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.
Kim, Byung-Tae;Lee, Kyung-Han;Kim, Sang-Eun;Choi, Yong;Chi, Dae-Yoon;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon;Chung, Hong-Keun
The Korean Journal of Nuclear Medicine
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v.29
no.3
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pp.332-342
/
1995
This study was designed to evaluate the effects of various factors on the therapeutic effect of the I-131 labeled anti-carcinoembryonic antigen monoclonal antibody(anti-CEA antibody). Tetrazolium-based colorimetric assay (MTT) was used to compare in vitro cytotoxicity of 3 Korean colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5) for selection of proper 2 cell lines in this study. The changes of the size of tumor which was xenografted to nude mice (balb/c nu/nu) were compared in 4 groups (group treated I-131 labeled anti-CEA antibody, group treated with non-radiolabeled anti-CEA antibody, group treated with I-131 labeled anti-human chorionic gonadotropin monoclonal antibody (anti-hCG antibody) as nonspecific antibody, and group injected with normal saline as a control). Immunohistochemical staining and in vivo autoradiography were performed after excision of the xenografted tumor. The results were as below mentioned. The in vitro cytotoxic effect of I-131 labeled anti-CEA antibody is most prominent in SNU-C5 cell line between 3 cancer cell lines. The changes of xenografted tumor size in both SNU-C4 and SNU-5S cell tumors at the thirteenth day after injection of the antibodies were smallest in the group treated with I-131 labeled anti-CEA antibody (SNU-C4/SNU-C5; 324/342%) comparing with other groups, group treated with anti-CEA antibody (622/660%), group treated with I-131 anti-hCG antibody (538/546%), and control group(1030/724%)(P<0.02 in SNU-C4 and P<0.1 in SNU-C5 at the 13th day after injection of antibodies). On the thirteenth day after injection of the antibodies nude mice were sacreficed to count the radiouptake of tumor and to check the changes of tumor size. Correlations between radiouptake and change of tumor size were calculated in each groups and significant negative correlation was only obtained in the group treated with I-131 anti-CEA antibody (p<0.05). There were no correlations between antigenic expression of carcinoembryonic antigen and distribution of anti-CEA antibody in both SNU-C4 and SNU-C5 cell tumors on immunoperoxidase staining. On in vivo autoradiography the distributions of anti-CEA antibody were heterogeneous and the intensities of binding were various in SNU-C4 and SNU-C5 cell tumors. It is concluded that I-131 labeled tumor-specific monoclonal antibody, anti-CEA antibody is effective in suppressing the xenografted tumor growth and the effect is influenced by sensitivity of tumor cell itself to the radiolabeled antibody and other local factors instead of specificity of antibody.
The artificially grown forests of larch, planted in accordance with the nationwide afforestation policy in the 1970s, are located inside national parks. This study intended to induce a forestation system by which the forests develop into an ecologically healthy and broadleaved ecosystem with broad species diversity. For this, the aspects of natural regeneration of broadleaves from 2010 to 2013 after thinning by density (30%, 50%, and 70%) in 2009 were surveyed using the larch forest in the Woljeong Temple region inside Odaesan National Park. There were no trees that were larger than 2 cm in in diameter at breast height among the trees recently introduced between 2012 and 2013. A significant number of herbs have been introduced to the subsurface alongside young arboreal trees species such as Bumalda bladdernut, Acer triflorum, Cornus controversa etc and shrubs. However, many woody species did not survive the competition with herbs and repeated withering and regeneration. The number of woody species generated within the 30% cutting area was 440 species in 2013 and this figure has been increasing twofold each year. The number of woody plants within the 50% cutting area also showed an upward tendency and most plants did not survive in the competition with herbs and Sasa borealis and withered in only 1 ~ 2 years after generation. Unlike other thinning areas, the 70% cutting area showed 608 broadleaved trees, reflecting a decrease from 748 trees in 2012. This appeared to be attributed to the luxuriance of S. borealis and the sharp increase of fatsia following the inflow of total sunlight to the forest floor. Herbs were hardly generated due to the influence of S. borealis. Regarding the density for thinning at 50% or upper height, the forest treatment division shall maintain a proper density in the course of inducing artificial forestation of larch into natural broadleaved forests considering the luxuriance of sasa borealis and herbs due to the inflow of total sunlight to the forest floor.
Purpose: To test the radiosensitizing effect of the newly synthesized novel histone deacetylase inhibitor, SK-7041 in vivo. Materials and Method: The RIF-l cell line was implanted into the back of a 6-week-old female C3H mouse, intradermally, The mice were grouped into control, drug, radiation (RT), and RT+drug group. SK-7041, 4 mg/kg was administered intraperitoneally for six cycles every 12 hours for mice in the drug and RT+drug group, An identical volume of phosphate buffered saline (PBS) was administered at the same frequency to mice in the control and RT groups. A single 5 Gy fraction was delivered to mice in RT and RT+drug group 6 hours after the fourth delivery. The volume of the implanted tumor was measured every 2~3 days to formulate the growth delay curve. Results: For the control, drug, RT, and RT +drug groups, the average duration for implanted tumor to reach a volume of $1,500mm^3$ was 10 days, 10 days, 9 days, and 12 days, respectively. Moreover, the tumor volume on D14 was $276.7mm^3$, $279.9mm^3$, $292.5mm^3$, and $185.5mm^3$, respectively (p=0.0004). The difference for the change in slope for the control and drug versus the RT and RT+drug groups were borderline significant (p=0.0650). Conclusion: The results of this study indicate that SK-7041 has a radiosensitizing effect for the RIF-1 cell line in vivo at a low concentration and this effect may be synergistic. Implementing this result to clinical trial is warranted.
Park, Sang Jo;Hwang, Tae Gyu;Son, Byeong Hee;Kim, Chul Min
Clinical and Experimental Pediatrics
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v.45
no.10
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pp.1263-1272
/
2002
Purpose : Rett syndrome(RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000-15,000 female births worldwide. It was initially described by Andreas Rett in 1966. RTT involves developmental regression characterized stereotypic hand movements, tremors, gait apraxia, seizures, deceleration of head growth after the age of 6-18 months. The disease-causing gene was identified as MECP2 on chromosome Xq28. We carried out mutational analysis of MECP2 genes in RTT patients. Methods : Whole blood(5 cc) of 34 sporadic RTT patients was collected in EDTA-anticoagulated tubes. Genomic DNA was extracted from peripheral blood using the E.Z.N.A. blood DNA kit. Four exons of the MECP2 gene were amplified by PCR in 34 Korean with RTT. We carried out PCR divided the exon three into two parts and the exon four into five parts. Primer sequences designed by Amir et al. in 1999 were almost used(AF030876). Sequencing primers used were the same as PCR. DNA sequencing reactions were performed using an ABI 377 DNA sequencer and ABI PRISM dye terminator cycle sequencing reaction kit(Perkin-elmer). The results were compared with the normal DNA sequence(X99686). To confirm the change of sequence on novel mutations, RFLP analysis was performed. Results : The MECP2 mutations were detected in 23(67.6%) of the 34 patients. The mutations consisted of 12 different types including nine missense and three nonsense mutations. Of these, three (L100V, G161E and T311M) mutations were newly identified. Most of the mutations discovered are located within MBD(39.1%) and TRD(39.1%). In this study, three(T158M, R270X, R306C) mutations were identified high frequency. Conclusion : MECP2 gene was also an important cause of Korean RTT patients. MECP2 gene study is an important tool for diagnosis of Korean RTT patients.
Kim, Eun-Hee;Jang, Young-Ah;Kim, Sol-Bi;Kim, Han-Hyuk;Lee, Jin-Tae
Journal of Applied Biological Chemistry
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v.61
no.3
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pp.297-304
/
2018
Coptis chinensis is used in oriental medicine for soothing, anti-inflammation, antimicrobial and antipyretic properties, and its main ingredient berberine is known to have strong antibacterial activity. In this study, we investigated the anti-microbial effect of hot water extract of Coptis chinensis (CW) on skin related microorganism and the airborne microbe, the antifungal effects of fungi, which are frequently detected in residential environments. CW showed antibacterial effect against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis, against the airborne microbe, which was collected in four different places. At the concentration of 100 mg/mL, the antimicrobial activity continued for 42 days, showed heat stability without change in the antimicrobial activity even after heat treatment. The MIC and MBC of CW against S. aureus was 0.03, 0.05 mg/mL, against S. epidermidis was 0.50, 0.75 mg/mL and against P. acne was 0.10, 0.15 mg/mL. As a result of measuring the MIC of four kinds of fungi with high detection frequency in the surrounding environment, Gliocladium virens was 65 mg/mL by determined as MIC which can inhibit one hundred percent of mycelial growth. The concentration 90 mg/mL was determined as MIC against Aureobasidium pullulans and 100 mg/mL against Penicilium pinophilum and Chaetomium globosum. CW was considered a safe extract that showed no irritation even in the ocular mucous membrane irritation evaluation test, a patch test. Therefore, these results suggest that Coptis chinensis has antimicrobial, antifungal and safety on human body and can be applied to the development of materials for cosmetic and residential environment industries.
Quality changes of lettuce were studied during storage to investigate the efficiency, cooling properties and the washing and storage effects of immersion-type hydrocooling. As a result of plotting the nondimensionalized lettuce temperature versus cooling time, its cooling rate coefficient was shown to be $-0.365\;min^{-1}{\sim}-0.255\;min^{-1}\;(R^2=0.99{\sim}0.88)$. Rate of weight loss was not significantly (p>0.05) different between lettuces with various treatment conditions during storage at $5^{\circ}C$. However, during storage at $15^{\circ}C$, weight loss of hydrocooled lettuce was lower than that of non-treated lettuce after from 10 to 15 days. Especially, The lettuce packed with PE was more effective than that packed with try in terms of packing condition after hydrocooling. Lettuce pretreated with sterilizing agent, packed with PE vinyl film, removed residual water after hydrocooling had lower decaying rate than any other lettuces. Changes of L and b values in hydrocooled lettuce were slower than those of non-treated one. During changes of chlorophyll content, the initial value, $115.7{\sim}147.3\;mg%$ was decreased to $50{\sim}60%$ after 25 days of storage at $5^{\circ}C$ and within 15 days of storage at $15^{\circ}C$. It could be presumed that the addition of sterilizing agent reduced the initial level of overall total and coliform count and its growth rate during storage. The respiration rate of hydrocooled lettuce at $5^{\circ}C$ was $23.95\;mg{\cdot}CO_2/kg\;hr$, which is 10% of those of non-treated lettuce.
Kim, Kyoung-Hee;Kim, Soo-Jeong;Yoon, Mi-Hyang;Byun, Myung-Woo;Jang, Soon-Ae;Yook, Hong-Sun
Journal of the Korean Society of Food Science and Nutrition
/
v.40
no.3
/
pp.335-342
/
2011
The purpose of this study was to investigate the effects of mugwort powder on the quality characteristics and antioxidant activity of Maejakgwa. Maejakgwa were prepared with mugwort powder at levels 0%, 1%, 3% and 5% ($60{\pm}1^{\circ}C$, 14 days). The lightness, redness, and yellowness values of Maejakgwa significantly reduced depending on mugwort powder. The hardness of Maejakgwa was decreased with the increase of storage period and increased with the increase of mugwort powder. In the sensory evaluations, the Maejakgwa prepared with 3% added mugwort powder received higher acceptance scores for the properties of color, taste, hardness, crispiness, adhesiveness and overall acceptability. As the mugwort powder content increased, acid value and peroxide value were decreased. With the increase of storage period, acid value and peroxide value of all sample increased but growth rate of these values decreased with the addition of the mugwort powder. DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity was improved significantly via the addition of mugwort powder and decreased as storage period increased. During storage period, Maejakgwa with mugwort powder showed a stronger antimicrobial effect in yeasts and molds than in total aerobic bacteria. Coliform bacteria were not detected in all samples. Also the antimicrobial activity was increased with the addition of the mugwort powder and decreased as storage period increased. The results show that addition of the mugwort powder to foods with fat such as Maejakgwa would be a useful way to enhance the antioxidant quality, sensory characteristics and shelf life.
This study was conducted to determine types of seed dormancy in Sambucus racemosa subsp. pendula (Nakai) H.I. Lim & C.S. Chang, an endemic tree species of Korea, whose seeds have been considered difficult to germinate. Seeds of S. racemosa subsp. pendula were stratified at 25/15 or $5^{\circ}C$ for 0, 6, or 12 weeks (wks) and incubated at 15/6, 20/10, 25/15, or $30/20^{\circ}C$ (12/12 h) under 14 h photoperiod. To determine the effect of $GA_3$ on seed germination of S. racemosa subsp. pendula, seeds were treated with 0, 500, or 1000 ppm $GA_3$ and then germinated at 25/15 or $5^{\circ}C$. The change in embryo length was investigated at 25/15 or $5^{\circ}C$. Seeds given 12 wks of cold stratification germinated to 33.4% at $15/6^{\circ}C$ and to 25.4% for seeds given 6 wks of warm stratification + 12 wks of cold stratification at $20/10^{\circ}C$. At $25/15^{\circ}C$, seeds given 12 wks of warm stratification + 6 wks of cold stratification germinated to 26.0%, and to 28.2% for seeds given 12 wks of warm stratification + 12 wks of cold stratification at $30/20^{\circ}C$. Warm stratification alone did not germinate seeds throughout the experiment, regardless of the thermoperiod. Linear embryos began to grow after 60 days of incubation at 25/15 or $5^{\circ}C$. The embryo length at day 69 increased from 1.4 mm to 1.50 or 1.62 mm at 25/15 or $5^{\circ}C$, respectively. Embryos of S. racemosa subsp. pendula seeds grew better at $5^{\circ}C$ than at $25/15^{\circ}C$. Gibberellin was effective to break seed dormancy of S. racemosa subsp. pendula. Seeds treated with 500 ppm $GA_3$ germinated up to 40.0% at $25/15^{\circ}C$ and to 62.7% for those treated with 100 ppm $GA_3$ at $5^{\circ}C$. With these results, seeds of S. racemosa subsp. pendula have both nondeep complex and intermediate complex morphophysiological dormancy.
The European Union(EU) has recently introduced its Directive 2008/101/EC to include aviation in the EU ETS(emissions trading system). As an amendment to Directive 2003/87/EC that regulates reduction of the green house gas(GHG) emissions in Europe in preparation for the Kyoto Protocol, 1997, it obliges both EU and non-EU airline operators to reduce the emission of the carbon dioxide(CO2) significantly in the year 2012 and thereafter from the level they made in 2004 to 2006. Emission allowances allowed free of charge for each airline operator is 97% in the first year 2012 and 95% from 2013 and thereafter from the average annual emissions during historical years 2004 to 2006. Taking into account the rapid growth of air traffic, i.e. 5% in recent years, airlines operating to EU have to reduce their emissions by about 30% in order to meet the requirements of the EU Directive, if not buy the emissions right in the emissions trading market. However, buying quantity is limited to 15% in the year 2012 subject to possible increase from the year 2013. Apart from the hard burden of the airline operators, in particular of those from non-European countries, which is not concern of this paper, the EU Directive has certain legal problems. First, while the Kyoto Protocol of universal application is binding on the Annex I countries of the Climate Change Convention, i.e. developed countries including all Member States of the European Union to reduce GHG at least by 5% in the implementation period from 2008 to 2012 over the 1990 level, non-Annex I countries which are not bound by the Kyoto Protocol see their airlines subjected to aircraft emissions reductions scheme of EU when operating to EU. This is against the provisions of the Kyoto Protocol dealing with the emissions of GHG including CO2, target of the EU Directive. While the Kyoto Protocol mandates ICAO to set up a worldwide scheme for aircraft emissions to contribute to stabilizing GHG concentrations in the atmosphere at a level that would prevent dangerous anthropogenic interference with the climate system, the EU ETS was drawn up outside the framework of the international Civil Aviation Organization(ICAO). Second, EU Directive 2008/101 defines 'aviation activities' as covering 'flights which depart from or arrive in the territory of a Member State to which the [EU] Treaty applies'. While the EU airlines are certainly subject to the EU regulations, obliging non-EU airlines to reduce their emissions even if the emissions are produced during the flight over the high seas and the airspace of the third countries is problematic. The point is whether the EU Directive can be legally applied to extra-territorial behavior of non-EU entities. Third, the EU Directive prescribes 2012 as the first year for implementation. However, the year 2012 is the last year of implementation of the Kyoto Protocol for Annex I countries including members of EU to reduce GHG including the emissions of CO2 coming out from domestic airlines operation. Consequently, EU airlines were already on the reduction scheme of CO2 emissions as long as their domestic operations are concerned from 2008 until the year 2012. But with the implementation of Directive 2008/101 from 2012 for all the airlines, regardless of the status of the country Annex I or not where they are registered, the EU airlines are no longer at the disadvantage compared with the airlines of non-Annex I countries. This unexpected premium for the EU airlines may result in a derogation of the Kyoto Protocol at least for the year 2012. Lastly, as a conclusion, the author shed light briefly on how the Korean aviation authorities are dealing with the EU restrictive measures.
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