• Title/Summary/Keyword: modes of action

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Effect of Low Doses of Genistein and Equol on Protein Expression Profile in MCF-7 Cells

  • Kim, Jang-Hoon;Lim, Hyun-Ae;Lee, Jeong-Soon;Sung, Mi-Kyung;Kim, Young-Kyoon;Yu, Ri-Na;Kim, Jong-Sang
    • Food Science and Biotechnology
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    • v.14 no.6
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    • pp.854-859
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    • 2005
  • Although action modes of equol and genistein have been extensively studied, their precise roles in tumor cells remain elusive. To address possible effects of these compounds on protein expression in mammary tumor cells, proteins modulated in MCF-7 mammary tumor cells when incubated in absence and presence of 10 uM equol or genistein were identified through 2-dimensional gel electrophoresis, MALDI-TOF MS/MS, and NCBInr database search using Mascot software. Most proteins differentially expressed in MCF-7 cells after treatment with 10 uM genistein or equol were identified as being the same. Exposure to both compounds caused decreased cellular expression of RNA-binding protein regulatory subunit and oncogene DJ1 tubulin beta-1 chain, and increased expression of heterogeneous ribonucleoproteins F and L, KH-type splicing regulatory protein, and translation elongation factor EF-Tu precursor. Genistein and equol at dose used in this study showed common action mechanism.

Systems pharmacology approaches in herbal medicine research: a brief review

  • Lee, Myunggyo;Shin, Hyejin;Park, Musun;Kim, Aeyung;Cha, Seongwon;Lee, Haeseung
    • BMB Reports
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    • v.55 no.9
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    • pp.417-428
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    • 2022
  • Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.

Bacterial Apoptosis-Like Death through Accumulation of Reactive Oxygen Species by Quercetin in Escherichia coli

  • Min Seok Kwun;Dong Gun Lee
    • Journal of Microbiology and Biotechnology
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    • v.34 no.7
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    • pp.1395-1400
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    • 2024
  • The antimicrobial activity of the natural compounds from plant and food have well discovered since the interest on the beneficial effect of the natural compounds was risen. Quercetin, a flavonoid derived from vegetables, including onions, red leaf lettuces and cherries has been studied for diverse biological characteristics as anti-cancer and anti-microbial activities. The aim of current study is to investigate the specific antibacterial modes of action of quercetin against Escherichia coli. Quercetin decreased the E. coli cell viability and induced the severe damages (oxidative stress, DNA fragmentation) leading to cell death. Reactive oxygen species (ROS) generation was observed during the process, which we confirmed that oxidative stress was the key action of antibacterial activity of quercetin exerting its influence potently. Based on the results of Annexin V and Caspace FITC-VAD-FMK assay, the oxidative damage in E. coli has led to the bacterial apoptosis-like death in E. coli. To sum up, the contribution of ROS generation exerts crucial impact in antibacterial activity of quercetin.

Behavior of polygonal concrete-filled steel tubular stub columns under axial loading

  • Zhang, Tao;Ding, Fa-xing;Wang, Liping;Liu, Xue-mei;Jiang, Guo-shuai
    • Steel and Composite Structures
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    • v.28 no.5
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    • pp.573-588
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    • 2018
  • The objective of this paper is to investigate the mechanical performances of polygonal concrete-filled circular steel tubular (CFT) stub columns under axial loading through combined experimental and numerical study. A total of 32 specimens were designed to investigate the effect of the concrete strength and steel ratio on the compressive behavior of polygonal CFT stub columns. The ultimate bearing capacity, ductility and confinement effect were analyzed based on the experimental results and the failure modes were discussed in detail. Besides, ABAQUS was adopted to establish the three dimensional FE model. The composite action between the core concrete and steel tube was further discussed and clarified. It was found that the behavior of CFT stub column changes with the change of the cross-section, and the change is continuous. Finally, based on both experimental and numerical results, a unified formula was developed to estimate the ultimate bearing capacity of polygonal CFT stub columns according to the superposition principle with rational simplification. The predicted results showed satisfactory agreement with both experimental and FE results.

Inhibitory Effects of EGCG on the Dopaminergic Neurons

  • Heo, Tag;Jang, Su-Jeong;Kim, Song-Hee;Jeong, Han-Seong;Park, Jong-Seong
    • Biomedical Science Letters
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    • v.15 no.2
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    • pp.127-133
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    • 2009
  • This study was designed to investigate the effects of high concentration of (-)-epigallocatechin-3-gallate(EGCG) on the neuronal activity of rat substantia nigra dopaminergic neurons. Sprague-Dawley rats aged 14 to 16 days were decapitated under ether anesthesia. After treatment with pronase and thermolysin, the dissociated dopaminergic neurons were transferred into a chamber on an inverted microscope. Spontaneous action potentials and potassium currents were recorded by standard patch-clamp techniques under current and voltage-clamp modes respectively. 18 dopaminergic neurons(80%) revealed inhibitory responses to 40 and 100 ${\mu}M$ of EGCG and 4 neurons(20%) did not respond to EGCG. The spike frequency and resting membrane potential of these cells were decreased by EGCG. The amplitude of afterhyperpolarization was increased by EGCG. Whole potassium currents of dopaminergic neurons were increased by EGCG(n=10). These experimental results suggest that high concentration EGCG decreases the neuronal activity of the dopaminergic neurons by altering the resting membrane potential and afterhyperpolarization.

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Experimental Study on the Flexural Capacity of the U-Flanged Truss Hybrid Beam (U-플랜지 트러스 복합보의 휨 내력에 대한 실험 연구)

  • Oh, Myoung Ho;Kim, Young Ho;Kim, Myeong Han
    • Journal of Korean Association for Spatial Structures
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    • v.18 no.4
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    • pp.123-130
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    • 2018
  • U-flanged truss beam is composed of u-shaped upper steel flange, lower steel plate of 8mm or more thickness, and connecting lattice bars welded on the upper and lower sides. The hybrid beam with U-flanged steel truss is made in the construction site through pouring the concrete, and designated as U-flanged truss hybrid beam. In this study the structural experiments on the 4 hybrid beams with the proposed basic shapes were performed, and the flexural capacities from the tests were compared with those from the theoretical approach. The failure modes of each specimen were quite similar. The peak load was reached with the ductile behavior after yielding, and the failure occurred through the concrete crushing. The considerable increasement of deformation was observed up to the concrete crushing. The composite action of concrete and steel member was considered to be reliable from the behavior of specimens. The flexural strength of hybrid beam has been evaluated exactly using the calculation method applied in the boubly reinforced concrete beam. The placement of additional rebars in the bottom instead of upper side is proposed for the efficient design of U-flanged truss hybrid beam.

p38 MAPK Inhibitor NJK14047 Suppresses CDNB-Induced Atopic Dermatitis-Like Symptoms in BALB/c Mice

  • Lee, Ju-Hyun;Son, Seung-Hwan;Kim, Nam-Jung;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.501-509
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    • 2022
  • Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Suppression of MAPKs and NF-κB is implicated as a vital mechanism of action of several traditional Chinese medicines for AD therapy. Although overexpression of MAPK mRNA in the skin tissue has been shown in the AD model, the roles of each MAPK in AD pathogenesis have rarely been studied. This study examined the effect of NJK14047, an inhibitor of p38 MAPKs, on AD-like skin lesions induced in BALB/c mice by sensitization and challenges with 1-chloro-2,4-dinitrobenzene (CDNB) on dorsal skin and ears, respectively. After induction of AD, NJK14047 (2.5 mg/kg) or dexamethasone (10 mg/kg) was administrated for 3 weeks via intraperitoneal injection. Following its administration, NJK14047 suppressed CDNB-induced AD-like symptoms such as skin hypertrophy and suppressed mast cell infiltration into the skin lesions. It also reduced CDNB-induced increase in TH2 cytokine (IL-13) and TH1 cytokines (interferon-γ and IL-12A) levels but did not decrease serum IgE level. Furthermore, NJK14047 blocked CDNB-induced lymph node enlargement. These results suggest that NJK14047, a p38 MAPK inhibitor, might be an optimal therapeutic option with unique modes of action for AD treatment.

Effects of Sphingosine-1-phosphate on Vestibular Nuclear Neurons

  • Lee, Jae-Hyuk;Jang, Su-Jeong;Kim, Song-Hee;Jeong, Han-Seong;Park, Jong-Seong
    • Biomedical Science Letters
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    • v.16 no.1
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    • pp.46-52
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    • 2010
  • This study was designed to investigate the effects of sphingosine-1-phosphate on the neuronal activity of rat medial vestibular nuclear neurons. Sprague-Dawley rats aged 14 to 16 days were decapitated under ether anesthesia. After treatment with pronase and thermolysin, the dissociated medial vestibular nuclear neurons were transferred into a chamber on an inverted microscope. Spontaneous action potentials and potassium currents were recorded by standard patch-clamp techniques under current and voltage-clamp modes respectively. 15 medial vestibular nuclear neurons revealed excitatory responses to 1 and $5\;{\mu}M$ of sphingosine-1-phosphate. The spike frequency and resting membrane potential of these cells were increased by sphingosine-1-phosphate. The amplitude of afterhyperpolarization was decreased by sphingosine-1-phosphate. Whole potassium currents of medial vestibular nuclear neurons were decreased by sphingosine-1-phosphate (n=12). Sphingosine-1-phosphate did not affect the charybdotoxin-treated potassium currents. These experimental results suggest that sphingosine-1-phosphate increases the neuronal activity of the medial vestibular nuclear neurons by altering the resting membrane potential and afterhyperpolarization.

Behavior of concrete-filled round-ended steel tubes under bending

  • Ding, Fa-xing;Zhang, Tao;Wang, Liping;Fu, Lei
    • Steel and Composite Structures
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    • v.25 no.4
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    • pp.457-472
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    • 2017
  • The objective of this paper is to investigate the flexural behavior of concrete-filled round-ended steel tubes (CFRTs) under bending. Beam specimens were tested to investigate the mechanical behavior of the CFRTs, including four CFTs with different concrete strengths and steel ratios, and three CFRTs with varied aspect ratios. The load vs. deflection relationships and the failure modes for CFRTs were analyzed in detail. The composite action between the core concrete and steel tube was also discussed and examined based on the experimental results. In addition, ABAQUS program was used to develop the full-scale finite element model and analyze the effect of different parameters on the moment vs. curvature curves of the CFRTs bending about the major and minor axis, respectively. Furthermore, design formulas were proposed to estimate the ultimate moment and the flexural stiffness of the CFRTs, and the simplified theoretical model of the moment vs. curvature curves was also developed. The predicted results showed satisfactory agreement with the experimental and FE results. Finally, the differences of the experimental, FE and predicted results using the existing codes were illustrated.

Finite element modelling of the shear behaviour of profiled composite walls incorporating steel-concrete interaction

  • Anwar Hossain, K.M.;Wright, H.D.
    • Structural Engineering and Mechanics
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    • v.21 no.6
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    • pp.659-676
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    • 2005
  • The novel form of composite walling system consists of two skins of profiled steel sheeting with an in-fill of concrete. The behaviour of such walling under in-plane shear is important in order to utilise this system as shear elements in a steel framed building. Steel sheet-concrete interface governs composite action, overall behaviour and failure modes of such walls. This paper describes the finite element (FE) modelling of the shear behaviour of walls with particular emphasis on the simulation of steel-concrete interface. The modelling of complex non-linear steel-concrete interaction in composite walls is conducted by using different FE models. Four FE models are developed and characterized by their approaches to simulate steel-concrete interface behaviour allowing either full or partial composite action. Non-linear interface or joint elements are introduced between steel and concrete to simulate partial composite action that allows steel-concrete in-plane slip or out of plane separation. The properties of such interface/joint elements are optimised through extensive parametric FE analysis using experimental results to achieve reliable and accurate simulation of actual steel-concrete interaction in a wall. The performance of developed FE models is validated through small-scale model tests. FE models are found to simulate strength, stiffness and strain characteristics reasonably well. The performance of a model with joint elements connecting steel and concrete layers is found better than full composite (without interface or joint elements) and other models with interface elements. The proposed FE model can be used to simulate the shear behaviour of composite walls in practical situation.