Search results for " FIBROSIS"
showing 10 items of 490 documents
Role of the small heat shock protein alphaB-crystallin in pulmonary fibrosis and its implication in the signaling pathway of the Transforming Growth …
2013
Idiopathic pulmonary fibrosis (IPF) has no effective current treatment. It is characterized by a sub-pleural onset and the presence of myofibroblasts, responsible for the excessive extracellular matrix synthesis. Transforming Growth Factor (TGF)-β1 is considered as the major profibrotic cytokine. Its signaling pathway occurs through the Smads proteins, including Smad4. TGF-β1 allows the differentiation of lung fibroblasts and epithelial and mesothelial cells into myofibroblasts. AB-crystallin is a small heat shock protein overexpressed in liver, renal and vascular fibrosis and can be induced by TGF-β1. In this study, we assessed the role of αB-crystallin in pleural and pulmonary fibrosis. W…
The selective advantage of cystic fibrosis heterozygotes tested by aDNA analysis: A preliminary investigation
2000
Recently a heterozygote advantage was suggested to explain the high incidence (1:25 carrier individuals in Europeans) of the cystic fibrosis gene. This selective advantage was speculated to be due to a high resistance to chloride-secreting diarrhea, including cholera. Up to now the major efforts to test directly this hypothesis have been limited to animal models.
Inversion of Left Atrial Appendage Will Cause Compressive Stresses in the Tissue: Simulation Study of Potential Therapy
2022
In atrial fibrillation (AF), thromboembolic events can result from the particular conformation of the left atrial appendage (LAA) bearing increased clot formation and accumulation. Current therapies to reduce the risk of adverse events rely on surgical exclusion or percutaneous occlusion, each of which has drawbacks limiting application and efficacy. We sought to quantify the hemodynamic and structural loads of a novel potential procedure to partially invert the “dead” LAA space to eliminate the auricle apex where clots develop. A realistic left atrial geometry was first achieved from the heart anatomy of the Living Heart Human Model (LHHM) and then the left atrial appendage inversion (LAAI…
OP03 Inhibition of autophagy exacerbates intestinal fibrosis and EMT
2019
High performance of intravoxel incoherent motion diffusion MRI in detecting viral hepatitis-b induced liver fibrosis.
2019
Background: Recently a small cohort study demonstrated that intravoxel incoherent motion (IVIM) diffusion MRI can detect early stage liver fibrosis. Using modified IVIM data acquisition parameters, the current study aims to confirm this finding. Methods: Twenty-six healthy volunteers, three patients of chronic viral hepatitis-b but without fibrosis and one mild liver steatosis subject, and 12 viral hepatitis-b patients with fibrosis (stage 1–2=7, stage 3–4=5) were included in this study. With a 1.5-T MR scanner and respiration-gating, IVIM diffusion imaging was acquired using a single-shot echo-planar sequence with a b -value series of 2, 0, 1, 15, 20, 30, 45, 50, 60, 80, 100, 200, 300, 600…
Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.
2009
The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-b-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0Æ70; P > 0Æ001) independently of liver iron concentration (r = 0Æ01; P = 0Æ932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0Æ997 (95% confidence interval [CI]: 0Æ925–1Æ000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69Æ0–100Æ0) and 95% specificity (95% CI: 84Æ2–99Æ3). Transient elastography is a reliable non-invasive tool f…
Current development of CFTR potentiators in the last decade
2020
Cystic fibrosis (CF) is a genetic disorder produced by the loss of function of CFTR, a main chloride channel involved in transepithelial salt and water transport. CFTR function can be rescued by small molecules called "potentiators" which increase gating activity of CFTR on epithelial surfaces. High throughput screening (HTS) assays allowed the identification of new chemical entities endowed with potentiator properties, further improved through medicinal chemistry optimization. In this review, the most relevant classes of CFTR potentiators developed in the last decade were explored, focusing on structure-activity relationships (SAR) of the different chemical entities, as a useful tool for t…
Investigating REPAIRv2 as a Tool to Edit CFTR mRNA with Premature Stop Codons
2020
Cystic fibrosis (CF) is caused by mutations in the gene encoding the transmembrane conductance regulator (CFTR) protein. Some CF patients are compound heterozygous or homozygous for nonsense mutations in the CFTR gene. This implies the presence in the transcript of premature termination codons (PTCs) responsible for a truncated CFTR protein and a more severe form of the disease. Aminoglycoside and PTC124 derivatives have been used for the read-through of PTCs to restore the full-length CFTR protein. However, in a precision medicine framework, the CRISPR/dCas13b-based molecular tool &ldquo
Cyclooxygenase inhibitors counteract pro-fibrotic signalling in experimental colitis through modulation of TGF-beta/SMAD network
2013
Aims. Cyclooxygenase isoforms (COX-1, COX-2) have been implicated in the development of fibrosis at gastrointestinal sites. Under bowel inflammation, transforming growth factor beta (TGF-beta) has been identified as the main regulator of fibrotic remodelling. The present study investigated the effects of cyclooxygenase inhibitors on pro-fibrotic signalling mediated by the TGF-beta/SMAD pathway in experimental colitis. Methods. Colitis was induced in rats by intrarectal 2,4-dinitrobenzenesulfonic acid (DNBS, 30 mg/rat in 0.25 ml ethanol 50%). After 6 days, systemic [body and spleen weight] and tissue inflammatory parameters [macroscopic and microscopic damage] were assessed. Three days befor…