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Cystatin C alleviates unconjugated bilirubin-induced neurotoxicity by promoting bilirubin clearance from neurocytes via exosomes, dependent on hepatocyte UGT1A1 activity.
Transl Neurosci
January 2024
Beijing Clinical Research Institute, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-An Road, Xi-Cheng District, Beijing, 100050, People's Republic of China.
There is an urgent need to identify effective drugs for the treatment of nerve injury caused by unconjugated bilirubin (UCB). Our previous research found that cystatin C (CST3) alleviates UCB-induced neurotoxicity by promoting autophagy in nerve cells, but that autophagy inhibitors did not completely inhibit the effects of CST3. This study investigated whether CST3 could alleviate the neurotoxicity of UCB by promoting the secretion and transport of exosomes containing UCB to the liver for metabolism.
View Article and Find Full Text PDF[UGT1A1 gene mutation spectrum with indirect hyperbilirubinemia in children].
Zhonghua Gan Zang Bing Za Zhi
February 2024
Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing 210008, China.
To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children. Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared.
View Article and Find Full Text PDF[Factors influencing bilirubin elevation and its correlation with gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt].
Zhonghua Gan Zang Bing Za Zhi
May 2023
Department of Hepatobiliary Internal Medicine, Fuzong Clinical Medical College of Fujian Medical University/ the 900th Hospital of the Joint Logistics Support Force, Fuzhou 350025, China, Fuzhou 350025, China.
To investigate the factors influencing total bilirubin elevation and its correlation with gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period.
View Article and Find Full Text PDFSuppressing Hepatic UGT1A1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways and Lipid Species and Improves Fatty Liver Disease.
Biomolecules
January 2023
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA.
Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR).
View Article and Find Full Text PDFBilirubin Levels Are Negatively Correlated with Adiposity in Obese Men and Women, and Its Catabolized Product, Urobilin, Is Positively Associated with Insulin Resistance.
Antioxidants (Basel)
January 2023
Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA.
Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein.
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