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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.
Jian-Rong Peng,Hsin-Fu Lee,Chi-Jen Chang,Chun-Li Wang,Ying-Chang Tung 대한심장학회 2017 Korean Circulation Journal Vol.47 No.1
Background and Objectives: The aim of this study was to identify clinical, lesional, and procedural predictors for adverse outcomes of coronary angioplasty and stenting in coronary bypass candidates. Subjects and Methods: This cohort study included 107 consecutive candidates for coronary artery bypass surgery who underwent percutaneous coronary intervention with multiple coronary stents between Jan 2004 and Dec 2011. The study endpoint was major adverse cardiovascular events (MACEs) including all-cause mortality, nonfatal myocardial infarction, repeat revascularization, and stent thrombosis. Follow up was from the date of index percutaneous coronary intervention to the date of the first MACE, date of death, or December 31, 2015, whichever came first. Results: In this study (age 62.3±11.2 years, 86% male), 38 patients (36%) had MACE. Among baseline, angiographic, and procedural parameters, there were significant differences in lower left ventricular ejection fraction (LVEF) and worse renal function. In a Cox regression model, LVEF and chronic kidney disease (CKD) were significant predictors for MACE. After a multivariate adjustment, CKD remained a significant predictor of MACEs (hazard ratio: 2.97, 95% confidence interval: 1.50-5.90). Conclusions: For coronary bypass candidates who were treated with coronary angioplasty and stenting, CKD seems to be the strongest predictor for adverse outcomes compared with other traditional factors.
Chi‑Shih Huang,Erh‑Jen Hou,Ying‑Chou Lee,Tzong‑Huei Lee,Yi‑Jun Pan,Ta Yu,Wei‑Hsin Lin,Chun‑Han Shih,Wei‑Che Chang 한국섬유공학회 2023 Fibers and polymers Vol.24 No.12
The study was inspired by the specialized facial masks made of rayon non-woven fabrics which contained collagen peptides for improving moisturizing function. This study explored the moisturizing function of a rayon fabric containing collagen peptides extracted from tilapia fish scales under various conditions of relative humidity. This research had implications for the development of clothing that can prevent dry skin. A two-stage nested design experiment was adopted. The first-stage factor such as the fabric has two levels and the second-stage factor such as the relative humidity with three levels nested under each level of the first-stage factor. Preliminary results indicated that introducing a new variable (i.e., fabric moisturizing value, which combines the moisture regains of adsorption and desorption) would be useful. The moisturizing value of the novel rayon fabric and regular rayon fabric increased with the increase in relative humidity, and moisturizing effect of the novel rayon fabric with collagen peptides was better than that of the regular rayon fabric. Therefore, the novel rayon fabric may be suitable for preventing dry skin in winter.
Ming-Chun Tseng,Dong-Sing Wuu,Chi-Lu Chen,Hsin-Ying Lee,Ray-Hua Horng 한국물리학회 2017 Current Applied Physics Vol.17 No.7
Aluminum-doped zinc oxide (AZO) thin films used for ohmic contact layers on carbon-doped GaP window layers (p-GaP:C) of AlGaInP light-emitting diodes were fabricated and characterized. AZO thin films with different Zn:Al cycle ratios (15:1, 20:1, and 25:1) were deposited on p-GaP:C window layers through atomic layer deposition. The contact characteristics of the AZO thin films on p-GaP:C were considerably changed from Schottky contact to ohmic contact after rapid thermal annealing (RTA) at 350 C for 1 min. The most favorable specific contact resistance of AZO/p-GaP:C was evaluated using a circular transmission line model as 6.3 103 U/cm2. Angle-resolved X-ray photoelectron spectroscopy was employed to understand the ohmic contact behavior of AZO/p-GaP:C. After RTA, Zn atoms in the AZO thin films notably diffused into the p-GaP:C layers and Ga atoms diffused out of the p-GaP:C layer. Therefore, the Ga vacancies were occupied by Zn atoms, which increased the doping concentration in the near-surface region of p-GaP:C and reduced the depletion region width of the semiconductor region. Thus, numerous carriers were able to tunnel through the reduced Schottky barrier and those carriers produced the ohmic contact behavior between the AZO and p-GaP:C.
Shieh-Yang Huang,Ming-Ting Chung,Ching-Wen Kung,Shu-Ying Chen,Yi-Wen Chen,Tong Pan,Pao-Yun Cheng,Hsin-Hsueh Shen,Yen-Mei Lee 대한비만학회 2024 Journal of obesity & metabolic syndrome Vol.33 No.2
Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion: ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.