• Radiation Oncology Journal
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• v.18 no.1
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• pp.51-58
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• 2000

Purpose :The effect of PTK inhibitors (herbimycin A and genistein) on the induction of radiation-induced apoptosis in Ph-positive KS62 leukemia cell line was investigated. Materials and Methods :K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For 6 MV X-ray irradiation and drug treatment, cultures were initiated at 2×106 cells/mL. The cells were irradiated with 10 Gy. Stock solutions of herbimycin A and genistein were prepared in dimethyl sulphoxide (DMSO). After incubation at 37$^{\circ}C$ for 0$\~$48 h, the extent of apoptosis was determined using agarose gel electrophoresis and TUNEL assay. The progression of cells through the cell cycle after irradiation and drug treatment was also determined with flow cytometry. Western blot analysis was used to monitor bel-2, bel-X$_{L}$ and bax protein levels. Results :Treatment with 10 Gy X-irradiation did not result in the induction of apoptosis. The HMA alone (500 nM) also failed to induce apoptosis. By contrast, incubation of K562 cells with HMA after irradiation resulted in a substantial induction of nuclear condensation and fragmentation by agarose gel electro-phoresis and TUNEL assay. Genistein failed to enhance the ability of X-irradiation to induce DNA fragmentation. Enhancement of apoptosis by HMA was not attributable to downregulation of the bel-2 or bel-X$_{L}$ anti-apoptotic proteins. When the cells were irradiated and maintained with HMA, the percentage of cells in G2/M phase decreased to 30$\~$40$\%$ at 48 h. On the other hand, cells exposed to 10 Gy X-irradiation alone or maintained with genistein did not show marked cell cycle redistribution. Conclusion : We have shown that nanomolar concentrations of the PTK inhibitor HMA synergize with X-irradiation in inducing the apoptosis in Ph (+) K562 leukemia cell line. While, genistein, a PTK inhibitor which is not selective for p210$^{bcr/abl}$ failed to enhance the radiation induced apoptosis in KS62 cells. It is unlikely that the ability of HMA to enhance apoptosis in K562 cells is attributable to bel-2 family. It is plausible that the relationship between cell cycle delays and cell death is essential for drug development based on molecular targeting designed to modify radiation-induced apoptosis.

• Structural Engineering and Mechanics
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• v.59 no.2
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• pp.313-326
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• 2016

In this study the three-dimensional nonlinear finite element method was used to analyze the stresses distribution in the adhesive layer used to joint two Aluminum 2024-T3 adherends. We consider in this study the effect of different parameters witch directly affect the values of different stresses. The experimental design method is used to investigate the effects of geometrical parameters of the single lap joint in order to achieve an optimization of the assembly with simple lap joint. As a result, it can be said that both the geometrical modifications of the adhesive and adherends edge have presented a significant effect at the overlap edge thereby causing a decrease in peel and shear stresses. In addition, an analytical model is also given to predict in a simple but effective way the joint strength and its dependence on the geometrical parameters. This approach can help the designers to improve the quality and the durability of the structural adhesive joints.

• Advances in aircraft and spacecraft science
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• v.4 no.6
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• pp.679-699
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• 2017

The aim of this study is to perform a finite element analysis of the Von Mises stresses distribution in the adhesive layer and of the J-Integral for a damaged plate repaired by a composite patch. Firstly, we study the effect of the fiber orientation, especially the position of the layers that have orientation angle different of $0^{\circ}$ from the first layer which is in all cases of our study oriented at ($0^{\circ}$) on the J-Integral. Secondly, we evaluate the effects of the mechanical properties of the patch and the use of a hybrid patch on the reduction of stresses distribution and J-Integral. The results show clearly that the stacking sequence for the composite patch must be selected to absorb optimally the stresses from the damaged area and to position the various layers of the composite under the first layer whose fibers orientation will remain in all cases equal to $0^{\circ}$. The use of a hybrid composite reduces significantly the J-Integral and the stresses in both damaged plate and the adhesive layer.

• Structural Engineering and Mechanics
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• v.78 no.2
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• pp.117-124
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• 2021

This work focused on the novel numerical tool for the bending responses of carbon nanotube reinforced composites (CNTRC) beams. The higher order shear deformation beam theory (HSDT) is used to determine strain-displacement relationships. A new exponential function was introduced into the carbon nanotube (CNT) volume fraction equation to show the effect of the CNT distribution on the CNTRC beams through displacements and stresses. To determine the mechanical properties of CNTRCs, the rule of the mixture was employed by assuming that the single-walled carbon nanotubes (SWCNTs)are aligned and distributed in the matrix. The governing equations were derived by Hamilton's principle, and the mathematical models presented in this work are numerically provided to verify the accuracy of the present theory. The effects of aspect ratio (l/d), CNT volume fraction (Vcnt), and the order of exponent (n) on the displacement and stresses are presented and discussed in detail. Based on the analytical results. It turns out that the increase of the exponent degree (n) makes the X-beam stiffer and the exponential CNTs distribution plays an indispensable role to improve the mechanical properties of the CNTRC beams.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.677-683
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• 2003

We investigated the effects of Insamsapye-tang (ISSPT) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with ISSPT extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that ISSPT treatment increased populations of apoptotic-sub G1 phase. In addition, proteolytic degradation of poly(ADP-ribose) polymerase (PARP) and β-catenin protein were observed after treatment of ISSPT extract. These apoptotic effects of ISSPT in A549 cells were associated with marked inhibition of Bel-xL expression in a dose-dependent manner, however the levels of Bcl-2 and Bax expression were not affected. ISSPT treatment also induced the expression of tumor suppressor p53 mRNA and inhibited the expression of caspase-3 mRNA. The previous and present results indicated that ISSPT-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.145-164
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• 1998

The purpose of this study is to evaluate the effect of Injinchunggantang-derivative on proliferation of hepatocyte in rats. Cell viability is studied by MTI assay. The gene related to cell replication such as p53, waf1, bcl-2 and $bcl-_{X_L}$ is quantitized by quantitative RT-PCR and the proteins coded by these genes are studied by Western blotting. The results are as follows. 1. The hepatocytes cultured in medium with lnjinchunggantang-derivative showed better viability compared with control grroup in MTI assay, and the hepatocytes cultured in medium with the Injinchunggantang-derivative-and-ethanol-mixed group showed better viability than the hepatocytes cultrued in 10% ethanol culture medium(control group), noting that Injinchunggantang-derivative has protective effect on hepatocyte injury. There was no dose- and time-dependence. 2. In quantitative RT-PCR, i) Bel-2 gene increased significantly both in Injinchunggantang-derivative group and in Injinchunggantang-derivative-and-ethanol-mixed group, while it showed no significant increase or decrease in other group. ii) $Bcl-_{X_L}$ gene increased significantly in Injinchunggantang-derivative group as well as in Injinchunggantang-deri vative-and-ethanol -mixed group. iii) P53 gene showed no significant increase or decrease in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchunggantang-derivative-and-ethanol-mixed group, suggesting that 10% ethanol induced cell toxicity, thus increased p53 gene expression. iv) Wafl gene showed no significant increase or decrease in hepatocytes cutured in medium with Injinchtrnggantang-derivative, while increased in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchtrnggantang-derivative-andethanol-mixed group, suggesting that 10% ethanol induced cell toxicity increased wafl gene expression. 3. In the study on protein by western blotting, the band of bcl-2 and $bcl-_{X_L}$ were widened in Injinchtrnggantang-derivative group. Especially the amount of $bcl-_{X_L}$ increased significantly compared with other groups. But in the study on p53 and wafl, there was no significant difference among those groups. Above study shows that Injinchunggantang-derivative has good effect on cell viability and that the genes resistant to cell death such as bcl-2 and $bcl-_{X_L}$ are induced by Injinchunggantang-derivative to resist to cell death by toxic agent And this is reconfirmed in protein study using' western blotting: These results suggest that Injinchunggantang-derivative has inhibitory effect on cell death as well as protective effect on hepatocyte. Therefore this prescription is recommended in various liver diseases such as chronic liver disease and-induced hepatic injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.451-456
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• 2003

We investigated the effects of Sabaek-san (SBS) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with SBS extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis. including condensation of chromatin. Flow cytometry analysis confirmed that SBS treatment increased populations of apoptotic-sub G1 phase. In addition. proteolytic cleavages of poly(ADP-ribose) polymerase and β-catenin protein were observed after treatment of SBS extract. These apoptotic effects of SBS in A549 cells were associated with marked inhibition of Bcl-2 and Bel-xL mRNA in a dose-dependent manner. however the levels of Bax expression were not affected, SBS treatment also induced a proteolytic activation of caspase-3. which is believed to play a central role In the apoptotic signaling pathway. The previous and present results indicated that SBS-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• Journal of Embryo Transfer
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• v.24 no.1
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• pp.57-64
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• 2009

This study was carried out to investigate expression of apoptosis-related differentially expressed gene (DEG) in ovaries of Korean cattle with follicular and luteal cysts and to identify the relationship between cyst and apoptosis using microarray, real-time PCR, TUNEL staining, and Western blot analysis. Microarray data showed that PIK3R2 and AKT1 were significantly up-regulated in follicular cyst, and TNF-RAF2, PRLR, FOXL2, STK4, and COL4A3 were up-regulated whereas INHA, CIDEB, BCL10, and FASLG were down-regulated in luteal cyst. Real-time PCR was performed to validate DEGs altered in luteal cyst. Of nine DEGs, four DEGs down-regulated in luteal cyst showed a positive corelation between microarray data and real-time PCR data. In this study, we focused on INHA, among many DEGs, which was highly down-regulated in both follicular and luteal cysts. Real-time PCR and micro array data showed that INHA was down-regulated by 12.3-fold and by 1.4-fold, respectively, in the bovine follicular cyst. TUNEL assay and Western blot analysis for ERK, JNK, p38, PI3K, and Akt, which were used to detect whether apoptosis is occurred, showed no significant changes in cystic ovaries (p>0.05). In the expression and activity of caspase-3, Bax, Bel-2, and Bel-xL, there was no significant changes between follicular cystic ovary and normal ovary. Rather, the expression levels of PI3K and p-Akt were decreased in follicular cystic ovary. These results suggest that deficiency of apoptosis in cystic ovary is associated with decreased expression of apoptotic effectors.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1226-1232
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• 2007

Phellinus linteus is a well-known Oriental medicinal fungus that has various biological activities, including immunomodulatory and anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the anti-proliferative activity of the methanol extract of P. linteus-Barley corn (MEPLB) in human lekemic U937 cells. It was found that exposure of U937 cells to MEPLB resulted morphological change and growth inhibition in a dose-dependent manner as measured by trypan blue count and MTT assay. Upon treatment with MEPLB, U937 cells developed many of the hallmark features of apoptosis, including condensation of chromatin and an increase in the sub-G1 population suggesting that the anti-proliferative effect of MEPLB is associated with the induction of apoptosis. The anti-proliferative and apoptotic effects of MEPLB were connected with a marked induction of the pro-apoptotic Bax and cyclin-dependent kinase (Cdk) inhibitor p21 in a p53-independent manner. Additionally, MEPLB treatment significantly induced the caspase-3 activity in U937 cells. Taken together, the present results suggest that apoptotic signals evoked by MEPLB in human leukemic U937 cells may converge caspase-3 activation through an up-regulation of Bax rather than a down-regulation of Bcl-2 or Bel-xL.