Molecular Therapy, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 24, 2025
Metabolic dysfunction-associated steatohepatitis (MASH) is a complex disease driven by diverse metabolic and inflammatory pathways. Farnesoid X receptor (FXR) promising target for MASH due to its role in bile acid lipid metabolism, while HSD17B13 regulates liver droplet homeostasis. However, the existing inhibitors have several druglike property challenges common phenolic structure, key pharmacophore inhibitor. In this study, two-round high-throughput screening was performed identify FXR agonist 2 as nonphenolic The multiparameter structural optimization led discovery of dual FXR/HSD17B13 modulator 6, with high selectivity, tissue distribution, suitable pharmacokinetic properties, safety profiles. Moreover, even at lower dose, compound 6 exerted better therapeutic effect than obeticholic (OCA) multiple models. With attractive pharmacological activity profiles, worthy further evaluation novel anti-MASH agent.
Language: Английский
Citations
2
Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown
Published: March 5, 2025
Dual modulation of FXR and HSD17B13 presents a promising strategy for treating metabolic dysfunction-associated fatty liver disease (MAFLD) steatohepatitis (MASH). Compound 6, groundbreaking dual modulator HSD17B13, validates the concept significantly enhancing function, reducing inflammation fibrosis across various MAFLD models.
Language: Английский
Citations
0
BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)
Published: May 5, 2025
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the predominant chronic condition globally. Bile acid (BA) metabolism contributes significantly to MASLD progression. In this multicenter clinical study, we aimed characterize serum BA profiles in patients with and identify specific alterations compared healthy controls. All cases were sourced from gastroenterology outpatient departments of Shanghai Baoshan Hospital Integrated Chinese Western Medicine, District Songnan Community Health Service Center, Lianyungang Oriental between June 2015 December 2019. The data analyzed using SPSS version 26.0, a p-value less than 0.05 considered significant. A total 215 participants (35.3% women) 49 controls (44.9% women), aged 18-65 years, included. showed higher levels (TBA), cholic (CA), chenodeoxycholic (CDCA), ursodeoxycholic (UDCA) (p < 0.05, p 0.01) when Furthermore, women demonstrated notably lithocholic (LCA), glycolithocholic (GLCA), taurolithocholic (TLCA) men 0.025, 0.01). Compared women, exhibited proportion primary secondary BAs. Additionally, MASLD, concentrations CA, CDCA, glycocholic (GCA), glycochenodeoxycholic (GCDCA), taurochenodeoxycholic (TCDCA) significant negative correlations ALT levels, while deoxycholic (DCA) TLCA BMI. Patients notable variations profiles, including sex-specific differences. This study provides corresponding evidence on association BAs MASLD. Clinical Trial Registry, NO: ChiCTR-OOC-15006157, registration date: March 25, 2015.
Language: Английский
Citations
0
npj Science of Food, Journal Year: 2025, Volume and Issue: 9(1)
Published: May 8, 2025
Abstract The relation between vitamin A (VA) level and cognitive function the underlying mechanisms have not been thoroughly investigated. Population-based cross-sectional animal diet intervention studies were conducted to analyze association VA nutritional status mechanisms. In population-based study, information from 1817 adults aged 50 years above was used for data analysis, we found that subjects with plasma greater than 0.539 μg/ml displayed a lower risk of mild impairment (MCI). experiment, metabolism disrupted in Alzheimer’s disease (AD) model mice, indicated by increased hepatic reduced retinol binding protein 4 (RBP4) level. AD mice fed low-VA showed worse nesting behavior, cerebral pathologies, including Aβ generation, exacerbated neuroinflammation, impaired brain glucose uptake insulin signaling pathway. conclusion, higher (≥ μg/ml) might decrease MCI middle-aged elderly individuals. Low disrupt through regulating pathway, promoting senile plaque deposit aggregating finally exacerbating pathology AD.
Language: Английский
Citations
0
Journal of Virology, Journal Year: 2025, Volume and Issue: unknown
Published: May 14, 2025
ABSTRACT Viruses subvert cells and evade host defense. They emerge unpredictably threaten humans livestock through their genetic phenotypic diversity. Despite more than 100 years since the discovery of viruses, molecular underpinnings virus infections are incompletely understood. The introduction new methodologies into field, such as that click chemistry some 10 ago, keeps uncovering facets viruses. Click uses bio-orthogonal reactions on chemical probes couples nucleic acids, proteins, lipids with tractable labels, fluorophores for single-cell single-molecule imaging, or biotin biochemical profiling infections. Its applications in single often achieve resolution provide important insights widely known phenomenon cell-to-cell infection variability. This review describes advances to unravel mechanisms a select set enveloped nonenveloped DNA RNA including adenovirus, herpesvirus, human immunodeficiency virus. It highlights recent breakthroughs viral DNA, RNA, protein, well host-derived lipid functions both live chemically fixed cells. discusses specific processes entry, uncoating, transcription, replication, packaging, assembly provides perspective explore cell biology, variability, genome organization particle.
Language: Английский
Citations
0
Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1724 - 1724
Published: Dec. 20, 2024
Liver fibrosis is a progressive scarring process primarily caused by chronic inflammation and injury, often closely associated with viral hepatitis, alcoholic liver disease, metabolic dysfunction-associated steatotic disease (MASLD), drug-induced autoimmune (AILD). Currently, there are very few clinical antifibrotic drugs available, effective targeted therapy lacking. Recently, emerging immunomodulators have shown promising results in animal studies, some entered research phases. This review aims to systematically the molecular mechanisms underlying fibrosis, focusing on advancements drug treatments for hepatic fibrosis. Furthermore, since progression or endpoint of many diseases, it crucial address etiological treatment secondary prevention We will also pharmacological available common hepatitis leading
Language: Английский
Citations
1
Molecular Therapy, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
0