ABSTRACT
Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Eucommiaceae , Lignans , Animals , Rats , AMP-Activated Protein Kinases/genetics , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/prevention & control , Eucommiaceae/chemistry , Eucommiaceae/metabolism , Lignans/pharmacology , Lignans/therapeutic use , Molecular Docking Simulation , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Tandem Mass SpectrometryABSTRACT
Liver X receptors (LXRs) are nuclear receptors that function as ligand-activated transcription factors regulating lipid metabolism and inflammation. Recent discoveries found LXRs could regulate tumor growth in a variety of cancer cell lines. In this study, we investigated the effect of LXR activation on melanoma cell proliferation and apoptosis both in vitro and in vivo. Treatment of B16F10 and A-375 melanoma cells with synthetic LXR agonist T0901317 significantly inhibited the proliferation of melanoma cells in vitro. Meanwhile, T0901317 induced the apoptosis of B16F10 melanoma cells in a dose-dependent manner. Furthermore, western blot assay showed that the pro-apoptotic effect of T0901317 on B16F10 melanoma cells was mediated through caspase-3 pathway. Oral administration of T0901317 inhibited the growth of B16F10 melanoma in C56BL/6 mice. Altogether, this study demonstrates the critical role of LXRs in the regulation of melanoma growth and presents the LXR agonist T0901317 as a potential anti-melanoma agent.
ABSTRACT
BACKGROUND: In recent years, significant growth has been observed in the field of plastic and reconstructive surgery. However, the national productivity to the field of plastic and reconstructive surgery remains unknown. We therefore intended to reveal national contributions in the field of plastic and reconstructive surgery. METHODS: Articles published in the 6 highly cited journals in plastic and reconstructive surgery in 2005-2009 were retrieved from the Medline and Web of Science. The number of total articles, the per capita numbers, 5-year impact factors (5y-IF), and citations were tabulated to assess the contribution of different countries. RESULTS: A total number of 5745 articles were published in the 6 journals from 2005 to 2009 worldwide. North America, West Europe, and East Asia were the most productive regions. High-income countries published 79.72% of the total articles. United States (USA) published most of the articles during 2005 to 2009 (2015/5745, 35.07%), followed by United Kingdom, Turkey, Japan, and China. Besides, USA also had the highest total 5y-IF (5010.76), the highest mean 5y-IF (2.49), and the highest total citations (11,788). When normalized to population size, Sweden had the highest number of articles per million persons (12.26), followed by Switzerland (8.02) and Netherlands (7.77). CONCLUSIONS: USA is the most productive country in the field of plastic and reconstructive surgery. When normalized to population size, some European countries might be more productive.
