• Title/Summary/Keyword: Human effects

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Gemcitabine-induced Cell Death in Lung Cancer Cells : the Role of p53 (폐암 세포에서 Gemcitabine에 의한 세포 사멸과 p53의 역할)

  • Kim, Doh-Hyung;Bae, Gang-U;Yong, Wha-Shim;Choi, Eun-Kyung;Kim, Youn-Seup;Park, Jae-Seuk;Jee, Young-Koo;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.275-284
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    • 2002
  • Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

The Effect of Inhibition of Heme Oxygenase-1 on Chemosensitivity of Cisplatin in Lung Cancer Cells (폐암세포주에서 Heme Oxygenase-1의 억제가 Cisplatin의 항암제 감수성에 미치는 영향)

  • Kim, So-Young;Kim, Eun-Jung;Jang, Hye-Yeon;Hwang, Ki-Eun;Park, Jung-Hyun;Kim, Hwi-Jung;Jo, Hyang-Jeong;Yang, Sei-Hoon;Jeong, Eun-Taik;Kim, Hak-Ryul
    • Tuberculosis and Respiratory Diseases
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    • v.62 no.1
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    • pp.33-42
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    • 2007
  • Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide ($H_2O_2$) generation was monitored fluoimetrically using 2',7'-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin.

A Study on the Measurement of the Dimensionless Light Extinction Constant for Particulate Matter from Fuel Oil for Marine and Land Diesel Engines (선박 및 육상 디젤 엔진용 연료유에서 발생하는 입자상물질에 대한 무차원 광소멸계수 계측에 관한 연구)

  • Rho, Beom-Seok;Choi, Jae-Hyuk;Cho, Kwon-Hae;Park, Seul-Hyun;Lee, Won-Ju
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.24 no.2
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    • pp.275-281
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    • 2018
  • It is known that he pollutant emitted from the combustion process of marine fuel oil causes air pollution and harmful effects to the human body. Accordingly, IMO regulates pollutants emitted from ships. However, the regulation of Particulate Matter (PM) is still in the process of debate, so preemptive action is needed. Fundamental research on PM is essential. In this study, the Dimensionless Light Extinction Constant ($K_e$) of fuel oil used in marine diesel engines was measured and analyzed to construct the basic data of the PM generated from marine-based fuel oil. The fuel oil used in the land diesel engine was measured in the same way for character comparison. Both fuel oils differ in sulfur content and density. The $K_e$ was measured via the optical method using a 633 nm laser and was determined by using the volume fraction of PM collected by the gravimetric filter method. The $K_e$ of the PM discharged from marine fuel oil is 8.28, and the land fuel oil is 8.44. The $K_e$ of two fuel oils was similar within the measurement uncertainty range. However, it was found by comparison with the value obtained by the Rayleigh-Limit solution that the light scattering portion could be large. Also, it was found that light extinction characteristics could be different due to the relationship between light transmittance and collected mass.

Antioxidant Effect and Component Analysis of Cardiospermum halicacabum Leaf Extracts (풍선덩굴 잎 추출물의 항산화 효과 및 성분 분석)

  • Jeong, Hyo Jin;Kim, A Rang;Lee, Keon Soo;Park, So Hyun;Shin, Hyuk Soo;Lee, Sang Rae;Song, Ba Reum;Lee, Yun Ju;An, Hyun Jin;Lee, Jae Duk;Park, Soo Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.43 no.2
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    • pp.175-187
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    • 2017
  • In this study, the antioxidant effect and component analysis for extract and fractions of Cardiospermum halicacabum leaf were investigated. All experiments were performed with 50% ethanol extract, ethyl acetate fraction and aglycone fraction obtained from dried C. halicacabum leaf. The yields of extract and fractions were 16.4, 0.9 and 0.3% per dried powder, respectively. DPPH (1,1-phenyl-2-picrylhydrazyl) radical scavenging activity ($FSC_{50}$) of ethyl acetate fraction ($92.5{\mu}g/mL$) was the greatest radical scavenging activity, but lower than (+)-${\alpha}$-tocopherol ($8.9{\mu}g/mL$). In reactive oxygen species (ROS) scavenging activity (total antioxidant capacity, $OSC_{50}$) on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system, aglycone fraction ($4.2{\mu}g/mL$) was the highest total antioxidant capacity and similar to L-ascorbic acid ($1.5{\mu}g/mL$). The cellular protective effects of C. halicacabum leaf extract and fractions on the $^1O_2$-induced cellular damage of human erythrocytes were exhibited at all concentration-dependent ($5.0-25.0{\mu}g/mL$). Especially, aglycone fraction (${\tau}_{50}$, 76.4 min) in $25.0{\mu}g/mL$ showed the most protective effect among extracts. Components of the ethyl acetate fraction obtained from C. halicacabum extracts were analyzed by TLC, HPLC chromatogram and LC/ESI-MS. Results showed that the ethyl acetate fraction contained some flavonoids, such as apigenin-7-O-glucuronide, apigenin-7-glucosdie and quercitrin hydrate. These results suggest that the extracts and fractions of C. halicacabum leaf may be applied as antioxidant functional cosmetic raw materials.

Negative apparent resistivity in dipole-dipole electrical surveys (쌍극자-쌍극자 전기비저항 탐사에서 나타나는 음의 겉보기 비저항)

  • Jung, Hyun-Key;Min, Dong-Joo;Lee, Hyo-Sun;Oh, Seok-Hoon;Chung, Ho-Joon
    • Geophysics and Geophysical Exploration
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    • v.12 no.1
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    • pp.33-40
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    • 2009
  • In field surveys using the dipole-dipole electrical resistivity method, we often encounter negative apparent resistivity. The term 'negative apparent resistivity' refers to apparent resistivity values with the opposite sign to surrounding data in a pseudosection. Because these negative apparent resistivity values have been regarded as measurement errors, we have discarded the negative apparent resistivity data. Some people have even used negative apparent resistivity data in an inversion process, by taking absolute values of the data. Our field experiments lead us to believe that the main cause for negative apparent resistivity is neither measurement errors nor the influence of self potentials. Furthermore, we also believe that it is not caused by the effects of induced polarization. One possible cause for negative apparent resistivity is the subsurface geological structure. In this study, we provide some numerical examples showing that negative apparent resistivity can arise from geological structures. In numerical examples, we simulate field data using a 3D numerical modelling algorithm, and then extract 2D sections. Our numerical experiments demonstrate that the negative apparent resistivity can be caused by geological structures modelled by U-shaped and crescent-shaped conductive models. Negative apparent resistivity usually occurs when potentials increase with distance from the current electrodes. By plotting the voltage-electrode position curves, we could confirm that when the voltage curves intersect each other, negative apparent resistivity appears. These numerical examples suggest that when we observe negative apparent resistivity in field surveys, we should consider the possibility that the negative apparent resistivity has been caused by geological structure.

EFFECTS OF GINSENG COMPONENTS ON RODENTICIDE VACOR-INDUCED DIABETES MELLITUS IN RATS (인삼성분이 살서제(Vacor)로 유발시킨 쥐의 당뇨에 미치는 영향)

  • Lee Min-wha;Lee Tai-hee;Ahn Bong-whan;Park Byung-ju;Yang Sung-yeul
    • Proceedings of the Ginseng society Conference
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    • 1984.09a
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    • pp.83-88
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    • 1984
  • It is now well established that the rodenticide Vacor (N-3-pyridyl-mehtyl-N'-p-nitropheny-lurea) causes a hyperglycemia in human and rats. It is also reported that there are some components (DPG-3) in ginseng radix which cause hypoglycemic effect on alloxan diabetic mice. In the present study, attempts were made to demonstrate in Vacor-poisoned rats the hypo-glycemic activity of red ginseng component(RGC), which was extracted by Kimura's DPG-3 extraction procedure and found to be effective for lowering a hyperglycemia in alloxan-diabetic rats. Vacor in a dose of $LD_{50}$ (10mg/kg) produced a glucose intolerance with a paradoxical moderate increase in blood immunoreactive insulin and derangement in glucose metabolism of epididymal adipocytes in rats. Although RGC (20mg/kg, i.p.) did not exert any significant influence on a hyperglycemia induced by large lethal doses (25mg/kg) of Vacor ingestion, it improved the LDso Vacor-induced glucose intolerance and caused a further increase in blood insulin levels in Vacor-poisoned rats. The administration of RGC (20mg/kg, i.p.) normalized Vacor-induced depression of glucose metabolism and lipogenesis in the epididymal adipocytes with an improvement of reduced responses to insulin of adipocytes from Vacor-poisoned rats. These results suggest that some red ginsneng components contained in RGC fraction normalize the depressed peripheral glucose unitlization and insulin response and eventually lead to an improvement of abnormal glucose tolerance developed in rats poisoned with small doses of Vacor.

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Anti-inflammatory Activity of Peel Extracts in Color-fleshed Potatoes (컬러감자외피 추출물의 항염활성)

  • Nam, Jung-Hwan;Jeong, Jin-Cheol;Kwon, Oh-Keun;Hong, Su-Young;Kim, Su-Jeong;Soh, Hwang-Bae;Lee, Jong-Nam;Lee, Kyung-Tea;Park, Hee-Jhun
    • Korean Journal of Plant Resources
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    • v.26 no.5
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    • pp.533-538
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    • 2013
  • Potatoes were first introduced outside the Andes region four centuries ago, and have become an integral part of much of the world's food. Potatoes were first introduced into Europe in the 16th century and Korea in the early 19th century. In the nutritional aspects, potatoes contain abundant vitamins and minerals, as well as an assortment of phytochemicals such as carotenoids and natural phenols. Chlorogenic acid constitutes up to 90% of potato natural phenols. Due to the high content of potato functional compounds, it has known that potatoes are effective in the prevention of various human diseases. Recently, color-fleshed potatoes 'Hongyoung' and 'Jayoung' were developed by RDA, and it has reported that they have high content of anthocyanin. Additionally they show higher radical scavenging activity compared to white or yellow fleshed potatoes. So it will be expected that the consumption of color-fleshed potatoes grandually increase by pre-peeled potatoes and color potato chips. This study was conducted to enhance the peel of color-fleshed potatoes utilization and to determine the biological activity of peel of color-fleshed potatoes extract. The anti-inflammatory effects on ethanol extract and its solvent fraction were also evaluated. The anti-inflammatory activities of $CHCl_3$ fraction was evaluated for inhibitory activities against lipopolysacchride(LPS) induced nitric oxide(NO) and prostaglandin $E_2(PGE_2)$ production as well as inducible nitric oxide synthase(iNOS) and cyclo oxygenase-2(COX-2) protein expressions in RAW264.7 cell lines. The fraction inhibitory activity for both tests with $IC_{50}$ values showed in the ranges of $25{\sim}50{\mu}g/ml$. This result revealed that $CHCl_3$ fraction of Jayoung's peel is expected to be good candidate for development into source of anti-inflammatory agent.

Antimicrobial Effect of Commercially Available Mouth Rinsing Solutions and Natural Herbal Extracts on Streptococcus mutans (시판되는 구강양치액과 천연한방 추출물의 Streptococcus mutans에 대한 항균효과 비교)

  • Kim, Sung-Im;Jeong, Moon-Jin;Ahn, Yong-Soon;Kim, A-Reum;Kim, Mi-Na;Lim, Do-Seon
    • Journal of dental hygiene science
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    • v.15 no.3
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    • pp.308-317
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    • 2015
  • This study attempted to identify the possibility of natural herbal extracts as an alternative, preventive agent of caries by comparing antimicrobial activities between natural herbal extracts and mouth rinsing solutions against Streptococcus mutans. Natural herbal plants were extracted with distilled water and ethanol, respectively, to measure the minimum growth inhibitory concentration of S. mutans depending on concentration, and among which, solvents showing high antimicrobial activity were selected to compare their antibiotic effects with those of mouth rinsing solutions. Also, to determine the concentration of natural medicinal herbs that can be used safely in the oral cavity, the extracts were treated to the normal gingival fibroblast cells depending on concentration in order to determine its cytotoxicity using MTT. In terms of the minimum growth inhibition concentration, the growth inhibition of S. mutans was more excellent in the ethanol extract than in the distilled water. When the minimum growth inhibition concentration was compared, Psoralea corylifolia of natural herbal ethanol extracts, and Hexamedine (Bukwang Pharm., Korea) of mouth rinsing solutions inhibited growth of S. mutans at the lowest concentration. When the minimum bactericidal concentration was compared, P. corylifolia of natural herbal extracts, and Hexamedine and Garglin (Dong-A Pharm., Korea) of mouth rinsing solutions eliminated S. mutans at a low concentration. The human gingival fibroblast was treated with natural herbal ethanol extracts at the minimum growth inhibition concentration of 10, 39, and $78{\mu}g/ml$. As the result, no cytotoxicity was found. When this was treated at different minimum bactericidal concentrations, natural herbal ethanol extracts showed cytotoxicity except P. corylifolia.

Evaluation of the testicular toxicity caused by 2-bromopropane in rats (랫드에 있어서 2-bromopropane에 의해 유발된 정소독성의 평가)

  • Kim, Jong-choon;Lee, Hyun-sook;Yun, Hyo-in;Chung, Moon-koo
    • Korean Journal of Veterinary Research
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    • v.40 no.2
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    • pp.361-371
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    • 2000
  • It has been recently reported that 2-bromopropane (2-BP) induces male reproductive toxicity in both human and experimental animals. However, delayed effects of 2-BP on male reproductive system have not been investigated in detail. The present study was conducted to investigate the testicular toxicity of 2-BP and to determine the recovery of normal spermatogenesis in Sprague-Dawley rats. Male rats aged 5 weeks were administered 1,000mg/kg 2-BP by gavage daily for 4 weeks and sacrificed sequentially at 1, 2, 3, 4 and 12 weeks after initiation of 2-BP treatment. Testicular toxicity was evaluated qualitatively by histopathological examinations and quantitatively by reproductive organ weights, spermatid head count, and repopulation index. In the 2-BP treated rats, the body weights was significantly suppressed and the weights of testes and epididymides were also decreased in a time-dependent manner. On histopathological examination, spermatogonia in stages I-VI and preleptotene and leptotene spermatocytes in stages VII-IX were strongly depleted at 1 week of dosing. Spermatogonia were depleted extensively in all spermatogenic stages at 2 weeks. Continuing with the evolution of spermatogenic cycle, zygotene spermatocytes, pachytene spermatocytes, and round spermatids were sequentially depleted at 2, 3, and 4 weeks of dosing due to the depletion of their precursor cells. Vacuolization of Sertoli cells and spermatid retention were also observed at all time points, suggesting that 2-BP induced Sertoli cell dysfunction. At 12 weeks, after 8 weeks recovery, most of the tubules appeared severely atrophic and were lined by Sertoli cells only. Leydig cell hyperplasia in the interstitial tissue was also found. In addition, dramatic reductions in the number of spermatid heads and repopulation index were observed, indicating that 2-BP-induced testicular injury is irreversible. These results indicate that 4 weeks repeated-dose of 1,000mg/kg 2-BP results in a progressive germ cell loss due to the depletion of spermatogonia followed by long-term testicular atrophy in SD rats.

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Ethanol Extract of Schisandra chinensis (Turcz.) Baill. Reduces AICAR-induced Muscle Atrophy in C2C12 Myotubes (마우스 C2C12 근관세포에서 AICAR로 유도된 근위축에 미치는 오미자 추출물의 영향)

  • Kang, Young-Soon;Park, Cheol;Han, Min-Ho;Hong, Su-Hyun;Hwang, Hye-Jin;Kim, Byung Woo;Kim, Cheol Min;Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.3
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    • pp.293-298
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    • 2015
  • Muscle atrophy, known as a sarcopenia, is defined as a loss of muscle mass resulting from a reduction in the muscle fiber area or density due to a decrease in muscle protein synthesis and an increase in protein breakdown. Schisandrae fructus (SF) extract of the fruits of Schisandra chinensis (Turcz) Baillon has been used as a tonic in traditional medicine for thousands of years. Although a great deal of work has been carried out on the therapeutic potential of SF, its pharmacological mechanisms of action in muscle diseases actions remain unclear. In the present study, we investigated the inhibitory effects of SF ethanol extracts on the production of muscle atrophy factors in C2C12 myotubes stimulated with 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR), an AMP-activated kinase (AMPK) activator, and sought to determine the underlying mechanisms of action. AICAR upregulated atrophy-related ubiquitin ligase muscle RING finger-1 (MuRF-1) and stimulated the levels of the forkhead box O3a (FoxO3a) transcription factor in the C2C12 myotubes. SF supplementation effectively and concentration- dependently counteracted AICAR-induced muscle cell atrophy and reversed the increased expression of MuRF-1 and FoxO3a. Our study demonstrates that SF can reverse the muscle cell atrophy caused by AICAR through regulation of the AMPK and FoxO3a signaling pathways, followed by inhibition of MuRF-1.