• Title/Summary/Keyword: Selective Mechanism

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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
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    • v.38 no.4
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    • pp.327-335
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    • 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.

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

  • Choe, Hwan;Hong, Seok-Jin;Kim, Yeon-Soo;Cho, Jae-Gu;Baek, Seung-Kuk;Woo, Jeong-Soo;Jung, Kwang-Yoon;Kwon, Soon-Young
    • Korean Journal of Bronchoesophagology
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    • v.16 no.2
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    • pp.121-125
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    • 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.

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

  • Jung, Ho-Sub
    • Strategy21
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    • s.44
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    • pp.5-27
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    • 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
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    • v.16 no.6
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    • pp.413-422
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    • 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
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    • v.16 no.3
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    • pp.181-186
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    • 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.

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

  • Jung, Bo-Sung;Lee, Jung-Hoon
    • The KIPS Transactions:PartA
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    • v.16A no.2
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    • pp.69-78
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    • 2009
  • One of the most effective way to improve cache performance is to exploit both temporal and spatial locality given by any program executive characteristics. In this paper we present a high performance and low power cache structure with a bank selection mechanism that enhances exploitation of spatial and temporal locality. The proposed cache system consists of two parts, i.e., a main direct-mapped cache with a small block size and a fully associative buffer with a large block size as a multiple of the small block size. Especially, the main direct-mapped cache is constructed as two banks for low power consumption and stores a small block which is selected from fully associative buffer by the proposed bank selection algorithm. By using the bank selection algorithm and three state bits, We selectively extend the lifetime of those small blocks with high temporal locality by storing them in the main direct-mapped caches. This approach effectively reduces conflict misses and cache pollution at the same time. According to the simulation results, the average miss ratio, compared with the Victim and STAS caches with the same size, is improved by about 23% and 32% for Mibench applications respectively. The average memory access time is reduced by about 14% and 18% compared with the he victim and STAS caches respectively. It is also shown that energy consumption of the proposed cache is around 10% lower than other cache systems that we examine.

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

  • Yun, Mi Sun;Yeon, Bo-Ram;Cho, Hae Me;Choi, Jung Sup;Kim, Songmun
    • Weed & Turfgrass Science
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    • v.1 no.4
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    • pp.44-49
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    • 2012
  • The objective of this study was to know the herbicidal activity of the essential oil from amyris (Amyris balsamifera). In a seed bioassay experiment, the amyris essential oil inhibited the growth of rapeseed (Brassica napus) by fifty percent at 8.8 ${\mu}g\;g^{-1}$. And in a greenhouse experiment, sorghum, barnyard grass and Indian jointvetch, which was applied in above-ground parts, with the amyris essential oil at 4,000 ${\mu}g\;ml^{-1}$ showed visual injuries of 90, 70, and 70, respectively (0, no damage; 100, total damage). However, soil application of the essential oil did not show such herbicidal injuries. In a field experiment, foliar application of the amyris essential oil at 5% controlled effectively weeds such as barnyardgrass, shepherd's purse, and clover in 24 hours. Our results indicated that the amyris essential oil had herbicidal activity. To understand the composition of the amyris essential oil, the oil was analyzed by gas chromatography-mass spectometry with solid-phase micro-extraction apparatus. There were 15 organic chemicals in the oil and the major constituents were calarene, elemol, ${\gamma}$-eudesmol, curcumene, ${\beta}$-sesquiphellandrene, zingiberene, selina-3,7(11)-diene, 1,3-diisopropenyl-6-methyl-cyclohexene, ${\beta}$-bisabolene, and ${\beta}$-maaliene. Overall results suggest that the amyris essential oil had a herbicidal activity with fast, contact, and non-selective mechanism.

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 (4주간 지구성 운동이 흰쥐의 Back Skin Hair Follicle에서 ERK 및 JNK의 활성화에 미치는 영향)

  • Kim, Mo-Kyung;Park, Han-Su;Jo, Sung-Cho;Chae, Jeong-Ryong;Kim, Mo-Young;Shin, Byung-Cheul
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1211-1216
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    • 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
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2022.10a
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    • pp.95-95
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    • 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.

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

  • Hyun-Seo Yoon;Hyun An;Chung Mu Park
    • Journal of Life Science
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    • v.33 no.10
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    • pp.776-782
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    • 2023
  • Silymarin, which is derived from dried Silybum marianum (milk thistle) seeds and fruits, possesses various beneficial properties, such as hepatoprotective, antioxidative, anti-inflammatory, and anticancer activity. This research aimed to explore the antioxidative activity of silymarin against oxidative stress and understand its molecular mechanism in RAW 264.7 cells. The study employed cell viability and reactive oxygen species (ROS) formation assays and western blot analysis. The results demonstrated that silymarin effectively reduced intracellular ROS levels induced by lipopolysaccharide (LPS) in a dose-dependent manner without causing any cytotoxic effects. Moreover, silymarin treatment significantly upregulated the expression of heme oxygenase (HO)-1, a phase II enzyme known for its potent antioxidative activity. Additionally, silymarin treatment significantly induced the expression of nuclear factor-erythroid 2 p45-related factor (Nrf) 2, a transcription factor responsible for regulating antioxidative enzymes, which was consistent with the upregulated HO-1 expression. To investigate the involvement of key signaling pathways in maintaining cellular redox homeostasis against oxidative stress, the phosphorylation status of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) was estimated by western blot analysis. The results showed that silymarin potently induced HO-1 expression, which was mediated by the phosphorylation of p38 MAPK. To further validate the antioxidative potential of silymarin-induced HO-1 expression, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was employed and attenuated by silymarin treatment, as identified by a selective inhibitor for each signaling molecule. In conclusion, silymarin robustly enhanced antioxidative activity by inducing HO-1 via the Nrf2/p38 MAPK signaling pathway in RAW 264.7 cells.