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      • KCI등재후보
      • KCI등재

        Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages

        Yuan-Shen Chen,Wei-Chu Chuang,Hsiu-Ni Kung,Ching-Yuan Cheng,Duen-Yi Huang,Ponarulselvam Sekar,Wan-Wan Lin 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.4

        In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

      • SCIESCOPUS

        Flexible tactile sensor array for foot pressure mapping system in a biped robot

        Chuang, Cheng-Hsin,Liou, Yi-Rong,Shieh, Ming-Yuan Techno-Press 2012 Smart Structures and Systems, An International Jou Vol.9 No.6

        Controlling the balance of motion in a context involving a biped robot navigating a rugged surface or a step is a difficult task. In the present study, a $3{\times}5$ flexible piezoelectric tactile sensor array is developed to provide a foot pressure map and zero moment point for a biped robot. We introduce an innovative concept involving structural electrodes on a piezoelectric film in order to improve the sensitivity. The tactile sensor consists of a polymer piezoelectric film, PVDF, between two patterned flexible print circuit substrates (FPC). Additionally, a silicon rubber bump-like structure is attached to the FPC and covered by a polydimethylsiloxane (PDMS) layer. Experimental results show that the output signal of the sensor exhibits a linear behavior within 0.2 N ~ 9 N, while its sensitivity is approximately 42 mV/N. According to the characteristic of the tactile sensor, the readout module is designed for an in-situ display of the pressure magnitudes and distribution within $3{\times}5$ taxels. Furthermore, the trajectory of the zero moment point (ZMP) can also be calculated by this program. Consequently, our tactile sensor module can provide the pressure map and ZMP information to the in-situ feedback to control the balance of moment for a biped robot.

      • KCI등재

        Profile of disposition, tissue distribution and excretion of the novel anti-human immunodeficiency virus (HIV) agent W-1 in rats

        Ying-Yuan Lu,Xiao-Wei Wang,Xin Wang,Wen-Bing Dai,Qiang Zhang,Pu Li,Ya-Qing Lou,Chuang Lu,Jun-Yi Liu,Guo-Liang Zhang 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.7

        The purpose of this study was to characterize the disposition, distribution, excretion and plasma protein binding of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W- 1) in rats. Concentrations of W-1 within biological samples were determined using a validated high performance liquid chromatography method. The plasma protein binding of W-1 was examined by equilibrium dialysis method. After oral administration of W-1 (50, 100 and 200 mg/kg, respectively) in self-microemulsifying drug delivery system formulation, the pharmacokinetic parameters of W-1 were as follows: the peak plasma concentrations (Cmax) were 0.42, 1.50 and 2.55 μg/mL, the area under the curve (AUC0-t) were 0.89, 2.27 and 3.96 lg/h mL and the plasma half-life (t1/2) were 5.15, 3.77 and 3.77 h, respectively. Moreover, the prototype of W-1 was rapidly and extensively distributed into fifteen tissues, especially higher concentrations were detected in intestine, stomach and liver, respectively. The plasma protein binding of W-1 in rat, beagle dog and human were in the range of 97.96–99.13 %. This study suggested that W-1 has an appropriate pharmacokinetics in rats, such as rapid absorption, moderate clearance, and rapid distribution to multiple tissues. Those properties provide important information for further development W-1 as an anti-HIV-1 drug candidate.

      • KCI등재후보

        Flexible tactile sensor array for foot pressure mapping system in a biped robot

        Cheng-Hsin Chuang,Yi-Rong Liou,Ming-Yuan Shieh 국제구조공학회 2012 Smart Structures and Systems, An International Jou Vol.9 No.6

        Controlling the balance of motion in a context involving a biped robot navigating a rugged surface or a step is a difficult task. In the present study, a 3×5 flexible piezoelectric tactile sensor array is developed to provide a foot pressure map and zero moment point for a biped robot. We introduce an innovative concept involving structural electrodes on a piezoelectric film in order to improve the sensitivity. The tactile sensor consists of a polymer piezoelectric film, PVDF, between two patterned flexible print circuit substrates (FPC). Additionally, a silicon rubber bump-like structure is attached to the FPC and covered by a polydimethylsiloxane (PDMS) layer. Experimental results show that the output signal of the sensor exhibits a linear behavior within 0.2 N ~ 9 N, while its sensitivity is approximately 42 mV/N. According to the characteristic of the tactile sensor, the readout module is designed for an in-situ display of the pressure magnitudes and distribution within 3×5 taxels. Furthermore, the trajectory of the zero moment point (ZMP) can also be calculated by this program. Consequently, our tactile sensor module can provide the pressure map and ZMP information to the in-situ feedback to control the balance of moment for a biped robot.

      • Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in CHC and CHB Coinfection Patients: A Phase 3 Study in Taiwan

        ( Chun-Jen Liu ),( Wan-Long Chuang ),( I-Shyan Sheen ),( Horng-Yuan Wang ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ting-Tsung Chang ),( Benede tta Massetto ),( Jenny Yang ),( Gregory Camus ),( Fangqiu Zh 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Patients co-infected with HCV and HBV have more rapid progression and worse outcomes than mono-infected patients. Taiwan has among the highest prevalence of chronic HCV/HBV coinfection in Southeast Asia. This study evaluated the safety and efficacy of an all-oral treatment with ledipasvir(LDV)/sofosbuvir(SOF) for 12 weeks in chronic HCV and HBV coinfection. Methods: Patients with or without compensated cirrhosis chronic HCV GT1/GT2 and HBV (HBsAg+) treatment naïve were enrolled into open-label, receiving LDV 90 mg/SOF 400 mg(QD) for 12 weeks. The primary efficacy endpoint is SVR12. HBV DNA was monitored at all study visits and it will be monitored for 2 years post-treatment. Results: A total of 111 patients (68[61%] with GT1 and 43[39%] with GT2) were enrolled and treated. The majority were female(62%), treatment naive(67%), and non-cirrhotic(85%), with a mean age of 55 years and mean BMI of 24.5kg/m2. All but one was HBeAg negative. Mean baseline HBV DNA was 2.1 log10IU/mL. SVR4 was 100%(111/111). The mean change in HBV DNA ranged from -0.06 log10IU/mL at week 1 to +0.49 log10IU/mL at follow-up visit 4; HBV DNA kinetics are shown in Fig 1. 60(54%) patients had an increase in HBV DNA> 10 x BL or became HBV DNA > LLOQ. No patients had ALT ≥ 2 X baseline. No patients discontinued treatment due to adverse events (AEs). Three patients had serious AEs(optic neuritis, post procedural bleeding and duodenal ulcer bleeding; none was considered drug related). Conclusions: In chronic HCV/HBV infection patients, LDV/SOF for 12 weeks resulted in an SVR4 rate of 100%. Although most patients had an increase in HBV DNA during treatment, this was not associated with ALT elevations ≥2 X baseline, and no patients started HBV therapy to date. This all-oral, interferon-free regimen was well tolerated, supporting its potential as a treatment option for HCV/HBV co-infected patients.

      • KCI등재

        Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

        Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5

        Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

      • KCI등재

        Species-specific primers in multiplex PCR for Bactrocera minax identification using an internal transcribed spacer

        Regmi Prakriti,Tsai Cheng-Lung,Lin Ming-Ying,Chuang Yi-Yuan,Yeh Wen-Bin 한국응용곤충학회 2023 Journal of Asia-Pacific Entomology Vol.26 No.4

        Bactrocera minax (Enderlein), commonly known as the Chinese citrus fly, is a citrus pest native to China and nearby countries. B. minax can cause substantial losses in citrus orchards. B. minax can be spread to countries free from it by the global trade of citrus and by travelers carrying citrus. Timely, convenient, and accurate identi fication of B. minax is essential in preventing its spread. In the present study, the nuclear ribosomal internal transcribed spacer 2 (ITS2) amplicon was used to design species-specific primer pairs that enable B. minax to be distinguished from 11 other fruit fly species. Four forward and four reverse species-specific primers were designed, and out of all possible sets of species-specific primer pairs obtained after intermixing them, seven sets of species-specific primer pairs were able to accurately identify B. minax. For B. minax identification, specific fragments ranging from 83 to 431 base pairs in length were amplified. The validity of the specific band only in B. minax was determined by visually inspecting the gel profile of the PCR product. B. minax was correctly identified using the designed species-specific primer pairs, with no cross-amplification with the 11 other fruit fly species included in the experiments. In addition to saving DNA sequencing costs, the application of these speciesspecific primer pairs facilitates rapid identification of B. minax, with identification in border scenarios being completable within 2–3 h.

      • KCI등재

        The occurrence of Scirtothrips dorsalis Hood in mango orchards and factors influencing its population dynamics in Taiwan

        Chun-Nan Lin,Miao-Ying Wei,Niann-Tai Chang,Yi-Yuan Chuang 한국응용곤충학회 2015 Journal of Asia-Pacific Entomology Vol.18 No.3

        The yellow tea thrips, Scirtothrips dorsalis Hood (Thysanoptera: Thripidae), has recently become one of the key pests causing economic damage to the fruit production of mango (Mangifera indica L.). In this study, we investigated the seasonal fluctuation of S. dorsalis populations using data mining techniques inwhich logistic regression (LR), decision tree (DT), and artificial neural networks (ANNs) were performed for cross analysis and the optimality of these three approaches. Subsequently, crucial factors that affect the population dynamics of S. dorsalis can be determined. Our results showed correctly classified instances of DT ≧ 83% by 10-fold cross-validation, which exhibited the highest degree of accuracy among the three methods followed by ANNs and LR.We anticipate that using an intelligent prediction model can increase prediction reliability to understand the occurrence and population dynamics of S. dorsalis under different environmental conditions. Therefore, our model could be useful for farmers to implement control measures against S. dorsalis and to manage its damages to plants. Furthermore, the model proposed can be used as a basis for assessing pesticide applications and for reducing excessive pesticide costs.

      • SCOPUSKCI등재

        Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn`s Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

        ( Chen Wang Chang ),( Shu Chen Wei ),( Jen Wei Chou ),( Tzu Chi Hsu ),( Chiao Hsiung Chuang ),( Ching Pin Lin ),( Wen Hung Hsu ),( Hsu Heng Yen ),( Jen Kou Lin ),( Yi Jen Fang ),( Horng Yuan Wang ),( 대한장연구학회 2014 Intestinal Research Vol.12 No.4

        Background/Aims: Only moderate to severe Crohn`s Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. Methods: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn`s Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. Results: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. Conclusions: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria. (Intest Res 2014;12:287-292)

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