Search results for "Fibrosis"

Novel tricyclic pyrrolo-quinolines as pharmacological correctors of the mutant CFTR chloride channel

2023

AbstractF508del, the most frequent mutation in cystic fibrosis (CF), impairs the stability and folding of the CFTR chloride channel, thus resulting in intracellular retention and CFTR degradation. The F508del defect can be targeted with pharmacological correctors, such as VX-809 and VX-445, that stabilize CFTR and improve its trafficking to plasma membrane. Using a functional test to evaluate a panel of chemical compounds, we have identified tricyclic pyrrolo-quinolines as novel F508del correctors with high efficacy on primary airway epithelial cells from CF patients. The most effective compound, PP028, showed synergy when combined with VX-809 and VX-661 but not with VX-445. By testing the …

P.20.3 Targeting fibrosis and inflammation in Duchenne Muscular Dystrophy

2013

Duchenne Muscular Dystrophy is the most frequent genetic muscle disease worldwide affecting ∼1:5000 male births. It is caused by a defective DMD gene, which leads to reduced and defective dystrophin protein expression. The constant breakdown of fibres leads to focal necrosis, myophagocytosis and a considerable influx of inflammatory cells into the muscle tissue, which is followed by increasing endomysial fibrosis. Both, inflammation and fibrosis as well as a putative relation are not yet understood immunologically. Fibrosis directly correlates with adverse outcome and early loss of ambulation. We have studied how inflammation is linked to fibrosis in DMD, with an emphasis on the communicati…

Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype-phenotype associations.

2009

Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype-phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL-negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplicat…

Role of heat shock protein in myeloproliferative neoplasms : involvement of HSP27 in myelofibrosis

2017

Myelofibrosis (MF) is the most aggressive myeloproliferative neoplasms (MPN) with the highest degree of morbidity and mortality, including progressive bone marrow fibrosis resulting into bone marrow failure. JAK2 kinase inhibitors have been successfully used for a few years in MPN and more particularly for MF treatment. Nevertheless, their beneficial effects are mainly restricted on symptoms and not on the course of the disease. Recently, heat shock protein 90 (HSP90) - known to stabilize JAK2 - has been reported as a promising therapeutic target in MPN. However HSP90 inhibitors show toxicity and induce the expression of stress-inducible proteins such as HSP70 and, most likely HSP27 as prev…

Reply to: “Is industrial fructose just a marker of an unhealthy dietary pattern?”

2014

We recently reported a link between fructose intake and the severity of liver fibrosis in a cohort of Italian patients with genotype 1 (G1) chronic hepatitis C (CHC) [1]. In particular, the association holds true for ‘‘industrial’’ only, not for ‘‘fruit’’ fructose intake. We thank Chiavaroli and colleagues for their comments that give us the opportunity to further strengthen data from our analyses.

The Fatty Liver Assessment in Germany (FLAG) cohort study identifies large heterogeneity in NAFLD care

2020

Background & Aims NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. Methods The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. Results In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fib…

Reply

2017

Determining a healthy reference range and factors potentially influencing PRO-C3 – A biomarker of liver fibrosis

2021

Background & Aims Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical studies in NAFLD/NASH patients support the utility of PRO-C3, a marker of type III collagen formation, as a marker for the degree of fibrosis, disease activity, and effect of treatment. Here we establish the healthy reference range, optimal sample handling conditions for both short- and long-term serum storage, and robustness for the PRO-C3 assay. Methods PRO-C3 was measured in 269 healthy volunteers…

Staphylococcal Biofilms:Challenges in the Discovery of Novel Antiinfective Agents

2011

Staphylococci can induce a wide spectrum of infectious diseases that are associated with remarkable morbidity and mortality [1]. In fact, community and hospital-acquired methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for novel therapeutic options [2]. Importantly, pathogenic staphylococci have not only an amazing ability to acquire resistance to antibiotics, but also to form biofilms, bacterial communities that grow on surfaces and are surrounded by a self-produced polymer matrix. This latter characteristic is likely the most important virulence factor of staphylococci in the development of the chronic form of infectious disease…

Xenotransplantation of parathyroids in rats using barium-alginate and polyacrylic acid multilayer microcapsules

2001

The integrity and function of encapsulated parathyroid tissue following xenotransplantation is limited by oxygen and nutrition supply and capsule fibrosis. Since some of these factors depend on stability and biocompatibility of the coating material, multilayer microcapsules have been developed. Parathyroid tissue pieces and digested single cells from pigs were encapsulated in barium-alginate and in polyacrylic acid (PAA) multilayer capsules. After 7 days of culture the function of the encapsulated cells were assessed. Subsequently, in a part of the cultured microcapsules the viability was directly assessed whereas the other part was transplanted in dark animal [DA] rats for 30 days. After e…