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Relation between ERCC1 Expression in Sputum and Survival after Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (비소세포 폐암환자의 객담 내 ERCC1 발현정도와 cisplatin 복합화학요법 후 치료반응)

  • Yang, Sung Woo;Choi, Pyoung Rak;You, Hong Jun;Kim, Jin Gu;Oak, Chul Ho;Jang, Tae Won;Jung, Maan Hong
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.2
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    • pp.151-159
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    • 2006
  • Background : Excision repair cross complementing gene 1 (ERCC1) not only has a protective role against carcinogens, but plays an important role in cisplatin-resistance via the repair of cisplatin-DNA adducts. This study investigated the association between the ERCC1 expression levels in sputum and survival after cisplatin-based chemotherapy in patients with inoperable non-small cell lung cancer (NSCLC). Methods : Using the sputum collected from 67 inoperable (stage IIIa-IV) NSCLC patients treated with either taxanes (33 cases) or gemcitabine (34 cases) plus cisplatin, the relative expression levels of ERCC1 and the expression of the tumor specific antigen, MAGE, were examined by the quantitative RT-PCR and RT-PCR, respectively. The response and survival were compared with the relative level of ERCC1 or MAGE expression and the treatment modality. Results : In the sputum, ERCC1 and MAGE was detected in 74.6% and 40.2% of patients, respectively. Using the median ERCC1 level, the patients were classified as having high or low ERCC1 expression. The median overall survival (MST) was significantly longer in patients with a high ERCC1 expression level than those with a low expression level (84 weeks vs. 44 weeks respectively, P=0.017). In the taxene-based treatment group, the MST was longer than the gemcitabine group (79 weeks vs. 47 weeks, respectively, P=0.03). The levels of ERCC1 were significantly higher in patients who were MAGE-positive (P=0.003). In the MAGE-negative patients, the MST was longer in the high ERCC1 group (103 weeks vs. 43 weeks, P=0.008), but not in the MAGE-positive patients (62 weeks vs. 44 weeks, P=0.348). Conclusion : ERCC1 expression in the sputum can be a prognostic factor for survival after chemotherapy in patients with inoperable NSCLC.

Inhibition of Type II Diabetes in ob/ob Mice and Enhancement of Mitochodrial Biogenesis in C2C12 Myotubes by Korean Mistletoe Extract (한국산 겨우살이 추출물(KME)의 2형 당뇨 억제 및 근육세포 미토콘드리아 생성 증가 효과)

  • Jung, Hoe-Yune;Yoo, Yung Choon;Kim, Inbo;Sung, Nak Yun;Choi, Ok-Byung;Choi, Bo-Hwa;Kim, Jong-Bae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.324-330
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    • 2015
  • In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

The Change of Podocyte ${\beta}$-Catenin by Puromycin Aminonucleoside (Puromycin aminonucleoside 투여에 따른 사구체 족세포 ${\beta}$-catenin의 변화)

  • Choi, Ji-Young;Ahn, Eun-Mi;Park, Hye-Young;Shin, Jae-Il;Ha, Tae-Sun
    • Childhood Kidney Diseases
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    • v.15 no.2
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    • pp.138-145
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    • 2011
  • Purpose : To test whether the expression of ${\beta}$-catenin, a component of podocyte as a filtration molecule, would be altered by puromycin aminonucleoside (PAN) in the cultured podocyte in vitro. Methods : We cultured rat glomerular epithelial cells (GEpC) with various concentrations of PAN and examined the distribution of ${\beta}$-catenin by confocal microscope and measured the change of ${\beta}$-catenin expression by Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Results :We found that ${\beta}$-catenin relocalized from peripheral cytoplasm to inner cytoplasm, therefore, intercellular separations were seen in confluently cultured cells by high concentrations of PAN in immunofluorescence views. In Western blotting of GEpC, PAN ($50{\mu}g/mL$) decreased ${\beta}$-catenin expression by 34.9% at 24 hrs and 34.3% at 48 hrs, compared to those in without PAN condition (P<0.05). In RT-PCR, high concentrations ($50{\mu}g/mL$) of PAN also decreased ${\beta}$-catenin mRNA expression similar to protein suppression by 25.4% at 24 hrs and 51.8% at 48 hrs (P<0.05). Conclusion : Exposure of podocytes to PAN in vitro relocates ${\beta}$-catenin internally and reduces ${\beta}$-catenin mRNA and protein expression, which could explain the development of proteinuria in experimental PAN-induced nephropathy.

GATA-3 is a Key Factor for Th1/Th2 Balance Regulation by Myristicin in a Murine Model of Asthma (Myristicin이 Ovalbumin으로 유도한 천식 생쥐모델에서 Th1/Th2 Balance를 조절하는 GATA-3에 미치는 효과)

  • Lee, Kyu;Lee, Chang-Min;Jung, In-Duk;Jeong, Young-Il;Chun, Sung-Hak;Park, Hee-Ju;Choi, Il-Whan;Ahn, Soon-Cheol;Shin, Yong-Kyoo;Lee, Sang-Yull;Yeom, Seok-Ran;Kim, Jong-Suk;Park, Yeong-Min
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1090-1099
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    • 2007
  • Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

Molecular identification and Phylogenetic relationship of the rook (Corvus frugilegus) population in Jeju-do Province, South Korea (제주도에 도래하는 떼까마귀 집단에 대한 분자 종 동정 및 계통 유연관계)

  • Han, Sang-Hyun;Kim, Tae-Wook;Kim, Yoo-Kyung;Park, Jun-Ho;Kim, Dong-Min;Adhikari, Preadeep;Park, Su-Gon;Park, Seon-Mi;Kim, Ga-Ram;Lee, Jun-Won;Oh, Hong-Shik
    • Korean Journal of Environment and Ecology
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    • v.29 no.5
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    • pp.693-702
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    • 2015
  • In order to identify the species and to reveal the phylogenetic relationship of rook populations found in Jeju-do Province in winter seasons, we determined the sequences of mitochondrial cytochrome c oxidase I (COI) gene and analyzed the genetic structure of maternal lineages and phylogenetic relationship. The rook DNAs were isolated from the post-mortem specimens and plumages collected from agricultural farms in Jeju-do Province including U-do Island. The obtained COI sequences (n=41) showed over 97.0% identities with those previously reported from Corvus frugeligus. Three COI haplotypes (J01-J03) were detected from COI sequences of the rooks obtained in Jeju-do Province but those did not show the site-specific patterns, showing that they might be derived from a common maternal origin. Eight maternal haplotypes were detected from all COI sequences obtained. Among those three haplotypes contained the COI sequences from Northeast Asia including eastern Russia, Mongolia and South Korea. On the other hand, the other five haplotypes contained the COI sequences reported from Central Asia, Middle East, western Russia and European countries. The COI sequences from Jeju-do Province were located on three haplotypes (CF01-CF03) belonging to Northeast Asian rook lineages. The NJ tree showed the distinct branch patterns suggesting two different maternal lineages of C. frugilegus, which proposed as two parapatric subspecies, C. f. frugilegus (Western) and C. f. pastinator (Eastern). These findings using DNA barcoding approaches will be contributed to provide the information about avian fauna for understanding the genetic structure of maternal lineage, phylogenetic relationship and their molecular ecology.

Induction of Apoptosis by Ethanol Extract of Lythrum anceps (Koehne) Makino in Human Leukemia U937 Cells (인체백혈병 U937 세포에서 부처꽃 에탄올추출물에 의한 apoptosis 유도)

  • Jeong, Jin-Woo;Kim, Chul Hwan;Lee, Young-Kyung;Hwang, Yong;Lee, Ki Won;Choi, Kyung-Min;Kim, Jung Il
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.279-286
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    • 2020
  • Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer effect are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins, depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

Anti-inflammatory Activity of Crinum asiaticum Linne var. Japonicum Extract and its Application as a Cosmeceutical Ingredient (문주란의 항염효과와 화장료적 특성)

  • Kim, Ki-Ho;Kim, Young-Heui;Kim, Ki-Soo;Park, Sun-Hee;Lee, Soo-Hee;Kim, Young-Jin;Kim, Young-Sil;Kim, Jong-Heon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.1 s.55
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    • pp.59-64
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    • 2006
  • Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, an anti-pyretic, an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by inhibition of iNOS (inducible nitric oxide synthase), and the release of PGE2, IL-6, and IL-8. HPLC experiment after extraction with 95% ethanol at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressant. The content of lycorine varied depending on the type of tissue analyzed and the extraction method. In anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)- activated mouse macrophage RAW 264.7 cells, the ethanolic extract of Crinum asiaticum showed inhibitory activity of NO production in dose-dependent manner ($IC_{50} = 83.5 {\mu}g/mL$). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show my cytotoxicity, but did show cell proliferation effect against LPS ($10{\sim}60%$ increase of tell viability). In an assay to determine inhibition of the $H_2O_2$-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentrations (> 0.0025%). The result showed that the extract of Crinum asiaticum Linne var. japonicum has sufficient anti-inflammatory effect. There-fore, Crinum asiaticum Linne var. japonicum extract may be useful as an ingredient of cosmetic products.

The Effect of Haliotidis Concha on the Growth and Ginsenoside Biosynthesis of Korean Ginseng Hairy Root (인삼 모상근의 생장과 Ginsenoside 생합성에 미치는 석결명의 영향)

  • Jeong, Dae-Young;Kim, Yu-Jin;Shim, Ju-Sun;Lee, Jung-Hye;Jung, Seok-Kyu;Kim, Se-Young;In, Jun-Gyo;Lee, Bum-Soo;Yang, Deok-Chun
    • Journal of Ginseng Research
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    • v.33 no.3
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    • pp.206-211
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    • 2009
  • In order to investigate the effects of elicitors on the growth and ginsenoside biosynthesis of ginseng hairy roots, we treated Panax ginseng hairy root with various concentrations of Haliotidis concha according to different time course. Haliotidis concha supplement increased the biomass and ginsenoside accumulation at 10 mg/L concentration. The growth rate of hairy root under a lighter concentration was greater than hairy root treated with a denser concentration. The highest content and productivity of ginsenosides appeared at 2 weeks after the treatment of 10 mg/L Haliotidis concha. The gene expression of squalene synthase, squalene epoxidase, dammarenediol synthase, cycloartenol synthase, $\beta$-amyrin synthase in hairy roots of ginseng were examined by RT-PCR. The Haliotidis concha treatment resulted in the obvious accumulation of the mRNA of triterpene biosynthesis in Panax ginseng hairy root as compared with the control. In this study, Haliotidis concha acts as a kind of elicitor for the production of ginsenosides.

Effect of Antioxidants for Porcine Oocytes during In Vitro Maturation, Fertilization and Development (돼지 난포란으로부터 체외수정란의 생산에 있어서 항산화제의 첨가가 배 발달에 미치는 효과)

  • Park H.;Kim J. Y.;Kim J. Y.;Lee J. H.;Park H. D.;Kim J. M.
    • Journal of Embryo Transfer
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    • v.19 no.3
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    • pp.245-255
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    • 2004
  • In recent years, an increasing number of studies on pig in vitro maturation(IVM) and in vitro fertilization(IVF) have been separated. the wide range of new technologies, including that in applied molecular genetics, has increased this interest. the production of viable porcine embryos in vitro is a prerequisites for the successful production of transgenic pigs to date. The efficiency of IVM/IVF techniques in the porcine is lower than that obtained in other species such as cattle and mouse. The several problems are generally thought to be the cause of poor results: the low rate of MPN formation derived from inadequate IVM of oocytes, the high incidence of polyspermy after IVF and cell blocking at 4 cell during embryos culture. For there reasons overcoming, many studies have been conducted to improve in vitro embryo-genic competence of oocytes. In the last several years, many maturation culture media have been evaluated and various exogenous factors such as hormones and grows factors have been tested to improve the efficiency of porcine in vitro system. In the study several antioxidants have been examined to improve in vitro fertilization and development of porcine oocytes. In this study, several antioxidants were examined to determine the effects on the development of oocytes to the cleavage, morula and blastocyst stage when added at the maturation(IVM) or in vitro fertilization(IVF) or in vitro culture(IVC) of porcine embryos. Porcine oocytes were matured, fertilized and embryos were cultured in defind conditioned medium in vitro with or without supplementation with the antioxidents of cysteine, catalase and glutathione. 1. Significant improvement of blastocyst rate (27.2% versus 15.4%, p<0.05) were achieved when catalase(500U/$m\ell$) were added to TCM-199 medium and morula rate(72.0% versus 53.9%, p<0.05) were significantly higher when glutathione(1.0mM/$m\ell$) were added to TCM-199 medium than those of control. 2. In mTBM medium for oocytes fertilization, the addition of cysteine, catalase and glutathione had no positive effect on embryonic development. glutathione had no positive effect on embryonic development. In conclusion, this study shows that addition of catalase, gluththione during IVM improved the rate of porcine embryo development.

The Production of Adventitious Sprouts by Water-soak and Vegetative Propagation of Plus tree of Ash Species Through Cuttings of Their Sprouts (물푸레나무속(屬) 수형목(秀型木)의 수심(水沈)에 의(依)한 지조맹아(枝條萌芽) 발생력(發生力)과 이를 이용(利用)한 녹지삽목(綠枝揷木) 증식시험(增殖試驗))

  • Han, Sang Don;Hong, Sung Ho;Min, Young Taek;Kim, Young Mo;Kim, Hong Eun
    • Journal of Korean Society of Forest Science
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    • v.83 no.2
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    • pp.148-154
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    • 1994
  • As a vegetative propagation method for ash species, which is a dioecism and a long cycle of fructification, cut-stem was soaked in water to induce adventitious sprouts, and 2-year-old ash seedling was cut in a nursery to induce adventitious sprouts. We obtained the 1,019 adventitious sprouts from branches of 101 plus trees througout the country. The mean ortet-age is 48. There is not a correlation between ortet ages and production of adventitious sprouts. These sprouts were placed in a cutting bed for rooting. Root ability varied with environmental factors of cuttings. The best rooting(87%) resulted from cutting performed in a vinyl-plastic greenhouse. Rooting was better on perlite+peat moss(2 : 1) medium than other media tested. The rooting ability was generally higher in 2-year-old ortet than plus tree ortet. In the root development of cuttings the non-container cuttings was better than container cuttings.

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