• Food preservation and processing industry
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• v.8 no.2
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• pp.6-12
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• 2009

면역반응은 외부 감염원으로부터 신체를 보호하고 외부감염원을 제거하고자 하는 주요항상성 유지기전의 하나이다. 이들 반응은 골수에서 생성되고 비장, 흉선 및 임파절 등에서 성숙되는 면역세포들에 의해 매개된다. 보통 태어나면서부터 얻어진 선천성 면역반응을 매개하는 대식세포, 수지상 세포 등과, 오랜기간 동안 감염된 다양한 면역원에 대한 경험을 토대로 얻어진 획득성 면역을 담당하는 T 임파구 등이 대표적인 면역세포로 알려져 있다. 다양한 면역질환이 최근 주요 사망률의 원인이 되고 있다. 최근, 암, 당뇨 및 뇌혈관질환 등이 생체에서 발생되는 급 만성염증에 의해 발생된다고 보고됨에 따라 면역세포 매개성 염증질환에 대한 치료제 개발을 서두르고 있다. 또한 암환자의 급격한 증가는 암발생의 주요 방어기전인 면역력 증강에 대한 요구들을 가중시키고 있다. 예로부터 사용되어 오던 고려인삼과 홍삼은 기를 보호하고 원기를 회복하는 명약으로 알려진 대표적인 우리나라 천연생약이다. 특별히, 홍삼은 단백질과 핵산의 합성을 촉진시키고, 조혈작용, 간기능 회복, 혈당강하, 운동수행 능력증대, 기억력 개선, 항피로작용 및 면역력 증대에 매우 효과가 좋은 것으로 보고되고 있다. 홍삼에 관한 많은 연구에 비해, 현재까지 홍삼이 면역력 증강에 미치는 효과에 대한 분자적 수준에서의 연구는 매우 미미한 것으로 확인되어져 있다. 홍삼의 투여는 NK 세포나 대식세포의 활성이 증가하고 항암제의 암세포 사멸을 증가시키는 것으로 확인되어졌다. 현재까지 알려진 주요 면역증강 성분은 산성다당류로 보고되었다. 또 한편으로 일부 진세노사이드류에서 항염증 효능이 확인되어졌으며, 이를 통해 피부염증 반응과 관절염에 대한 치료 효과가 있는 것으로 추측되고 있다 [본 연구는 KT&G 연구출연금 (2009-2010) 지원을 받아 이루어졌기에 이에 감사드린다]. 면역반응은 외부 감염물질의 침입으로 유도된 질병환경을 제거하고 수복하는 중요한 생체적 방어작용의 하나이다. 이들 과정은 체내로 유입된 미생물이나 미세화학물질들과 같은 독성물질을 소거하거나 파괴하는 것을 주요 역할로 한다. 외부로 부터 인체에 들어온 이물질에 대한 방어기전은 현재 두 가지 종류의 면역반응으로 구분해서 설명한다. 즉, 선천성 면역 반응 (innate immunity)과 후천성 면역 반응 (adaptive immunity)이 그것이다. 선천성 면역반응은 1) 피부나 점막의 표면과 같은 해부학적인 보호벽 구조와 2) 체온과 낮은 pH 및 chemical mediator (리소자임, collectin류) 등과 같은 생리적 방어구조, 3) phagocyte류 (대식세포, 수지상세포 및 호중구 등)에 의한 phagocytic/endocytic 방어, 그리고 4) 마지막으로 염증반응을 통한 감염에 저항하는 면역반응 등으로 구분된다. 후천성 면역반응은 획득성면역이라고도 불리고 특이성, 다양성, 기억 및 자기/비자기의 인식이라는 네 가지의 특징을 가지고 있으며, 외부 유입물질을 제거하는 반응에 따라 체액성 면역 반응 (humoral immune response)과 세포성 면역반응 (cell-mediated immune response)으로 구분된다. 체액성 면역은 침입한 항원의 구조 특이적으로 생성된 B cell 유래 항체와의 반응과 간이나 대식세포 등에서 합성되어 분비된 혈청내 보체 등에 의해 매개되는 반응으로 구성되어 있다. 세포성 면역반응은 T helper cell (CD4+), cytotoxic T cell (CD8+), B cell 및antigen presenting cell 중개를 통한 세포간 상호 작용에 의해 발생되는 면역반응이다. 선천성 면역반응의 하나인 염증은 우리 몸에서 가장 빈번히 발생되고 있는 방어작용의 하나이다. 예를 들면 감기에 걸렸을 경우, 환자의 편도선내 대식세포나 수지상세포류는 감염된 바이러스 단독 혹은 동시에 감염된 박테리아를 상대로 다양한 염증성 반응을 유도하게 된다. 또한, 상처가 생겼을 경우에도 감염원을 통해 유입된 병원성 세균과 주위조직내 선천성 면역담당 세포들 간의 면역학적 전투가 발생되게 된다. 이들 과정을 통해, 주위 세포나 조직이 손상되면, 즉각적으로 이들 면역세포들 (주로 phagocytes류)은 신속하게 손상을 극소화하고 더 나가서 손상된 부위를 원상으로 회복시키려는 일련의 염증반응을 유도하게 된다. 이들 반응은 우리가 흔히 알고 있는 발적 (redness), 부종 (swelling), 발열 (heat), 통증 (pain) 등의 증상으로 나타나게 된다. 즉, 손상된 부위 주변에 존재하는 모세혈관에 흐르는 혈류의 양이 증가하면서 혈관의 직경이 늘어나게 되고, 이로 인한 조직의 홍반과, 부어 오른 혈관에 의해 발열과 부종이 초래되는 것이다. 확장된 모세혈관의 투과성 증가는 체액과 세포들이 혈관에서 조직으로 이동하게 하는 원동력이 되고, 이를 통해 축적된 삼출물들은 단백질의 농도를 높여, 최종적으로 혈관에 존재하는 체액들이 조직으로 더 많이 이동되도록 유도하여 부종을 형성시킨다. 마지막으로 혈관 내 존재하는 면역세포들은 혈판 내벽에 점착되고 (margination), 혈관벽의 간극을 넓히는 역할을 하는 히스타민 (histamine)이나 일산화질소(nitric oxide : NO), 프로스타그린딘 (prostagladins : PGE2) 및 류코트리엔 (leukotriens) 등과 같은 chemical mediator의 도움으로 인해 혈관벽 사이로 삼출하게 되어 (extravasation), 손상된 부위로 이동하여 직접적인 외부 침입 물질의 파괴나 다른 면역세포들을 모으기 위한 cytokine (tumor necrosis factor [TNF]-$\alpha$, interleukin [IL]-1, IL-6 등) 혹은 chemokine (MIP-l, IL-8, MCP-l등)의 분비 등을 수행함으로써 염증반응을 매개하게 된다. 염증과정시 발생되는 여러 mediator 중 PGE2나 NO 및 TNF-$\alpha$ 등은 실험적 평가가 용이하여 이들 mediator 자체나 생성관련효소 (cyclooxygenase [COX] 및 nitric oxide synthase [NOS] 등)들은 현재항염증 치료제의 개발 연구시 주요 표적으로 연구되고 있다. 염증 반응은 지속기간에 따라 크게 급성염증과 만성염증으로 나뉘며, 삼출물의 종류에 따라서는 장액성, 섬유소성, 화농성 및 출혈성 염증 등으로 구분된다. 급성 염증 (acute inflammation)반응은 수일 내지 수주간 지속되는 일반적인 염증반응이라고 볼 수 있다. 국소반응은 기본징후인 발열과 발적, 부종, 통증 및 기능 상실이 특징적이며, 현미경적 소견으로는 혈관성 변화와 삼출물 형성이 주 작용이므로 일명 삼출성 염증이라고 한다. 만성 염증 (chronic inflammation)은, 급성 염증으로부터 이행되거나 만성으로 시작된다. 염증지속 기간은 보통 4주 이상 장기화 된다. 보통 염증의 경우에는 염증 생성 cytokine인 Th1 cytokine (IL-2, interferone [IFN]-$\gamma$ 및 TNF-$\alpha$ 등)의 생성 후, 거의 즉각적으로 항 염증성 cytokine인 Th2 cytokine(IL-4, IL-6, IL-10 및 transforming growth factor [TGF]-$\beta$ 등)이 생성되어 정상반응으로 회복된다. 그러나, 어떤 원인에서든 면역세포에 의한 염증원 제거 반응이 문제가 되면, 만성염증으로 진행된다. 이 반응에 주로 작용을 하는 염증세포로는 단핵구와 대식세포, 림프구, 형질세포 등이 있다. 암은 전세계적으로 사망률 1위의 원인이 되는 면역질환의 하나이다. 산화적 스트레스나 자외선 조사 혹은 암유발 물질들에 의해 염색체내 protooncogene, tumor-suppressor gene 혹은 DNA repairing gene의 일부 DNA의 돌연변이 혹은 결손 등이 발행되면 정상세포는 암화과정을 시작하게 된다. 양성세포 수준에서 약 5에서 10여년 후 악성수준의 암세포가 생성되게 되면 이들 세포는 새로운 환경을 찾아 전이하게 되는데 이를 통해 암환자들은 다양한 장기에 동인 오리진의 암세포들이 생성한 종양들을 가지게 된다. 이들 종양세포는 정상 장기의 기능을 손상시켜며 결국 생명을 잃게 만든다. 이들 염색체 수준에서의 돌연변이 유래 암세포는 거의 대부분이 체내 면역시스템에 의해 사멸되는 것으로 알려져 있다. 그러나 계속되는 스트레스나 암유발 물질의 노출은 체내 면역체계를 파괴하면서 최후의 방어선을 무너뜨리면서 암발생에 무방비 상태를 만들게 된다. 이런 이유로 체내 면역시스템의 정상적 가동 및 증강을 유도하게 하는 전략이 암예방시 매우 중요한 표적으로 인식되면서 다양한 형태의 면역증강 물질 개발을 시도하고 있다. 인삼은 두릅나무과의 여러해살이 풀로써, 오랜동안 한방 및 민간에서 원기를 회복시키고, 각종 질병을 치료할 수단으로 사용되고 있는 대표적인 전통생약이다. 예로부터 불로(不老), 장생(長生), 익기(益氣), 경신(經身)의 명약으로 구전되어졌는데, 이는 약 2천년 전 중국의 신농본초경(神農本草經)에서 "인삼은 오장(五腸)을 보하고, 정신을 안정시키고, 혼백을 고정하며 경계를 멈추게 하고, 외부로부터 침입하는 병사를 제거하여주며, 눈을 밝게 하고 마음을 열어 더욱 지혜롭게 하고 오랫동안 복용하면 몸이 가벼워지고 장수한다" 라고 기술되어있는 데에서 유래한 것이다. 다양한 연구를 통해 우리나라에서 생산되는 고려인삼 (Panax ginseng)이 효능 면에서 가장 탁월한 것으로 알려져 있으며 특별이 고려인삼으로부터 제조된 고려홍삼은 전세계적으로도 그 효능이 우수한 것으로 보고되어 있다. 대부분의 홍삼 약효는 dammarane계열의 triterpenoid인 ginsenosides라고 불리는 인삼 saponin에 의해 기인된 것으로 알려져 있다. 이들 화합물군의 기본 골격에 따라, protopanaxadiol (PD)계 (22종) 및 protopanaxatriol (PT)계 (10종)으로 구분되고 있다 (표 1). 실험적 접근을 통해 인삼의 약리작용 이해를 위한 다양한 노력들이 경주되고 있으나, 여전히 많은 부분에서 충분히 이해되고 있지 않다. 그러나, 현재까지 연구된 인삼의 약리작용 관련 연구들은 심혈관, 당뇨, 항암 및 항스트레스 등과 같은 분야에서 인삼효능이 우수한 것으로 보고하고 있다. 그러나 면역조절 및 염증현상과 관련된 최근 연구결과들은 많지 않으나, 향후 다양하게 연구될 효능부분으로 인식되고 있다.

• The KIPS Transactions:PartC
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• v.10C no.5
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• pp.625-634
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• 2003

More than a decade after its initial proposal, deployment of IP Multicast has been limited due to the problem of traffic control in multicast routing, multicast address allocation in global internet, reliable multicast transport techniques etc. Lately, according to increase of multicast application service such as internet broadcast, real time security information service etc., overlay multicast is developed as a new internet multicast technology. In this paper, we describe an overlay multicast protocol and propose fast join mechanism that considers switching of the tree. To find a potential parent, an existing search algorithm descends the tree from the root by one level at a time, and it causes long joining latency. Also, it is try to select the nearest node as a potential parent. However, it can't select the nearest node by the degree limit of the node. As a result, the generated tree has low efficiency. To reduce long joining latency and improve the efficiency of the tree, we propose searching two levels of the tree at a time. This method forwards joining request message to own children node. So, at ordinary times, there is no overhead to keep the tree. But the joining request came, the increasing number of searching messages will reduce a long joining latency. Also searching more nodes will be helpful to construct more efficient trees. In order to evaluate the performance of our fast join mechanism, we measure the metrics such as the search latency and the number of searched node and the number of switching by the number of members and degree limit. The simulation results show that the performance of our mechanism is superior to that of the existing mechanism.

• Journal of the Korean Institute of Landscape Architecture
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• v.44 no.2
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• pp.37-51
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• 2016

Modern optical mechanisms slanted toward Ocular-centrism have neglected diverse functions of vision, judged objects in abstract and binary perspectives, and organized spaces accordingly, there by neglecting the function of eyes groping objects. Recently, various experiences have been induced through communication with other senses by the complex perception beyond the binary perception system of vision. Haptic perception is dynamic vision that induces accompanying bodily experiences through interaction among the various senses; it recognizes the characteristics of material properties and various sensitive stimulations of human beings. This study elaborates on the major features of haptic perception by examining the theoretical background of this concept, which stimulates the active experience of the subject and determines how characteristics of haptic perception are displayed in picturesque gardens. In order to identify the major features of haptic perception, this study examines how Adolf Hildebrand's theory of vision is developed, expanded, and reinterpreted by Alois Riegl, Wilhelm Worringer, Walter Benjamin, Maurice Merleau Ponty, and Gilles Deleuze in the histories of philosophy and aesthetics. Based thereon, the core differences in haptic perception models and visual perception models are analyzed, and the features of haptic perception are identified. Then, classical gardens are set for visual perception and picturesque gardens are set for haptic perception so that the features from haptic perception identified previously are projected onto the picturesque gardens. The research results drawn from this study regarding features of haptic perception presented in picturesque gardens are as follows. The core differences of haptic perception in contrast to visual perception can be summarized as ambiguity and obscureness of boundaries, generation of dynamic perspectives, induction of motility by indefinite circulation, and strangeness and sublime beauty by the impossibility of perception. In picturesque gardens, the ambiguity and obscureness of boundaries are presented in the irregularity and asymmetric elements of planes and the rejection of a single view, and the generation of dynamic perspectives results from the adoption of narrative structure and overlapping of spaces through the creation of complete views, medium range views, and distant views, which the existing gardens lack. Thus, the scene composition technique is reproduced. The induction of motility by indefinite circulation is created by branching circulation, and strangeness and sublime beauty are presented through the use of various elements and the adoption of 'roughness', 'irregularity', and 'ruins' in the gardens.

• Cartoon and Animation Studies
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• s.33
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• pp.1-29
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• 2013

Surrealism with the excavation of unconsciousness, seeking for the infinity etc. has established views on aesthetics that conflict traditional western rationalism. The main concern of surrealism is problem of identity and difference. They attempted their own mysterious concept such as 'the marvelous', 'convulsive beauty', 'object chance' etc. These unique views on aesthetics was expressed as various style of art. It is the d$\acute{e}$paysemant that exists one of the typical style in surrealism. D$\acute{e}$paysemant means that objects are taken from be originally place. Therefore, The real world's objects is to leave and change environment from real space as use, ability, meaning of origin. or it is the technique to create surreal illusion that combined to a strange place where relates to extraneous attribute of objects. Namely, objects are newly arranged in expression space. Reconstitutive objects by positioning object over the time and space have given us the marvelous and psychological shock and get unfamiliar meaning and feeling over. This paper is tried to look at the way to use the d$\acute{e}$paysemant which applicated in the media, Especially, focusing on animation. Unlike the other media, animation has its unique artistic characters. First, One of the media characteristics of the animation is creativity images of the hand drawn animation by shooting of frame by frame. The animation image which is created through arrangement obtain life force by unique motility. Works of Norman McLaren and Harry Smith are very interesting that the structural characteristics of the d$\acute{e}$paysemant. It consists with abstract forms and various moving images to let audience the feel characteristics of film. We can experience from these cases, numerous illusion fantasy like change over from creature to inanimate object, space and time, creation and extinction, repetition and metamorphosis etc. One of the main apparat is the emphasis of d$\acute{e}$paysemant in space of frame. In conclusion, d$\acute{e}$paysemant is one of the most characteristic expression technique of surrealism while having inevitable linkage with animation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.759-764
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• 2017

Reactive oxygen species (ROS) and advanced glycation end products (AGEs) are valuable therapeutic targets for the regulation of diabetic complications. Activity-guided isolation of the ethylacetate (EtOAc)-soluble portion of 70% ethanolic extract from aerial parts of Ainsliaea acerifolia was performed, followed by AGE formation inhibition assay for the characterization of four dicaffeoylquinic acid derivatives of a previously known structure, methyl 3,5-di-O-caffeoyl-epi-quinate (1), 3,5-di-O-caffeoyl-epi-quinic acid (2), 4,5-di-O-caffeoyl-quinic acid (3), and methyl 4,5-di-O-caffeoyl-quinate (4). The structures of these compounds were confirmed by interpretation of nuclear magnetic resonance (NMR, $^1H-$, $^{13}C-NMR$, two-dimensional NMR) and mass spectroscopic data. Among the isolates, the major secondary metabolites, 3,5-di-O-caffeoyl-epi-quinic acid (2) and 4,5-di-O-caffeoyl-quinic acid (3) showed the most potent inhibitory effects against AGE formation with $IC_{50}$ values of $0.6{\pm}0.1{\mu}M$ and $0.4{\pm}0.1{\mu}M$, respectively. Furthermore, all isolated dicaffeoylquinic acid derivatives were evaluated for their radical scavenging activities using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical, and compound 3 exhibited the most potent inhibitory effect in a concentration-dependent manner. This result suggests that the caffeoylquinic acid dimers isolated from A. acerifolia might be beneficial for the prevention of diabetic complications and related diseases.

• Economic and Environmental Geology
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• v.32 no.4
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• pp.323-337
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• 1999

Late Cretaceous to early Tertiary volcanic rocks in the Kyongsang basin exhibit high-K calc-alkaline characteristics, and originated from the magmatism related genetically to subduction of Kula-Pacific plate. They represent HFSE depletion and LlLE enrichment characteristics as shown by magmas related to subduction. Early studies on the depth of magma generation has been estimated as 180-230 km based on K-h relation should be reevaluated, because the depth of peridotite partial melting with 0.4 wt. % water is 80-120 km at subduction zone, and subducting slab in premature arc can melted even lower than 70 km. Moreover the increase of potassium contents depends on either contamination of crustal material and fluids of subducting slab or low degree of partial melting. If the inclination of subduction zone is 30 degrees and the depth to the Benioff zone is 180-230 km, the calculated distance between the volcanic zone and trench axis would be 310-400 km. It is unlikely because the distance between the Kyongsang basin and trench during late Cretaceous to early Tertiary is closer than this value and not comparable with generally-accepted models in subduction zone magmatism. $K_{55}$ of the volcanics in the Kyongsang basin is 0.3-2.3 wt.% and the average indicate that the depth ranges between 80-170 km on the diagram of Marsh, Carmichael (1974). Fractionation from garnet lherzolite, assumed the depth of 180-230km, is not consistent with the REE patterns of the volcanoes in the Kyongsang basin. Futhermore, the range of depth suggested by many workers, who studied magmatism related to subduction, imply shallower than this depth. Crustal thickness calculated by the content of CaO and $Na_2O$ is about 30 km and about 35 km, respectively. Paleo-crustal thickness during late Cretaceous to early Tertiary times in the Kyongsang basin inferred about 30 km calculated by La/Sm versus LaJYb data, which is also supported by many previous studies.

• Journal of Chest Surgery
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• v.29 no.4
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• pp.373-380
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• 1996

Prevention of thromboembolism is the most important task in the development of bioconpatible small caliber artificial vascular graft. In normal vessels, vascular endothelial cells maintain homeosatsis by secreting numerous factors. The aim of this study is to develope a method which Improves biocompatibility of small caliver polyurethane graft using endothelial cell culture technique, and ev luate the efTectiveness of extracelluar matrix for endothelization which was produced by cultured fibroblast. Methods ; Multiporous polyurethane tube of 3 mm diameter, 0.3 mm thickness was manufactured for vascular graft. Three mongrel dogs were intubated and internal jugular veins removed. Extracelluar matrix produced by cultured flbrobast which was obtained from dog's internal jugular vein were coated to the polyurethane graft. Then, endothelial cells extracted from Jugular vein were cultured and fixed on the extracelluar matrix layer of vascular graft. Endothelial cell coated vascular grafts were implanted to the carotid arteries of experimental dogs as interposed autograft. Implanted grafts were removed after 3 and 6 weeks. As a control, PTFE graft was interposed on carotid artery. These experiments demonstrated that extracelluar matrix produced by fibroblast can afford a base for endothelial cell linings of polyurethane graft. Although thrombosis were developed on autografted en othelial cell coated graft, 33% opening was noticed, and showed less adhesion to adjacent tissue layer. These findings suggest that fiboblast produced extracelluar matrix which can be used for edothelial cell lining vascular graft, and by improving the cultured endothelial cell function, there will be a new modality for reducing thrombosis on small vascular graft.

• Applied Biological Chemistry
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• v.48 no.1
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• pp.1-15
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• 2005

Pathogens, insects and weeds have significantly reduced agricultural productivity. Thus, to increase the productivity, synthetic agricultural chemicals have been overused. However, these synthetic compounds that are different from natural products cannot be broken down easily in natural systems, causing the destruction of soil quality and agricultural environments and the gradually difficulty in continuous agriculture. Now agriculture is faced with the various problems of minimizing the damage in agricultural environments, securing the safety of human health, while simultaneously increasing agricultural productivity. Meanwhile, plants produce secondary metabolites to protect themselves from external invaders and to secure their region for survival. Plants infected with pathogens produce antibiotics phytoalexin; monocotyledonous plants produce flavonoids and diterpenoids phytoalexins, and dicotylodoneous plant, despite of infected pathogens, produce family-specific phytoalexin such as flavonoids in Leguminosae, indole derivatives in Cruciferae, sesquitepenoids in Solanaceae, coumarins in Umbelliferae, making the plant resistant to specific pathogen. Growth inhibitor or antifeedant substances to insects are terpenoids pyrethrin, azadirachtin, limonin, cedrelanoid, toosendanin and fraxinellone/dictamnine, and terpenoid-alkaloid mixed compounds sesquiterpene pyridine and norditerpenoids, and azepine-, amide-, loline-, stemofoline-, pyrrolizidine-alkaloids and so on. Also plants produces the substances to inhibit other plant growths to secure the regions for plant itself, which is including terpenoids essential oil and sesquiterpene lactone, and additionally, benzoxazinoids, glucosinolate, quassinoid, cyanogenic glycoside, saponin, sorgolennone, juglone and lots of other different of secondary metabolites. Hence, phytoalexin, an antibiotic compound produced by plants infected with pathogens, can be employed for pathogen control. Terpenoids and alkaloids inhibiting insect growth can be utilized for insect control. Allelochemicals, a compound released from a certain plant to hinder the growth of other plants for their survival, can be also used directly as a herbicides for weed control as well. Therefore, the use of the natural secondary metabolites for pest control might be one of the alternatives for environmentally friendly agriculture. However, the natural substances are destroyed easily causing low the pest-control efficacy, and also there is the limitation to producing the substances using plant cell. In the future, effects should be made to try to find the secondary metabolites with good pest-control effect and no harmful to human health. Also the biosynthetic pathways of secondary metabolites have to be elucidated continuously, and the metabolic engineering should be applied to improve transgenics having the resistance to specific pest.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.30-38
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• 2005

Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.304-313
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• 2006

Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.