Browsing by Subject "Chalcones"

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    Aramchol improves hepatic fibrosis in metabolic dysfunction-associated steatohepatitis: Results of multimodality assessment using both conventional and digital pathology
    (Wolters Kluwer, 2025) Ratziu, Vlad; Yilmaz, Yusuf; Lazas, Don; Friedman, Scott L.; Lackner, Caroline; Behling, Cynthia; Cummings, Oscar W.; Chen, Li; Petitjean, Mathieu; Gilgun-Sherki, Yossi; Gorfine, Tali; Kadosh, Shaul; Eyal, Eli; Sanyal, Arun J.; Pathology and Laboratory Medicine, School of Medicine
    Background and aims: Antifibrotic trials rely on conventional pathology despite recognized limitations. We compared single-fiber digital image analysis with conventional pathology to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic dysfunction-associated steatohepatitis. Approach and results: Fifty-one patients with metabolic dysfunction-associated steatohepatitis enrolled in the open-label part of the ARMOR trial received Aramchol 300 mg BID and had paired pre-post treatment liver biopsies scored by consensus among 3 hepatopathologists, and separately assessed by a digital image analysis platform (PharmaNest) that generates a continuous phenotypic Fibrosis Composite Severity (Ph-FCS) score. Fibrosis improvement was defined as: ≥1 NASH Clinical Research Network (NASH-CRN) stage reduction; "improved" by ranked pair assessment; reduction in Ph-FCS ("any" for ≥0.3 absolute reduction and "substantial" for ≥25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (ranked pair assessment), 74.5% (any Ph-FCS reduction), and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or ranked pair assessment had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks versus 39% for ≥48 weeks by NASH-CRN; 43% versus 61% by ranked pair assessment, mean Ph-FCS reduction -0.54 (SD: 1.22) versus -1.72 (SD: 1.02); Ph-FCS reduction (any in 54% vs. 100%, substantial in 21% vs. 65%). The antifibrotic effect of Aramchol was corroborated by reductions in liver stiffness, Pro-C3, and enhanced liver fibrosis. Changes in Ph-FCS were positively correlated with changes in liver stiffness. Conclusions: Continuous fibrosis scores generated in antifibrotic trials by digital image analysis quantify antifibrotic effects with greater sensitivity and a larger dynamic range than conventional pathology.
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    Catalytic Transfer Hydrogenation of 1,3-diphenyl-2-propen-1-one with Palladium on Carbon and Formate Salts
    (Office of the Vice Chancellor for Research, 2013-04-05) Piltz, Joshua
    Chalcones have become significantly important due to their biological applications including antifungal, antiviral, antimicrobial, anti-allergic, anti-inflammatory and anti-cancer properties. Previous mechanistic investigations into the conjugate reduction of chalcones by catalytic transfer hydrogenation (CTH) with palladium on carbon (Pd/C) and formate salts were not thoroughly supported. A full understanding of this process would be useful to such an important class of biomolecules. Therefore, conjugate reduction of 1,3-diphenyl-2-propen-1-one was investigated with CTH using formate salts and Pd/C. Experiments varying substrate concentration and reaction pH were performed. Deuterated sodium formate was utilized to determine if hydrogen transfer from the formate to palladium is involved in the rate determining step, as suggested in other catalytic transfer hydrogenation reactions. A mechanistic discussion will be presented.