Triptolide is a major active component of Tripterygium wilfordii Hook F, which exerts marked immunosuppressive, anti-inflammatory and podocyte-protective effects. In this study, the ability of triptolide to inhibit inflammation and attenuate podocyte injury was examined in a rat model of diabetic nephropathy (DN). Type II diabetic rats with DN were treated with triptolide at a dose of 100 μg.kg−1.day−1. Following 8 weeks of triptolide treatment, the urine albumin level, kidney weight/body weight and the number of cells positive for ED-1 (a marker for rat mononuclear macrophages) in the kidney were assessed. The effects of triptolide on podocyte injury and chronic inflammation were analyzed using quantitative polymerase chain reaction (qPCR), western blotting and immunohistochemistry. Following triptolide treatment, the albuminuria in the type II diabetic rats was significantly reduced. Furthermore, the glomerular hypertrophy and foot process effacement were improved, and there was a recovery of the slit diaphragm associated with nephrin and podocin expression. The inflammation in the kidneys was also attenuated. Furthermore, triptolide significantly reduced the expression of transforming growth factor-β1 and osteopontin, and the infiltration of ED-1-positive cells into the kidney. The results demonstrated that triptolide markedly attenuated albuminuria and podocyte injury in the rat model of DN, which may have been correlated with the inhibition of inflammation and macrophage infiltration in the kidneys.
Objectives. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. Methods. GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. Results. There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. Conclusions. We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.
The response of microbial communities to changes in precipitation can regulate the nutrition cycling of terrestrial ecosystems, but the effect on the structure and interaction of microbial communities and the relationship with environmental factors in arid and semiarid areas are unclear. Here, a field simulation experiment using three precipitation gradients, 50% of normal precipitation (P50), normal precipitation (P100) and 150% of normal precipitation (P150), was carried out in the typical grassland of the Loess Plateau. We applied high-throughput sequencing and network analysis to explore the effect of precipitation changes to soil microbial communities. The results indicated that the structural composition of the microbial community responded to precipitation treatments dramatically. The Top 50 microbials were divided into resource-limited, drought-tolerant and sensitive groups based on their response to altered precipitation. The network of bacteria was more complex and stronger than fungi. Bacterial networks were less stable but more adaptable under drought than fungal. Increasing precipitation promoted the complication and firmness of fungi networks. These findings are crucial for revealing the effects of climate change on soil microbial communities in arid-land and elsewhere and can provide valuable guidance for ecological restoration and response to climate change of the Loess Plateau.
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