Je pagina wordt geladen…
Journal of cachexia, sarcopenia and muscle
Door Winant AM, Moreno-Justicia R, Paolini L en 8 anderen.
Inhoud in het Engels
Skeletal muscle atrophy is a pervasive complication of critical illness that worsens survival and recovery, yet remains poorly explained by current clinical or molecular markers.
Ward zet deze artikelen in dezelfde app als je kaarten en vragen. Eén gratis account voor Ward, Suture, Osler en Prognia.
To directly connect disease-associated molecular states to the contractile machinery, this study combined sequential functional, transcriptomic and proteomic profiling of the same single human skeletal myofibres from critically ill patients in the intensive care unit with acquired weakness (ICU-AW) and controls. This integrated approach provides a framework for validating molecular signals directly within the cellular and biomechanical context.
Differential expression analyses between control and ICU-AW myofibres show marked donor-level heterogeneity, with no differentially expressed features (FDR < 0.05). Ranked gene set enrichment analyses revealed distinct transcriptional and proteomic signatures between conditions, as well as a subtle yet conserved myofibre state enriched in ICU-AW, characterised by inflammatory and chemotactic gene programmes, intracellular structural remodelling and bioenergetic adaptation. Nineteen features were significantly (FDR < 0.05) altered at both RNA and protein levels from the same myofibre. Overall, these 19 overlapping features link an inflammatory transcriptional landscape to a proteomic shift toward mitochondrial and translational machinery, revealing a coordinated stress-adaptation programme with selective post-translational control in fibres from patients with ICU-AW. Further integration with the functional dataset revealed fibres in this state displayed selectively disrupted myosin dynamics, evidenced by prolonged ATP turnover time of myosin heads in their super-relaxed conformation, suggesting altered myosin energetics as a contributor to muscle dysfunction.
These findings define a discrete, disease-associated myofibre state and validate a proof-of-concept integrative single-fibre framework for connecting multi-omic heterogeneity to molecular motor function in complex human disease. The identification of coordinated transcriptomic and proteomic programmes, validated through functional measurement, suggests that targeting this fibre state may offer new therapeutic opportunities in ICU-acquired dysfunction and related muscle disorders.
Gepubliceerd in Journal of cachexia, sarcopenia and muscle. Het abstract staat hier zoals het is gepubliceerd en blijft het werk van de auteurs; lees het volledige artikel bij de bron.
Prognia toont dit artikel als naslag en voor onderwijs. Het is geen medisch advies. Lees altijd het origineel en volg de actuele richtlijnen en lokale protocollen voordat je ernaar handelt.
