Browsing by Author "Ismail, AbdiGhani"

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    Bile Acids in Autoimmune Liver Disease: Unveiling the Nexus of Inflammation, Inflammatory Cells, and Treatment Strategies
    (MDPI, 2023-11-29) Zhou, Tianhao; Ismail, AbdiGhani; Francis, Heather; Medicine, School of Medicine
    As bile acids not solely play an essential role in nutrition absorption, but also in regulating metabolic functions as well as immune response, bile acids and their signaling pathways are increasingly acknowledged as potential therapeutic targets in the context of chronic liver diseases. Bile acid receptors such as G protein bile acid-activated receptor 1 and farnesoid X receptor are expressed in different immune cells engaged in innate immunity. Recently, a series of studies have revealed distinct functions of bile acids and bile acid receptors within the adaptive immune system. In addition, a variety of molecules targeting bile acid receptors and transporters are currently in advanced stages of clinical development. Autoimmune liver diseases including conditions like primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis can lead to chronic inflammation, fibrosis, and even cirrhosis and liver failure. In this review, we focus on the role of bile acids in the inflammatory aspects of autoimmune liver diseases.
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    Sex-Dependent Differences in Cholestasis: Why Estrogen Signaling May Be a Key Pathophysiological Driver
    (Elsevier, 2023) Ismail, AbdiGhani; Kennedy, Lindsey; Francis, Heather; Medicine, School of Medicine
    Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are cholestatic liver diseases that have significant clinical impact with debilitating symptoms and mortality. While PBC is predominantly seen in perimenopausal and postmenopausal women, men who are diagnosed with PBC have worse clinical outcomes and all-cause mortality. In contrast, 60% to 70% of patients with PSC are men; the data indicate that female sex may be an independent factor against PSC-related complications. These findings suggest a sex-dependent biological basis for these differences. Estrogen has been implicated in the pathogenesis of intrahepatic cholestasis of pregnancy and may induce cholestasis through a variety of interactions. However, it is unclear why some sexual dimorphic features may provide a protective effect despite known estrogen models that induce cholestasis. This article provides a brief introductory background and discusses the sexual dimorphism in clinical presentation in PSC and PBC. It also explores the role of estrogen signaling in pathogenesis and how it relates to intrahepatic cholestasis of pregnancy. Studies have already targeted certain molecules involved in estrogen signaling, and this review discusses these studies that identify estrogen-related receptor, estrogen receptor-α, estrogen receptor-β, farnesoid X receptor, and mast cells as possible targets, in addition to long noncoding RNA H19-induced cholestasis and sexual dimorphism. It also explores these interactions and their role in the pathogenesis of PBC and PSC.