• 대한통합의학회지
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• 제12권1호
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• pp.1-10
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• 2024

Purpose: Lycopene is abundantly contained in Tomatoes and is known for diverse biological activities such as antioxidant, anti-inflammatory, and anticancer effects. In this study, the antioxidative potential of lycopene was investigated through the induction of hemeoxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor2 (Nrf2) and upstream signaling molecules, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Aktin RAW 264.7 cells. Methods: The antioxidative potential of lycopene against oxidative stress and its molecular mechanisms were determined by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results: Lycopene treatment significantly attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS formation in a dose-dependent manner without any cytotoxicity. In addition, 50 µM of lycopene for 6 h treatment induced potent HO-1 expression and its transcription factor, Nrf2. MAPK and PI3K/Aktwere also analyzed due to their critical roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, phosphorylation of extracellular regulated kinase (ERK) was significantly induced by lycopene treatment while the activated status of c-Jun NH2-terminal kinase (JNK), p38, and Akt, were not given any effect. To confirm the antioxidative mechanism of HO-1 mediated by ERK activation, each selective inhibitor was employed in a protection assay, in which oxidative damage occurred by t-BHP. Lycopene, SnPP, and CoPP treatments reflected accelerated HO-1 expression could be a protective role against oxidative damage-initiated cell death. A selective inhibitor for ERK significantly inhibited the lycopene-induced cytoprotective effect but selective inhibitors for other signaling molecules did not attenuate the rate of t-BHP-induced cell death. Conclusion: In conclusion, lycopene potently scavenged intracellular ROS formation and enhanced the HO-1 mediated antioxidative potential through the modulation of Nrf2, MAPK signaling pathway in RAW 264.7 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제17권6호
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• pp.511-516
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• 2013

Bladder cancer is the seventh most common cancer in men that smoke, and the incidence of disease increases with age. The mechanism of occurrence has not yet been established. Potassium channels have been linked with cell proliferation. Some two-pore domain $K^+$ channels (K2P), such as TASK3 and TREK1, have recently been shown to be overexpressed in cancer cells. Here we focused on the relationship between cell growth and the mechanosensitive K2P channel, TREK2, in the human bladder cancer cell line, 253J. We confirmed that TREK2 was expressed in bladder cancer cell lines by Western blot and quantitative real-time PCR. Using the patch-clamp technique, the mechanosensitive TREK2 channel was recorded in the presence of symmetrical 150 mM KCl solutions. In 253J cells, the TREK2 channel was activated by polyunsaturated fatty acids, intracellular acidosis at -60 mV and mechanical stretch at -40 mV or 40 mV. Furthermore, small interfering RNA (siRNA)-mediated TREK2 knockdown resulted in a slight depolarization from $-19.9mV{\pm}0.8$ (n=116) to $-8.5mV{\pm}1.4$ (n=74) and decreased proliferation of 253J cells, compared to negative control siRNA. 253J cells treated with TREK2 siRNA showed a significant increase in the expression of cell cycle boundary proteins p21 and p53 and also a remarkable decrease in protein expression of cyclins D1 and D3. Taken together, the TREK2 channel is present in bladder cancer cell lines and may, at least in part, contribute to cell cycle-dependent growth.

• Journal of Ginseng Research
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• 제41권3호
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• pp.247-256
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• 2017

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

• The Korean Journal of Physiology and Pharmacology
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• 제26권1호
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• pp.37-45
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• 2022

The aim of the present study was to investigate the physiological role of nicotinamide phosphoribosyltransferase (NAMPT) associated with odontogenic differentiation during tooth development in mice. Mouse dental papilla cell-23 (MDPC-23) cells cultured in differentiation media were stimulated with the specific NAMPT inhibitor, FK866, and Visfatin (NAMPT) for up to 10 days. The cells were evaluated after 0, 4, 7, and 10 days. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mineralization assay was performed by staining MDPC-23 cells with Alizarin Red S solution. After cultivation, MDPC-23 cells were harvested for quantitative PCR or Western blotting. Analysis of variance was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at p < 0.05. The expression of NAMPT increased during the differentiation of murine odontoblast-like MDPC-23 cells. Furthermore, the up-regulation of NAMPT promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers, such as dentin sialophosphoprotein, dentin matrix protein-1, and alkaline phosphatase in MDPC-23 cells. However, treatment of the cells with the NAMPT inhibitor, FK866, attenuated odontogenic differentiation, as evidenced by the suppression of odontoblastic biomarkers. These data indicate that NAMPT regulated odontoblastic differentiation through the regulation of odontoblastic biomarkers. The increase in NAMPT expression in odontoblasts was closely related to the formation of the extracellular matrix and dentin via the Runx signaling pathway. Therefore, these data suggest that NAMPT is a critical regulator of odontoblast differentiation during tooth development.

• Animal cells and systems
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• 제14권4호
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• pp.275-282
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• 2010

Chunghyul-dan (CHD) is a combinatorial drug known to exert anti-inflammatory effects in endothelial cells. In this study, we employed global transcriptional profiling using cDNA microarrays to identify molecular mechanisms responsible for the anti-inflammatory activity of CHD in endothelial cells. An analysis of the microarray data revealed that transcript levels of monocyte chemotactic protein-1 (MCP-1), vascular cell-adhesion molecule-1 (VCAM-1) and activated leukocyte cell-adhesion molecule were dramatically altered in CHD-treated endothelial cells. These changes in gene expression were confirmed by RT-PCR, Western blotting and ELISA. Chronic CHD treatment also appeared to decrease MCP-1 secretion, probably as a result of decreased MCP-1 expression. In addition, we determined that chronic CHD treatment inhibited lipopolysaccharide-stimulated adhesion of THP-1 leukocytes to endothelial cells. The inhibitory effect of CHD on LPS-stimulated adhesion resulted from downregulation of VCAM-1 expression. Transmigration of THP-1 leukocytes through endothelial cells was also inhibited by chronic CHD treatment. In conclusion, CHD controls a variety of inflammatory activities by regulating MCP-1 and VCAM-1 gene expression.

• 여성건강간호학회지
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• 제4권2호
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• pp.145-161
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• 1998

This correlational study sought to find the relationship among women's health status and the level of importance & performance of postpartal care. One hundred thirty three women who live in Seoul and rural area including hospitalized in a general hospital and midwifery clinic were studied from 1st April, 1998 to 25th April, 1998 for 25 days. Data analysis consisted of frequency, percentage, Pearson Correlation Coefficiency, t-test, ANOVA and Sheffe test as a post hoc, using SPSS. The results of analysis were as follows ; mean age of respondents was 31.9 years and mean number of children was 1.8. The most of family type was nuclear family and lived int apartment. Mean frequency of pregnancy was 2.7 times and most women delivered at local clinic, general or University hospital. Mean period of after delivery was 53.7 month. The level of importance and performance of traditional postpartal care (Sanhujori) was more higher than hospital postpartal care. The level of importance, performance of postpartum care and health status had significant relationship. The higher level of importance was, & the higher level of performance was higher, and the higher degree of health status. The factors related to health status were postabortal sahujori period after abortion, nuclear family, the evaluation of sahujori, whether women and followed the caregiver's advice well or not and whether they have physical symptoms or not, at the level of $5{\sim}0.1%$ of significance statistically. The factors related to the level of importance of postpartal care were the number of child, present health status and health status of pre-post of delivery, deliver place and the opinion of effective postpartum care method at the level of $5{\sim}0.1%$ of significance statistically. The factors related to the level of performance of postpartal care were delivery place, the opinion of whether they can do at the hospital or not and whether they have physical symptom or not at the level of $1{\sim}0.1%$ of significance statistically. In conclusion, this finding reconfirmed the relationship among women's health status and the postpartal care. It provides a challenge to the health professional caregivers to research continually and repeatedly and confirm the conceptual model of Sanhujori, reestablish effective and integrative postpartal caring system which contains oriental and western paradigm for women's life long health toward the 21C.

• 한국식품과학회지
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• 제37권2호
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• pp.321-327
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• 2005

본 연구는 서부경남지역 딸기 농장 세 곳에서 Staphylococcus aureus를 검색하기 위하여 수행하였다. 본 연구를 위하여 각 농장의 토양과 수질, 재배시설, 포장시설, 작업자 그리고 딸기와 잎으로부터 총 71점의 시료를 채취하였다. 채취된 시료 중 16%의 시료가 Staphylococcus aureus에 오염되어 있는 것으로 나타났으며 이들 균들이 내열성 독소인 enterotoxin A, B, C를 생성할 수 있는 gene의 유무를 확인하기 위하여 PCR를 수행하였다. 그 결과 분리된 균주의 92%가 sea gene을 가지는 것으로 나타났으며 seb gene의 경우는 분리된 균주의 38%에서 나타났다. 그러나 sec를 생성하는 균주는 없었다. 따라서 딸기의 미생물학적 오염을 예방하기 위해서는 체계적인 위생관리 시스템인 운수농산물관리제도(GAP)를 도입해야 할 것으로 사료된다.

• 한국식품과학회지
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• 제38권2호
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• pp.295-303
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• 2006

본 연구는 서부 경남지역 토마토 농장 5 곳에서 총 120점의 시료를 수집하여 S. aureus를 분리하였으며, 분리된 S. aureus 에대하여 PCR에 방법을 이용, 내독소 유전자(enterotoxin genes)와디스크 확산방법(disk diffusion method)을 이용하여 22가지 항생제에 대하여 항생제 감수성 실험을 수행하였다. 본 연구의 결과 14점의 시료(11.7%)가 S. aureus에 오염되어 있었다. 가장 빈번하게 검출된 시료로는 관개용수, 양액, 작업자의 손 그리고 토마토였다. 또한 14개의 시료에서 enterotoxin 유전자가 검출되었고, 이들 중 sea 유전자를 갖는 균주는 2주(14.3%), sea와 sed 유전자를 동시에 갖는 균주가 3주(21.4%), sea, sed 및 see 유전자가 모두 검출된 균주는 7주(50.0%)였다. 그러나 sec, sed와 tsst유전자를 갖는 균주는 검출되지 않았다. 분리된 균주를 대상으로 항생제 내성실험결과 penicillin에 대한 항생제 내성이 64.3%로 뚜렷하게 높은 것으로 나타났다. 그 외 novobiocin(57.1%)에 대하여 8 균주, amphicillin(42.9%)에 대하여 6균주, erythromycin(13.4%), oxacillin (14.2%)에 대하여 2 균주, kanamycin(7.2%), doxycycline(7.2%)에대하여 1 균주가 내성을 나타내었다. 특히 B 농장의 롤러와 D 농장의 양액에서 분리된 균주는 oxacillin에 내성을 갖는 MRSA(Methicillin Resistant S. aureur)균주였다. 따라서 본 연구결과는 안전 농산물 생산을 위한 미생물학적 정보를 제공할 수 있을 것으로 사료되는 바이다.

• 과학기술학연구
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• 제5권1호
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• pp.55-92
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• 2005

한국에서 중요한 과학적 개념의 형성과 그 사회적 유통에 기여하는 것은 미국과 유럽, 그리고 일본에서 형성, 성숙, 정립된 후에 한국으로 유입되고 수용되는 과학 지식과 한국 사회가 근대화의 과정에 형성한 제도이다. 유전적 정보라는 개념도 이러한 맥락에서 예외일 수는 없다. 유전적 정보 개념은 고전적 유전학의 틀에서 이해되는 유전, 또는 계승성의 개념에서 인간유전체 연구사업의 와중에서 등장하여 성숙한 유전체학과 생물정보학에 의해 확대 심화된 것이다. 본 연구는 서구적 개념 및 지식 생산 구조를 모델로 하는 개념적, 과학지식적, 제도적 통합성을 기준으로 한국에서 유전적 정보의 생산 구조가 어떻게 형성되어 있는가에 대한 것이다. 한국에서 1980년대 중반에 나타났던 유전공학 담론은 한국에서 분자생물학의 발달은 촉진시켰지만, 생화학-생화학교실과 같은 균형성이 없이 유전공학-유전학교실의 불균형성이 존재하게되었다. 주로 의과대학의 (인간)유전학과 혹은 유전학교실의 수와 질에 있어서의 부족함 때문에 생명과학 전체에 미치는 영향력에서도 크게 성공하지 못했고, 통합적, 거시적 발전을 이루지 못한 것으로 보인다. 유전학의 발전적 재구성이라고 할 수 있는 유전체학은 한국에서는 유럽, 미국, 일본의 인간유전체연구사업의 발전 궤적의 '기초단계' 혹은 '제 1기' 형태에는 거의 인프라, 투자, 연구개발이 없었고 기능유전체학과 단백체학을 중심으로 하는 '성숙단계' 혹은 '제 2기' 형태를 주축으로 하여 한국의 연구개발이 진행되고 있다. 유전체학과 같이 발달한 생물정보학에는 내적 구조에 이미 정보학과 연결되는 논리와 내용을 가지고 있는데, 한국에서는 정보기술(IT)의 아류 정도로 보는 편협하고 왜곡된 시각이 주도적인 가운데 시작된 것으로 보인다. 결과적으로 한국 생물정보학은 유전학 및 생명과학과의 통합적인 면에서는 결함을 노출하고 있다. 이러한 유전적 정보의 생산 구조가 가지는 문제점으로 인하여 한국에서 유전적 정보는 기초가 부실한 편이며 파편화된 유형으로 생산되어 나올 개연성을 가진다. 개념적, 제도적인 파편화의 사례는 개인식별의 유전학이 기존의 유전공학-유전학교실 체제로 흡수되지 못하고 의과대학 법의학교실에서 전문성과 연구실천을 확보한 것에서도 확인된다. 유전적 정보의 생산 구조에 영향을 미치는 환경은 한국의 생명공학과 시민사회운동으로 존재한다.