BACKGROUND/OBJECTIVES: Obesity is a complex metabolic disorder characterized by excessive adipose tissue accumulation, dysregulated lipid metabolism, and insulin resistance, leading to an increased risk of metabolic disease. While Withania somnifera (AS) and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C) have traditionally been used for their metabolic regulatory properties, their combined effects on adipogenesis, lipogenesis, lipolysis, and insulin signaling remain unexplored. Therefore, this study aimed to evaluate the anti-obesity effects of AS, C, and their optimal combination (ASC) in 3T3-L1 adipocytes by investigating their impact on lipid metabolism and glucose homeostasis.MATERIALS/METHODS: Following adipogenic differentiation, 3T3-L1 adipocytes were treated with AS, C, and ASC at different concentrations. RESULTS: AS, C, and ASC significantly inhibited adipogenesis by downregulating cyclic adenosine monophosphate (cAMP) response element-binding protein, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins alpha and beta phosphorylation, thereby reducing lipid accumulation in adipocytes. They also suppressed lipogenesis by downregulating the expression of dephosphorylated acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. In contrast, they markedly enhanced lipolysis, as evidenced by increased hormone-sensitive lipase and protein kinase A expression, along with elevated glycerol release and cAMP levels. Furthermore, AS, C, and ASC activated energy metabolism pathways, as indicated by the upregulation of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1A, suggesting a transition toward enhanced mitochondrial fatty acid oxidation. Notably, AS, C, and ASC significantly improved insulin signaling by restoring insulin receptor substrate 1, phosphoinositide 3-kinase, and Akt phosphorylation, while upregulating glucose transporter type 4 expression, indicating enhanced glucose uptake. Among all treatments, ASC showed relatively greater efficacy compared to AS or C alone, suggesting a potential additive effect. CONCLUSION These findings demonstrate that ASC effectively modulates multiple metabolic pathways in adipocytes, including adipogenesis, lipogenesis, lipolysis, energy metabolism, and insulin signaling, to exert its anti-obesity effects.

Liver fibrosis arises from chronic hepatic injury and remains a major clinical challenge due to the lack of effective therapies.Although G-protein-coupled receptor 119 (GPR119) has been explored as a metabolic target in type 2 diabetes, its role in liver fibrogenesis is not well understood. In this study, the protein and mRNA expression of GPR119 were detected in mouse primary hepatic stellate cells (HSCs) using immunostaining and reverse transcriptase-polymerase chain reaction. The anti-fibrotic activities of GPR119 agonists were assessed in primary HSCs, LX-2 cells, and a carbon tetrachloride (CCl₄)–induced mouse model of liver fibrosis. Treatment with the GPR119 agonists MBX-2982 and GSK1292263 inhibited HSC activation, suppressed transforming growth factor-β1 (TGFβ1)–induced Smad2/3 phosphorylation, and reduced the expression of fibrogenic genes. In vivo, oral administration of MBX-2982 attenuated collagen accumulation and decreased hepatic α-smooth muscle actin and TGFβ expression in CCl₄-treated mice. Mechanistically, MBX-2982 activated AMP-activated protein kinase (AMPK), and pharmacological inhibition of AMPK reversed its anti-fibrogenic effects. MBX-2982 further reduced Smad3 acetylation by disrupting the interaction between Smad3 and p300 and promoting AMPK-dependent proteasomal degradation of p300. These results identify GPR119 as a regulator of HSC activation and highlight GPR119 agonists as promising therapeutic candidates for liver fibrosis.

Purpose: Dorsal comminution is widely accepted as a prognostic factor for reduction loss in the nonoperative treatment of distal radius fractures. However, the reliability of measuring dorsal comminution in simple radiographs has not been adequately studied. This study investigated the reliability of dorsal comminution measurements from simple radiographs, based on inter- and intra-rater reliability indices. Methods: We included 40 patients with distal radius fractures who underwent operative treatment from March 2016 to March 2017. We established three definitions for dorsal comminution: first, the rater’s subjective judgment; second, the presence of a free-floating piece of dorsal cortex; and third, the presence of a dorsal cortical defect of 5 mm or greater. Reliability was measured using Fleiss’ or Cohen’s kappa. Results: Based on Cohen’s kappa values, the intra-rater reliability of dorsal comminution assessment demonstrated fair to good agreement. In contrast, inter-rater reliability was generally poor to fair, and subgroup analysis by rater experience revealed poor agreement among less experienced surgeons. Conclusion The radiological predictors of dorsal comminution exhibited overall low reliability, limiting their usefulness in predicting reduction loss in distal radius fractures. A more precise definition of dorsal comminution is necessary, and additional methods, such as computed tomography and artificial intelligence, should be considered to increase reliability.

Purpose: Dorsal comminution is widely accepted as a prognostic factor for reduction loss in the nonoperative treatment of distal radius fractures. However, the reliability of measuring dorsal comminution in simple radiographs has not been adequately studied. This study investigated the reliability of dorsal comminution measurements from simple radiographs, based on inter- and intra-rater reliability indices. Methods: We included 40 patients with distal radius fractures who underwent operative treatment from March 2016 to March 2017. We established three definitions for dorsal comminution: first, the rater’s subjective judgment; second, the presence of a free-floating piece of dorsal cortex; and third, the presence of a dorsal cortical defect of 5 mm or greater. Reliability was measured using Fleiss’ or Cohen’s kappa. Results: Based on Cohen’s kappa values, the intra-rater reliability of dorsal comminution assessment demonstrated fair to good agreement. In contrast, inter-rater reliability was generally poor to fair, and subgroup analysis by rater experience revealed poor agreement among less experienced surgeons. Conclusion The radiological predictors of dorsal comminution exhibited overall low reliability, limiting their usefulness in predicting reduction loss in distal radius fractures. A more precise definition of dorsal comminution is necessary, and additional methods, such as computed tomography and artificial intelligence, should be considered to increase reliability.