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        Dual role of reactive oxygen species in autophagy and apoptosis induced by compound PN in prostate cancer cells

        최현덕,김광연,박광일,김상헌,Park Sul-Gi,Yu Sun-Nyoung,김영우,김동섭,정경태,안순철 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.1

        Background Pharbitis nil (L.) Choisy (PN) is used as a traditional herb in East Asia and exhibits anti-parasitic, purgative, diuretic, anti-inflammatory, and anti-cancer activities. However, the molecular mechanisms underlying the anti-cancer activity are not well understood. Objective This study aims to elucidate the effects of reactive oxygen species (ROS), generated after treatment with the compound PN, on the induction of apoptosis and autophagy, which are pathways that underly the mechanisms of cell death and cell survival in human prostate cancer cells. Results The MTT assay and western blot analysis were used to assess the effects of compound PN on cell viability and the expression of apoptosis- and autophagy-related proteins in prostate cancer PC-3 cells. The effects of PN on apoptosis (via annexin V/propidium iodide staining), autophagy (via acridine orange staining), and ROS (via DCFH-DA staining) were investigated using flow cytometry. Compound PN induced the production of intracellular and mitochondrial ROS leading to increased apoptosis and autophagy in PC-3 cells. Interestingly, pretreatment with N-acetyl-L-cysteine (NAC), an intracellular ROS scavenger, enhanced compound PN-induced apoptosis, but reduced levels of autophagy. In contrast, pretreatment with diphenyleneiodonium (DPI), an inhibitor of mitochondrial ROS, reduced compound PN-induced apoptosis and enhanced autophagy. Inhibition of autophagy led to acceleration of apoptosis in a PN-induced ROS-dependent manner. Compound PN-induced ROS production from two different sources, an intracellular source and mitochondrial source. ROS production in these differing locations had different effects on apoptosis and autophagy. They acted either by promoting cell death or cell survival through regulating autophagy to either escape or enhance apoptotic cell death. Conclusion This crosstalk between ROS-activated signals in apoptosis and autophagy induction by PN provides new insights into the molecular mechanisms of this compound and suggests that PN may be a potential therapy for prostate cancer treatment. Background Pharbitis nil (L.) Choisy (PN) is used as a traditional herb in East Asia and exhibits anti-parasitic, purgative, diuretic, anti-inflammatory, and anti-cancer activities. However, the molecular mechanisms underlying the anti-cancer activity are not well understood. Objective This study aims to elucidate the effects of reactive oxygen species (ROS), generated after treatment with the compound PN, on the induction of apoptosis and autophagy, which are pathways that underly the mechanisms of cell death and cell survival in human prostate cancer cells. Results The MTT assay and western blot analysis were used to assess the effects of compound PN on cell viability and the expression of apoptosis- and autophagy-related proteins in prostate cancer PC-3 cells. The effects of PN on apoptosis (via annexin V/propidium iodide staining), autophagy (via acridine orange staining), and ROS (via DCFH-DA staining) were investigated using flow cytometry. Compound PN induced the production of intracellular and mitochondrial ROS leading to increased apoptosis and autophagy in PC-3 cells. Interestingly, pretreatment with N-acetyl-L-cysteine (NAC), an intracellular ROS scavenger, enhanced compound PN-induced apoptosis, but reduced levels of autophagy. In contrast, pretreatment with diphenyleneiodonium (DPI), an inhibitor of mitochondrial ROS, reduced compound PN-induced apoptosis and enhanced autophagy. Inhibition of autophagy led to acceleration of apoptosis in a PN-induced ROS-dependent manner. Compound PN-induced ROS production from two different sources, an intracellular source and mitochondrial source. ROS production in these differing locations had different effects on apoptosis and autophagy. They acted either by promoting cell death or cell survival through regulating autophagy to either escape or enhance apoptotic cell death. Conclusion This crosstalk between ROS-activated signals in apoptosis and autophagy induction by PN provides new insights into the molecular mechanisms of this compound and suggests that PN may be a potential therapy for prostate cancer treatment.

      • KCI등재

        경계와 상호문화성 : 상호문화 철학의 기본 과제

        최현덕 부산대학교 인문학연구소 2009 코기토 Vol.- No.66

        이 글은, 상호문화 철학을 소개하는 글로서, 무엇보다도, 상호문화 철학의 현실적 콘텍스트를 이루는 경계의 문제, 즉 세계화의 과정 속에서 한편으로는 사라지며, 다른 한 편으로는 강화되거나 새로 생기고 있는 역설적 현상으로서의 경계의 문제를 강하게 의식한다. 이 글은 크게 두 부분으로 나누어지는데, 전반부에서는 상호문화성의 개념에 초점을 맞춘다. 경계에 대한 관점과 입장의 차이에 따라 ‘다문화성’ ‘초문화성’ 혹은 ‘상호문화성’ 개념의 사용을 선호하게 되는데, 여기서는 이 개념들을 비교한 후, 각 개념이 가진 장점을 살릴 수 있는 개념으로서의 상호문화성 개념의 재정립을 시도한다. 후반부에서는 상호문화 철학의 기본적 과제에 대해 논의한다. 상호문화 철학이 중심주의를 극복하고 다양한 문화들이 동등하게 어우러지는 사회의 실현과 이의 철학적 정초 및 철학적 재현을 목적으로 한다면, 차별과 배제의 선으로서의 경계, 중심과 주변을 가르는 경계의 극복을 기본적인 출발점으로 삼을 수밖에 없으며, 이는 중심과 주변의 위계질서 극복에 관한 문제로 이어진다. 진정한 극복은, 위계질서 내에서의 자리바꿈이 아닌, 위계질서 자체의 변혁에 있는데, 이를 위한 철학적 성찰의 원형을 우리는 함석헌의 역사철학, 특히 그의 고난의 해석학에서 발견할 수 있다. 고난 속에서, 즉 주변에 처해져서 자기를 상실한 경험으로 하여 금 불의한 구조를 변혁할 잠재력으로 해석해 내는 고난의 해석학은 동시에 상호문화적 만남의 기반을 제공한다. 이런 맥락에서 중심주의에 대한 비판과 주변의 창조적 잠재력의 현재화가 가능해지는 조건의 탐구는 상호문화 철학의 기본적 과제라 할 수 있다. The aim of this paper is to introduce the intercultural philosophy. Herein a special attention is paid to the problem of border as the real context of the intercultural philosophy. In the process of globalization the borders are, on the one hand, disappearing; on the other hand, they are reinforced or newly produced. This article consists of two main parts. In the first part it is focused on the concept of interculturality. Based on the differences of standpoints one prefers the concept "multiculturality" "transculturality" or "interculturality". After these concepts are compared with one another, it is attempted to modify the concept of interculturality so that it can encompass the advantages of the concept of transculturality. In the second part the basic assignments of intercultural philosophy are elaborated. If intercultural philosophy aims at the realization of the society, in which diverse cultures equally existing together, as well as its philosophical foundation and representation, it is not avoidable to deal with the problem to overcome the border dividing the "center" and the "periphery"-the border as the line of discrimination and exclusion. It concerns the question of overcoming the hierarchical order of the "center" and the "periphery". The way to truly overcome the position of the "periphery" does not mean to take over the position of the "center" but to transform the hierarchial structure itself. A prototype of a philosophical reflection of this theme is found in the philosophy of history by Ham, Seok-Heon, especially his hermeneutics of suffering. He interprets the experience of self-losing in the "periphery" as the potential to transform the unjust structure and offers a basis for intercultural encountering. It is in this context that we identify the critic of the centrisms and the search for the conditions of the possibility to actualize the creative potentials of the "periphery" as the basic assignments of intercultural philosophy.

      • KCI등재

        Mainstream smoke level of harmful substances in korean domestic cigarette brands

        최현덕,홍석호,조훈식,김형경,이진희,윤순병,허석,박형준 한국분석과학회 2018 분석과학 Vol.31 No.1

        After signing the WHO FCTC in 2003, South Korea ratified the FCTC in 2005. This study was conducted to provide data on toxic constituents that can be used as useful information for the level of exposure to Korean smokers. Emissions data from five brands of cigarettes were tested under the ISO and “Canadian Intense (HCI)” smoking regimes, respectively. We conducted an analysis of 25 compounds containing nicotine, tar, carbonyls, phenolics, volatile organic compounds (VOCs), and semi-VOC cigarette smoke. Tar and nicotine showed levels of 4.3 to 5.8 mg/cig and 0.4 to 0.5 mg/cig, respectively, which are within the range of tolerance presented in ISO 8243. In the case of carbonyls, formaldehyde was detected within a range of 8.2 to 14.3 μg/cig, and acetaldehyde was present within a range of 224.7 to 327.2 μg/cig under the ISO smoke regime. Crotonaldehyde was not detected under the ISO regime, and all of the carbonyls showed values 2.3 to 4.5 times higher under the HCI regime than those under the ISO regime. Catechol, which showed a level of 47.0 to 80.5 μg/cig under the ISO regime and 117.5 to 184.7 μg/cig under the HCI regime, was the highest constituent among the phenols. The amount of isoprene was 91.7 to 158.3 μg/cig under the ISO regime and 221.0 to 377.0 under the HCI regime. To summarize, most of the constituents showed a tendency to be detected at levels 2 to 4 times higher under the HCI regime than under the ISO regime. Above all, these results represent the first analysis in Korea from an independent institute of tobacco companies under accreditation of ISO 17025.

      • KCI등재

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