Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis

Background and aims Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles (CeNP-PEG) with strong ROS scavenging and anti-inflammatory activities have been applied for mitochondrial oxidative stress and inflammatory diseases. The present study aims to determine whether CeNP-PEG has therapeutic value for renal fibrosis. Methods The unilateral ureteral obstructive fibrosis model was used to assess the therapeutic effects in vivo. Transforming growth factor beta1-induced epithelial-to-mesenchymal transition in HK-2 cells was used as the in vitro cell model. The seahorse bioscience X96 extracellular flux analyzer was used to measure the oxygen consumption rate and extracellular acidification rate. Results In the present study, CeNP-PEG treatment significantly ameliorated renal fibrosis by increased E-cadherin protein expression, and decreased α-SMA, Vimentin and Fibronectin expression both in vitro and in vivo. Additionally, CeNP-PEG significantly reduced the ROS formation and improved the levels of mitochondrial ATP. The seahorse analyzer assay demonstrated that the extracellular acidification rate markedly decreased, whereas the oxygen consumption rate markedly increased, in the presence of CeNP-PEG. Furthermore, the mitochondrial membrane potential markedly enhanced, hexokinase 1 and hexokinase 2 expression significantly decreased after treatment with CeNP-PEG. Conclusions CeNP-PEG can block the dysregulated metabolic status and exert protective function on renal fibrosis. This may provide another therapeutic option for renal fibrosis. Graphical Abstract

Phase composition, morphology, properties and improved catalytic activity of hydrothermally-derived manganese-doped ceria nanoparticles

Manganese-doped ceria nanoparticles were prepared by hydrothermal synthesis and the prepared samples were thermally treated at 500 °C for 2 hours. The samples were investigated using X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), energydispersive X-ray spectroscopy (EDS), N2 adsorption and X-ray photoelectron spectroscopy (XPS). XRD revealed that nanocrystalline ceria is the main phase in all samples, while a romanechite-like phase (Na2Mn O5 10) appears in the sample doped with 30% of Mn. TEM coupled with EDS exposed the presence of the same phase in the sample doped with 20% Mn. While ceria particles have spherical morphology and particle size ranging from 4.3 to 9.2 nm, the rare crystals of the romanechite-like phase adopt a tubular morphology with a length of at least 1 μm. However, the decrease in the ceria lattice constant and the EDS spectra of the ceria nanoparticles clearly indicate that a substantial amount of manganese entered the ceria crystal lattice. Manganese doping has a beneficial impact on the specific surface area of ceria. XPS measurements reveal a decrease in the Ce3+/Ce3++Ce4+ content in the doped samples which is replaced by Mn3+. Moreover, a drasticincrease in adsorbed oxygen is observed in the doped samples which is the consequence of the increase in Mn3+ species that promotes oxygen migrations to the surface of the sample. Compared to the pure sample, the doped samples showed significantly higher catalytic activity for the process of toluene oxidation.

Determination of Uric Acid in Biological Fluids by Ceria Nanoparticles Doped Reduced Graphene Oxide Nanocomposite Voltammetric Sensor

High levels of uric acid (UA) in the human body usually cause diabetes, hypertension and atherosclerosis, kidney diseases, and neurological diseases. Hence, it is important to develop sensitive methods for UA determination. In this paper, nanocomposite composed of ceria nanoparticles and reduced graphene was successfully modified on the surface of glassy carbon electrode (ceria NPs-rGO/GCE) by a simple electroreduction method. The morphology, structure and property of the ceria NPs-rGO/GCE was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The electrocatalytic activity of the ceria NPs-rGO/GCE for uric acid (UA) oxidation was studied in detail. The results showed that the ceria NPs-rGO/GCE exhibited excellent selectivity and high sensitivity for UA detection. In 0.05 M H2SO4 solution, a linear range of 0.02-20 M and a low detection limit of 8.0 nM of UA were obtained on the ceria NPs-rGO/GCE. This developed method was successfully applied for the detection of UA in human serum and urine samples, and its recoveries reached 95.8%-105.0%.