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Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways.
BMC Gastroenterol
January 2025
Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
Background: Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin proved to play a protective role in MAFLD cells. But the presice echanism has not been fully illustrated. This study aimed to investigate the role of NRG1 via the ERK/SIRT1 signaling in the pathogenesis of MAFLD.
View Article and Find Full Text PDFUncovering the impact of COVID-19-mediated bidirectional dysregulation of cytochrome P450 3A4 on systemic and pulmonary drug concentrations using physiologically based pharmacokinetic modeling.
Drug Metab Dispos
January 2025
Current affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Current affiliation: OneDrug Inc., Toronto, Ontario, Canada; Program in Translational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Centre for Applied Pharmacokinetic Research, School of Health Sciences, University of Manchester, Manchester, United Kingdom. Electronic address:
Several clinical studies have shown that COVID-19 increases the systemic concentration of drugs in hospitalized patients with COVID-19. However, it is unclear how COVID-19-mediated bidirectional dysregulation of hepatic and pulmonary cytochrome P450 (CYP) 3A4 affects drug concentrations, especially in the lung tissue, which is most affected by the disease. Herein, physiologically based pharmacokinetic modeling was used to demonstrate the differences in systemic and pulmonary concentrations of 4 respiratory infectious disease drugs when CYP3A4 is concurrently downregulated in the liver and upregulated in the lung based on existing clinical data on COVID-19-CYP3A4 interactions at varying severity levels including outpatients, non-intensive care unit (ICU), and ICU patients.
View Article and Find Full Text PDFEfficacy and Safety of Dapagliflozin Compared to Pioglitazone in Diabetic and Non-Diabetic Patients with Non-alcoholic Steatohepatitis: A Randomized Clinical Trial.
Clin Res Hepatol Gastroenterol
January 2025
Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Egypt. Electronic address:
Background: Non-alcoholic steatohepatitis (NASH) is a serious end-stage spectrum of non-alcoholic fatty liver disease (NAFLD) with associated high risk of hepatic and extrahepatic complications. Several studies showed the significant beneficial effect of dapagliflozin on body composition, hepatic and metabolic parameters on NAFLD/NASH patients. The study aimed to investigate the efficacy and safety of dapagliflozin in both diabetic and non-diabetic biopsy-proven NASH patients; compared to pioglitazone.
View Article and Find Full Text PDFThe absorption, distribution, metabolism and elimination characteristics of small interfering RNA therapeutics and the opportunity to predict disposition in pregnant women.
Drug Metab Dispos
January 2025
ReNAgade Therapeutics Management Inc, Cambridge, Massachusetts. Electronic address:
Small interfering RNA (siRNA) therapeutics represent an emerging class of pharmacotherapy with the potential to address previously hard-to-treat diseases. Currently approved siRNA therapeutics include lipid nanoparticle-encapsulated siRNA and tri-N-acetylated galactosamine-conjugated siRNA. These siRNA therapeutics exhibit distinct pharmacokinetic characteristics and unique absorption, distribution, metabolism, and elimination (ADME) properties.
View Article and Find Full Text PDFPhysiologically based pharmacokinetic modeling of small molecules: How much progress have we made?
Drug Metab Dispos
January 2025
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington. Electronic address:
Physiologically based pharmacokinetic (PBPK) models of small molecules have become mainstream in drug development and in academic research. The use of PBPK models is continuously expanding, with the majority of work now focusing on predictions of drug-drug interactions, drug-disease interactions, and changes in drug disposition across lifespan. Recently, publications that use PBPK modeling to predict drug disposition during pregnancy and in organ impairment have increased reflecting the advances in incorporating diverse physiologic changes into the models.
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