• Title/Summary/Keyword: Molecular Flow

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Genetic and Phylogenetic Relationships of Genus Hemerocallis in Korea Using ISSR (ISSR에 의한 한국 내 원추리속 식물의 유전적 및 계통학적 연구)

  • Choi, Joo-Soo;Huh, Hong-Wook;Lee, Seol-A;Huh, Man-Kyu
    • Journal of Life Science
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    • v.18 no.6
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    • pp.753-758
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    • 2008
  • Genus Hemerocallis is a herbaceous species and some species among their taxa are very important herbal medicines. We evaluated representative samples of the eight taxa in Korea with inter simple sequence repeats (ISSR) markers to estimate phylogenetic relationships within taxa of this genus. The studied taxa were Hemerocallis fulva L., H. fulva for. kwanso, H. dumortieri Morren, H. coreana Nakai, H. hongdoensis M.G.Chung & S.S.Kang, H. middendorffi Trautv. et Mayer, H. thunbergii Baker, H. minor Miller. In addition, we investigated the genetic variation and structure of Korean populations of these taxa. The mean genetic diversity was 0.098 across species, varying from 0.068 to 0.123. A low level of genetic variation was found in populations of Hemerocallis species. Specially, gene diversity for H. minor was maintained the highest among genus Hemerocallis. An indirect estimate of the number of migrants per generation (Nm=0.218) indicated that gene flow was not extensive among Korean populations of Hemerocallis species. The phylogenic tree showed distinct three clades. One includes H. fulva, H. fulva for. kwanso and H. middendorffi. Another includes three Hemerocallis species, H. dumortieri, H. thunbergii and H. minor. The H. coreana and H. hongdoensis were shown as the sister group to the second clades. Although the size of sampling was not large enough for eight Korean Hemerocallis species, the analyses of ISSRs will certainly provide an enhanced view on the phylogeny of species.

Induction of Apaopotis by Water Extract of Cordyceps militaris (WECM) in Human Hepatocellular Carcinoma HepG2 Cells. (동충하초 열수 추출물에 의한 인체 간암세포 성장억제 및 apoptosis 유발에 관한 연구)

  • Kim, Kyung-Mi;Park, Cheol;Choi, Yung-Hyun;Lee, Won-Ho
    • Journal of Life Science
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    • v.18 no.6
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    • pp.804-813
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    • 2008
  • Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. However, the molecular mechanisms of C. militaris on biochemical actions in cancer have not been clearly elucidated yet. In the present study, we investigated the anti-proliferative activity of the water extract of C. militaris (WECM) in human hepatocellular carcinoma HepG2 cells. It was found that WECM could inhibit the cell growth in a dose-dependent manner, which was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies and increased populations of apoptotic sub-G1 phase. Apoptotic cell death of HepG2 cells by WECM was connected with a up-regulation of pro-apoptotic Bax expression, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1). In addition, WECM treatment induced the proteolytic activation of caspase-3 and a concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), ${\beta}-catenin$ and phospholipase $(PLC)-{\gamma}1$ protein. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited WECM-induced apoptosis demonstrating the important role of caspase-3 in the observed cytotoxic effect. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of C. militaris.

Apoptotic Cell Death of Human Leukemia U937 Cells by Essential Oil purified from Schisandrae Semen (오미자 종자 정유에 의한 인체백혈병 U937 세포의 apoptosis 유도)

  • Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.2
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    • pp.249-255
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    • 2015
  • Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.

Determination of 10${\alpha}$-Methoxy-9,10-dihydrolysergol (MDL), Main Metabolite of Nicergoline, in Human Plasma by HPLC-MS and Applicability to Oral Bioavailability in Korean Healthy Male Volunteers (HPLC-MS를 이용한 생체시료 중 니세르골린의 주대사체인 10${\alpha}$-Methoxy-9,10-dihydrolysergol(MDL)의 분석 및 이를 이용한 한국인 성인 남성에 대한 생체이용률 응용)

  • Lim, Hyon-Kyun;Yoo, Sun-Dong;Kim, Kyeong-Ho;Han, Sang-Beom;Youm, Jeong-Rok
    • YAKHAK HOEJI
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    • v.51 no.2
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    • pp.133-139
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    • 2007
  • A simple and sensitive HPLC-MS method for quantitation of 10${\alpha}$-methoxy-9,10-dihydrolysergol (MDL), the main metabolite of nicergoline, in human plasma was developed and the bioavailability parameters of MDL was assessed in Korean healthy male volunteers. Clomipramine was used as an internal standard. MDL and internal standard in plasma sample were extracted using ethyl acetate. A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 10 mM ammonium acetate-acetonitrile (10 : 90, v/v). The reconstituted samples were injected into a Zorbax SB-C8 column (2.1${\times}$150 mm,5 ${\mu}$m) at a flow-rate of 0.3 ml/min. Using MS with selected ion monitoring (SIM) mode, MDL and clomipramine were detected without severe interference from human plasma matrix. MDL produced a protonated molecular ion ([M+H]$^+$) at m/z 287. Internal standard produced a protonated molecular ion ([M+H]$^+$) at m/z 315. A linear relationship for MDL was found in the range of 2.5${\sim}$100 ng/ml. The lower limit of quantitation (LLOQ) was 2.5 ng/ml with acceptable precision and accuracy. The intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. Main pharmacokinetic parameters of 30 mg of nicergoline were revealed as follows: AUC$_t$ 321.1${\pm}$64.5 ng${\cdot}$hr/ml, C$_{max}$, 51.2${\pm}$25.3 ng/ml, T$_{max}$ 3.6${\pm}$1.5 hr, K$_{el}$ 0.12${\pm}$0.07 hr$^{-1}$ and t$_{1/2}$ 7.6${\pm}$3.4 hr. Inter subject variations and race differences were shown in comparison with the published data in the literature.

Induction of G2/M Arrest of the Cell Cycle by Genistein in Human Bladder Carcinoma and Leukemic Cells (인체 방광암 및 백혈병세포에서 genistein에 의한 세포주기 G2/M arrest 유발에 관한 연구)

  • Kim, Eu-Kyum;Myong, You-Ho;Song, Kwan-Sung;Lee, Ki-Hong;Rhu, Chung-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.16 no.4
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    • pp.589-597
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    • 2006
  • Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase activities. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis by genistein as a chemopreventive agent in a variety of cancer cell lines; however, its mechanism of action and its molecular targets on human bladder carcinoma and leukemic cells remain unclear. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of T24 bladder carcinoma and U937 leukemic cells. Genistein significantly inhibited the cell growth and induced morphological changes, and induced the G2/M arrest of the cell cycle in both T24 and U937 cells with a relatively stronger cytotoxicity in U937. The G2/M arrest in T24 cells was associated with the inhibition of cyclin A, cyclin B1 and Cdc25C protein expression without alteration of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1). However, the inhibitory effects of genistein on the cell growth of U937 cells were connected with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 proteins by p53-independent manner. These data suggest that genistein may exert a strong anticancer effect and additional studies will be needed to evaluate the different mechanisms between T24 and U937 cells.

Induction of Apoptosis by Bee Venom in A549 Human Lung Epithelial Cancer Cells through Modulation of Bcl-2 and IAP Family and Activation of Caspases (Bcl-2 및 IAP family의 발현 변화와 caspase 활성을 통한 봉독의 인체폐암세포 apoptosis 유도)

  • Woo, Hyun-Joo;Kim, Hyun-Joong;Hong, Su-Hyun;Hong, Sang-Hoon;Choi, Byung-Tae;Lee, Yong-Tae;Park, Dong-Il;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.11
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    • pp.1596-1600
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    • 2007
  • Bee venom is used to treat inflammatory diseases in Korean traditional medicine and has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in bee venom-induced apoptosis are still uncharacterized in human lung cancer cells. In the present study, we investigated the effects of bee venom on the apoptosis of A549 human lung epithelial cancer cells. Treatment of bee venom inhibited the cell viability and induced apoptosis in a concentration-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. Bee venom-induced apoptosis in A549 cells was associated with a marked inhibition of anti-apoptotic Bcl-2 expression without significant changes in the levels of Bax and Bcl-xL. Bee venom treatment also inhibited the levels of IAP family members such as cIAP-1 and cIAP-2 and induced the proteolytic activation of caspase-3 and caspase-9. Although further studies are needed, the present results suggest that apoptotic signals evoked by bee vemon in A549 cancer cells may converge caspases activation through a down-regulation of Bcl-2 rather than an up-regulation of Bax. These findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of bee vemon in human cancer cells.

Angiogenic Effect of Cardiac Ankyrin Repeat Protein Overexpression in Vascular Endo-thelial Cell (Cardiac Ankyrin Repeat Protein의 과량발현이 혈관내피세포에서 갖는 혈관신생 촉진 효과)

  • Kong, Hoon-Young;Byun, Jong-Hoe
    • Korean Journal of Microbiology
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    • v.44 no.4
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    • pp.282-288
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    • 2008
  • Tissue ischemia resulting from the constriction or obstruction of blood vessels leads to an illness that may affect many organs including the heart, brain, and legs. In recent years, considerable progress has been made in the field of therapeutic angiogenesis and the new approaches are expected to cure those "no-option patients" who are unsuited to conventional therapies. Although single angiogenic growth factor may be successful in inducing angiogenesis, combination of multiple growth factors is increasingly sought these days to augment the therapeutic responses. This trend is proper in light of the fact that blood vessel formation is a complex and multi-step process that requires the actions of many different factors. To meet the growing need for functionally significant blood flow recovery in the ischemic tissues, a novel strategy that can provide concerted actions of multiple factors is required. One way to achieve such a goal is to use a transcription factor that can orchestrate the expression of multiple target genes in the ischemic region and thus induce significant level of angiogenesis. Here, a putative transcription factor, cardiac ankyrin repeat protein (CARP), was evaluated in adenoviral vector context for angiogenic activity in human umbilical vein endothelial cells. The results indicated significant increase in proliferation, capillary-like structure formation, and induction of vascular endothelial growth factor, a typical angiogenic gene. Taken together, these results suggest that CARP represents itself as a novel target for therapeutic angiogenesis and warrants further investigation.

Gene Expression Profile of Lung Cancer Cells Following Photodynamic Therapy (폐암 세포주에서 광역학 치료에 의한 유전자 발현 분석)

  • Sung, Ji Hyun;Lee, Mi-Eun;Han, Seon-Sook;Lee, Seung-Joon;Ha, Kwon-Soo;Kim, Woo Jin
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.1
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    • pp.52-58
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    • 2007
  • Background: Photodynamic therapy is a viable option for lung cancer treatment, and many studies have shown that it is capable of inducing cell death in lung cancer cells. However, the precise mechanism of this cell death has not been fully elucidated. To investigate the early changes in cancer cell transcription, we treated A549 cells with the photosensitizer DH-I-180-3 and then we illuminated the cells. Methods: We investigated the gene expression profiles of the the A549 lung cancer cell line, using a DEG kit, following photodynamic therapy and we evaluated the cell viability by performing flow cytometry. We identified the genes that were significantly changed following photodynamic therapy by performing DNA sequencing. Results: The FACS data showed that the cell death of the lung cancer cells was mainly caused by necrosis. We found nine genes that were significantly changed and we identified eight of these genes. We evaluated the expression of two genes, 3-phosphoglycerate dehydrogenase and ribosomal protein S29. The expressed level of carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein and integrin beta 1 were decreased. Conclusion: Many of the gene products are membrane-associated proteins. The main mechanism of photodynamic therapy with using the photosensitizing agent DH-I-180-3 appears to be necrosis and this may be associated with the altered production of membrane proteins.

Characterization of the Alzheimer's disease-related network based on the dynamic network approach (동적인 개념을 적용한 알츠하이머 질병 네트워크의 특성 분석)

  • Kim, Man-Sun;Kim, Jeong-Rae
    • Journal of the Korean Institute of Intelligent Systems
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    • v.25 no.6
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    • pp.529-535
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    • 2015
  • Biological networks have been handled with the static concept. However, life phenomena in cells occur depending on the cellular state and the external environment, and only a few proteins and their interactions are selectively activated. Therefore, we should adopt the dynamic network concept that the structure of a biological network varies along the flow of time. This concept is effective to analyze the progressive transition of the disease. In this paper, we applied the proposed method to Alzheimer's disease to analyze the structural and functional characteristics of the disease network. Using gene expression data and protein-protein interaction data, we constructed the sub-networks in accordance with the progress of disease (normal, early, middle and late). Based on this, we analyzed structural properties of the network. Furthermore, we found module structures in the network to analyze the functional properties of the sub-networks using the gene ontology analysis (GO). As a result, it was shown that the functional characteristics of the dynamics network is well compatible with the stage of the disease which shows that it can be used to describe important biological events of the disease. Via the proposed approach, it is possible to observe the molecular network change involved in the disease progression which is not generally investigated, and to understand the pathogenesis and progression mechanism of the disease at a molecular level.

Simultaneous Analyses for Trace Multi-Odorous and Volatile Organic Compounds in Gas using a Triple-bed Adsorbent Tube (Triple-bed Adsorbent Tube를 이용한 가스상 극미량 복합 악취 및 휘발성 유기화합물의 동시 분석)

  • Seo, Yong Soo;Lee, Jea Keun
    • Korean Chemical Engineering Research
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    • v.48 no.2
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    • pp.244-252
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    • 2010
  • The objective of this study is to assess feasibility of simultaneous analysis for trace multi-components odorous and volatile organic compounds using a Triple-bed adsorbent tube with a thermal desorber and GC-MS. Triple-bed adsorbent tube is 3 bed packed Tenax-TA with small amount of Carbopack B and Carbosieve SIII in order of adsorption strength in a tube. The operating conditions of GC-MS was possibly able to and effectively detect high volatile and low molecular weight compounds at the mass range of 20~350 m/z using a below impurity 1ppm of Helium carrier gas, of which quantitatively analyzed by target ion extracts. According to the experiment, $C_1{\sim}C_5$ of 14 components; sulfur containing compounds(2), ketones(2), alcohols(4) and aldehydes(6) were simultaneously analyzed with recoveries of 99%, and good repeatability and linearity. High volatile and low molecular weight compounds such as methyl alcohol and acetaldehyde can be safely quantified with high recovery at a condition of 50mL/min of flow rate, below 2L of adsorption volume, and 45% of relative humidity. Target ion extract can also simultaneously quantify multicomponents with odorous and volatile organic compounds in an occasion of piled up two peaks.