• Title/Summary/Keyword: molecular mechanism

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Efficacy Evaluation of Tissue Inhibitor of Metalloproteinases-2 and Endostatin on Angiogenesis (Tissue Inhibitor of Metalloproteinases-2와 Endostatin의 혈관신생 제어 효능 평가)

  • Kim, Soo-Hyeon;Cho, Young-Rak;Yoon, Hyun-Jae;Ko, Hee-Young;Kim, Pyeung-Hyeun;Seo, Dong-Wan
    • YAKHAK HOEJI
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    • v.54 no.6
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    • pp.488-493
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    • 2010
  • Therapeutic manipulation of angiogenesis, the formation of new vascular sprouts from existing capillaries, is one of the promising strategies for treatment of human diseases such as cancer, arthritis, and cardiovascular disorder. In the present study, we examined the effects and molecular mechanism of tissue inhibitor of metalloproteinases-2 (TIMP-2) and endostatin on fibroblast growth factor-2 (FGF-2)-stimulated endothelial cell proliferation, migration and adhesion in vitro, and angiogenesis in vivo. TIMP-2 and endostatin showed potent anti-angiogenic activity in vitro and in vivo. These effects appear to be mediated through different angiogenic signaling pathways. Collectively, our findings demonstrate that TIMP-2 and endostatin strongly inhibit FGF-2-induced angiogenic responses, and the establishment of fast and reproducible evaluation system in vitro and in vivo for the development of anti-angiogenic biomaterials and therapeutics.

Channel Capacity Analysis of DNA-based Molecular Communication with Length Encoding Mechanism

  • Xie, Jialin;Liu, Qiang;Yang, Kun;Lin, Lin
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.15 no.8
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    • pp.2923-2943
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    • 2021
  • The double helix structure of DNA makes it diverse, stable and can store information with high density, and these characteristics are consistent with the requirements of molecular communication for transport carriers. In this paper, a specific structure of molecular communication system based on DNA length coding is proposed. Transmitter (Tx) adopts the multi-layer golden foil design to control the release of DNA molecules of different lengths accurately, and receiver (Rx) adopts an effective and sensitive design of nanopore, and the biological information can be converted to the electric signal at Rx. The effect of some key factors, e.g., the length of time slot, transmission distance, the number of releasing molecules, the priori probability, on channel capacity is demonstrated exhaustively. Moreover, we also compare the transmission capacity of DNA-based molecular communication (DNA-MC) system and concentration-based molecular communication (MC) system under the same parameter setting, and the peak value of capacity of DNA-MC system can achieve 0.08 bps, while the capacity of MC system remains 0.025 bps. The simulation results show that DNA-MC system has obvious advantages over MC system in saving molecular resources and improving transmission stability.

Hepatitis B virus X protein enhances liver cancer cell migration by regulating calmodulin-associated actin polymerization

  • Kim, Mi-jee;Kim, Jinchul;Im, Jin-su;Kang, Inho;Ahn, Jeong Keun
    • BMB Reports
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    • v.54 no.12
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    • pp.614-619
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    • 2021
  • Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), which is a highly aggressive cancer. HBV X protein (HBx), one of four HBV gene products, plays pivotal roles in the development and metastasis of HCC. It has been reported that HBx induces liver cancer cell migration and reorganizes actin cytoskeleton, however the molecular basis for actin cytoskeleton reorganization remains obscure. In this study, we for the first time report that HBx promotes actin polymerization and liver cancer cell migration by regulating calcium modulated protein, calmodulin (CaM). HBx physically interacts with CaM to control the level of phosphorylated cofilin, an actin depolymerizing factor. Mechanistically, HBx interacts with CaM, liberates Hsp90 from its inhibitory partner CaM, and increases the activity of Hsp90, thus activating LIMK1/cofilin pathway. Interestingly, the interaction between HBx and CaM is calcium-dependent and requires the CaM binding motif on HBx. These results indicate that HBx modulates CaM which plays a regulatory role in Hsp90/LIMK1/cofilin pathway of actin reorganization, suggesting a new mechanism of HBV-induced HCC metastasis specifically derived by HBx.

Investigation of the effect of Erythrosine B on a β-amyloid (1-40) peptide using molecular modeling method

  • Lee, Juho;Kwon, Inchan;Cho, Art E.;Jang, Seung Soon
    • Proceeding of EDISON Challenge
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    • 2015.03a
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    • pp.14-23
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    • 2015
  • Alzheimer's disease is one of the most common types of degenerative dementia. As a considerable cause of Alzheimer's disease, neurotoxic plaques composed of 39 to 42 residue-long amyloid beta($A{\beta}$) fibrils have been found in the patient's brain in large quantity. A previous study found that erythrosine B (ER), a red color food dye approved by FDA, inhibits the formation of amyloid beta fibril structures. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics simulations to demonstrate the conformational change of $A{\beta}40$ induced by 2 ERs in atomistic detail. During the simulation, the ERs bound to the surfaces of both N-terminus and C-terminus regions of $A{\beta}40$ rapidly. The observed stacking of the ERs and the aromatic side chains near the N-terminus region suggests a possible inhibition mechanism in which disturbing the inter-chain stacking of PHEs destabilizes beta-sheet enriched in amyloid beta fibrils. The bound ERs block water molecules and thereby help stabilizing alpha helical structure at the main chain of C-terminus and interrupt the formation of the salt-bridge ASP23-LYS28 at the same time. Our findings can help better understanding of the current and upcoming treatment studies for Alzheimer's disease by suggesting inhibition mechanism of ER on the conformational transition of $A{\beta}40$ at the molecular level.

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Monitoring the Change of Protein Expression in Human Colon Cancer Cell SNU-81 treated with the Water-Extract of Coptis japonica (황련 열수추출물을 처치한 인간 대장암 세포 SNU-81에서의 단백질 발현 변화)

  • Yoo, Tae-Mo;Kim, Byung-Soo;Yoo, Byong-Chul;Yoo, Hwa-Seung
    • Journal of Pharmacopuncture
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    • v.12 no.1
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    • pp.5-12
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    • 2009
  • Background : Anticancer effects of herbal medicine have been reported in various types of cancer, but the systematic approaches to explain molecular mechanism(s) are not established yet. Objective : To find the anticancer-effect and mechanism(s) of Water Extract of Coptis japonica (WECJ) colon cancer cell (SNU-81). Methods : We first selected 11 herbals, and anti-cancer effects of water-extracts from those herbals have been tested in human colon cancer cell line, SNU-81. Among the tested herbals, the WECJ significantly reduced proliferation of SNU-81. To establish a basis of understanding for anti-cancer mechanism, whole proteins have been obtained from SNU-81 harvested at 48 and 96 hrs after the treatment of WECJ, protein expression has been profiled by 2DE-based proteomic approach. Results : Various changes of the protein expression have been monitored, and most frequent dysregulation was found in the molecular chaperons including heat shock protein 90-alpha (Hsp90-alpha), 14-3-3 protein epsilon, T-complex protein 1 subunit alpha, protein disulfide-isomerase A3, and calreticulin. Interestingly, proliferation-associated protein 2G4 has been up-regulated, and it suggests the possible effect of Coptis japonica on ErbB3-regulated signal transduction pathway and growth control of human colon cancer cells. Conclusion : Based upon the present findings, the further study will focus on monitoring various cancer survival factors after artificial regulation of the proteins identified, and it would be the basis for the understanding of the Coptis japonica anti-cancer effect(s) at the molecular level.

Promoter Structure Which Affects on the Expression of Yeast MGMT Gene

  • Choe, Soo-Young
    • BMB Reports
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    • v.30 no.1
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    • pp.41-45
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    • 1997
  • The present study was performed to analyze the molecular mechanism which dictates the transcription regulation of the $O^6$-methylguanine-DNA methyltransferase (MGMT) gene in Saccharomyces cerevisiae. Previously we identified one possible upstream repressing sequence (URS) in MGMT promoter by promoter deletion and competition analysis. In this paper we report another regulatory element (UAS: upstream activating sequence. -213 to -136) which affects the transcription activity of MGMT promoter. Gel mobility shift assay and Southwestern blot analysis using UAS probe showed several specific proteins which were able to bind to this sequence.

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Molecular Structure of Muscle Filaments Determined by Electron Microscopy

  • Craig, Roger
    • Applied Microscopy
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    • v.47 no.4
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    • pp.226-232
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    • 2017
  • Electron microscopy and X-ray diffraction have together played a key role in our understanding of the molecular structure and mechanism of contraction of muscle. This review highlights the role of electron microscopy, from early insights into thick and thin filament structure by negative staining, to studies of single myosin molecule structure, and finally to recent high-resolution structures by cryo-electron microscopy. Muscle filaments are designed for movement. Their labile structures thus present challenges to obtaining near-atomic detail, which are also discussed.

Molecular Aspects of Some Photobiological Receptors

  • Song, Pill-Soon
    • Applied Biological Chemistry
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    • v.20 no.1
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    • pp.10-25
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    • 1977
  • The photobiological receptors of phototactic, phototropic, and photomorphogenic responses of various organisms have been described in terms of spectroscopic, photophysical and photochemical properties which may be relevant in elucidating the energy transduct ion mechanism(s) in photobiology. The photoreceptors discussed include carotenoids, flavins, stentorin and phytochrome. Although the molecular modes of their photobiological action still remain largely unexplained, it is possible to suggest several primary molecul ar processes of the photoreceptors in eliciting responses of various organisms to light.

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Small RNAs: Classification, Biogenesis, and Function

  • Kim, V. Narry
    • Molecules and Cells
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    • v.19 no.1
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    • pp.1-15
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    • 2005
  • Eukaryotes produce various types of small RNAs of 19-28 nt in length. With rapidly increasing numbers of small RNAs listed in recent years, we have come to realize how widespread their functions are and how diverse the biogenesis pathways have evolved. At the same time, we are beginning to grasp the common features and rules governing the key steps in small RNA pathways. In this review, I will summarize the current classification, biogenesis, action mechanism and function of these fascinating molecules.

PROTEIN-CROSS-LINKING BY METHYLGLYOXAL

  • Lee, Cheolju;Kang, Sa-Ouk
    • Proceedings of the Korean Biophysical Society Conference
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    • 1996.07a
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    • pp.46-46
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    • 1996
  • To elucidate the mechanism for the cross-linking reaction in the glycation or Maillard reaction, we studied the reaction between proteins, and a three-carbon ${\alpha}$-ketoaldehyde, methylglyoxal. When Cu, Zn-SOD was incubated with 200 mM of methylglyoxal, the peroxidase activity as well as the superoxide dismutase activity was reduced. This reduction is accompanied by the decrease of the anion binding affinity of the enzyme. (omitted)

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