ORCID Profile
0000-0003-4172-5529
Current Organisation
Universidade Federal de Goiás
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Publisher: MDPI AG
Date: 21-10-2021
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive terminal lung disease, and therapies aim to block fibrosis. Fibroblast proliferation is controlled by C/EBP-β, microRNA cluster 17-92 (miR17-92), and Erk1/2 mitogen-activated protein kinase. This study assessed the role of miR17-92 in IPF-fibroblast proliferation and its modification by treprostinil. Fibroblasts were isolated from eight IPF patients, five interstitial lung fibrosis patients, and seven control lungs. Fibroblasts were stimulated with TGF-β1 over 24 h. The miR17-92 expression was analyzed by RT-qPCR, and protein expression by Western blotting. TGF-β1 upregulated C/EBP-β in all fibroblasts, which was reduced by treprostinil in control-fibroblasts, but not in IPF-fibroblasts. Compared to controls, the guide strands miR-19a-3p, miR-19b-3p, miR-20a-5p, and miR-92a-3p, as well as the passenger strands miR-17-3p, miR-18-3p, miR-19a-1-5p, and miR-92a-5p were significantly increased in IPF-fibroblasts. In controls, TGF-β1 and treprostinil significantly reduced specific miR17-92 members. IPF-fibroblast proliferation was inhibited by treprostinil through increased expression of the Erk1/2 inhibitor DUSP1. These data suggest that proliferation control via miR17-92 and C/EBP-β is disrupted in IPF-fibroblasts. Therefore, the inhibition of early stages of signaling cascades or specific mitogen receptors might be less effective. However, the increased proliferation is sensitive to Erk1/2 inhibition by treprostinil-induced DUSP1.
Publisher: Hindawi Limited
Date: 20-01-2019
DOI: 10.1155/2019/8480468
Abstract: Ischemic stroke is a neurovascular disorder caused by reduced or blockage of blood flow to the brain, which may permanently affect motor and cognitive abilities. The diagnostic of stroke is performed using imaging technologies, clinical evaluation, and neuropsychological protocols, but no blood test is available yet. In this work, we analyzed amino acid concentrations in blood plasma from poststroke patients in order to identify differences that could characterize the stroke etiology. Plasma concentrations of sixteen amino acids from patients with chronic ischemic stroke (n = 73) and the control group (n = 16) were determined using gas chromatography coupled to mass spectrometry (GC-MS). The concentration data was processed by Partial Least Squares-Discriminant Analysis (PLS-DA) to classify patients with stroke and control. The amino acid analysis generated a first model able to discriminate ischemic stroke patients from control group. Proline was the most important amino acid for classification of the stroke s les in PLS-DA, followed by lysine, phenylalanine, leucine, and glycine, and while higher levels of methionine and alanine were mostly related to the control s les. The second model was able to discriminate the stroke subtypes like atherothrombotic etiology from cardioembolic and lacunar etiologies, with lysine, leucine, and cysteine plasmatic concentrations being the most important metabolites. Our results suggest an amino acid biosignature for patients with chronic stroke in plasma s les, which can be helpful in diagnosis, prognosis, and therapeutics of these patients.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JCHEMNEU.2013.11.002
Abstract: The analysis of amino acid levels is crucial for neuroscience studies because of the roles of these molecules as neurotransmitters and their influence on behavior. The present study describes the distribution and levels of 16 amino acids (alanine, asparagine, aspartic acid, cysteine, glycine, glutamic acid, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, valine, and threonine) in brain tissues (prefrontal cortex, striatum, hippoc us and cerebellum) and the serum. Neurochemical analysis was performed on Wistar rats and C57BL/6 mice using an efficient method for extraction, a fast microwave-assisted derivatization and gas chromatography-mass spectrometry analysis. The amino acid concentration varied across brain regions for 14 of the 16 analyzed molecules, with detection limits ranging from 0.02±0.005μmolL(-1) to 7.07±0.05μmolL(-1). In rats, the concentrations of alanine, glycine, methionine, serine and threonine were higher in prefrontal cortex than in other areas, whereas in mice, the concentrations of glutamic acid, leucine and proline were highest in the hippoc us. In conclusion, this study provides a cerebral profile of amino acids in brain regions and the serum of rats and mice.
Publisher: MDPI AG
Date: 29-07-2023
Abstract: Idiopathic pulmonary fibrosis (IPF) presents as an incurable change in the lung tissue and mitochondrial dysfunction of unknown origin. Treprostinil, a prostacyclin analogue, has been suggested for IPF therapy. This study assessed the effect of treprostinil on the cAMP signalling and mitochondrial activity in healthy lung fibroblasts and fibroblast-like cells from IPF patients. Six control fibroblast strains and six fibroblast-like IPF cell strains were isolated and expanded from freshly resected lung tissue. The cells were grown to confluence before being treated with either transforming growth factor (TGF)-β1, treprostinil, their combination, or a vehicle for up to 2 days. Mitochondria-regulating proteins were analysed using Western blotting and immunofluorescence, and the mitochondria were analysed using cytochrome C, mitochondrial cytochrome C oxidase II (MTCO2), and MTCO4. The IPF cells showed an increased rate of damaged mitochondria, which were significantly reduced when the cells were treated with treprostinil over 24 h. In the control cells, treprostinil prevented TGF-β-induced mitochondrial damage. Treatment with treprostinil modified the expression of several mitochondria-regulating proteins. In both cell types, treprostinil upregulated the expression of PTEN, p21(Waf1/Cip1), beclin1, LC3 II, parkin, PINK1, MTCO2, and MTCO4. In contrast, treprostinil downregulated the phosphorylation of mTOR and the expression of p62, mitofusin1, and mtiofusin2 in IPF cells. This might explain the reduced mitochondrial damage observed in treprostinil-treated IPF cells and suggest an improvement in the mitochondrial function in IPF. In this study, treprostinil improved mitochondrial impairment in vitro, which might, in part, explain the beneficial clinical effects documented in patients.
Location: Brazil
Location: United States of America
No related grants have been discovered for Wei-Chih Chen.