• Title/Summary/Keyword: Biological mechanism

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Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

  • Jeon, Kyung-Hwa;Shrestha, Aarajana;Jang, Hae Jin;Kim, Jeong-Ahn;Sheen, Naeun;Seo, Minjung;Lee, Eung-Seok;Kwon, Youngjoo
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.562-570
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    • 2021
  • Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Role of Exogenous Nitric Oxide Generated through Microwave Plasma Activate the Oxidative Signaling Components in Differentiation of Myoblast cells into Myotube

  • Kumar, Naresh;Shaw, Priyanka;Attri, Pankaj;Uhm, Han Sup;Choi, Eun Ha
    • Proceedings of the Korean Vacuum Society Conference
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    • 2015.08a
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    • pp.158-158
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    • 2015
  • Myoblast are myogenic precursors that proliferate, activate, and differentiate on muscle injury to sustain the regenerative capacity of skeletal muscle; The neuronal isoform of nitric oxide synthase (nNOS, termed also NOS-I) is expressed in normal adult skeletal muscle, suggesting important functions for Nitric oxide (NO) in muscle biology1,2,3. However, the expression and subcellular localization of NO in muscle development and myoblast differentiation are largely unknown. In this study, we examined effects of the nitric oxide generated by a microwave plasma torch, on proliferation/differentiation of rat myoblastic L6 cells. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimetres per minute. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the ratio of oxygen gas, and the microwave power4. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to L6 skeletal muscles. Differentiation of L6 cells into myotubes was significantly enhanced the differentiation after nitric oxide treatment. Nitric oxide treatment also increase the expression of myogenesis marker proteins and mRNA level, such as myogenin and myosin heavy chain (MHC), as well as cyclic guanosine monophosphate (cGMP), However during the myotube differentiation we found that NO activate oxidative stress signaling erks expression. Therefore, these results establish a role of NO and cGMP in regulating myoblast differentiation and elucidate their mechanism of action, providing a direct link with oxidative stress signalling, which is a key player in myogenesis. Based on these findings, nitric oxide generated by plasma can be used as a possible activator of cell differentiation and tissue regeneration.

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The Within-Host Population Dynamics of Normal Flora in the Presence of an Invading Pathogen and Antibiotic Treatments

  • Kim, Jung-Mo;Lee, Dong-Hwan;Song, Yoon-Seok;Kang, Seong-Woo;Kim, Seung-Wook
    • Journal of Microbiology and Biotechnology
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    • v.17 no.1
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    • pp.146-153
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    • 2007
  • A mathematical competition model between normal flora and an invading pathogen was devised to allow analysis of bacterial infections in a host. The normal flora includes the various microorganisms that live on or within the host and act as a primary human immune system. Despite the important role of the normal flora, no mathematical study has been undertaken on models of the interaction between it and invading pathogens against a background of antibiotic treatment. To quantify key elements of bacterial behavior in a host, pairs of nonlinear differential equations were used to describe three categories of human health conditions, namely, healthy, latent infection, and active infection. In addition, a cutoff value was proposed to represent the minimum population level required for survival. The recovery of normal flora after antibiotic treatment was also included in the simulation because of its relation to human health recovery. The significance of each simulation parameter for the bacterial growth model was investigated. The devised simulation showed that bacterial proliferation rate, carrying capacity, initial population levels, and competition intensity have a significant effect on bacterial behavior. Consequently, a model was established to describe competition between normal flora and an infiltrating pathogen. Unlike other population models, the recovery process described by the devised model can describe the human health recovery mechanism.

Effect of Mild-Thiol Reducing Agents and ${\alpha}2,3$-Sialyltransferase Expression on Secretion and Sialylation of Recombinant EPO in CHO Cells

  • Chang, Kern Hee;Jeong, Yeon Tae;Kwak, Chan Yeong;Choi, One;Kim, Jung Hoe
    • Journal of Microbiology and Biotechnology
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    • v.23 no.5
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    • pp.699-706
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    • 2013
  • We have previously reported that N-acetylcysteine (NAC) not only delayed apoptosis but also enhanced the production of recombinant erythropoietin (EPO) in Chinese hamster ovary (CHO) cell culture. To investigate the production enhancement mechanism, the effects of similar thiol-reducing agents were studied. Intriguingly, all mild reducing agents examined including mercaptoethanesulfonic acid (MESNA), thiolactic acid (TLA), and thioglycolate (TG) were shown to block apoptosis and increase EPO production. A pulse-chase study of EPO secretion revealed that all four thiol-reducing agents increased the EPO secretion rate; among them TLA showed the highest rate. In terms of product quality, the sialic acid content of the glycoprotein is one of the most important factors. It was reported that a number of glycoproteins produced by CHO cells often have incomplete sialylation, particularly under high-producing conditions. Human ${\alpha}2,3$-sialyltransferase (${\alpha}2,3$-ST) was introduced into EPO-producing CHO cells in order to compensate for the reduced sialylation during supplementation with NAC. When ${\alpha}2,3$-ST was expressed in the presence of NAC, reduced sialylation was restored and an even more sialylated EPO was produced. Thus, our study is significant in that it offers increased EPO production while still allowing the prevention of decreased sialylation of EPO.

Induction of Apoptosis and Autophagy by Resveratrol via Activation of AMPK Pathway in 5-Fluorouracil-Resistant Colon Cancer Cells

  • Lee, Seung Young;Jung, Ji Young;Choi, Hee Won;Choi, Kyung Min;Jeong, Jin-Woo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.101-101
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    • 2018
  • Resveratrol is a polyphenolic compound, which is a naturally occurring phytochemical and is found in a variety of plants, including food such as grapes, berries and peanuts. Although several studies have demonstrated that resveratrol possesses anti-cancer activity against various types of human cancer, the molecular mechanisms of resveratrol-mediated overcome drug resistance potential are unclear. In this study, we determined whether resveratrol attenuates drug resistance responses in 5-fluorouracil-resistant colon cancer (SNUC5/5-FUR) cells. Treatment with resveratrol significantly enhanced apoptosis in a concentration-dependent manner, which was associated with the modulation of anti- and/or pro-apoptotic protein expression, activation of caspases and activation of AMP-activated protein kinase. Resveratrol treatment also increased the induction of autophagy through up-regulation of autophagy-related genes such as Microtubule-associated protein 1A/1B-light chain 3, P62 and beclin-1. However, blocking of autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that resveratrol-induced autophagy functions as a cell death mechanism in SNUC5/5-FU cells. Although the further studies are needed, these findings suggest that resveratrol may have therapeutic potential to overcome drug resistance in colon cancer patients.

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Temporal and Spatial Downregulation of Arabidopsis MET1 Activity Results in Global DNA Hypomethylation and Developmental Defects

  • Kim, Minhee;Ohr, Hyonhwa;Lee, Jee Woong;Hyun, Youbong;Fischer, Robert L.;Choi, Yeonhee
    • Molecules and Cells
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    • v.26 no.6
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    • pp.611-615
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    • 2008
  • DNA methylation is an epigenetic mechanism for gene silencing. In Arabidopsis, MET1 is the primary DNA methyltransferase that maintains CG DNA methylation. Plants having an overall reduction of MET1 activity, caused by a met1 mutation or a constitutively expressed MET1 antisense gene, display genome hypomethylation, inappropriate gene and transposon transcription, and developmental abnormalities. However, the effect of a transient reduction in MET1 activity caused by inhibiting MET1 expression in a restricted set of cells is not known. For this reason, we generated transgenic plants with a MET1 antisense gene fused to the DEMETER (DME) promoter (DME:MET1 a/s). Here we show that DME is expressed in leaf primordia, lateral root primoridia, in the region distal to the primary root apical meristem, which are regions that include proliferating cells. Endogenous MET1 expression was normal in organs where the DME:MET1 a/s was not expressed. Although DME promoter is active only in a small set of cells, these plants displayed global developmental abnormalities. Moreover, centromeric repeats were hypomethylated. The developmental defects were accumulated by the generations. Thus, not maintaining CG methylation in a small population of proliferating cells flanking the meristems causes global developmental and epigenetic abnormalities that cannot be rescued by restoring MET1 activity. These results suggest that during plant development there is little or no short-term molecular memory for reestablishing certain patterns of CG methylation that are maintained by MET1. Thus, continuous MET1 activity in dividing cells is essential for proper patterns of CG DNA methylation and development.

The Biological Effects of Bovine Lactoferrin on Inflammatory Cytokine Expression in the PMA Stimulated Cells (PMA로 자극되어진 세포에서 염증 Cytokine 발현에 미치는 Bovine Lactoferrin의 생물활성 영향)

  • Chung, Sung-Hee;Kang, Ho-Bum;Kim, Jae-Wha;Yoon, Sung-Sik;Nam, Myoung-Soo
    • Food Science of Animal Resources
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    • v.32 no.3
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    • pp.364-368
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    • 2012
  • Bovine lactoferrin is well known as biological activator in defense mechanism related some cells. In this study, we was investigated about the immune modulator as a role of lactoferrin through the transcriptional regulation of genes associated with hypersensitivity such as allergy, athma and inflammatory disease. Effects of inflammatory reaction of bovine lactoferrin was carried out by RT-PCR analysis from isolated total RNA treated with lactoferrin 0, 10, 50, 100, 500 ${\mu}g/mL$ and PMA 100 ng/mL. The expression of the TYROBP, PITPNA, IL-10, SLP1, DC-stamp and ICAM-1 mRNA were increased by synergy effect of bovine lactoferrin and PMA. The results of RT-PCR showed that bovine lactoferrin and PMA had an effect of immune modulator by enhancement of TYROBP, PITPNA, SLP1, DC-stamp, IL-10 and ICAM-1 gene transcription in U937, Mutz-3 and NK92 cells, respectively. Bovine lactoferrin showed a potential of biological function which could be used for industrial applications as a material of food and pharmaceutical.

High Ambient Temperature Accelerates Leaf Senescence via PHYTOCHROME-INTERACTING FACTOR 4 and 5 in Arabidopsis

  • Kim, Chanhee;Kim, Sun Ji;Jeong, Jinkil;Park, Eunae;Oh, Eunkyoo;Park, Youn-Il;Lim, Pyung Ok;Choi, Giltsu
    • Molecules and Cells
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    • v.43 no.7
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    • pp.645-661
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    • 2020
  • Leaf senescence is a developmental process by which a plant actively remobilizes nutrients from aged and photosynthetically inefficient leaves to young growing ones by disassembling organelles and degrading macromolecules. Senescence is accelerated by age and environmental stresses such as prolonged darkness. Phytochrome B (phyB) inhibits leaf senescence by inhibiting phytochrome-interacting factor 4 (PIF4) and PIF5 in prolonged darkness. However, it remains unknown whether phyB mediates the temperature signal that regulates leaf senescence. We found the light-activated form of phyB (Pfr) remains active at least four days after a transfer to darkness at 20℃ but is inactivated more rapidly at 28℃. This faster inactivation of Pfr further increases PIF4 protein levels at the higher ambient temperature. In addition, PIF4 mRNA levels rise faster after the transfer to darkness at high ambient temperature via a mechanism that depends on ELF3 but not phyB. Increased PIF4 protein then binds to the ORE1 promoter and activates its expression together with ABA and ethylene signaling, accelerating leaf senescence at high ambient temperature. Our results support a role for the phy-PIF signaling module in integrating not only light signaling but also temperature signaling in the regulation of leaf senescence.

Expanded Graphite Negative Electrode for Lithium-ion Batteries

  • Yoo, Hyun-D.;Ryu, Ji-Heon;Park, Seong-Ho;Park, Yu-Won;Ka, Bok-H.;Oh, Seung-M.
    • Journal of Electrochemical Science and Technology
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    • v.2 no.1
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    • pp.45-50
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    • 2011
  • A series of expanded graphites is prepared from graphite oxide by changing the heat-treatment temperature, and their lithiation/de-lithiation mechanism and rate performance are examined. A featureless sloping profile is observed in their charge-discharge voltage and dilatometry profiles, which is contrasted by the stepwise plateau-like profiles observed with the pristine graphite. With an increase in the heat-treatment temperature from $250^{\circ}C$ to $850^{\circ}C$, the interlayer distance becomes smaller whereas the electric conductivity becomes larger, both of which are resulted from a removal of foreign atoms (mainly oxygen) from the interlayer gaps. The expanded graphite that is prepared by a heat-treatment at $450^{\circ}C$ delivers the best rate performance, which seems to be a trade-off between the $Li^+$ ion diffusivity that is affected by the interlayer distance and electrical conductivity.

The Relevance between Biological Nursing Subjects and Registered Nurse Licensure Examination Workbook in Republic of Korea and the United States of America (한국과 미국의 간호사 국가시험 문항과 기초간호과목의 연관성 분석)

  • Lee, Haeyoung;Kim, Youn Jung;Chang, Hee Kyung;Chang, Sun Ju;Choi, Heejung;Park, Myung Sook
    • Journal of Korean Biological Nursing Science
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    • v.20 no.1
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    • pp.1-10
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    • 2018
  • Purpose: This is a descriptive study to investigate the relevance between biological nursing science subjects (structure and function of the human body (SFHB), mechanism and effects of drugs (MED), clinical microbiology) and examination workbook items for Registered Nurse Licensure Examination (RNLE) in Republic of Korea (ROK) and the United States of America (USA). Methods: RNLE 8 workbooks which were published by the Korean Nurses Association were utilized for analysis of Korean RNLE. Saunders comprehensive review for the $NCLEX-RN^{(R)}$ examination was used for analysis of US RNLE. The relevance between items in the standard syllabuses of biological nursing science subjects (SFHB, MED, clinical microbiology) and the RNLE items of these workbooks in ROK and the USA was analyzed. Results: The relevance rates of ROK and the USA were 3.6% vs 0.4% in SFHB, 8.9% vs 23.0% in MED, and 4.5% vs 5.8% in clinical microbiology. Conclusion: In SFHB, the relevance of the RNLE in ROK was higher than that of the USA. However in MED the relevance of the RNLE in USA was higher than that of the ROK. Since medications are one of major tasks of nurses, it is necessary to increase the number of related items in the RNLE in ROK.