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Interplay between genetics and epigenetics in lung fibrosis.
Int J Biochem Cell Biol
January 2025
Centre for Respiratory Research, Translational Medical Sciences, School of Medicine, University of Nottingham, UK; Nottingham NIHR Biomedical Research Centre, Nottingham, UK; Biodiscovery Institute, University Park, University of Nottingham, UK. Electronic address:
Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms.
View Article and Find Full Text PDFTofersen and other antisense oligonucleotides in ALS.
Ther Adv Neurol Disord
January 2025
Department of Neurology, Ulm University, Ulm, Germany.
The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R.
View Article and Find Full Text PDF[Biomarkers in complex regional pain syndrome].
Schmerz
January 2025
Klinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Zentrum für interdisziplinäre Schmerzmedizin (ZiS), Universitätsklinikum Würzburg, Oberdürrbacher Straße 6, 97080, Würzburg, Deutschland.
Complex regional pain syndrome (CRPS) is a severe pain disorder with an unclear pathophysiology. Biomarkers offer opportunities to enhance diagnosis, stratification, prognosis, and monitoring. Serum markers such as cytokines and microRNAs show potential but require further research.
View Article and Find Full Text PDFStructure- and Ligand-Based Virtual Screening for Identification of Novel TRPV4 Antagonists.
Molecules
December 2024
Structural Bioinformatics Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland.
Transient receptor potential vanilloid (TRPV) 4 is involved in signaling pathways specifically mediating pain and inflammation, making it a promising target for the treatment of various painful and inflammatory conditions. However, only one drug candidate targeting TRPV4 has entered the clinical trials. To identify potential TRPV4 inhibitors for drug development, we screened a library of ion channel-modulating compounds using both structure- and ligand-based virtual screening approaches.
View Article and Find Full Text PDFIntracerebroventricular anaerobic dopamine in Parkinson's disease with L-dopa-related complications: a phase 1/2 randomized-controlled trial.
Nat Med
January 2025
Parkinson's Disease Centre of Excellence, Department of Neurology, Univeristy of Lille, CHU Lille, INSERM U1172-Degenerative & Vascular Cognitive Disorders, Lille, France.
Continuous compensation for cerebral dopamine deficiency represents an ideal treatment for Parkinson's disease. Dopamine does not cross the digestive and blood-brain barriers and is rapidly oxidized. The new concept is the intracerebroventricular administration of anaerobic dopamine (A-dopamine) using an abdominal pump connected to a subcutaneous catheter implanted in the third ventricle, near the striatum.
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