No abstract

Background. Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease throughout the world. In kidney disease, oxidative stress has been linked to both antioxidant depletions and increased reactive oxygen species (ROS) production. Thus, the objective of this study was to identify biomarkers related to oxidative stress in DKD. Methods. The gene expression profile of the DKD was extracted from the Gene Expression Omnibus (GEO) database. The identification of the differentially expressed genes (DEGs) was performed using the “limma” R package, and weighted gene coexpression network analysis (WGCNA) was used to find the gene modules that were most related to DKD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using “Org.Hs.eg.db” R package. The protein-protein interaction (PPI) network was constructed using the STRING database. The hub genes were identified by the Molecular Complex Detection (MCODE) plug-in of Cytoscape software. The diagnostic capacity of hub genes was verified using the receiver operating characteristic (ROC) curve. Correlations between diagnostic genes were analyzed using the “corrplot” package. In addition, the miRNA gene transcription factor (TF) network was used to explain the regulatory mechanism of hub genes in DKD. Results. DEGs analysis and WGCNA-identified 160 key genes were identified in DKD patients. Among them, nine oxidative stress-related genes were identified as candidate hub genes for DKD. Using the PPI network, five hub genes, NR4A2, DUSP1, FOS, JUN, and PTGS2, were subsequently identified. All the hub genes were downregulated in DKD and had a high diagnostic value of DKD. The regulatory mechanism of hub genes was analyzed from the miRNA gene-TF network. Conclusion. Our study identified NR4A2, DUSP1, FOS, JUN, and PTGS2 as hub genes of DKD. These genes may serve as potential therapeutic targets for DKD patients.

Objective. Renshen Baidu Powder (RBP) is a famous classic compound of traditional Chinese medicine (TCM) and is commonly used for treating ulcerative colitis (UC). However, the pharmacological mechanism of RBP in treating UC remains unclear. This study investigates the possible mechanism of RBP for UC treatment by network pharmacological analysis and rat validation. Methods. First, the main chemical constituents of RBP were identified using ultrahigh-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Then, we obtained targets of identified compounds from the SwissTargetPrediction database and targets associated with UC from GeneCards database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by RBP. Hematoxylin-eosin (HE) staining was used to observe the pathological change of colon in UC rats after treating RBP, and terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP Nick end labeling (TUNEL) staining was used to detect apoptosis after RBP treatment. The enzyme-linked immunosorbent assay (ELISA) was employed to evaluate cytokine levels of TNF-α, IL-1β, and IL-6. The protein expressions of Bax, Bcl-2, PI3K, AKT, and NF-κB in colonic tissue were detected using immunohistochemistry (IHC). Real-time quantitative polymerase chain reaction (RT-QPCR) was employed to evaluate mRNA expression of PI3K, AKT, and NF-κB. Results. We found a total of 24 main compounds and 329 potential targets related to UC. According to KEGG results, 3 main pathways were identified as responsible for UC, including PI3K-AKT, HIF-1, and VEGF signaling pathway. Animal experiments showed that RBP treatment significantly attenuated colon damage in rats with UC. Mechanistically, RBP could inhibit PI3K/AKT/NF-κB pathway; decrease cell apoptosis; and downregulate the expression of TNF-α, IL-1β, and IL-6. Conclusions. This study demonstrated that RBP may exert anti-inflammatory and antiapoptotic therapeutic benefits in UC by regulating the PI3K/AKT/NF-κB signaling pathways, providing a scientific basis for understanding the mechanism of RBP against UC.

Aim. The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, but there are currently limited treatment options available. Therefore, it is necessary to research new treatment strategies. Zhuyu Pill (ZYP) is a well-known herbal recipe consisting of Huanglian (Coptidis rhizoma) and Wuzhuyu (Evodiae Fructus) that has been clinically used to treat NAFLD. This study aimed to investigate the impact of ZYP on NAFLD induced by a high-fat diet (HFD) and to identify its potential mechanism. Methods. In this investigation, we used ZYP to treat a mouse model of NAFLD induced by an HFD. We conducted various analyses including assessment of serum biochemical indices, histological evaluation, fecal metabonomics analysis, western blot, and quantitative real-time polymerase chain reaction. Results. ZYP effectively improved blood lipid levels and reduced inflammatory response in HFD mice, while also alleviating liver cell damage and lipid accumulation. Additionally, ZYP influenced the fecal bile acid (BA) metabolism profiles of HFD mice by inhibiting the signal transduction of ileal farnesoid X receptor (FXR) fibroblast growth factor 15 (FGF15), enhancing the expression of cytochrome P450 family 7 subfamily A member 1­(CYP7A1), promoting BA synthesis and increasing the metabolic elimination of cholesterol. Conclusion. ZYP shows promise as a potential treatment for alleviating NAFLD by modulating BA metabolism through the FXR-FGF15-CYP7A1 pathway.