• Title/Summary/Keyword: Molecular Flow

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Folate-Targeted Nanostructured Lipid Carriers (NLCs) Enhance (Letrozol) Efficacy in MCF-7 Breast Cancer Cells

  • Sabzichi, Mehdi;Mohammadian, Jamal;Khosroushahi, Ahmad Yari;Bazzaz, Roya;Hamishehkar, Hamed
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5185-5188
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    • 2016
  • Objective: Targeted-drug-delivery based lipid nanoparticles has emerged as a new and effective approach in cancer chemotherapy. Here, we investigated the ability of folate-modified nanostructured lipid carriers (NLCs) to enhance letrozol (LTZ) efficacy in MCF-7 breast cancer cells. Methods: New formulations were evaluated regarding to particle size and scanning electron microscope (SEM) features. Anti-proliferative effects of LTZ loaded nanoparticles were examined by MTT assay. To understand molecular mechanisms of apoptosis and cell cycle progression, flow cytometric assays were applied. Results: Optimum size of nanoparticles was obtained in mean average of $98{\pm}7nm$ with a poly dispersity index (PDI) of 0.165. The IC50 value was achieved for LTZ was $2.2{\pm}0.2{\mu}M$. Folate-NLC-LTZ increased the percentage of apoptotic cells from 24.6% to 42.2% compared LTZ alone (p<0.05). Furthermore, LTZ loaded folate targeted NLCs caused marked accumulation of cells in the subG1 phase. Conclusion: Taken together, our results concluded that folate targeted LTZ can be considered as potential delivery system which may overcome limitations of clinical application of LTZ and improve drug efficacy in tumor tissue.

Vitamin C increases the apoptosis via up-regulation p53 during cisplatin treatment in human colon cancer cells

  • An, Sung-Ho;Kang, Jung-Hoon;Kim, Dong-Heui;Lee, Myeong-Seon
    • BMB Reports
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    • v.44 no.3
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    • pp.211-216
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    • 2011
  • Vitamin C (VC) is an important antioxidant and enzyme co-factor that works by stimulating the immune system and protecting against infections. It is well known that melanoma cells are more susceptible to VC than any other tumor cells. However, the role of VC in the treatment of colon cancer has not been studied. Cisplatin (CDDP) is a DNA damaging agent and is widely used for treating cancer, while the role of p53 in CDDP-induced cell death has been stressed. Using cell growth assays, morphological methods, Western blotting, flow cytometry, and DNA fragmentation analysis, we measured the expression of p53 level involved in the effect of VC on CDDP-induced apoptosis of HCT116, a human colon cancer cell line. CDDP plus VC treatment resulted in significantly increased apoptosis along with upregulation of p53 compared to untreated cells and/or CDDP-treated cells. These results suggest that VC enhanced CDDP sensitivity and apoptosis via upregulation of p53.

Mouse models of polycystic kidney disease induced by defects of ciliary proteins

  • Ko, Je Yeong;Park, Jong Hoon
    • BMB Reports
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    • v.46 no.2
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    • pp.73-79
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    • 2013
  • Polycystic kidney disease (PKD) is a common hereditary disorder which is characterized by fluid-filled cysts in the kidney. Mutation in either PKD1, encoding polycystin-1 (PC1), or PKD2, encoding polycystin-2 (PC2), are causative genes of PKD. Recent studies indicate that renal cilia, known as mechanosensors, detecting flow stimulation through renal tubules, have a critical function in maintaining homeostasis of renal epithelial cells. Because most proteins related to PKD are localized to renal cilia or have a function in ciliogenesis. PC1/PC2 heterodimer is localized to the cilia, playing a role in calcium channels. Also, disruptions of ciliary proteins, except for PC1 and PC2, could be involved in the induction of polycystic kidney disease. Based on these findings, various PKD mice models were produced to understand the roles of primary cilia defects in renal cyst formation. In this review, we will describe the general role of cilia in renal epithelial cells, and the relationship between ciliary defects and PKD. We also discuss mouse models of PKD related to ciliary defects based on recent studies.

Analysis of rarefied compressible boundary layers in transition regime (천이영역의 희박기체 압축성 경계층 해석)

  • Choe, Seo-Won
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.21 no.4
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    • pp.509-517
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    • 1997
  • Results of flat plate compressible boundary layer calculation, based on discrete formulation of DSMC method, are presented in low Mach number and low Knudsen number range. The free stream is a uniform flow of pure nitrogen at various Mach numbers in low pressures (i.e. rarefied gas). Complete thermal accommodation and diffuse molecular reflections are used as the wall boundary condition, replacing unreal no-slip condition used in continuum calculations. In the discrete formulation of DSMC method, there is no need to use ad hoc assumptions on transport properties like viscosity and thermal conductivity, instead viscosity is calculated from values of other field variables (velocity and shear stress). Also the results are compared with existing self-similar continuum solutions. In all Mach number cases computed, velocity slip is most pronounced in regions near the leading edge where continuum formulation renders the solution singular. As the boundary layer develops further downstream, velocity slips asymptote to values that are between 10 to 20% of the magnitude of free stream velocity. When the free stream number density is reduced, so the gas more rarefied, the velocity slip increases as expected.

Nonsteroidal Anti-inflammatory Drugs (비스테로이드 항염제)

  • Lee, Choong-Ki
    • Journal of Yeungnam Medical Science
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    • v.17 no.1
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    • pp.1-11
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    • 2000
  • Inhibition of cyclooxygenase(COX), and thus prevention of the formation of prostaglandins, provided a unifying explanation of the therapeutic and toxic actions of nonsteroidal anti-inflammatory drugs (NSAIDs). Recently, the discovery of the two isoforms of COX was made by molecular biologists studying neoplastic transformation in chick embryo cells. The constitutive enzyme, COX-1, is obviously responsible for the production of prostaglandins involved in housekeeping functions such as maintenance of integrity of the gastric mucosa, renal blood flow and platelet aggregation. The inducible form of COX (COX-2) is responsible for the formation of prostaglandins that pathologically affects inflammation, pain and fever. Clearly, all the experimental and clinical data support the hypothesis that the beneficial effects of NSAIDs are due to inhibition of the COX-2 enzyme, whereas the gastrotoxicity is due to inhibition of COX-1. The cox-2/COX-1 ratios of the NSAIDs in common use have been measured and compared with epidemiological data on their side effects. There is little evidence to suggest that one NSAID is clearly more effective than another, But substantial individual variability is present with respect to the pharmacology and pharmacokinetics of these drugs: therefore it is essential to adjust the dosage and choose specific drug to the patient's response.

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Synergistic Anticancer Activity of 5-Aminolevulinic Acid Photodynamic Therapy in Combination with Low-dose Cisplatin on Hela Cells

  • Wei, Xiao-Qiang;Ma, Hui-Qing;Liu, Ai-Hong;Zhang, You-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3023-3028
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    • 2013
  • Objective: Photodynamic therapy (PDT ) is a promising modality for the treatment of various tumors. In order to assist in optimizing treatment, we applied 5-ALA/PDT in combination with low-dose cisplatin to evaluate cytotoxicity in Hela cells. Methods: Antiproliferative effects of 5-ALA/PDT and cisplatin, alone and in combination, were assessed using MTT assay. To examine levels of apoptosis, Hela cells treated with 5-ALA/PDT, and combination treatment were assessed with Annexin-V/PI by flow cytometry. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, Western blot analysis was conducted to determine the expression of p53, p21, Bax and Bcl-2 proteins. Results: MTT assays indicated that combination treatment obviously decreased the viability of Hela cells compared to individual drug treatment. In addition, it was confirmed that exposure of Hela cells to 5-ALA/PDT in combination with low-dose cisplatin resulted in more apoptosis in vitro. Synergistic anticancer activity was related to upregulation p53 expression and alteration in expression of p21, Bcl-2 and Bax. Conclusion: Our findings suggest that administration of 5-ALA/PDT in combination with the low-dose cisplatin may be an effective and feasible therapy for cervical cancer.

Rheological Properties of Exopolysaccharide Produced by Xanthomonas sp. EPS-1 (Xanthomonas sp. EPS-1이 생산하는 다당류의 리올로지 특성)

  • Son, Bong-Soo;Park, Seok-Kyu;Kang, Shin-Kwon;Lee, Sang-Won;Sung, Nack-Kie
    • Microbiology and Biotechnology Letters
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    • v.23 no.3
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    • pp.269-274
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    • 1995
  • For the screening of a new functional exopolysaccharide, sugar composition and rheological properties of exopolysaccharide produced from Xanthomonas sp. EPS-1 were investigated. The average molecular weight of exopolysaccharide was determined to be approximately 2.l $\times$ 10$^{6}$ dalton. The new exopolysaccharide EPS-1 was composed of mannose, glucose, galactose and gluco- samine. IR analysis showed that the exopolysaccharide EPS-1 was assumed to be polymer with carbohydrates. NMR analysis showed that exopolysaccharide EPS-1 was presumed to be 4 units of sugar and trace of CH$_{3}$ group. Exopolysaccharide EPS-1 solution showed a characteristic of non-Newtonian fluid properties. At the concentration of 1.0%, the consistency index and the flow behavior index were shown at 10.8352 poise-sec and 0.4419, respectively. All dispersions were pseudoplastic fluids described accurately by Power-law model. Exopolysaccharide EPS-1 was highly viscous at low concentration, with good stability over a wide range of pH 5 to 13. The excellent compatibility of exopolysaccharide EPS-1 was represented with salts such as sodium chloride.

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Platelets Induce Proliferation of Human Umbilical Vein Endothelial Cells via CD154-CD40 Pathway Independently of VEGF

  • Cho, Wha-Jung;Ko, Eun-Mi;Cheon, In-Su;Jeoung, Doo-Il;Kim, Young-Myeong;Choe, Jong-Seon
    • IMMUNE NETWORK
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    • v.8 no.3
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    • pp.75-81
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    • 2008
  • Background: Platelets take part in repairing the lesions of endothelial damage. To understand the molecular mechanism of this process, we tested the hypothesis that CD154 expressed on activated platelets stimulates proliferation of human endothelial cells. Methods: The expression levels of CD154 and CD40 on platelets and endothelial cells, respectively, were measured by flow cytometry and confocal microscopy. Function-blocking monoclonal antibody against CD154 was developed after immunization with CD154-transfected L cells. Results: An anti-CD40 agonist antibody and soluble CD154 both induced significant proliferation of endothelial cells. In addition, a function-blocking anti-CD154 antibody inhibited the platelet-induced proliferation of endothelial cells, indicating that the CD154-CD40 pathway is involved in these cellular interactions. An anti-VEGF antibody failed to inhibit the proliferation. This, in addition to the fact that very small amounts of VEGF are released from platelets or endothelial cells, suggests that VEGF does not play an important role in the platelet-stimulated proliferation of endothelial cells. Conclusion: Our results indicate that platelets induce proliferation of endothelial cells by CD154-CD40 interactions independently of VEGF.

A Study on the Transfer of the Oscillator's Motion Information with 2 Degrees of Freedom;Thermal Boundary Resistance (2자유도 진동계의 운동정보 전달에 관한 연구;경계면열저항)

  • Choi, Soon-Ho;Choi, Hyun-Kye;Jin, Chang-Fu;Kim, Kyung-Kun;Yoon, Seok-Hun;Oh, Cheol
    • Proceedings of the Korean Society of Marine Engineers Conference
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    • 2005.06a
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    • pp.1102-1107
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    • 2005
  • The analysis of the thermal boundary resistance is very important in the both cases of microscale and macroscale systems because it plays a role of thermal barrier against a heat flow. Especially, since fairly large heat energy is generated in microscale or nanoscale systems with electronic chips, the thermal boundary resistance is a key factor to guarantee the performance of those devices. In this study, the transfer of the oscillator's motion information with 2 degrees of freedom is investigated for clarifying the mechanism of a thermal boundary resistance. We found that the transfer of the oscillator's motion information is defined as a cross-correlation coefficient and the magnitude of it determines the temperature jump over a solid interface. That is, the temperature jump over an interface increases as the magnitude of a cross-correlation coefficient decreases and vice versa.

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Transcriptional Profile and Cellular Effects on Time Course & Doses Treatment of Methylmercury using Human cDNA Microarray System

  • Kim, Youn-Jung;Yun, Hye-Jung;Kim, Eun-Young;Ryu, Jae-Chun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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    • pp.176-176
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    • 2003
  • Methylmercury is known to have devastating effects on the mammalian nervous system. When human neuroblastoma SH-SY5Y cells were treated with methylmercury at sublethal concentrations (6.25 uM), up-regulated genes (39) & down-regulated genes (19) were identified by human 8k cDNA microarray. These genes are related with microtubule process, signal transduction pathway and cell death (apoptosis), Apoptosis-associated genes, HSP70, CDK inhibitor 1, FOS-like antigen were up-regulated and microtubule related genes like villin and dynein down-regultaed. To confirm the presence of apoptosis in cultured SH-SY5Y cells treated 6.25 and 1 uM methylmercury, we applied Annexin V-FITC assay followed by flow cytometric measurements after 6 and 24h. Studies on transcriptional and molecular effect by methylmercury may provide an insight into the neurotoxic effects of methylmercury in human neuronal cells and a possibility to develop more efficient and exact monitoring system of heavy metals as ubiquitous environmental pollutants.

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