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FGF-based drug discovery: advances and challenges.
Nat Rev Drug Discov
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Institute of Cell Growth Factor, Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health, Wenzhou, Zhejiang, China.
The fibroblast growth factor (FGF) family comprises 15 paracrine-acting and 3 endocrine-acting polypeptides, which govern a multitude of processes in human development, metabolism and tissue homeostasis. Therapeutic endocrine FGFs have recently advanced in clinical trials, with FGF19 and FGF21-based therapies on the cusp of approval for the treatment of primary sclerosing cholangitis and metabolic syndrome-associated steatohepatitis, respectively. By contrast, while paracrine FGFs were once thought to be promising drug candidates for wound healing, burns, tissue repair and ischaemic ailments based on their potent mitogenic and angiogenic properties, repeated failures in clinical trials have led to the widespread perception that the development of paracrine FGF-based drugs is not feasible.
View Article and Find Full Text PDFSurveillance of primary sclerosing cholangitis - a comparison of scheduled or on-demand ERCP with annual MRI surveillance: a multicenter study.
Endoscopy
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Department of Gastroenterology, HUS Abdominal Center, Helsinki University Central Hospital, Helsinki, Finland.
Primary sclerosing cholangitis (PSC) is associated with a high risk of hepatobiliary malignancy, especially cholangiocarcinoma (CCA). There are no good tumor markers to screen for CCA, and current recommendations for PSC monitoring are mainly based on expert opinions. The optimal strategy to assess disease progression and screen for CCA - the main cause of death of PSC patients - remains unclear.
View Article and Find Full Text PDFThe liver lymphatic system plays a critical role in maintaining interstitial fluid balance and immune regulation. Efficient lymphatic drainage is essential for liver homeostasis, but its role in liver disease progression remains poorly understood. In cirrhosis, lymphangiogenesis initially compensates for increased lymph production, but impaired lymphatic drainage in advanced stages may lead to complications such as ascites and portal hypertension.
View Article and Find Full Text PDFThe Role of Sulfatides in Liver Health and Disease.
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Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands.
Sulfatides or 3-O-sulfogalactosylceramide are negatively charged sulfated glycosphingolipids abundant in the brain and kidneys and play crucial roles in nerve impulse conduction and urinary pH regulation. Sulfatides are present in the liver, specifically in the biliary tract. Sulfatides are self-lipid antigens presented by cholangiocytes to activate cluster of differentiation 1d (CD1d)-restricted type II natural killer T (NKT) cells.
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