Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states.

Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown. Here, we demonstrate that quiescent MuSCs are morphologically heterogeneous and exhibit different patterns of cellular protrusions. We classified quiescent MuSCs into three functionally distinct stem cell states: responsive, intermediate, and sensory. We demonstrate that the shift between different stem cell states promotes regeneration and is regulated by the sensing protein Piezo1. Pharmacological activation of Piezo1 is sufficient to prime MuSCs toward more responsive cells. Piezo1 deletion in MuSCs shifts the distribution toward less responsive cells, mimicking the disease phenotype we find in dystrophic muscles. We further demonstrate that Piezo1 reactivation ameliorates the MuSC morphological and regenerative defects of dystrophic muscles. These findings advance our fundamental understanding of how stem cells respond to injury and identify Piezo1 as a key regulator for adjusting stem cell states essential for regeneration.

Persistent NF-κB activation in muscle stem cells induces proliferation-independent telomere shortening.

During the repeated cycles of damage and repair in many muscle disorders, including Duchenne muscular dystrophy (DMD), the muscle stem cell (MuSC) pool becomes less efficient at responding to and repairing damage. The underlying mechanism of such stem cell dysfunction is not fully known. Here, we demonstrate that the distinct early telomere shortening of diseased MuSCs in both mice and young DMD patients is associated with aberrant NF-κB activation. We find that prolonged NF-κB activation in MuSCs in chronic injuries leads to shortened telomeres and Ku80 dysregulation and results in severe skeletal muscle defects. Our studies provide evidence of a role for NF-κB in regulating stem-cell-specific telomere length, independently of cell replication, and could be a congruent mechanism that is applicable to additional tissues and/or diseases characterized by systemic chronic inflammation.

Cero muertes maternas comunitarias por hemorragia postparto: urge intervenir / Zero community maternal deaths by postpartum hemorrhage: a need for urgent intervention

La hemorragia vaginal post parto continúa siendo una de las primeras causas de muerte materna en países con desarrollo social y económico pobre o detenido. Existen a la fecha intervenciones de éxito que son utilizadas a nivel hospitalario y comunitario en países con altas tasas de parto en el hogar . Propósito: Sugerir intervenciones que mejoren la salud materna de la población indígena, rural y pobre del país. Material y método: Se realizó un análisis secundario de bases de datos sobre vigilancia de muerte materna . Se revisó la base de datos del Sistema Gerencial de Salud (SIGSA y SIGSA2) sobre muertes en mujeres de edad fértil y muertes maternas de 17 municipios y 19 distritos del departamento de Alta Verapaz y 32 municipios de del departamento de Huehuetenango, previamente analizados por los comités de mortalidad materna. ..AU