Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits YAP/TAZ activity by potentiating its phosphorylation-mediated proteasomal degradation via the ubiquitin ligase adaptor protein β-TrCP. In mouse models of fibrosis, pharmacologic inhibition of aCDase or genetic knockout of aCDase in HSCs reduces fibrosis, stromal stiffness, and YAP/TAZ activity. In patients with advanced fibrosis, aCDase expression in HSCs is increased. Consistently, a signature of the genes most down-regulated by ceramide identifies patients with advanced fibrosis who could benefit from aCDase targeting. The findings implicate ceramide as a critical regulator of YAP/TAZ signaling and HSC activation and highlight aCDase as a therapeutic target for the treatment of fibrosis.

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Innovations in interventional cardiology historically predate those in neuro-intervention. As such, studying trends in interventional cardiology can be useful in exploring avenues to optimise neuro-interventional techniques. One such cardiology innovation has been the steady conversion of arterial puncture sites from transfemoral access (TFA) to transradial access (TRA), a paradigm shift supported by safety benefits for patients. While neuro-intervention has unique anatomical challenges, the access itself is identical. As such, examining the extensive cardiology literature on the radial approach has the potential to offer valuable lessons for the neuro-interventionalist audience who may be unfamiliar with this body of work. Therefore, we present here a report, particularly for neuro-interventionalists, regarding the best practices for TRA by reviewing the relevant cardiology literature. We focused our review on the data most relevant to our audience, namely that surrounding the access itself. By reviewing the cardiology literature on metrics such as safety profiles, cost and patient satisfaction differences between TFA and TRA, as well as examining the technical nuances of the procedure and post-procedural care, we hope to give physicians treating complex cerebrovascular disease a broader data-driven understanding of TRA.

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