Background: The farnesoid X receptor (FXR) is a leading therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH)-related fibrosis. INT-767, a potent FXR agonist, has shown promise in preclinical models. We aimed to define the mechanisms of INT-767 activity in experimental MASH and dissect cellular and molecular targets of FXR agonism in human disease.
View Article and Find Full Text PDFThe liver has a unique ability to regenerate; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2 migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration.
View Article and Find Full Text PDFT cells must adapt to variations in tissue microenvironments; these adaptations include the degree of oxygen availability. The hypoxia-inducible factor (HIF) transcription factors control much of this adaptation, and thus regulate many aspects of T cell activation and function. The HIFs are in turn regulated by oxygen-dependent hydroxylases: both the prolyl hydroxylases (PHDs) which interact with the VHL tumour suppressor and control HIF turnover, and the asparaginyl hydroxylase known as the Factor inhibiting HIF (FIH), which modulates HIF transcriptional activity.
View Article and Find Full Text PDFUnderstanding microplastic particles (MPs) accumulation and transport along rivers represents a major task due to the complexity and heterogeneity of rivers, and their interactions with their wider corridor. The identification of MPs hotspots and their potential sources is especially challenging in coarse-bed rivers transporting a wide range of particle sizes with a high degree of variability in time and space. This research focuses on the gravel-bed Ain River (Rhône River tributary, France) which is managed by means of various dams and also hosts one of the major plastic production centres in Europe (Oyonnax and Bienne Plastic Valleys).
View Article and Find Full Text PDFJ Trauma Acute Care Surg
August 2022
Background: During the last 20 years of conflict in the Middle East, improvements in body armor and the use of improvised explosive devices have resulted in an increased incidence of complex craniofacial trauma (CFT). Currently, CFT comprises up to 40% of all casualties. We present new data from the recent conflict in Iraq and Syria during Operation Inherent Resolve.
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