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280 results on '"Wu, Yu-Sheng"'

16. Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

Author

Veit, Guido, Avramescu, Radu G, Perdomo, Doranda, Phuan, Puay-Wah, Bagdany, Miklos, Apaja, Pirjo M, Borot, Florence, Szollosi, Daniel, Wu, Yu-Sheng, Finkbeiner, Walter E, Hegedus, Tamas, Verkman, Alan S, and Lukacs, Gergely L

Subjects
Clinical Research, Cystic Fibrosis, Lung, Rare Diseases, Congenital, Aminophenols, Bronchi, Cell Membrane, Chlorides, Cystic Fibrosis Transmembrane Conductance Regulator, Down-Regulation, Endocytosis, Epithelial Cells, Humans, Ion Channel Gating, Mutation, Quinolones, Suppression, Genetic, Time Factors, Biological Sciences, Medical and Health Sciences
Abstract

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF.

Published
2014

34. Mucosal Macrophage Polarization Role in the Immune Modulation

Author

Wu, Yu-Sheng, Wu, Tsung-Meng, and Chen, Shiu-Nan

Subjects
Medical / Microbiology
Abstract

Immunotherapy has advantages including few side effects and low probability of abuse by patients. Recently, functional materials with immunomodulatory functions, which act through reduction of free radicals, have been developed for cancer and anti-inflammatory therapy. However, the therapeutic application of natural functional materials involves a complex mechanism along with various organic factors. These substances, including polysaccharides and triterpenoids, have immunomodulatory effects. However, to our knowledge, the mechanism underlying the action of such substances in the physiological immunity of animals remains unclear. Immune cells, particularly macrophages, are crucial in the modulation of immune response. Macrophages polarise into two types, namely, M1 and M2, from the M0 form, based on the physiological microenvironment factors. M1 macrophages have functions in pathogen elimination through phagocytosis, oxidative damage, and complement system activation. M2 macrophages are involved in tissue recovery and tumour tissues containing ample M2 macrophages that release growth factors, which promote angiogenesis. In this study, we focus on the immunomodulation of the macrophage to further understand the effects of the physiological microenvironment factors on macrophage polarisation.

Published
2022

37. Effect of Methylmercury Exposure on Bioaccumulation and Nonspecific Immune Respsonses in Hybrid Grouper Epinephelus fuscoguttatus × Epinephelus lanceolatus

Author

Chuang, Hsiang-Chieh, primary, Huang, Huai-Ting, additional, Dewi, Novi-Rosmala, additional, Hsiao, Hsi-Hua, additional, Chen, Bo-Ying, additional, Liao, Zhen-Hao, additional, Lee, Meng-Chou, additional, Lee, Po-Tsang, additional, Wu, Yu-Sheng, additional, Lin, Yu-Ju, additional, and Nan, Fan-Hua, additional

Published
2022
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