Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells

Joo Heon Kim,김경민,Jin Uk Jeong,Jong-Ho Shin,신재민,방기태 대한신장학회 2019 Kidney Research and Clinical Practice Vol.38 No.3

Background: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. Methods: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. Results: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. Conclusion: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

Regulatory Effect of Matcha Green Tea on Fine Dust-Exposed Cytotoxicity in Respiratory System

Jong Min Kim,Jong Hyun Moon,Min Ji Kim,Hyo Lim Lee,Hye Rin Jeong,Min Ji Go,Tae Yoon Kim,Seung Gyum Joo,Jong Cheol Kim,Ho Jin Heo 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

This study was performed to evaluate the protective effect of matcha green tea on particulate matter (PM)2.5-indued nasal and pulmonary cytotoxicity. The matcha green tea increased the cell viability and inhibited the ROS production in PM2.5-induced cytotoxicity in nasal RPMI2650 and pulmonary A549 cells. The matcha green tea regulated the expression of apoptosis, such as p-Akt, BCl-2, caspase-3, caspase-1 and HO-1, and inflammation, such as TLR4, TLR4 and Nrf2, in PM2.5-indued RPMI2650 cells. In addition, the matcha green tea showed regulatory effect of the apoptosis and inflammatory effect by increasing the BCl-2 and suppressing the caspase-3, TLR4, TNF-α and COX-2 in A549 cells. In addition, the matcha green tea suppressed antioxidant deficits by regulating the reduced GSH contents, SOD activities and MDA levels, and ameliorated the mitochondrial dysfunction by regulating the mitochondrial ROS production, mitochondrial membrane potential and ATP contents in pulmonary tissue. Ultimately, consumption of matcha green tea down-regulated the inflammatory proteins such as TNF-α, p-JNK, p-IκB-α, p-NF-κB and COX-2 in lung tissue.

연잎, 연자육, 연자방 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.4

연은 아시아 국가에서 음식과 약재로 널리 사용되는 재료이다. 본 연구에서는 연의 잎(leaf, NL), 자육(seed, NS), 자방(seedpod, NSP)으로부터 에탄올 추출물을 제조하고 이들의 항염증 활성과 작용기전을 규명하였다. 이들의 항염증 활성을 연구하기 위하여 LPS로 자극된 RAW 264.7 세포에서 nitric oxide (NO) 생산을 측정하였다. NL, NS, NSP는 세포 생존율에 영향을 주지 않으면서, 농도의존적으로 NO의 생산을 현저하게 저해하였으며, iNOS 및 COX-2와 같은 pro-inflammatory 중재자들의 단백질 발현을 감소시켰다. 또한, NL, NS, NSP는 MAPKs 단백질의 인신화를 감소시키고 NF-κB p65의 핵으로의 이동을 저해함으로써, 세 추출물에 의한 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 제시한다. 게다가, ROS의 생성이 세 추출물에 의해서 모두 저해되었으며, HO-1의 발현과 HO-1의 전사조절인자인 Nrf2의 핵으로의 이동이 증가되었다. 결론적으로, 이러한 연구결과는 연의 다양한 부위의 추출물인 NL, NS 그리고 NSP는 항염증 활성을 가지고 있으며, MAPKs, NF-κB, Nrf2/HO-1 등 다양한 신호경로를 통해 조절할 수 있음을 제시한다. Nelumbo nucifera, also known as sacred lotus, has mainly been used as a food throughout the Asian countries. In the present study, we prepared ethanol extracts from leaf (NL), seed (NS), and seedpod (NSP) of Nelumbo nucifera and investigated their anti-inflammatory activities in mouse macrophage RAW 264.7 cells. To evaluate the anti-inflammatory activities of NL, NS, and NSP, nitric oxide (NO) production was measured in LPS-stimulated RAW 264.7 cells. NL, NS, and NSP significantly reduced NO production in a dose-dependent manner without affecting cell viabilities. NL, NS, and NSP dramatically decreased the protein expression of pro-inflammatory genes such as iNOS and COX-2. NL, NS, and NSP also suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating they have their anti-inflammatory activities via regulating mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways. In addition, we analyzed the production of reactive oxygen species (ROS) by the treatment of NL, NS, and NSP. All extracts reduced ROS production in a dose-dependent manner. And also, they increased heme oxygenase-1 (HO-1) protein expression and the nuclear translocation of nuclear respiratory factor 2 (Nrf2). In conclusion, our results suggest that Nelumbo nucifera has its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

사과 추출물과 phloretin에 의한 항염증 활성

김근호(Geun-Ho Kim),이은주(Eun-Joo Lee),류승민(Seung-Min Ryu),손호용(Ho-Yong Sohn),김종식(Jong-Sik Kim) 한국생명과학회 2021 생명과학회지 Vol.31 No.2

본 연구에서는 풋사과의 열수추출물(GAHW)과 에탄올추출물(GAE), 그리고 애사과 열수추출물(UAHW)을 제조하고 LPS로 활성화된 RAW264.7세포주를 이용하여 이들의 항염증 활성을 연구하였다. 모든 추출물이 세포생존율에는 영향을 미치지 않고 nitric oxide (NO) 생산을 저해하였으며, iNOS의 발현도 감소시켰다. 반면, UAHW만이 COX-2의 발현을 저해하였다. 또한 모든 추출물이 모든 MAPKs의 인산화를 감소시켰다. 모든 추출물이 ROS의 생산을 농도의존적으로 감소시켰으며, GAHW와 GAE에 의해 HO-1의 발현이 증가됨을 확인하였다. 또한, 사과 flavonoid인 phloretin과 phloridzin의 항염증 활성을 연구하였다. Phloretin은 농도의존적으로 NO의 생산을 저해하였으나, phloridzin은 NO 생산에 아무 영향이 없었다. 또한, phloretin은 iNOS와 COX-2 단백질의 발현을 감소시킨 반면, phloridzin은 두 단백질 발현에 영향을 주지 못하였다. 따라서, 이러한 연구결과는 사과 추출물은 MAPK 경로와 HO-1 경로를 조절함으로써 항염증 활성을 가지며, phloretin이 사과의 항염증 활성을 담당하는 파이토케미칼의 하나가 될 수 있음을 제시한다. In the present study, we prepared hot water extracts of green apple (GAHW) and unripe apple (UAHW), and ethanol extract of green apple (GAE), and investigated their anti-inflammatory activities in LPS-activated RAW264.7 cells. All extracts dramatically suppressed nitric oxide (NO) production in a dose-dependent manner in LPS-stimulated RAW264.7 cells without affecting cell viability. In addition, all extracts decreased the expression of iNOS, whereas UAHW only reduced the expression of COX-2. All extracts suppressed the phosphorylation of MAPKs (p38, ERK, and JNK) indicating all extracts show their anti-inflammatory activities via regulating MAPK pathway. Furthermore, all extracts reduced the production of reactive oxygen species in a dose-dependent manner and they increased the expression of heme oxygenase-I (HO-I) whereas UAHW could not. We also investigated whether apple flavonoids phloretin and phloridzin can have their anti-inflammatory activities in same in vitro model. Phloretin dramatically decreased NO production in a dose dependent manner without affecting cell viability, whereas phloridzin have no effects. Phloretin also reduced the expression of iNOS as well as COX-2, whereas phloridzin could not. Overall, these results suggest that apple extracts have their anti-inflammatory activities via regulating MAPKs and HO-1 pathways, and apple flavonoid phloretin can be one of phytochemicals responsible for anti-inflammatory effect of apple.

건조 상추 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.3

상추는 가장 선호하는 녹색 채소 중 하나이다. 상추는 폴리페놀성 화합물을 비롯한 다양한 성분을 함유하고 있으며, 항균, 항산화, 항염증 등의 생리활성을 가지고 있는 것으로 알려져 있다. 본 연구에서는 건조상추의 에탄올 추출물(DLE)을 제조하고 이들의 항염증 활성을 연구하였다. DLE의 항염증 활성을 측정하기 위하여 LPS로 활성화된 마우스 대식세포 RAW 264.7 세포주에서 nitric oxide (NO) 생성을 측정하였다. DLE는 세포주의 생존에는 영향을 미치지 않으면서 NO 생산을 현저하게 저해하였다. DLE에 의해 염증 유전자인 iNOS와 COX-2의 유전자와 단백질의 발현이 모두 감소하였으며, 6개의 염증관련 cytokine 유전자(IL-1α, IL-1β, IL-1F6, TNF-α, CSF2, 그리고 CXCL10)의 발현이 모두 감소하였다. 또한, DLE의 처리는 MAPKs 경로의 인산화를 모두 저해하였으며, NF-κB p65의 핵으로의 이동을 저해하였다. 이러한 결과는 DLE의 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 시사한다. 또한, DLE는 농도의존적으로 reactive oxygen species (ROS)의 생산을 저해하였으며, hemeoxygenase-1 (HO-1) 단백질의 발현을 증가시켰으며, HO-1의 전사조절인자인 Nrf2의 핵으로의 이동을 증가시켰다. 결론적으로, 이러한 연구결과는 DLE가 염증관련 유전자의 발현을 감소시키며, MAPKs, NF-κB, 그리고 Nrf2/HO-1 등 다양한 경로를 조절함으로써 항염증 활성을 가지는 것을 제시한다. Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including IL-1α, IL-1β, IL-1F6, TNF-α, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and NF-κB pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

케타민과 리도카인으로 시행한 소아 탈장 수술 2,230명

주종수,주현호,주인호,Joo, Jong Soo,Joo, Hyun Ho,Joo, In Ho 대한소아외과학회 2013 소아외과 Vol.19 No.2

Ketamine is a safe and effective drug for pediatric anesthesia, sedation and analgesia. We hoped to identify that surgeons could operate a pediatric hernia with the ketamine anesthesia without general anesthesia. The study was a consecutive case series of 2230 inguinal hernia patients aged 1 months to 17 years in a Joo's day-surgical clinic during 11-year period. The patients had pediatric inguinal hernia surgery without general anesthesia under the day-surgery system. We retrospectively analyzed the medical record of patients who were registered with the Diagnosis Related Group (DRG) system. All patients received ketamine (5mg/kg) and atropine (0.01mg/kg) intramuscularly before surgery. After anesthesia, we injected 1~2% lidocaine (Less than 5ml) subcutaneously at the site of incision and started operation. The surgical method was the high ligation method of the hernia sac.) In total 2230 patients, male were 1756 and female were 474. 2076 patients were a unilateral inguinal hernia at the time of surgery and 154 were bilateral hernia patients. Less than three months, depending on the age of the patients was 391, and less than 12 months the patient was 592 people (26.5%). After surgery, there were no accidents or long term complications associated with ketamine anesthesia. We think the surgeon can safely do the pediatric inguinal hernia surgery using ketamine and lidocaine without anesthesiologist through 11 years of our surgical experiences.

혐기성 변성 아크릴계 접착제의 제조 및 접착 특성

주혁종,오인석,권호길,최돈묵 忠南大學校 産業技術硏究所 1991 산업기술연구논문집 Vol.6 No.2

An experimental study was performed to prepare the anaerobic acrylic adhesives with TEGDMA(Trietylene Glycol Dimethacrylate), acrylic acid, p-benzoquinnone and CTBN(Carboxyl Terminated Butadiene Nitrile) To characterize the anaerobic modifided acrylic adhesives, tensile shear adhesion strength, DSC, FT-IR, water resistance, chemicals resistance and oil resistance of adhesives were tested. The results obtained in this study could be summerized as follows; 1. Tensile adhesion shear strength was increased with increasing the adding amounts of p-benzoquinone up to 75kgf/㎠ when 0.163wt% added. 2. After a water resistance test for 72hrs, tensile shear adhension strength maintenance was dominant(about 72%) in the C-3 as compared with the others and alkaline solution resistance of adhesives was excellent on the whole as compare to acid solution. 3. The gasoline, light oil resistance of adhesives were very good enough that could be used in the field of mechanical connecting parts.

자궁내막에 발생한 점막 연관 림프조직 (MALT) 림프종 1예

전균호,조현진,박성균,김천복,김대연,김종혁,김용만,김영탁,목정은,남주현 대한부인종양 콜포스코피학회 2003 Journal of Gynecologic Oncology Vol.14 No.4

Non-Hodgkin's 림프종의 약 40%는 결절외(extranodal) 림프종으로 대개 위장관에서 발생하며 이들 중 점막 연관 림프조직(mucosa-associated lymphoid tissue: MALT)에서 기원한 림프종은 MALT 림프종으로 분류된다. 위 외의 부위에서 원발성으로 발생하는 MALT 림프종은 매우 드물지만 실제 거의 모든 신체 장기에 발생하는 것으로 알려져 있는데, 가장 흔한 부위인 위 외에도 폐, 갑상선, 침샘, 눈물샘에 발생하고, 드물게 안구, 유방, 방광, 신장, 흉선 등에도 보고된 바 있다. MALT 림프종은 오랜 기간동안 원격 전이하지 않고 국소 병변으로 남아 있는 특징이 있어 치료 방향 또한 국소 병변의 치료에 집중되며, 예후도 림프절 기원의 림프종에 비해 양호한 것으로 알려져 있다. 본 저자 등은 자궁 내막에 원발성으로 발생한 MALT 림프종 1예를 경험하였기에 문헌 고찰과 함께 이를 보고하고자 한다. Mucosa associated lymphoid tissue (MALT) lymphoma can rarely develop primarily in extranodal sites other than stomach which is the most common site for it. Other rare primary sites are small intestine, colorectum, esophagus, lung, thyroid, salivary gland, lacrymal gland, breast and skin. MALT lymphoma represents a distinct clinicopathologic features: it is usually localized to their original site for a long time and shows much more favorable prognosis than lymphoma at other site, but some MALT lymphoma can arise simultaneously or successively in different organ or give rise to another MALT lymphoma of other organ and can be multifocally disseminated or recurred. We report a very rare case of high grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) of the uterine endometrium, which was confirmed by immunohistochemical assay.

새마을廣域圈 開發政策의 方向設定에 關한 硏究 : 廣域圈의 槪念, 圈域設定 및 方向設定

高秉浩,趙喆柱,朴鍾浩 청주대학교 새마을연구소 1984 새마을硏究論文集 Vol.1 No.-

During last two decades, the policies and strategies of regional development has changed gradually in accordance with the shift of the economic and social environment which is mainly distinguished by economic growth, and enlargement and differentiation of the social structure in Korea. Most of all, the first decade was marked by economic rationalism based on efficiency strategies and quatitative growth, but the second decade conducted the pursuit of socio-economic balance of the spatial development in the regional dimension as well as in the national based on equity. And so it may be recognized that recently the trends and strategies of regional development have directed to equity-oriented development policies. In this context, the Saemaul Movement must be understood as an equity-oriented micro regional development to accomplish self-reliance for an integrated rural development in village unit level. Looking back upon the Saemaul Movement, even since it began in the year 1970, it has been developed more powerfully with the slogan of diligence, self-reliance and cooperation throughout the country, and the objectives of the movement: improved life environment, provision of community facilities, increased income and changes in the attitudes and values of inhabitants resulting from their participation and cooperation in village-level developing projects, have been almost achieved. However, since the beginning of 1980's, the Saemaul Movement has been under the necessity of establishing a new development policy for area-wide development because the basic objectives of village-level have been approximately accomplished and then it is necessary to pursue area-wide projects in need of scale-economics in village group level. That is to say, in the period of 1980's the policies and strategies of Saemaul Movement have been toward a cooperative development between villages, an area-wide development, apart from village unit development, which is called now "Saemaul Kwang Yeok Kwon" in Korean word. As stated above, the trend of regional development is toward the necessity of area-wide development in Saemaul Movement with special reference to micro-level regional development. However, the meaning, rolls and guidelines of it are not defined exactly. And so, this paper is intended to define the meaning of area-wide development in Saemaul Movement (Saemaul Kwang Seok Kwon), to define the roll and basic guidelines for development policy for it and to delineate the boundaries of it. Area-wide Development in Saemaul Movement is hard to define but generally speaking, it may be said that its meaning is the developing of a group of villages composed of 5-10 village units communally with express purpose of working jointly and constructing the integrated settlement area. In developing the, area-wide development in Saemaul Movement successfully, first of all, it is especially desirable that it has proper boundary in accordance with homogeneous characteristics and functional interaction between village units. And then it is necsssary to establish the basic principles for its development in detail. Briefly speaking the main emphasis of the development policy of area-wide development in this paper is given to the following. Firstly, systematizing hierarchical structure of micro-level regional development with special reference to the spatial arrangement of village unit, area-wide development in Saemaul Movement, Eup, Myon integrated settlement area and Gun(county) integrated settlement area. Secondly, establishing the integrated rural development and providing the communal facilities based on village group, especially placing the focus on basic need approach. Thirdly, Inducing the evolutional change of village cooperative scheme (VCS) into area-wide development. Fourthly, promoting inhabitants participation in public developing projects and enhancing the autonomous management of area-wide development in Saemaul Movement based on communal cooperative consciousness.