3-deazaneplanocin A (3-DZNeP) has been used as an inhibitor of enhancer of zeste homolog 2 (EZH2). Here, we explore the role and underlying mechanisms action of 3-DZNeP in abrogating cisplatin nephrotoxicity. Exposure of cultured mouse renal proximal tubular epithelial cells (mTECs) to cisplatin resulted in dose and time-dependent cleavage of caspase-3, decrease of cell viability, and increase of histone H3 lysine 27 trimethylation (H3K27me3), whereas expression levels of EZH2, a major methyltransferase of H3K27me3, were not affected. Treatment with 3-DZNeP significantly inhibited cisplatin-induced activation of caspase-3, apoptosis, loss of cell viability but did not alter levels of EZH2 and H3K27me3 in cultured mTECs. 3-DZNeP treatment did not affect activation of extracellular signal-regulated kinase (ERK) 1/2, p38 or c-Jun N-terminal kinases (JNK) 1/2, which contribute to renal epithelial cell death, but caused dose-dependent restoration of E-cadherin in mTECs exposed to cisplatin. Silencing of E-cadherin expression by siRNA abolished the cytoprotective effects of 3-DZNeP. In contrast, 3-DZNeP treatment potentiated the cytotoxic effect of cisplatin in H1299, a non-small cell lung cancer cell line that expresses lower E-cadherin levels. Finally, administration of 3-DZNeP attenuated renal dysfunction, morphological damage, and renal tubular cell death, which was accompanied by E-cadherin preservation, in a mouse model of cisplatin nephrotoxicity. Overall, these data indicate that 3-DZNeP suppresses cisplatin-induced tubular epithelial cell apoptosis and acute kidney injury via an E-cadherin-dependent mechanism, and suggest that combined application of 3-DZNeP with cisplatin would be a novel chemotherapeutic strategy that enhances the anti-tumor effect of cisplatin and reduces its nephrotoxicity.
Renal iron recycling preserves filtered iron from urinary excretion. However, it remains debated whether ferroportin (FPN), the only known iron exporter, is functionally involved in renal iron recycling and whether renal iron recycling is required for systemic iron homeostasis. We deleted FPN in whole nephrons by use of a Nestin-Cre and in the distal nephrons and collecting ducts, using a Ksp-Cre, and investigated its impacts on renal iron recycling and systemic iron homeostasis. FPN deletion by Nestin-Cre, but not by Ksp-Cre, caused excess iron retention and increased ferritin heavy chain (FTH1) specifically in the proximal tubules and resulted in the reduction of serum and hepatic iron. The systemic iron redistribution was aggravated, resulting in anemia and the marked downregulation of hepatic hepcidin in elderly FPN knockout (KO)/Nestin-Cre mice. Similarly, in iron-deficient FPN KO/Nestin-Cre mice, the renal iron retention worsened anemia with the activation of the erythropoietin-erythroferrone-hepcidin pathway and the downregulation of hepatic hepcidin. Hence, FPN likely located at the basolateral membrane of the proximal tubules to export iron into the circulation and was required for renal iron recycling and systemic iron homeostasis particularly in elderly and iron-deficient mice. Moreover, FPN deletion in the proximal tubules alleviated ischemic acute kidney injury, possibly by upregulating FTH1 to limit catalytic iron and by priming antioxidant mechanisms, indicating that FPN could be deleterious in the pathophysiology of ischemic acute kidney injury (AKI) and thus may be a potential target for the prevention and mitigation of ischemic AKI.
In this paper, we introduce a fully automatic framework for 3D face recognition under expression variation. For 3D data preprocessing, an improved nose detection method is presented. The small pose is corrected at the same time. A new facial expression processing method which is based on sparse representation is proposed subsequently. As a result, this framework enhances the recognition rate because facial expression is the biggest obstacle for 3D face recognition. Then, the facial representation, which is based on the dual-tree complex wavelet transform (DT-CWT), is extracted from depth images. It contains the facial information and six subregions' information. Recognition is achieved by linear discriminant analysis (LDA) and nearest neighbor classifier. We have performed different experiments on the Face Recognition Grand Challenge database and Bosphorus database. It achieves the verification rate of 98.86% on the all vs. all experiment at 0.1% false acceptance rate (FAR) in the Face Recognition Grand Challenge (FRGC) and 95.03% verification rate on nearly frontal faces with expression changes and occlusions in the Bosphorus database.
In this work, we demonstrate the use of direct ink writing (DIW) technology to create 3D catalytic electrodes for electrochemical applications. Hybrid MoS2/graphene aerogels are made by mixing commercially available MoS2 and graphene oxide powders into a thixotropic, high concentration, viscous ink. A porous 3D structure of 2D graphene sheets and MoS2 particles was created after post treatment by freeze-drying and reducing graphene oxide through annealing. The composition and morphology of the samples were fully characterized through XPS, BET, and SEM/EDS. The resulting 3D printed MoS2/graphene aerogel electrodes had a remarkable electrochemically active surface area (>1700 cm2) and were able to achieve currents over 100 mA in acidic media. Notably, the catalytic activity of the MoS2/graphene aerogel electrodes was maintained with minimal loss in surface area compared to the non-3D printed electrodes, suggesting that DIW can be a viable method of producing durable electrodes with a high surface area for water splitting. This demonstrates that 3D printing a MoS2/graphene 3D porous network directly using our approach not only improves electrolyte dispersion and facilitates catalyst utilization but also provides multidimensional electron transport channels for improving electronic conductivity.
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