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Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.
Sci Rep
January 2025
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
α-Klotho (KLA) is a type-1 membranous protein that can associate with fibroblast growth factor receptor (FGFR) to form co-receptor for FGF23. The ectodomain of unassociated KLA is shed as soluble KLA (sKLA) to exert FGFR/FGF23-independent pleiotropic functions. The previously determined X-ray crystal structure of the extracellular region of sKLA in complex with FGF23 and FGFR1c suggests that sKLA functions solely as an on-demand coreceptor for FGF23.
View Article and Find Full Text PDFEpigenetics of Homocystinuria, Hydrogen Sulfide, and Circadian Clock Ablation in Cardiovascular-Renal Disease.
Curr Issues Mol Biol
December 2024
Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Morning-time heart attacks are associated with an ablation in the sleep-time dip in blood pressure, the mechanism of which is unknown. The epigenetic changes are the hallmark of sleep and circadian clock disruption and homocystinuria (HHcy). The homocystinuria causes ablation in the dip in blood pressure during sleep.
View Article and Find Full Text PDFGlycerol-3-phosphate contributes to the increase in FGF23 production in chronic kidney disease.
Am J Physiol Renal Physiol
December 2024
Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA , USAXXXX, XXX.
Why fibroblast growth factor 23 (FGF23) levels increase markedly in chronic kidney disease (CKD) is unknown. Recently, we found that phosphate stimulates renal production of glycerol-3-phosphate (G-3-P), which circulates to bone to trigger FGF23 production. To assess the impact of G-3-P on FGF23 production in CKD, we compared the effect of adenine-induced CKD in mice deficient in glycerol-3-phosphate dehydrogenase 1 (Gpd1), an enzyme that synthesizes G-3-P, along with wild-type littermates.
View Article and Find Full Text PDFHesperidin ameliorates thioacetamide-induced liver fibrosis via antioxidative and anti-inflammatory mechanisms targeting TGF-β/α-SMA pathways in rats.
Int J Immunopathol Pharmacol
December 2024
Clinical Pathology Department, Veterinary Medicine Faculty, University of Mansoura, Mansoura, Egypt.
Our study intended to explore Hesp antioxidant and anti-inflammatory effects against TAA hepatic fibrosis in rats. Hesperidin (Hesp), is a pharmacologically active flavonoid, found abundantly in citrus species. Our present research attempts to inspect the potential hepatoprotective role of Hesp against thioacetamide (TAA)-induced hepatic fibrosis.
View Article and Find Full Text PDFPotential cardioprotective effect of paroxetine against ventricular remodeling in an animal model of myocardial infarction: a comparative study.
BMC Pharmacol Toxicol
December 2024
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Background: Post-myocardial infarction (MI) remodeling involves various structural and functional changes, such as inflammation and fibrosis. Upregulation of G protein-coupled receptor kinase 2 (GRK2) is linked to the progression of cardiovascular diseases, including myocardial infarction. The inhibitory effects of paroxetine on GRK2 are recognized, yet its protective effect on post-MI remodeling has not been elucidated.
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