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Lin Chih-Hsin,Hsieh Yu-Shao,Sun Ying-Chieh,Huang Wun-Han,Chen Shu-Ling,Weng Zheng-Kui,Lin Te-Hsien,Wu Yih-Ru,Chang Kuo-Hsuan,Huang Hei-Jen,Lee Guan-Chiun,Hsieh-Li Hsiu Mei,Lee-Chen Guey-Jen 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.1
Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.
Chih-Hsien Lin,Shao-Kung Hung,Mei-Yung Chen,Shan-Tsung Li,Li-Chen Fu 제어로봇시스템학회 2008 제어로봇시스템학회 국제학술대회 논문집 Vol.2008 No.10
This paper proposes a novel planar electromagnetic-actuated positioning stage. The stage is suspended by the monolithic parallel flexure mechanism, which motion comes from the deformation of the flexure. A linear electromagnetic actuator which consists of a near-uniform magnetic field and four coils is designed and implementation to provide the propelling force for 3-DOF motions. In order to suppress the vibration of the flexure suspension mechanism, an eddy current damper is designed and integrated with the electromagnetic actuator. The non-contact damper is more advanced than the contact damper used in our previous researches. The design traveling range is 3mm × 3mm in planar motion. The experimental results show the vibration of the flexure mechanism could be suppressed by the designed eddy current damper. The results also show the regulation and tracking performance by a well-designed robust adaptive sliding mode controller, which can overcome the disturbance and modeling uncertainty and guarantee a satisfactory performance.
INVESTIGATING SATISFIED BUT DISLOYAL BUSINESS CUSTOMERS
Ming-Chih Tsai,Rico Merkert,Shiau-Chi Lin,Mei-Ting Tsai 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07
Satisfaction paradox indicates customer satisfaction does not necessarily translate into customer repurchase. Competitor’s attractiveness and customer demographics are two main moderators for the paradoxical phenomenon. Competitor’s attractiveness exhibits customer switching effect, whereas customer demographics imply customers moored with their current service provider. Still, the cases were few investigated in B2B settings where customers are in general more complex than consumers as involving more intricate organizational network influences. In a business network, transactions may incur buyer/seller relational activities that mitigate paradoxical behavior. Nonetheless, the variable is yet identified and the interacting effects between the moderating variables are not clarified. Thus, this study aims to develop an operational model to classify satisfied customers into loyal, moored and paradoxical segments using three genres of moderators: competitor’s attractiveness, organizational and transactional variables in a B2B setting. In the model, the theoretical bases of switching behaviors are applied for four statistical analysis executed in a logic sequence, including a factor analysis to consolidate quality measurements, a quadrant analysis to locate the effect of competitor’s attractiveness, a clustering analysis to segment satisfied customers into four segments, and finally, nonparametric tests to validate the organizational and transactional segmentation variables. Empirically, we study Taiwanese manufacturers who engaged in global trade and have had experiences in choosing the global air express services that form an oligopolistic market and a strategic group so competitor’s attractiveness can be better calibrated. A total of 180 valid samples are collected and analyzed. The results contribute to the literatures of B2B service marketing.
Angelica dahurica attenuates melanogenesis in B16F0 cells by repressing Wnt/β-catenin signaling
Fang Chien-Liang,Goswami Debakshee,Kuo Chia-Hua,Day Cecilia Hsuan,Lin Mei-Yi,Ho Tsung-Jung,Yang Liang-Yo,Hsieh Dennis Jine-Yuan,Lin Tzu-Kai,Huang Chih-Yang 대한독성 유전단백체 학회 2023 Molecular & cellular toxicology Vol.19 No.1
Background Melanogenesis is a complex process which is tightly regulated by several enzymes. However, abnormal melanogenesis can cause severe dermatological problems. Roots of Angelica dahurica have been used for skin care as a part of traditional Chinese medicine for many generations. However, the role of A. dahurica in melanogenesis remains unclear. Objective Previous in vitro and in vivo studies have demonstrated that NK-1R exerts positive effects in melanogenesis via the Wnt/βcatenin signaling pathway. In this study, we investigated the effects of A. dahurica ethanol extract (ADE) on NK-1R and Wnt/β-catenin signaling, and evaluated the effect of NK-1R on melanogenesis in B16F0 cells. Results Angelica dahurica ethanol extract efficiently downregulated Neurokinin-1 receptor and Wnt/β-catenin signaling by decreasing the expression of β-catenin, MITF, LEF-1, TYR, TRP1, and TRP2 and increasing the expression of GSK3β, which resulted from the weakened expression of the Neurokinin-1 receptor inhibitor [Sar9,Met(O2 )11]-Substance P (SMSP). Furthermore, the intracellular melanin assay and cellular tyrosinase activity confirmed these findings. Conclusion This study suggests that ADE has potential to downregulate Neurokinin-1 receptor in SMSP-induced B16F0 cells, thereby repressing the Wnt/β-catenin signaling and reduces melanin production.
Chun-Jen Huang,Hui-Min Hsieh,Herng-Chia Chiu,Peng-Wei Wang,Mei-Hsuan Lee,Chih-Yi Li,Ching-Hua Lin 대한신경정신의학회 2017 PSYCHIATRY INVESTIGATION Vol.14 No.6
Objective: The study investigated to compare health care utilization and expenditures between diabetic patients with and without depression in Taiwan. Methods: Health care utilization and expenditure among diabetic patients with and without depression disorder during 2000 and 2004 were examined using Taiwan’s population-based National Health Insurance claims database. Health care utilization included outpatient visits and the use of inpatient services, and health expenditures were outpatient, inpatient, and total medical expenditures. Moreover, general estimation equation models were used for analyzing the factors associated with outpatient visits and expenditures. Multiple logistic regression analysis was applied for identifying the factors associated with hospitalization. Results: The average annual outpatient visits and annual total medical expenditures in the study period were 44.23–52.20; NT$87,496–133,077 and 30.75–32.92; NT$64,411–80,955 for diabetic patients with and without depression. After adjustment for covariates, our results revealed that gender and complication were associated with out-patient visits. Moreover, the time factor was associated with the total medical expenditure, and residential urbanization and complication factors were associated with hospitalization. Conclusion: Health care utilization and expenditures for diabetic patients with depression were significantly higher than those without depression. Sex, complications, time, and urbanization are the factors associated with health care utilization and expenditures.
Screening of Nitrosamine Impurities in Sartan Pharmaceuticals by GC-MS/MS
( Shu-Han Chang ),( Hui-Yu Ho ),( Chi-Zong Zang ),( Ya-Hui Hsu ),( Mei-Chih Lin ),( Su-Hsiang Tseng ),( Der-Yuan Wang ) 한국질량분석학회 2021 Mass spectrometry letters Vol.12 No.2
Probable human carcinogenic compounds nitrosamines, have been detected as by-product impurities in sartan pharmaceuticals in recent years which has drawn worries for medication safety. To provide a sensitive and effective method for the quality control of sartan pharmaceuticals, this study established a feasible gas chromatography-tandem mass spectrometry (GC-MS/MS) method for simultaneous determination of 13 nitrosamines. The target analytes were separated on a DB-WAX Ultra Inert column (30 m × 0.25 mm; i.d., 0.25 μm) and were then subjected to electron impact ionization in multiple reaction monitoring mode. The established method was validated and further employed to analyze authentic samples. Limits of detection (LODs) and limits of quantification (LOQs) of the 13 nitrosamines were 15-250 ng/g and 50-250 ng/g, respectively, which also exhibited intra-day and inter-day accuracies of 91.4-104.8%, thereby satisfying validation criteria. Five nitrosamines, viz., Nnitrosodiethylamine, N-nitrosodimethylamine, N-nitrosodiphenylamine, N-nitrosomorpholine, and N-nitrosopiperidine were detected at concentrations above their LODs in 68 positive samples out of 594 authentic samples from seven sartans.
Wang Hui-Ching,Moi Sin-Hua,Chan Leong-Perng,Wu Chun-Chieh,Du Jeng-Shiun,Liu Pei-Lin,Chou Meng-Chun,Wu Che-Wei,Huang Chih-Jen,Hsiao Hui-Hua,Pan Mei-Ren,Chen Li-Tzong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.