P><B>Abstract</B></P> <P>Estrogen is known to have a protective effect in colorectal cancer (CRC) development. Previously, we reported the anti-inflammatory and antitumorigenic effects of 17β-estradiol (E2) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated male mice. The aim of this study was to investigate whether ovariectomy in a female AOM/DSS mouse model increases colorectal tumorigenesis and whether tumorigenesis is reduced by estrogen supplementation after ovariectomy. Clinical symptoms and histological severity of colitis and the levels of inflammatory mediators were evaluated in the colon of AOM/DSS-treated ovariectomized (OVX) mice. The levels of E2, myeloperoxidase (MPO), and NF-κB-dependent cytokines (interleukin (IL)-1β and IL-6) were measured by ELISA. Furthermore, quantitative real-time (qRT) PCR and Western blot analysis were performed. Ovariectomy did not aggravate AOM/DSS-induced colitis at 2 weeks. At weeks 10 and 16, ovariectomy significantly increased tumor number and incidence rate in only the proximal colon after AOM/DSS treatment (F_AOM/DSS vs OVX_AOM/DSS), and these increases were significantly reduced by E2 supplementation (OVX_AOM/DSS vs OVX_AOM/DSS/E2). However, ovariectomy did not affect CRC development in the distal colon (F_AOM/DSS vs OVX_AOM/DSS). At week 2, E2 administration to AOM/DSS-treated OVX mice attenuated the histological severity of colitis by decreasing the protein and/or mRNA levels of estrogen receptor alpha (ERα) and NF-κB-related mediators (i.e., COX-2, TNF-α, and IL-6) and by enhancing estrogen receptor beta (ERβ) and nuclear Nrf2 protein expression and the mRNA expression of related antioxidant enzyme genes (i.e., HO-1, GCLC, GCLM, and NQO1). Endogenous estrogen in females protects against the development of proximal colon cancer, and exogenous E2 replacement in OVX female mice showed protective effects against AOM/DSS-induced colitis and carcinogenesis. The mechanism could involve modulating ERs-, NF-κB- and Nrf2-mediated pathways.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

자궁경부암 선별검진을 위한 PapSure 검사에서 Spiral Brush의 유용성에 관한 연구

송언호,김어진,명나혜,박충학 대한부인종양 콜포스코피학회 2002 Journal of Gynecologic Oncology Vol.13 No.4

2001년 12월 1일부터 2002년 6월 30일까지 만 7개월 간 단국대학교의료원 산부인과 부인종양 Clinic에서 자궁경부암 선별검진을 위한 PapSure 검사를 시행한 환자 중 SpiraBrush Cx_® 검사를 실시한 33예를 대상으로 하여, 기존의 Papanicolaou 세포진 검사의 진단과 SPiraBrush Cx_®)에 의한 Papanicolaou 세포진 검사의 진단 및 최종적인 병리조직학적 진단을 비교, 분석하여 SpiraBrush Cx_®에 의한 세포진 검사가 생검에 의한 조직검사를 대체할만한 유용성이 있는지 그 여부를 조사하기 위하여 본 연구를 시행하여 다음과 같은 결과를 얻었다. 1. 환자의 연령별 분포는 21세에서 70세까지였으며 40-49세 군이 42%로 가장 많은 분포를 보였고, 평균 연령은 45.7세였다. 2. 환자의 평균 임신횟수는 3.6회였으며, 평균 출산횟수는 2.0회였다. 3. 기존의 자궁경부 세포진 검사(Conventional Papanicolaou cytology)상 진단이 음성으로 나온 경우가 19예(57.6%)였고, ASC를 포함하여 양성으로 나온 경우가 14예(42.4%)였다. 자궁경부 형광경진 검사(Speculoscopy)에서는 음성이 13예(39.4%)였고, Suspicious 진단을 포함하여 양성으로 나온 경우가 20예(60.6%)였다. SpiraBrush Cx®에 의한 세포진 검사(SpiraBrush Cx_® Papanicolaou cytology)에서는 진단이 음성인 경우가 8예(24.2%)였고, ASC를 포함하여 양성으로 나온 경우가 25예(75.8%)였다. 4. 병리조직학적 검사의 진단은 음성 12예(52.2%), 저등급 편평상피내병변(Low-grade Squamous Intraepithelial Lesion: 이하 LSIL이라 함) 2예(8.7%), 고등급 편평상피내병변(High-grade Squamous Intraepithelial lesoin: 이하 HSIL이라 함) 3예(13.0%), 편평세포암(Squamous Cell Carcinoma: 이하 SCC라 함) 6예(26.1%)였다. 5. 검사 결과의 양성판정 기준을 세포진 검사의 경우는 ASC 이상으로 하고 조직학적 검사의 경우는 LSIL이상으로 정할 경우, 기존의 Papanicolaou 세포진 검사의 민감도는 63.6%이고 특이도는 66.7%였으며, SpiraBrush Cx_®세포진 검사의 민감도는 90.9%이고 특이도는 33.3%였다. 이상의 결과로 미루어 볼 때 연구 대상의 숫자가 적어서 통계학적인 유의성은 찾을 수 없으나 SpiraBrush Cx_®가 자궁경부암 선별검진에서 생검에 의한 자궁경부의 조직학적 진단을 대체하지는 않는다고 판단된다. 그러나 기존의 Papanicolaou 세포진 검사의 민감도가 63.6%인데 반하여 SpiraBrush Cx_® 세포진 검사의 민감도는 90.9%로 훨씬 더 높았으며 이로 인해 SpiraBrush Cx_® 세포진 검사의 특이도는 33.3%로 훨씬 낮았는데 이는 매우 흥미있는 사실로서 향후 많은 Data로 더욱 연구하여 진위를 구분함이 필요하리라 사료된다. 또한 본 연구에서는 SpiraBrush Cx_® 기구의 강모들이 단단하고 날카로워서 기저막층까지의 조직과 상피층 세포들을 탈락시키면서 많은 출혈을 초래하여 슬라이드 판독에 어려움을 주었고 이는 연구 결과에 지대한 영향을 미쳤으리라고 생각되는 바, 이러한 출혈로 인한 요인을 최대한 배제하기 위하며 향후 SpiraBrush Cx_® 세포를 채취한 후 최신의 자궁경부 세포진 검사법인 ThinPrep Pap Test를 이용하거나 조직표본을 만들기 위한 Cellblock 기법을 사용하여야 한다고 판단된다. Objective : The purpose of this study was to investigate the clinical efficacy of a new stiff bristled spiral shaped brush (SpiraBrush Cx_(??))∼in) PapSure Test for cervical cancer screening, by comparing SpiraBrush Cx_(??) cytologic diagnoses with conventional Papanicolaou cytologic diagnoses and final histologic diagnoses. Methods : This study was performed in Gynecologic Oncology Clinic of Department of Obstetrics and Gynecology at Dankook University Medical Center from December I, 2001 to June 30, 2002. Thirty three cases who underwent PapSure Test (Pap cytology t Speculoscopy) were analyzed. SpiraBrush Cx_(??) Papanicolaou cytologic diagnoses were compared with conventional Papanicolaou cytologic diagnoses and histologic diagnoses as a reference standard. Results : Followings are the results summarized. 1. Age distribution was between 21 and 70. The mean age was 45.7 years. 2. The mean gravidity was 3.6 and the mean parity was 2.0. 3. There were 19 (57.6%) conventional Papanicolaou cytologic diagnoses of Negative, and 14 (42.4%) of Positive including ASC. There were 13 (39.4%) Speculoscopy diagnoses of Negative, and 20 (60.6%) of Positive including Suspicious. There were 8 (24.2%) SpiraBrush Cx_(??) cytologic diagnoses of Negative and 25 (75.8%) of Positive including ASC. 4. There were 12 (52.2%) histologic diagnoses of Negative, 2 (8.7%) of LSIL, 3 (13.0%) of HSIL, and 6 (26.1%) of SCC, according to the criteria of TBS, 2001. 5. For detecting LSIL or worse lesions, conventional Papanicolaou cytologic test yielded sensitivity of 63.6% and specificity of 66.7%. On the other hand, SpiraBrush Cx_(??) cytologic test yielded sensitivity of 90.9% and specificity of 33.3%. Conclusion : SpiraBrush Cx_(??) cytologic diagnosis does not seem to have clinical efficacy replacing the histologic diagnosis by punch biopsy in cervical cancer screening in this study. But further studies using ThinPrep Pap Test or Cellblock techniques with large data will be required and anticipated.

HYPER 빔창주위의 열유동 해석에 의한 안전성 평가에 관한 연구

송민근,최진호,주은선,송태영 경상대학교 생산기술연구소 2000 生産技術硏究所論文集 Vol.16 No.-

A spent fuel problem has prevented the nuclear power from claiming to be a completely clean energy source. The nuclear transmutation technology to incinerate the long lived radioactive nuclides and produce energy during the incineration process is believed to be one or the best solutions. HYPER(Hybrid Power Extraction Reactor)is the accelerator driven transmutation system which is being developed by KAERI(Korea Atomic Energy Research Institute). Some major feature of HYPER have been developed and employed. On-power fueling concepts are employed to keep system power constant with minimum variation of accelerator power. A hollow cylinder-type metal fuel is designed for the on-line refueling concept. Lead-bismuth(Pb-Bi) is adopted as a coolant and Spallation target material. One of the issues related to the HYPER target system is the thermal and mechanical loads imposed on the Pb-Bi and the beam window. FLUENT is used for thermal-hydraulic calculation, and finally stress calculation is performed by ANSYS. A beam condition such as current is varied. The initial velocity of Pb-Bi is also varied.

Classification과 Ordination에 依한 俗離山 森林群集의 分析

兪在殷,宋鎬京 忠南大學校 環境問題硏究所 1989 環境硏究 Vol.7 No.-

Vegetational data from Mt Sokri in central Korea were analysed in relation to 17 environmental variables. Two multivariate methods were applied two-way indicator species analysis (TWINSPAN) for classification and detrended canonical correspondence analysis (DCCA), a recent technique which extracts ordination axes that can be related to environmental factors. The relationship between the distribution of dominant species of forest vegetation and soil condition in Mt Sokri was investigated by analyzing altitude and soil nutrition gradient. Quercus mongolica forest was distributed in the high altitude and good nutrition area, Quercus serrata-Acer pseudo-sieboldianum forest in the medium altitude and good nutrition area, Quercus variabilis and Quercus serrata forest in the medium altitude and medium nutrition area, and Pinus densiflora forest in the low altitude and poor nutrition area. Quercus mongolica forests were distributed in the xeric parts of northern part of warm-temperate deciduous boardleaf forest and in the mesic parts of cool-temperate deciduous boardleaf forest in Korea. The dominant compositional gradient related to altitude.

자작나무 및 벚나무 껍질추출물이 抗알레르기 效果에 대한 實驗的 연구

朴殷秀,辛民敎,宋昊埈 대한본초학회 1998 大韓本草學會誌 Vol.13 No.2

Anti-allergic effects resulted by Cortex Betula Platyphyllae(CB) or Cortex Pruni Serrulatae(CP) extract were observed from the mast cell before or after treatment with Compound 48/80, anti-DNP IgE and Substance P, respectively. In addition, it was investigated on inhibition of IgE release from B cell line and spleen cell after treatment with two extracts. The results were as follows ; 1. CB or CP extract inhibited Anaphylaxis shock induced by intraperitoneal injection with Compound 48/80. 2. Both extracts inhibited histamine release from the mast cell after treatment with Compound 48/80, anti-DNP IgE or Substance P. 3. The IgE release stimulated from spleen cell of mouse after treatment with LPS or LPS plus IL-4 was inhibited with increasing concentrations of extracts. The level of IgE release was significantly much lower in treatment of CB extract than that of CP extract when compared to high concentrations of extracts. 4. The IgE release from U266B1 of human myeloma was inhibited dependently to the concentrations of CB and CP extract, respectively, and CB extract inhibited effectively more IgE release than that after treatment of CP extract.

수지상세포의 방사선 저항성에 대한 연구

김은실,김종순,이명호,범희승,민정준,정환정,김성민,허영준,송호천,이제중 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.3

목적 : 림프구와 비교되는 수지상 세포의 방사선 민감성을 보기 위하여 본 연구를 시행하였다. 대상 및 방법 : 말초혈액에서 분리한 T 림프구에 0 Gy, 10 Gy, 30 Gy의 방사선을 조사하고 4시간 후에 유세포 분석기를 이용하여 선량별 세포고사 빈도를 관찰하였다. 또한 조혈모세포에서 미성숙 및 성숙 수지상 세포를 단계적으로 분리 배양하여 각각 0 Gy, 10 Gy, 30 Gy, 100 Gy의 방사선을 조사하고 4시간, 24시간 그리고 48 시간 후에 선량별 세포고사 빈도를 관찰하였다. 사이토스핀(cytospin)슬라이드에 림프구와 미성숙 및 성숙 수지상세포를 3×104개 씩 분주하고 May Grunwald-Giemsa 염색한 후, 광학 현미경 하에서 각각의 세포군 당 100개의 세포에서 세포 면적당 핵의 면적 비를 측정하였다. 결과 : 림프구에서는 방사선조사 선량별로 세포고사 빈도가 유의하게 증가하였으나, 수지상 세포에서는 그 분화정도나 방사선조사 선량에 따른 세포고사의 빈도차이가 없었다. 또한 수지상 세포는 방사선선량과 관계없이 용량에 의존적으로 강력한 T-세포 자극능을 보였다. 림프구의 세포에 대한 핵의 면적 비는 미성숙 및 성숙 수지상세포의 세포에 대한 핵의 면적 비보다 현저히 큰 반면, 두 가지 수지상세포간에 유의한 차이는 없었다. 결론 : 수지상세포는 그 분화도와 상관없이 림프구에 비하여 방사선 저항성을 나타내었고, 이는 세포의 형태적 차이에 따른 표적의 크기와 관련이 있을 것으로 생각되며, 향후 분자 생물학적인 연구의 기초 자료로 활용할 수 있을 것으로 생각된다. Purpose : To evaluate radiation sensitivity of dendritic cells in comparison with lymphocytes. Materials and methods : T lymphocytes captured from peripheral blood were irradiated by 0 Gy, 10 Gy, 30Gy. Apoptosis was measured by flowcytometry for staining of Annexin V 4 hours after irradiation. Immature and mature dendritic cells processed from blood hematopoietic stern cell were irradiated by 0 Gy, 10 Gy, 30 Gy, 100 Gy respectively and apoptosis was measured by flowcytometry with time difference as 4h, 24h and 48h after irradiation. Morphometric analysis by percent nucleus was measured in three cell groups, also. Results : Lymphocytes showed radiation sensitivity by increasing apoptotic fraction according to radiation dose. However, both mature and immature dendritic cells showed consistent fraction of apoptosis in spite of increasing radiation dose. Percent nucleus ratio is significantly higher in lymphocytes than that of mature or immature dendritic cells. Stimulation of T-cell by dendritic cells was not changed after irradiation. Conclusion : Dendritic cells showed radioresistance which was associated with small size of nucleus in comparison with lymphocytes and this result would be used as a basal data of radio-labelling for the cellular trafficking studies in nuclear medicine fields.