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.

Lead-Free NaNbO₃ Nanowires for a High Output Piezoelectric Nanogenerator

Jung, Jong Hoon,Lee, Minbaek,Hong, Jung-Il,Ding, Yong,Chen, Chih-Yen,Chou, Li-Jen,Wang, Zhong Lin American Chemical Society 2011 ACS NANO Vol.5 No.12

<P>Perovskite ferroelectric nanowires have rarely been used for the conversion of tiny mechanical vibrations into electricity, in spite of their large piezoelectricity. Here we present a lead-free NaNbO<SUB>3</SUB> nanowire-based piezoelectric device as a high output and cost-effective flexible nanogenerator. The device consists of a NaNbO<SUB>3</SUB> nanowire–poly(dimethylsiloxane) (PDMS) polymer composite and Au/Cr-coated polymer films. High-quality NaNbO<SUB>3</SUB> nanowires can be grown by hydrothermal method at low temperature and can be poled by an electric field at room temperature. The NaNbO<SUB>3</SUB> nanowire–PDMS polymer composite device shows an output voltage of 3.2 V and output current of 72 nA (current density of 16 nA/cm<SUP>2</SUP>) under a compressive strain of 0.23%. These results imply that NaNbO<SUB>3</SUB> nanowires should be quite useful for large-scale lead-free piezoelectric nanogenerator applications.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2011/ancac3.2011.5.issue-12/nn2039033/production/images/medium/nn-2011-039033_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn2039033'>ACS Electronic Supporting Info</A></P>

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.

Individual and common inhibitors of coronavirus and picornavirus main proteases

Kuo, Chih-Jung,Liu, Hun-Ge,Lo, Yueh-Kuei,Seong, Churl-Min,Lee, Kee-In,Jung, Young-Sik,Liang, Po-Huang Elsevier 2009 FEBS letters Vol.583 No.3

<P><B>Abstract</B></P><P>Picornaviruses (PV) and coronaviruses (CoV) are positive-stranded RNA viruses which infect millions of people worldwide each year, resulting in a wide range of clinical outcomes. As reported in this study, using high throughput screening against ∼6800 small molecules, we have identified several novel inhibitors of SARS-CoV 3CL<SUP>pro</SUP> with IC<SUB>50</SUB> of low μM. Interestingly, one of them equally inhibited both 3C<SUP>pro</SUP> and 3CL<SUP>pro</SUP> from PV and CoV, respectively. Using computer modeling, the structural features of these compounds as individual and common protease inhibitors were elucidated to enhance our knowledge for developing anti-viral agents against PV and CoV.</P>

SIMULATION OF A BUBBLING FLUIDIZED BED BIOMASS GASIFIER USING ASPEN PLUS

Jung-Chin TSAI,Chen-Yaw CHIU,Chih-Shen CHEN 한국신재생에너지학회 2012 AFORE Vol.2012 No.-

A P2P-to-UPnP Proxy Gateway Architecture for Home Multimedia Content Distribution

( Chih-lin Hu ),( Hsin-cheng Lin ),( Yu-feng Hsu ),( Bing-jung Hsieh ) 한국인터넷정보학회 2012 KSII Transactions on Internet and Information Syst Vol.6 No.1

Deploying advanced home networking technologies and modern home-networked devices in residential environments provides a playground for new home applications and services. Because home multimedia entertainment is among the most essential home applications, this paper presents an appealing home media content sharing scenario: home-networked devices can discover neighboring devices and share local media content, as well as enormous amounts of Internet media content in a convenient and networked manner. This ideal scenario differs from traditional usages that merely offer local media content and require tedious manual operations of connection setup and file transfer among various devices. To achieve this goal, this study proposes a proxy gateway architecture for home multimedia content distribution. The proposed architecture integrates several functional mechanisms, including UPnP-based device discovery, home gateway, Internet media provision, and in-home media content delivery. This design addresses several inherent limitations of device heterogeneity and network interoperability on home and public networks, and allows diverse home-networked devices to play media content in an identical and networked manner. Prototypical implementation of the proposed proxy gateway architecture develops a proof-of-concept software, integrating a BitTorrent peer-to-peer client, a UPnP protocol stack, and a UPnP AV media server, as well as media distribution and management components on the OSGi home gateway platform. Practical demonstration shows the proposed design and scenario realization, offering users an unlimited volume of media content for home multimedia entertainment.

Antiproliferative and Antitumorigenic Activity of Toona sinensis Leaf Extracts in Lung Adenocarcinoma

Chih-Jen Yang,Yu-Jung Huang,Cheng-Yuan Wang,Chuan-Sheng Wang,Pei-Hui Wang,Jen-Yu Hung,Tung-Heng Wang,Hseng-Kuang Hsu,Hurng-Wern Huang,S.P. Anand Kumar,Ming-Shyan Huang,Ching-Feng Weng 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.1

Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G1 peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G1 arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti–lung cancer drug.

Quantitative phosphoproteomic analysis identifies the potential therapeutic target EphA2 for overcoming sorafenib resistance in hepatocellular carcinoma cells

Chih-Ta Chen,Li-Zhu Liao,Ching-Hui Lu,Yung-Hsuan Huang,Yu-Kie Lin,Jung-Hsin Lin,Lu-Ping Chow 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Limited therapeutic options are available for advanced-stage hepatocellular carcinoma owing to its poor diagnosis. Drug resistance to sorafenib, the only available targeted agent, is commonly reported. The comprehensive elucidation of the mechanisms underlying sorafenib resistance may thus aid in the development of more efficacious therapeutic agents. To clarify the signaling changes contributing to resistance, we applied quantitative phosphoproteomics to analyze the differential phosphorylation changes between parental and sorafenib-resistant HuH-7 cells. Consequently, an average of ~1500 differential phosphoproteins were identified and quantified, among which 533 were significantly upregulated in resistant cells. Further bioinformatic integration via functional categorization annotation, pathway enrichment and interaction linkage analysis led to the discovery of alterations in pathways associated with cell adhesion and motility, cell survival and cell growth and the identification of a novel target, EphA2, in resistant HuH-7R cells. In vitro functional analysis indicated that the suppression of EphA2 function impairs cell proliferation and motility and, most importantly, overcomes sorafenib resistance. The attenuation of sorafenib resistance may be achieved prior to its development through the modulation of EphA2 and the subsequent inhibition of Akt activity. Binding analyses and in silico modeling revealed a ligand mimic lead compound, prazosin, that could abate the ligand-independent oncogenic activity of EphA2. Finally, data obtained from in vivo animal models verified that the simultaneous inhibition of EphA2 with sorafenib treatment can effectively overcome sorafenib resistance and extend the projected survival of resistant tumor-bearing mice. Thus our findings regarding the targeting of EphA2 may provide an effective approach for overcoming sorafenib resistance and may contribute to the management of advanced hepatocellular carcinoma.

Transferrable single-crystal silicon nanomembranes and their application to flexible microwave systems

Jung-Hun Seo,Hao-Chih Yuan,Lei Sun,Weidong Zhou,Zhenqiang Ma 한국정보디스플레이학회 2011 Journal of information display Vol.12 No.2

This paper summarizes the recent fabrication and characterizations of flexible high-speed radio frequency (RF) transistors,PIN-diode single-pole single-throw switches, as well as flexible inductors and capacitors, based on single-crystalline Si nanomembranes transferred on polyethylene terephthalate substrates. Flexible thin-film transistors (TFTs) on plastic substrates have reached RF operation speed with a record cut-off/maximum oscillation frequency (fT/fmax) values of 3.8/12 GHz. PIN diode switches exhibit excellent ON/OFF behaviors at high RF frequencies. Flexible inductors and capacitors compatible with high-speed TFT fabrication show resonance frequencies (fres) up to 9.1 and 13.5 GHz, respectively. Robust mechanical characteristics were also demonstrated with these high-frequency passives components.

Novel Nonlinear Backstepping Control of Synchronous Reluctance Motor Drive System for Position Tracking of Periodic Reference Inputs with Torque Ripple Consideration

Chih-Hong Lin,Jung-Chu Ting 제어·로봇·시스템학회 2019 International Journal of Control, Automation, and Vol.17 No.1

Owing to air-gap field harmonic, cogging torque, stator’s current time harmonic and the influence offlux saturation, a synchronous reluctance motor (SynRM) drive system has highly nonlinear uncertainties. Thus thelinear control method for the SynRM drive system is difficult to achieved good performance under the nonlinearuncertainty action. To obtain better control performance the novel nonlinear backstepping control system using upperbound with switching function is firstly proposed for controlling the SynRM drive system to prevail the lumpeduncertainty. With the proposed control system, the SynRM servo-drive system holds in robustness to uncertaintiesfor the tracking of periodic reference trajectories. To enhance the robustness of the SynRM drive system, the novelnonlinear backstepping control system using adaptive law is proposed for estimating the required lumped uncertaintyto reduce chattering phenomenon. When the inertia of the counterweight is varying, this proposed methodcan perform well in general situations, but cannot get a satisfactory performance. The novel nonlinear backsteppingcontrol system using reformed recurrent Hermite polynomial neural network with adaptive law and error estimatedlaw is thus proposed to estimate the lumped uncertainty and compensate estimated error for obtaining better controlperformance. Furthermore, two varied learning rates of the reformed recurrent Hermite polynomial neural networkis derived according to increment type Lyapunov function to speed-up parameter’s convergence. Finally, someexperimental results with comparative control performances are demonstrated, and then the effectiveness of theproposed control system with better control performance is verified for the position tracking of periodic referenceinputs with torque ripple consideration.