A5065111059- Drug Transport and Resistance Mechanisms
- Estrogen and related hormone effects
- Liver Disease Diagnosis and Treatment
- Pharmacogenetics and Drug Metabolism
- Liver Disease and Transplantation
- Cholesterol and Lipid Metabolism
- X-ray Diffraction in Crystallography
- Eicosanoids and Hypertension Pharmacology
- Hormonal Regulation and Hypertension
- Liver Diseases and Immunity
- Advanced Drug Delivery Systems
- Nanoparticle-Based Drug Delivery
- Pregnancy and Medication Impact
- Analytical Chemistry and Chromatography
- Inflammatory mediators and NSAID effects
- DNA and Nucleic Acid Chemistry
- Computational Drug Discovery Methods
- Crystallization and Solubility Studies
- Synthesis and Biological Evaluation
- RNA Interference and Gene Delivery
- Pediatric Hepatobiliary Diseases and Treatments
Charles University
2020-2025
University of Hradec Králové
2021-2023
Macrophages possess an innate ability to scavenge heterogenous objects from the systemic circulation and regulate inflammatory diseases in various organs via cytokine production. That makes them attractive targets for nanomedicine-based therapeutic approaches diseases. In present study, we have prepared several different poly(lactic-co-glycolic acid) (PLGA) polymer nanospheres macrophage-targeted drug delivery using both nanoprecipitation emulsification solvent evaporation methods. Two...
The nuclear constitutive androstane receptor (CAR, NR1I3) plays significant roles in many hepatic functions, such as fatty acid oxidation, biotransformation, liver regeneration, well clearance of steroid hormones, cholesterol, and bilirubin. CAR has been proposed a hypothetical target for metabolic or disease therapy. Currently known prototype high-affinity human agonists CITCO (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime) have limited...
Abstract The Takeda G protein‐coupled receptor 5 (TGR5), also known as GPBAR1 (G bile acid receptor), is a membrane‐type that regulates blood glucose levels and energy expenditure. These essential functions make TGR5 promising target for the treatment of type 2 diabetes metabolic disorders. Currently, most research on developing agonists focuses modifying structure acids, which are endogenous ligands TGR5. However, with nonsteroidal structures have not been widely explored. This study aimed...
Cholestatic liver diseases are characterized by intrahepatic accumulation of bile acids (BAs), exacerbating inflammation, and fibrosis. Dimethyl fumarate (DMF) is a clinically approved antiinflammatory drug that demonstrated protective effects in several experimental models injury. Still, its effect on BA homeostasis fibrosis has not been thoroughly studied. Herein, we hypothesized DMF could improve mitigate the progression cholestasis-induced The was administered to mice with...
Bile acids (BA) play a significant role in the pathophysiology of nonalcoholic steatohepatitis (NASH). The present study evaluates modulation bile acid metabolomics by atorvastatin, cholesterol-lowering agent commonly used to treat cardiovascular complications accompanying NASH. NASH was induced mice 24 weeks consuming high–saturated fat, high-fructose, and high-cholesterol diet (F), with atorvastatin administered orally (20 mg/kg/day) during last three weeks. Biochemical histological...
Abstract Farnesoid X receptor (FXR) is a nuclear with an essential role in regulating bile acid synthesis and cholesterol homeostasis. FXR activation by agonists explained αAF‐2‐trapping mechanism; however, antagonism mechanisms are diverse. We discuss microsecond molecular dynamics (MD) simulations investigating our recently reported antagonists 2a 2 h. study the antagonist‐induced conformational changes ligand‐binding domain, when compared to synthetic (GW4064) or steroidal...
Bile acids (BAs) are key signaling steroidal molecules that regulate glucose, lipid, and energy homeostasis via interactions with the farnesoid X receptor (FXR) G-protein bile acid 1 (GPBAR1). Extensive medicinal chemistry modifications of BA scaffold led to discovery potent selective or dual FXR GPBAR1 agonists. Herein, we discovered 7-ethylidene-lithocholic (7-ELCA) as a novel combined antagonist/GPBAR1 agonist (IC 50 = 15 μM/EC 26 nM) no off-target activation in library 7-alkyl...
Abstract Carvedilol is a widely used beta-adrenoreceptor antagonist for multiple cardiovascular indications; however, it may induce cholestasis in patients, but the mechanism this effect unclear. also prevents development of various forms experimental liver injury, its on nonalcoholic steatohepatitis (NASH) largely unknown. In study, we determined carvedilol (10 mg/kg/day p.o.) bile formation and acid (BA) turnover male C57BL/6 mice consuming either chow diet or western-type NASH-inducing...
The constitutive androstane receptor (CAR) is the essential regulator of genes involved both in xenobiotic and endobiotic metabolism. Diazepam has been shown as a potent stimulator CAR nuclear translocation assumed an indirect activator not interacting with cavity. In this study, we sought to determine if diazepam ligand directly binding domain (LBD) it regulates its target therapeutically relevant concentration. We used different constructs luciferase reporter assays, recombinant CAR-LBD...