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BACKGROUND AND AIMS: The applicability of the proposed metabolic dysfunction-associated steatotic liver disease (MASLD) definition has not been validated. We aimed to characterize the profiles and long-term survival of people meeting the criteria for MASLD, but not that of metabolic dysfunction-associated fatty liver disease (MAFLD), i.e. MASLD only. METHODS: Using data from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, 7791 adult participants were included and categorized into four distinct groups: no SLD, non-MAFLD MASLD, MASLD-MAFLD, and cryptogenic SLD (steatosis without metabolic dysfunction). RESULTS: Participants in the MASLD-only group were younger and had better metabolic profiles and fibrosis degree compared to those with MASLD-MAFLD and those with no SLD. Their profiles were comparable to those with cryptogenic SLD. Similarly, the MASLD-only group tend to have lower cumulative incidence of all-cause and cardiovascular mortality. Clustering analysis showed that MASLD only clusters differently from individuals with MASLD-MAFLD. CONCLUSIONS: MASLD only is a distinct clinical group with substantial heterogeneity compared to those captured using the MAFLD criteria.
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OBJECTIVE: Traditional Chinese Medicine compound HuangQi decoction is widely used in clinical treatment of chronic kidney disease, but its role on renal interstitial fibrosis and the underlying mechanism remains unclear. The aim of this study is to investigate the effect of HuangQi decoction on renal interstitial fibrosis and its association with the TGF-ß/Smad signaling pathway Methods: A total of 120 C57/BL mice were randomly divided into six groups: sham group, sham plus high-dose HuangQi decoction (1.08g/kg) group, unilateral ureteral obstruction (UUO) model group, and UUO model plus low to high doses of HuangQi decoction (0.12g/kg, 0.36g/kg and 1.08g/kg respectively) groups. Animals were sacrificed 14 days after the administration and ipsilateral kidney tissue was sampled for pathologic examinations. Immunohistochemistry, PCR and western blot were used to detect the expressions of related molecules in the TGF-ß/Smad signaling pathway. TGF-ß1 was used in in vitro experiments to induce human kidney proximal tubule epithelial cells (HK2). RESULTS: HuangQi decoction improved ipsilateral kidney fibrosis in UUO mice and downregulated the expressions of TGF-ß1, TßRI, TßRII, Smad4, Smad2/3, P-Smad2/3, α-SMA, collagen type I, III and IV in a dose-dependent manner while upregulated the expression of Smad7 in the same fashion. Similar results were found in in vitro studies. CONCLUSION: The protective effect of HuangQi decoction for unilateral ureteral obstruction kidney damage in mice was mediated by downregulating the TGF-ß/Smad signaling pathway.
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Medicamentos Herbarios Chinos/farmacología , Fibrosis/tratamiento farmacológico , Enfermedades Renales/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Astragalus propinquus , Línea Celular , Transdiferenciación Celular/efectos de los fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Fibrosis/metabolismo , Fibrosis/patología , Humanos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Medicina Tradicional China , Ratones , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Obstrucción Ureteral/tratamiento farmacológico , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patologíaRESUMEN
OBJECT: To explore the effects of HuangQi decoction on tubulointerstitial fibrosis in mice and the Wnt/ß-catenin signaling pathway. METHODS: Unilateral ureteral obstruction (UUO) model was used. A total of 120 C57/BL mice were randomly divided into 6 groups, sham group, sham+HuangQi decoction group (1.08 g/kg), UUO group, UUO+HuangQi decoction group (0.12, 0.36, 1.08 g/kg). Immunohistochemical analysis, RT-PCR and Western blot were employed to examine the proteins and genes related to the Wnt/ß-catenin signaling pathway. RESULTS: In UUO mice models, expression levels of Wnt3,4, Frizzled4, LRP5,6, ß-catenin, LEF-1, TCF-1, Snail, MMP2,7 genes were positively correlated with the degree of renal tubulointerstitial fibrosis, while expression levels of GSK-3ß, Axin, APC, CK1 were negatively correlated. HuangQi decoction could down-regulate expression levels of Wnt3,4, Frizzled4, LRP5,6, ß-catenin, LEF-1, TCF-1, Snail, Twist, MMP2,7 and up-regulate expression levels of GSK-3ß, Axin, APC, CK1 and E-cadherin. CONCLUSION: HuangQi decoction could effectively inhibit the up-regulation of Wnt/ß-catenin signaling pathway induced by UUO, implying a possible role in improving renal interstitial fibrosis.
