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Apoptosis Induction by Dendropanax morbiferus Leaves Extract in Human Breast Cancer Cells SK-BR-3 through MAPK Pathway (유방암 세포에서 황칠나무 잎 추출물의 MAPK 경로를 통한 apoptosis 유도)

  • Jung, Gi Hwan;Kim, Sung Hyun;Woo, Joong Seok;Yoo, Eun Seon;Lee, Jae Han;Han, So Hee;Jung, Soo Hyun;Kim, Sae Man;Kim, Eun Gee;Shin, Man Jae;Cho, Ho Min;Jung, Ji Youn
    • Journal of Life Science
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    • v.31 no.9
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    • pp.827-833
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    • 2021
  • Dendropanax morbiferus leaves (DPL) has been used as a medicine since ancient times in various diseases such as inflammation, diabetes, and cancer. In particular, it has been found to have anticancer effects on several types of cancer cells, but the anticancer effect on breast cancer cells SK-BR-3 has not yet been revealed. Therefore, in this study, DPL caused proliferation inhibition in breast cancer cells SK-BR-3 and the anticancer effect by inducing apoptosis was confirmed, through an in vitro experiment. In order to examine the effect of DPL on cell viability, MTT assay was performed to confirm a significant decrease in the concentration of cell viability. DAPI staining was performed to examine the effect of DPL on cellular morphological changes and increase of apoptotic bodies. To supplement this, an increase in the apoptosis rate was also confirmed through flow cytometry after staining with annexin V/PI. Western blot was performed to confirm apoptosis-related proteins. DPL increased the expression of Cleaved-PARP, Bax whereas decreased the expression of Bcl-2. Changes in the expression levels of MAPK pathway proteins p-ERK1/2, p-JNK, and p-p38 were also confirmed, and a significant increase in p-p38 was observed. These results indicated that DPL induced apoptosis, through p-p38 MAPK signal pathway in SK-BR-3 breast cancer cells.

Protective effect of Eucommia ulmoides oliver leaves against PM2.5-induced oxidative stress in neuronal cells in vitro (미세먼지(PM2.5)로 유도된 산화적 스트레스에 대한 두충(Eucommia ulmoides Oliver) 잎의 in vitro 뇌 신경세포 보호 효과)

  • Kim, Min Ji;Kang, Jin Yong;Park, Seon Kyeong;Kim, Jong Min;Moon, Jong Hyun;Kim, Gil Han;Lee, Hyo Lim;Jeong, Hye Rin;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.53 no.4
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    • pp.423-433
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    • 2021
  • This study was performed to examine the neuroprotective effect of the ethyl acetate fraction from Eucommia ulmoides oliver leaf (EFEL) on PM2.5-induced cytotoxicity. EFEL had higher total phenolic and flavonoid contents than the other fractions. In ABTS and DPPH radical scavenging activities, the IC50 of EFEL was measured as 212.80 and 359.13 ㎍/mL, respectively. To investigate the neuroprotective effect of EFEL, MTT and DCF-DA assays were performed on HT22, MC-IXC, and BV-2 cells. EFEL effectively decreased PM2.5-induced intercellular reactive oxygen species (ROS) content and inhibited PM2.5-induced cell death. In the results of protein expression related to cellular cytotoxicity on microglial cells (BV-2), EFEL had an improvement effect on cell apoptosis and inflammatory pathways. Rutin and chlorogenic acid were identified as the main physiological compounds. Moreover, it was expected that EFEL, including rutin and chlorogenic acid, could be functional food substances with neuroprotective effects against PM2.5-induced oxidative stress.

The Quantity and Pattern of Leaf Fall and Nitrogen Resorption Strategy by Leaf-litter in the Gwangneung Natural Broadleaved Forest (광릉숲 천연활엽수림의 수종별 낙엽 현상과 질소 재전류 특성)

  • Kwon, Boram;Kim, Hyunseok;Yi, Myong Jong
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.21 no.3
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    • pp.208-220
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    • 2019
  • The seasonality of leaf fall has important implications for understanding the response of trees' phenology to climate change. In this study, we quantified the leaf fall pattern with a model to estimate the timing and speed of leaf litter according to species and considered the nutrient use strategy of canopy species. In the autumns of 2015 and 2016, leaf litter was collected periodically using 36 litter-traps from the deciduous forests in Gwangneung and sorted by species. The seasonal leaf fall pattern was estimated using the non-linear regression model of Dixon. Additionally, the resorption rate was calculated by analyzing the nitrogen concentration of the leaf litter at each collection time. The leaf litter generally began in early October and ended in mid-November depending on the species. At the peak time (T50) of leaf fall, on average, Carpinus laxiflora was first, and Quercus serrata was last. The rate of leaf fall was fastest (18.6 days) for Sorbus alnifolia in 2016 and slowest (40.8 days) for C. cordata in 2015. The nitrogen resorption rates at T50 were 0.45% for Q. serrata and 0.48% for C. laxiflora, and the resorption rate in 2015 with less precipitation was higher than in 2016. Since falling of leaf litter is affected by environmental factors such as temperature, precipitation, photoperiod, and $CO_2$ during the period attached foliage, the leaf fall pattern and nitrogen resorption differed year by year depending on the species. If we quantify the fall phenomena of deciduous trees and analyze them according to various conditions, we can predict whether the changes in leaf fall timing and speed due to climate change will prolong or shorten the growth period of trees. In addition, it may be possible to consider how this affects their nutrient use strategy.

Development of Analytical Method for Kasugamycin in Agricultural Products using LC-MS/MS (LC-MS/MS를 이용한 농산물 중 Kasugamycin 시험법 개발)

  • Lee, Han Sol;Do, Jung-Ah;Park, Ji-Su;Cho, Sung Min;Shin, Hye-Sun;Jang, Dong Eun;Jung, Yong-hyun;Lee, Kangbong
    • Journal of Food Hygiene and Safety
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    • v.34 no.3
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    • pp.235-241
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    • 2019
  • An analytical method was developed for the determination of an antibiotic fungicide, kasugamycin, in agricultural products (hulled rice, potato, soybean, mandarin and green pepper) using liquid chromatographytandem mass spectrometry (LC-MS/MS). Samples were extracted with methanol adjusted to pH 13 using 1 N sodium hydroxide, and purified with a HLB (hydrophilic lipophilic balance) cartridge. Linearity of a matrix-matched calibration curve using seven concentration levels, from 0.001 to 0.1 mg/kg, was excellent with a correlation coefficient ($R^2$) of more than 0.9998. The limits of detection (LOD) and quantification (LOQ) of instrument were 0.0005 and $0.001{\mu}g/mL$, respectively, and the LOQ of analytical method calculated as 0.01 mg/kg. The average recoveries at three spiking levels (LOQ, $LOQ{\times}10$, $LOQ{\times}50$, n=5) were in the range of 71.2~95.4% with relative standard deviation of less than 12.1%. The developed method was simple and all optimized results was satisfied with the criteria ranges requested in the Codex guidelines and Food Safety Evaluation Department guidelines. The present study could be served as a reference for the establishment of maximum residue limits (MRL) of kasugamycin and be used as basic data for safety management relative to kasugamycin residues in imported and domestic agricultural products.

Anti-obesogenic Effect of Brassica juncea Extract on Bisphenol-A Induced Adipogenesis of 3T3-L1 Cells (비스페놀 A (Bisphenol-A)로 유도된 지방세포 분화에 미치는 갓 추출물의 항오비소겐 효과)

  • Lee, Se-jeong;Na, Uoon-Joo;Choi, Sun-Il;Han, Xionggao;Men, Xiao;Lee, Youn Hwan;Kim, Hyun Duk;Kim, Yoon Jung;Lee, Ok-Hwan
    • Journal of Food Hygiene and Safety
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    • v.36 no.6
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    • pp.528-536
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    • 2021
  • The purpose of the study was to investigate the content of sinigrin, an index component, in Brassica juncea extract and to evaluate the differentiation of lipocytes, inhibition of production of reactive oxygen species (ROS) and reduction of protein production by lipogenic factors (PPARγ, C/EBPα, aP2) in the processing of Brassica juncea extract and sinigrin in 3T3-L1 preadipocytes which induces Bisphenol A (BPA), an endocrine disrupting environmental hormone. From the investigation, the content of sinigrin in Brassica juncea extract, measured by HPLC, is found to be 21.27±0.2 mg/g. The XTT assay result on BPA-derived 3T3-L1 adipocytes shows there is no cytotoxicity found from 180 µM of sinigrin and 300 ㎍/mL of Brassica juncea extract. Moreover, both intracellular lipid accumulation and ROS production during differentiation of lipocyte are significantly reduced in cells processed with Brassica juncea extract and sinigrin. Lastly, it was also found that the production of transcription factors of lipocyte differentiation, PPARγ, C/EBPα and aP2, were found to be suppressed by the application of Brassica juncea extract and sinigrin. Such results reveals that Brassica juncea is effective in not only suppressing lipid accumulation in the environmental hormone bisphenol A-derived lipocyte, but also in reducing the ROS. The sinigrin-containing Brassica juncea is highly expected to be used in natural functional supplements that prevents the lipid metabolism disorders caused by BPA. There are necessities for additional clinical research and follow-up studies on the in vivo model to verify the relevant mechanisms.

Inhibitory Effect of Protaetiamycine 9 Derived from Protaetia brevitarsis seulensis Larvae on LPS-mediated Inflammation in RAW264.7 Cells (LPS로 자극한 RAW264.7 대식세포에서 흰점박이꽃무지 유충 유래 Protaetiamycine 9의 항염증 효과)

  • Choi, Ra-Yeong;Seo, Minchul;Lee, Joon Ha;Kim, In-Woo;Kim, Mi-Ae;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.31 no.11
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    • pp.987-994
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    • 2021
  • Our previous studies have reported that antimicrobial peptides (AMPs) derived from the larvae of white-spotted flower chafer (Protaetia brevitarsis seulensis) exert anti-inflammatory and neuroprotective activities. This study explored the anti-inflammatory effects of protaetiamycine 9 (CVLKKAYFLTNLKLRG-NH2), a novel AMP, derived from P. b. seulensis against lipopolysaccharide (LPS)-mediated inflammatory response in RAW264.7 macrophage cells. Protaetiamycine 9 (25, 50, 75, and 100 ㎍/ml) did not cause cytotoxic effects against RAW264.7 cells. The RAW264.7 cells were pre-treated with various concentrations of protaetiamycine 9 (25-100 ㎍/ml) for 1 hr and then exposed to LPS (100 ng/ml) for 24 hr. Protaetiamycine 9 treatments decreased the LPS-induced secretion of inflammatory mediators, such as nitric oxide (NO), in a dose-dependent manner. Protaetiamycine 9 (25-100 ㎍/ml) effectively downregulated the LPS-induced increase in mRNA and the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. Protaetiamycine 9 also suppressed the production and gene expression of pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, compared to the presence of LPS alone. Furthermore, protaetiamycine 9 inhibited the degradation of inhibitory kappa B alpha (IκB-α) and the phosphorylation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In conclusion, these results suggest that protaetiamycine 9 exhibits LPS-mediated inflammatory responses by blocking IκB-α degradation and MAPK phosphorylation.

A Comparative Study of Production of [68Ga]PSMA-11 with or without Cassette Type Modules (비 카세트 방식과 카세트 방식을 이용한 [68Ga]PSMA-11의 자동 합성 방법 비교)

  • Hyun-Sik, Park;Byeong-Min, Jo;Hyun-Ho, An;Hong-Jin, Lee;Jin-Hyeong, Lee;Gyeong-Jae, Lee;Byung-Chul, Lee;Won-Woo, Lee
    • The Korean Journal of Nuclear Medicine Technology
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    • v.26 no.2
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    • pp.15-19
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    • 2022
  • Purpose [68Ga]PSMA-11 is needed the high reproducibility, excellent radiochemical yield and purity. In term of radiation safety, the radiation exposure of operator for its production also should be considered. In this work, we performed a comparative study for the fully automated synthesis of [68Ga]PSMA-11 between non-cassette type and cassette type. Materials and Methods Two different type of modules (TRACERlab FX N pro for non-cassette type and BIKBox for cassette type) were used for the automated production of [68Ga]PSMA-11. According to the previously identified elution profile, Only 2.5 ml with high radioactivity was used for the reaction. After adjusting the pH of the reaction solution with HEPES buffer solution, the precursor was added and reacted with at 95 ℃ for 15 minutes. The reaction mixture was separated and purified using a C18 light cartridge. The product was eluted with 50% EtOH/saline solution and diluted with saline. It was completed by sterilizing filter. In the non-cassette type, the aforementioned process must be prepared directly. However, in the cassette method, synthesis was possible simply by installing a kit that was already completed. Results Both total [68Ga]PSMA-11 production time were 25±3(non-cassette type) and 23±3 minutes(cassette type). The radiochemical yield of the non-cassette type(65.5±5.7%) was higher than that of the cassette type(61.6±4.8%) after sterilization filter. The non-cassette type took about 120 minutes of preparation time before synthesis due to washing of synthesizer and reagent preparation. However, since the cassette type does not require washing and reagent preparation, it took about 20 minutes to prepare before synthesis. Both type of synthesizer had a radiochemical high purity(>99%). Conclusion The non-cassette type production of [68Ga]PSMA-11 showed higher radiochemical yield and lower cost than the cassette type. However, The cassette type has an advantage in terms of preparation time, convenience, and equipment maintenance.

홍삼 유래 성분들의 면역조절 효능

  • Jo, Jae-Yeol
    • 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.

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Inflammatory Reponse of the Lung to Hypothermia and Fluid Therapy after Hemorrhagic Shock in Rats (흰쥐에서 출혈성 쇼크 후 회복 시 저체온법 및 수액 치료에 따른 폐장의 염증성 변화)

  • Jang, Won-Chae;Beom, Min-Sun;Jeong, In-Seok;Hong, Young-Ju;Oh, Bong-Suk
    • Journal of Chest Surgery
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    • v.39 no.12 s.269
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    • pp.879-890
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    • 2006
  • Background: The dysfunction of multiple organs is found to be caused by reactive oxygen species as a major modulator of microvascular injury after hemorrhagic shock. Hemorrhagic shock, one of many causes inducing acute lung injury, is associated with increase in alveolocapillary permeability and characterized by edema, neutrophil infiltration, and hemorrhage in the interstitial and alveolar space. Aggressive and rapid fluid resuscitation potentially might increased the risk of pulmonary dysfunction by the interstitial edema. Therefore, in order to improve the pulmonary dysfunction induced by hemorrhagic shock, the present study was attempted to investigate how to reduce the inflammatory responses and edema in lung. Material and Method: Male Sprague-Dawley rats, weight 300 to 350 gm were anesthetized with ketamine(7 mg/kg) intramuscular Hemorrhagic Shock(HS) was induced by withdrawal of 3 mL/100 g over 10 min. through right jugular vein. Mean arterial pressure was then maintained at $35{\sim}40$ mmHg by further blood withdrawal. At 60 min. after HS, the shed blood and Ringer's solution or 5% albumin was infused to restore mean carotid arterial pressure over 80 mmHg. Rats were divided into three groups according to rectal temperature level($37^{\circ}C$[normothermia] vs $33^{\circ}C$[mild hypothermia]) and resuscitation fluid(lactate Ringer's solution vs 5% albumin solution). Group I consisted of rats with the normothermia and lactate Ringer's solution infusion. Group II consisted of rats with the systemic hypothermia and lactate Ringer's solution infusion. Group III consisted of rats with the systemic hypothermia and 5% albumin solution infusion. Hemodynamic parameters(heart rate, mean carotid arterial pressure), metabolism, and pulmonary tissue damage were observed for 4 hours. Result: In all experimental groups including 6 rats in group I, totally 26 rats were alive in 3rd stage. However, bleeding volume of group I in first stage was $3.2{\pm}0.5$ mL/100 g less than those of group II($3.9{\pm}0.8$ mL/100 g) and group III($4.1{\pm}0.7$ mL/100 g). Fluid volume infused in 2nd stage was $28.6{\pm}6.0$ mL(group I), $20.6{\pm}4.0$ mL(group II) and $14.7{\pm}2.7$ mL(group III), retrospectively in which there was statistically a significance between all groups(p<0.05). Plasma potassium level was markedly elevated in comparison with other groups(II and III), whereas glucose level was obviously reduced in 2nd stage of group I. Level of interleukine-8 in group I was obviously higher than that of group II or III(p<0.05). They were $1.834{\pm}437$ pg/mL(group I), $1,006{\pm}532$ pg/mL(group II), and $764{\pm}302$ pg/mL(group III), retrospectively. In histologic score, the score of group III($1.6{\pm}0.6$) was significantly lower than that of group I($2.8{\pm}1.2$)(p<0.05). Conclusion: In pressure-controlled hemorrhagic shock model, it is suggested that hypothermia might inhibit the direct damage of ischemic tissue through reduction of basic metabolic rate in shock state compared to normothermia. It seems that hypothermia should be benefit to recovery pulmonary function by reducing replaced fluid volume, inhibiting anti-inflammatory agent(IL-8) and leukocyte infiltration in state of ischemia-reperfusion injury. However, if is considered that other changes in pulmonary damage and inflammatory responses might induce by not only kinds of fluid solutions but also hypothermia, and that the detailed evaluation should be study.

The Effect of Platelets on Endothelin Production in Bovine Pulmonary Artery Endothelial Cells (혈소판이 소 폐동백 내피세포의 Endothelin 생산에 미치는 효과)

  • Lee, Sang-Do;Shim, Tae-Sun;Kwon, Seog-Woon;Ryu, Jin-Sook;Lee, Jae-Dam;Lim, Chae-Man;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.5
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    • pp.1114-1124
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    • 1997
  • Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

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