Identification of Novel Key Molecular Signatures in the Pathogenesis of Experimental Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a long-term major microvascular complication of uncontrolled hyperglycemia and one of the leading causes of end-stage renal disease (ESDR). The pathogenesis of DKD has not been fully elucidated, and effective therapy to completely halt DKD progression to ESDR is lacking. This study aimed to identify critical molecular signatures and develop novel therapeutic targets for DKD. This study enrolled 10 datasets consisting of 93 renal samples from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). Networkanalyst, Enrichr, STRING, and Cytoscape were used to conduct the differentially expressed genes (DEGs) analysis, pathway enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene screening. The shared DEGs of type 1 diabetic kidney disease (T1DKD) and type 2 diabetic kidney disease (T2DKD) datasets were performed to identify the shared vital pathways and hub genes. Strepotozocin-induced Type 1 diabetes mellitus (T1DM) rat model was prepared, followed by hematoxylin & eosin (HE) staining, and Oil Red O staining to observe the lipid-related morphological changes. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to validate the key DEGs of interest from a meta-analysis in the T1DKD rat. Using meta-analysis, 305 shared DEGs were obtained. Among the top 5 shared DEGs, Tmem43, Mpv17l, and Slco1a1, have not been reported relevant to DKD. Ketone body metabolism ranked in the top 1 in the KEGG enrichment analysis. Coasy, Idi1, Fads2, Acsl3, Oxct1, and Bdh1, as the top 10 down-regulated hub genes, were first identified to be involved in DKD. The qRT-PCR verification results of the novel hub genes were mostly consistent with the meta-analysis. The positive Oil Red O staining showed that the steatosis appeared in tubuloepithelial cells at 6 w after DM onset. Taken together, abnormal ketone body metabolism may be the key factor in the progression of DKD. Targeting metabolic abnormalities of ketone bodies may represent a novel therapeutic strategy for DKD. These identified novel molecular signatures in DKD merit further clinical investigation.

Fabrication of macroporous microspheres with core-shell structure for negative chromatography purification of virus.

The macroporous microspheres with core-shell structure, based on a copolymer of 4-Vinylbenzyl chloride, glycidyl methacrylate, and ethylene glycol dimethacrylate, were fabricated through atom transfer radical polymerization suspension polymerization. The microspheres showed 100-200 nm pores in shell and 500-900 nm pores in core. The shell was hydrophilic modified through grafting of poly(N-hydroxyethyl acrylamide) onto the shell surface for reducing adsorption of proteins. The core was coupled with a ligand of poly(ethylene imine) that could bind the proteins. Feedstock of avian influenza virus could be purified on these modified microspheres through negative chromatography. Avian influenza virus cannot enter the core and was recovered from the flow-through, while other proteins with negative charges were able to penetrate into the core and bind to the poly(ethylene imine) ligands. The dynamic binding capacity of proteins was higher on this medium (61 mg/mL) than the commercially available resin (12 mg/mL, Capto Core 700).