• 제목/요약/키워드: Selective mechanism

검색결과 444건 처리시간 0.03초

Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine

  • Lee, Ha-Na;Jin, Hyeon-Ok;Park, Jin-Ah;Kim, Jin-Hee;Kim, Ji-Young;Kim, BoRa;Kim, Wonki;Hong, Sung-Eun;Lee, Yun-Han;Chang, Yoon Hwan;Hong, Seok-Il;Hong, Young Jun;Park, In-Chul;Surh, Young-Joon;Lee, Jin Kyung
    • Molecules and Cells
    • /
    • 제38권4호
    • /
    • pp.327-335
    • /
    • 2015
  • Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic ${\alpha},{\beta}$-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine.

관통성 경부 손상에 관한 임상적 고찰 (Clinical Analysis of Penetrating Neck Injury: Review of 42 Operated Cases)

  • 최환;홍석진;김연수;조재구;백승국;우정수;정광윤;권순영
    • 대한기관식도과학회지
    • /
    • 제16권2호
    • /
    • pp.121-125
    • /
    • 2010
  • Background: Penetrating neck injuries are potentially dangerous and require emergency management because of the presence of vital structures in the neck. The risk of airway, vascular, neurological, and pharyngoesophageal injuries leads to many difficult diagnostic decisions. The purpose of this retrospective study is to evaluate our experience with management of penetrating neck injuries, and to assess treatment outcome. Material and Method: Forty-two consecutive patients were identified (26 patients from Korea university Ansan hospital, 16 patients from Guro hospital) as having penetrating neck injuries from 2003 to 2009. With review of medical records, variables were collected and evaluated including the location of injury, mechanism of injury, number of significant injuries, diagnostic modalities, duration of hospital stay and outcome. Results: The location of injury was zone I (lower neck) in 13 cases (31%), zone II (midportion of the neck) in 22 (52%), and zone III (upper neck) in 7 (17%). Injuries were caused by stab wounds in 23 patients, penetrating foreign bodies in 12. Among 35 patients who had deep injuries that violated the platysma, significant injuries, including major vascular (20), trachea (5) Pharyngoesophageal injuries (5) were identified in 24 patients. The mean hospital stay was 9.5 days. Conclusion: The penetrating trauma in the neck may show various degrees of severity. However, Cervical penetrating injury should not be underestimated in spite of the minimal width of the lesion.

  • PDF

강대국 간의 경쟁시대와 미 해군의 증강 노력 (USN's Efforts to Rebuild its Combat Power in an Era of Great Power Competition)

  • 정호섭
    • Strategy21
    • /
    • 통권44호
    • /
    • pp.5-27
    • /
    • 2018
  • The purpose of this paper is to look at USN's efforts to rebuild its combat power in the face of a reemergence of great powers competition, and to propose some recommendations for the ROKN. In addition to the plan to augment its fleet towards a 355-ships capacity, the USN is pursuing to improve exponentially combat lethality(quality) of its existing fleet by means of innovative science and technology. In other words, the USN is putting its utmost efforts to improve readiness of current forces, to modernize maintenance facilities such as naval shipyards, and simultaneously to invest in innovative weapons system R&D for the future. After all, the USN seems to pursue innovations in advanced military Science & Technology as the best way to ensure continued supremacy in the coming strategic competition between great powers. However, it is to be seen whether the USN can smoothly continue these efforts to rebuild combat strength vis-a-vis its new competition peers, namely China and Russian navy, due to the stringent fiscal constraints, originating, among others, from the 2011 Budget Control Act effective yet. Then, it seems to be China's unilateral and assertive behaviors to expand its maritime jurisdiction in the South China Sea that drives the USN's rebuild-up efforts of the future. Now, some changes began to be perceived in the basic framework of the hitherto regional maritime security, in the name of declining sea control of the USN as well as withering maritime order based on international law and norms. However, the ROK-US alliance system is the most excellent security mechanism upon which the ROK, as a trading power, depends for its survival and prosperity. In addition, as denuclearization of North Korea seems to take significant time and efforts to accomplish in the years to come, nuclear umbrella and extended deterrence by the US is still noting but indispensible for the security of the ROK. In this connection, the naval cooperation between ROKN and USN should be seen and strengthened as the most important deterrents to North Korean nuclear and missile threats, as well as to potential maritime provocation by neighboring countries. Based on these observations, this paper argues that the ROK Navy should try to expand its own deterrent capability by pursuing selective technological innovation in order to prevent this country's destiny from being dictated by other powers. In doing so, however, it may be too risky for the ROK to pursue the emerging, disruptive innovative technologies such as rail gun, hypersonic weapon... etc., due to enormous budget, time, and very thin chance of success. This paper recommends, therefore, to carefully select and extensively invest on the most cost-effective technological innovations, suitable in the operational environments of the ROK. In particular, this paper stresses the following six areas as most potential naval innovations for the ROK Navy: long range precision strike; air and missile defense at sea; ASW with various unmanned maritime system (UMS) such as USV, UUV based on advanced hydraulic acoustic sensor (Sonar) technology; network; digitalization for the use of AI and big data; and nuclear-powered attack submarines as a strategic deterrent.

The Effect of Lidocaine.HCl on the Fluidity of Native and Model Membrane Lipid Bilayers

  • Park, Jun-Seop;Jung, Tae-Sang;Noh, Yang-Ho;Kim, Woo-Sung;Park, Won-Ick;Kim, Young-Soo;Chung, In-Kyo;Sohn, Uy Dong;Bae, Soo-Kyung;Bae, Moon-Kyoung;Jang, Hye-Ock;Yun, Il
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제16권6호
    • /
    • pp.413-422
    • /
    • 2012
  • The purpose of this study is to investigated the mechanism of pharmacological action of local anesthetic and provide the basic information about the development of new effective local anesthetics. Fluorescent probe techniques were used to evaluate the effect of lidocaine HCl on the physical properties (transbilayer asymmetric lateral and rotational mobility, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py. Lidocaine HCl increased the bulk lateral and rotational mobility of neuronal and model membrane lipid bilayes, and had a greater fluidizing effect on the inner monolayer than the outer monolayer. Lidocaine HCl increased annular lipid fluidity in SPMV lipid bilayers. It also caused membrane proteins to cluster. The most important finding of this study is that there is far greater increase in annular lipid fluidity than that in lateral and rotational mobilities by lidocaine HCl. Lidocaine HCl alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that lidocaine, in addition to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membrane lipid.

Reduction of Food Intake by Fenofibrate is Associated with Cholecystokinin Release in Long-Evans Tokushima Rats

  • Park, Mi-Kyoung;Han, Ying;Kim, Mi-Sun;Seo, Eun-Hui;Kang, Soo-Jeong;Park, So-Young;Koh, Hyeong-Jong;Kim, Duk-Kyu;Lee, Hye-Jeong
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제16권3호
    • /
    • pp.181-186
    • /
    • 2012
  • Fenofibrate is a selective peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) activator and is prescribed to treat hyperlipidemia. The mechanism through which $PPAR{\alpha}$ agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.

내장형 시스템을 위한 선택적 뱅크 알고리즘을 이용한 데이터 캐쉬 시스템 (Data Cache System based on the Selective Bank Algorithm for Embedded System)

  • 정보성;이정훈
    • 정보처리학회논문지A
    • /
    • 제16A권2호
    • /
    • pp.69-78
    • /
    • 2009
  • 캐쉬의 성능을 향상시키는 가장 효과적인 방법은 프로그램 수행 특성에 내재되어 있는 시간적 (temporal locality) 지역성과 공간적 지역성(spatial locality)을 활용하는 것이다. 본 논문은 프로그램 수행 특성에 적합한 시간적/공간적 지역성을 이용하기 위한 뱅크 선택 메커니즘을 가진 고성능 저전력 캐쉬 구조를 제안하였다. 제안하는 캐쉬 시스템은 다른 블록 크기와 다른 연관도를 가지는 두개의 캐쉬로 구성되어 진다. 즉 작은 블록 크기를 지원하는 직접사상 구조의 주 캐쉬(main direct-mapped cache)와 큰 블록을 지원하는 완전연관 버퍼 (fully associative buffer)로 구성되어 진다. 특히 주 캐쉬는 저전력을 위해 2-뱅크로 구성되며, 완전연관 버퍼에서 선택되어진 작은 블록은 제안된 뱅크 선택 알고리즘에 의해 주 캐쉬의 뱅크에 저장된다. 제안된 뱅크 선택 알고리즘과 3비트 상태 비트를 이용하여 시간적 지역성이 높은 데이터들을 주 캐쉬에 선택적으로 저장함으로써 고성능의 효과를 얻을 수 있었다. 제안된 알고리즘은 또한 충돌 미스 (conflict miss)와 캐쉬 오염 (cache pollution)을 효과적으로 줄여준다. 시뮬레이션 결과에 따르면, 평균 접근 실패율의 경우 Mibench 응용군에 대해 Victim 캐쉬에 비해 23%, STAS 캐쉬에 비해 32%의 감소효과를 보여준다. 평균 메모리 접근 시간의 경우 Victim 캐쉬에 비해 14%, STAS 캐쉬에 비해 18%의 감소효과를 얻을 수 있었다. 에너지 소비의 관점에서도 제안된 캐쉬 시스템은 Victim 캐쉬와 STAS 캐쉬에 비해 약 10% 감소 효과를 얻을 수 있었다.

아미리스 정유의 제초활성 (Herbicidal Activity of Essential Oil from Amyris (Amyris balsamifera))

  • 윤미선;연보람;조해미;최정섭;김성문
    • Weed & Turfgrass Science
    • /
    • 제1권4호
    • /
    • pp.44-49
    • /
    • 2012
  • 본 연구의 목적은 아미리스 정유의 제초활성을 검정하는데 있다. 아미리스 정유의 기내 종자발아 제초활성 검정 결과 유채에 대한 $GR_{50}$값은 8.8 ${\mu}g\;g^{-1}$ 이었으며, 온실 제초활성 검정 결과 바랭이에 대한 완전고사 경엽처리 약량은 1,250 ${\mu}g\;ml^{-1}$ 이었다. 화본과잡초 4종과 광엽잡초 5종을 대상으로한 온실실험에서 4,000 ${\mu}g\;ml^{-1}$ 약량처리시 아미리스 정유는 수수, 돌피, 자귀풀에 대해 각각 90%, 70% 그리고 70%의 약효를 나타내었으며, 아미리스 정유에 처리된 잎은 모두 건조되는 증상을 나타내었다. 포장시험에서 아미리스 정유 5%의 피, 냉이, 토끼풀에 대한 제초효과는 모두 70%이었으며, 10%에서는 100%이었다. 아미리스 10% 정유의 제초활성은 처리후 6시간부터 발현되기 시작하였으며, 아미리스 정유 처리구 잡초의 지상부위 생체중은 대조구와 비교하여 41.5%이었으나 지하부위 생체중은 대조구와 비교하여 차이가 없었다. 아미리스 정유에는 총 15종의 화학물질이 검출되었으며 주된 화합물은 calarene(27.24%), elemol(19.38%), ${\gamma}$-eudesmol(9.24%), curcumene(5.85%), ${\beta}$-sesquiphellandrene(5.63%), zingiberene(5.50%), selina-3,7(11)-diene(5.29), 1,3-diisopropenyl-6-methyl-cyclohexene(4.18), ${\beta}$-bisabolene(4.13%), ${\beta}$-maaliene(3.62%)이었다. 본 연구의 결과 아미리스 정유는 속효성, 비선택적, 비이행성 제초특성을 갖는 것으로 추론된다.

4주간 지구성 운동이 흰쥐의 Back Skin Hair Follicle에서 ERK 및 JNK의 활성화에 미치는 영향 (Effects of 4 Weeks Endurance Exercise on Expression of Extracellular Signal-Regulated Kinases and c-Jun N-terminal Kinase in Rat Back Skin Hair Follicle)

  • 김모경;박한수;조성초;채정룡;김모영;신병철
    • 동의생리병리학회지
    • /
    • 제20권5호
    • /
    • pp.1211-1216
    • /
    • 2006
  • The effect of a chronic programme of either low- or moderate-to-high-intensity treadmill running on the activation of the Extracellular-signal regulated protein kinase (ERK1/2), Phosphorylated ERK 1/2(pERK1/2) and the Phosphorylated c-Jun N-terminal kinase(pJNK) pathways was determined in rat Back skin Hair follicle. Sprague-Dawley rats were assigned to one of three groups: (i) sedentary group(NE; n=10); (ii) low-intensity exercise group (Bm/min; LIE; n=10); and (iii) moderate-high-intensity exercise group(28m1min; HIE; n=10). The training regimens were planned so that animals covered the same distance and had similar utilization for both LIE and HIE exercise sessions. The report runs as follows; A single bout of LIE or HIE following 4 weeks of exercise led to a twofold increase in the phosphorylation of ERK2, pERK2 and a threefold increase in pJNKl, pERKl. ERKI phosphorylation in LIE Back skin sampled and pJNK2 in HIE Back skin sampled 48h after the last exercise bout was similar to sedentary values, while pJNK2 phosphorylation in LIE Back skin sampled was 70-80% lower than sedentary. 48h after the last exercise bout of LIE or HIE increased ERK2, pERKl and pJNKl expression, with the magnitude of this increase being independent of prior exercise intensity or duration. PERK1/2, pJNKl expression was increased Three- to fourfold in Back skin Hair follicle sampled 48h after the last exercise bout irrespective of the prior exercise programme, but ERKI expression in HIE Back skin sampled was approximately 90% lower than sedentary values. In conclusion, exercise-training of different jntensities/durations results in selective postexercise activation of intracellular signal pathways, which may be one mechanism regulating specific adaptations induced by diverse training programmes.

Alleviation Technology of Cold Stress of Maize(Zea mays L.) by Low Temperatures Damage

  • Youngchul Yoo;Mi-jin Chae;Jeong Ju Kim;Seuk Ki Lee;AReum Han;Won Tae Jeon;Dae-Woo Lee;Beom-Young Son
    • 한국작물학회:학술대회논문집
    • /
    • 한국작물학회 2022년도 추계학술대회
    • /
    • pp.95-95
    • /
    • 2022
  • Maize is one of the world's three largest crops and has a long cultivation history, and is an important crop used for various purposes such as food, feed, and industrial raw materials. Recently, the agricultural environment is changing, in which the limit of cultivation of crops is shifted to the north due to the rise in temperature due to climate change. This study was conducted in experimental field of Suwon in 2022 by setting a seeding period earlier than the sowing time to establish the North Korean agricultural climatic zone and meteorological conditions. The test cultivars were silage cultivars, Kwangpyeongok and Dacheongok. As a priming test method, it was used to directly plant seeds in the field through immersion using 4mM zinc (Zn) and 2.5mM manganese (Mn), which are trace elements for seeds. The planting season was early on March 15th, April 1st, and April 15th. The number of days from sowing to silk stage of the two cultivars sown on March 15, April 1, and April 15 was 107, 93, and 85 days for Kwangpyeongok and 109, 95, and 87 days for Dacheongok, respectively. The seed priming test did not show any difference from the control group in the growth survey up to the middle stage of growth. In another test, low-temperature recovery was confirmed through nitrogen (2-5%) foliar fertilization after 3 days, 5 days, and 7 days in refrigeration (0 degrees), a selective low temperature treatment for com in the third leaf stage. As a result of this study, it was confirmed that the low-temperature damaged com treated at 0℃ showed the same growth as that of the untreated com through nitrogen foliar fertilization. These results suggest that urea foliar fertilization for low-temperature damage reduction of corn for silage in high-latitude climates will be helpful. In addition, through the results of the study, additional studies are needed on the recovery mechanism and field application through urea foliar fertilization.

  • PDF

RAW 264.7 세포에서 Nrf2/MAPK 의 활성을 통한 HO-1 과발현에 의한 silymarin의 항산화 효과 (Enhanced Antioxidative Potential by Silymarin Treatment through the Inductionof Nrf2/MAPK Mediated HO-1 Signaling Pathway in RAW 264.7 Cells)

  • 윤현서;안현;박충무
    • 생명과학회지
    • /
    • 제33권10호
    • /
    • pp.776-782
    • /
    • 2023
  • Silymarin은 간 보호, 항산화, 항염, 항암 등 다양한 생리 활성을 나타내는 것으로 보고되었고, 본 연구에서는 산화 스트레스에 대한 항산화 잠재력과 그 기전을 세포 생존력 및 활성산소종 생성 분석과 Western blot 분석을 통해 RAW 264.7 세포에서 알아보고자 하였다. Silymarin은 세포 독성 없이 lipopolysaccharide(LPS)에 의해 자극된 세포 내 활성산소종을 농도 의존적으로 소거하였다. 그리고 항산화 효과를 보여주는 것으로 알려진 제2상 효소 중 하나인 heme oxygenase (HO)-1의 발현은 silymarin 처리에 의해 강하게 유도되었다. 또한 silymarin 처리는 항산화 효소의 전사인자인 nuclear factor-erythroid 2 p45-related factor (Nrf)-2의 발현을 유의미하게 유도하였고, 이는 HO-1 발현증가와 일치하였다. 세포내 산화와 환원 항상성 조절과 관련된 신호 전달물질인 mitogen activated protein kinase (MAPK)와 phosphoinositde 3-kinase (PI3K)의 인산화 정도 또한 Western blot으로 분석하였고, 그 결과 silymarin 은 p38 MAPK 인산화에 의해 HO-1 발현을 유도하는 것으로 나타났다. 그리고 tert-butyl hydroperoxide (t-BHP)를 이용하여 세포내 지질 과산화를 유도함으로써 silymarin에 의해 유도된 HO-1의 항산화 효과를 확인하였다. 그 결과 silymarin 처리에 의해 세포사멸이 유의적으로 억제되었고, p38의 선택적 저해제를 처리한 세포군에서는 t-BHP에 의해 유의적인 세포사멸이 발생하였다. 이 결과를 통해 silymarin은 Nrf-2/p38 MAPK 신호 전달 경로를 통해 HO-1의 발현을 유도하고, 이를 통해 항산화 효과를 높이는 것을 확인할 수 있었다.