Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Chih-Jung Yao,Jyh-Ming Chow,Shuang-En Chuang,Chia-Lun Chang,Ming-De Yan,Hsin-Lun Lee,I-Chun Lai,Pei-Chun Lin,Gi-Ming Lai 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG- 135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Yao, Chih-Jung,Chow, Jyh-Ming,Chuang, Shuang-En,Chang, Chia-Lun,Yan, Ming-De,Lee, Hsin-Lun,Lai, I-Chun,Lin, Pei-Chun,Lai, Gi-Ming The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

IBM Zigbee Positioning Method for Smart Home Applications

Ming-Hui Jin,Chung-Jung Fu,Chih-Hao Yu,Hung-Ren Lai,Ming-Whei Feng 보안공학연구지원센터 2008 International Journal of Smart Home Vol.2 No.2

This paper presents a smart home system prototype which employs an indoor positioning system called the III Beacon Match (I3BM) positioning method to intelligently trigger the appropriately services for the home members. To overcome the ninja problem in the I3BM method, the signal filtering, adjustment and smooth procedures are proposed. The proposed system prototype employs the Zigbee module to implement the prototypes of the components for the I3BM positioning method, and the prototypes had passed the ZigBee Compliant Platform (ZCP) certification test. The proposed system prototype which intelligently controls the air condition and light system for smart home applications is also verifying in our demo room and in the smart house in National Taiwan University.

Issues in Simulating Falling Weight Deflectometer Test on Concrete Pavements

Chen-Ming Kuo,Chih-Chiang Lin,Cheng-Hao Huang,Yi-Cheng Lai 대한토목학회 2016 KSCE JOURNAL OF CIVIL ENGINEERING Vol.20 No.2

Falling Weight Deflectometer (FWD) produces pavement responses using a falling mass drop. This study investigated the features involved in the finite element modeling of FWD tests to help in the calibration of backcalculation. Falling mass, model size, subgrade damping, and boundary conditions were studied to reveal the significances of these factors on pavement responses. By modeling the falling mass in finite element models, this study has justified the idea that field-measured time history of impact force can be used as an alternative to falling mass. It is also concluded that subgrade damping, self-weight of slab, and boundary conditions are significant in modeling and interpretation of FWD finite element analysis. Finite element model with at least six times radius of relative stiffness is required to simulate dynamic responses of a continuously reinforced concrete slab.

Numerical study of viscosity and inertial effects on tank-treading and tumbling motions of vesicles under shear flow.

Kim, Yongsam,Lai, Ming-Chih Published by the American Physical Society through 2012 Physical review. E, Statistical, nonlinear, and so Vol.86 No.6

<P>An inextensible vesicle under shear flow experiences a tank-treading motion on its membrane if the viscosity contrast between the interior and exterior fluids is small. Above a critical threshold of viscosity contrast, the vesicle undergoes a tumbling bifurcation. In this paper, we extend our previous work [Kim and Lai, J. Comput. Phys. 229, 4840 (2010)] to the case of different viscosity and investigate the transition between the tank-treading and tumbling motions in detail. The present numerical results are in a good agreement with other numerical and theoretical studies qualitatively. In addition, we study the inertial effect on this transition and find that the inertial effect might inhibit the tumbling motion in favor of the tank-treading motion, which is observed recently in the literature. The critical viscosity contrast for the transition to the tumbling motion usually increases as the reduced area increases in the Stokes regime. However, we surprisingly observe that the critical viscosity contrast decreases as the reduced area increases to some point in the flow of slightly higher Reynolds number. Our numerical result also shows that the inertial effect has stronger inhibition to tumbling motion when the reduced area is small.</P>

Lattice Relations and Solidification of the Complex Regular Eutectic (Cr,Fe)-(Cr,Fe)23C6

Hsuan-Han Lai,Chih-Chun Hsieh,Chi-Ming Lin,Weite Wu 대한금속·재료학회 2017 METALS AND MATERIALS International Vol.23 No.3

The eutectic (Cr,Fe)-(Cr,Fe)23C6 showed a triaxial fishbone structure and could be categorized as a “complexregular structure”. In this study, the lattice relations of the fishbone (Cr,Fe)23C6 were examined and the solidificationprocess was observed using a transmission electron microscope and a confocal laser scanning microscope. Forone of the three fish bones in a eutectic cell, parallel (Cr,Fe)23C6 lamellas at one side of the spine had the samelattice direction, as did those in the (Cr,Fe) phase. The lattices of neighboring (Cr,Fe)23C6 and (Cr,Fe) phases werenot coherent. Lamellar (Cr,Fe)23C6 on opposite sides of a spine had different lattice directions, and their latticeboundary was in the spine. By using the confocal laser scanning microscope, the solidification of lamellar eutecticstructure could be observed. At the low cooling rate of 5oC·min-1, parallel lamellas would grow thick blocksinstead of thin plates. To obtain a thin lamellar eutectic structure, the cooling rate should be higher, likethe rate in welding.

A penalty immersed boundary method for viscoelastic particulate flows

Kim, Yongsam,Lai, Ming-Chih,Seol, Yunchang Elsevier 2018 Journal of non-Newtonian fluid mechanics Vol.258 No.-

<P><B>Abstract</B></P> <P>We extend the penalty immersed boundary (pIB) method to investigate the interaction between circular rigid particles and a surrounding viscoelastic Oldroyd-B fluid. The basic idea of the pIB method is the splitting of an immersed boundary, which here is a rigid body, notionally into two Lagrangian components: one is a massive component carrying all mass of the rigid body, and the other is massless. These two components are connected by a system of stiff springs with zero rest length. The massive component has no direct interaction with the surrounding fluid and behaves as though in a vacuum, following the dynamics of a rigid body, in which the acting forces and torques are generated from the system of stiff springs that connects the two Lagrangian components. The massless component interacts with the surrounding Oldroyd-B fluid: it moves at the local fluid velocity and exerts force locally on the fluid. We verify the pIB method combined with Oldroyd-B fluid model by investigating the effects of the wall and elasticity of the fluid on the lateral position of a circular particle falling under the influence of gravity and by studying convergence of the numerical solutions. We also simulate the interaction between multiple circular particles and the surrounding Oldroyd-B fluid and compare the dynamics of the particles in various flow conditions.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A numerical method is introduced to investigate particulate viscoelastic fluid. </LI> <LI> The method is tested by a convergence study. </LI> <LI> The effect of the elasticity number and channel wall is presented. </LI> <LI> A chain is formed with multiple particles falling in an Oldroyd-B fluid. </LI> </UL> </P>

Simulation of a Soap Film Möbius Strip Transformation

Kim, Yongsam,Lai, Ming-Chih,Seol, Yunchang Global Science Press 2017 East Asian Journal on Applied Mathematics Vol.7 No.3

<B>Abstract</B><P>If the closed wire frame of a soap film having the shape of a Möbius strip is pulled apart and gradually deformed into a planar circle, the soap film transforms into a two-sided orientable surface. In the presence of a finite-time twist singularity, which changes the linking number of the film's Plateau border and the centreline of the wire, the topological transformation involves the collapse of the film toward the wire. In contrast to experimental studies of this process reported elsewhere, we use a numerical approach based on the immersed boundary method, which treats the soap film as a massless membrane in a Navier-Stokes fluid. In addition to known effects, we discover vibrating motions of the film arising after the topological change is completed, similar to the vibration of a circular membrane.</P>

Numerical simulations of vesicle and bubble dynamics in two-dimensional four-roll mill flows

Kim, Yongsam,Lai, Ming-Chih,Seol, Yunchang American Physical Society 2017 Physical Review E Vol.95 No.5

Effects of Vanadium Content on the Microstructure and Dry Sand Abrasive Wear of a Eutectic Cr-Fe-C Hardfacing Alloy

Hsuan-Han Lai,Chih-Chun Hsieh,Chi-Ming Lin,Weite Wu 대한금속·재료학회 2016 METALS AND MATERIALS International Vol.22 No.1

In this study, the effects of vanadium on the morphology and wear behavior of a eutectic Cr-Fe-C hardfacing alloy were discussed. The alloys tested contained different amounts of vanadium, ranging from 0 to 2.39 wt%. A fibrous V4C3 was found when the alloy contained 0.93 wt% vanadium. The addition of vanadium was found to decrease the fraction of eutectic M23C6 and increase the width of the interspaces between the eutectic cells. The DTA results revealed that V4C3 formed just before the eutectic α+M23C6 during solidification. The surface hardness was shown to increase with increasing vanadium content, which also caused the hardness deviation and wear loss to decrease; however, the addition of vanadium was not shown to affect the hardness of eutectic α+M23C6. The V4C3 could be scratched off during the wear test due to the increase in the width of the interspaces between the eutectic cells; therefore, the alloys that contained 0.93 and 2.39 wt% vanadium exhibited similar wear loss results.