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The mechanism of MaiFuSheng (MFS) on inhibiting Nonalcoholic Fatty Liver Disease (NAFLD) were investigated based on the exploration of chemical compositions, the techniques of network pharmacology and molecular docking, and the validation using NAFLD mice model. The components of MFS were identified through UPLC-Zeno TOF-MS/MS. The Swiss Bioinformatics Research Platform were applied to obtain active components and potential targets of MFS. The DisGeNet and OMIM databases were used to screen disease targets of NAFLD. The intersection between disease targets and potential targets of MFS were obtained from Venn diagram, which were analyzed by constructing cross-target protein-protein interaction (PPI) network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted on Metascape database. The molecular docking about core targets and active components of MFS were carried out. Using high-fat diet (HFD)-induced C57BL/6J mice as NAFLD animal model to validate key targets. A total of 130 compounds were recognized, 54 active constituents and 176 potential targets of NAFLD were collected. The molecular docking experiments for the top 10 components with the targets are based on the degree value. We found docking models with the best binding energy for TNF-α with Quercetin, IL-17 with Asiatic acid, and IL-1β with Quercetin. We applied qPCR technique to detect above inflammation and lipid metabolism related indicators. Enrichment analysis demonstrated that MFS protects NAFLD via biological processes such as fatty acid transformation and positive regulation of lipid metabolism, as well as signaling pathways such as AGE-RAGE, HIF-1, and IL-17. Compared to the control groups, the model group's ALT, TG, and LDL-C indicators increased, whereas HDL-C indicators dropped (P<0.05) . MFS and Simvastatin treatment groups significantly reduced body weight, liver weight, and fat weight compared to the model groups (P<0.05). Higher doses resulted in significant reductions in serum levels and expression of TNF-α, IL-1β, and IL-17 (P<0.01). Compared to the control groups, the MFS treatment groups can minimize liver lipid accumulation by modulating the expression of lipid metabolism-related genes and improving hepatic fat breakdown. [ABSTRACT FROM AUTHOR]

Our research aimed to investigate the therapeutic effects of Tubastatin-A, a glucocorticoid receptor (GR) mitochondrial translocation inhibitor, and mitoquinone (MitoQ), an antioxidant, on attenuating dexamethasone (DEX)-induced macrophage apoptosis. We treated RAW264.7 macrophages with different combinations of DEX and either Tubastatin-A or MitoQ. Parameters such as mitochondrial GR translocation, mitochondrial reactive oxygen species levels, mitochondrial membrane potential, mitochondrial permeability transition pore opening, cytochrome C efflux to the cytosol, and apoptosis were subsequently evaluated in the different treatment groups via qRT–PCR, western blotting, and immunofluorescence assays. DEX intervention increased the translocation of GRs into the mitochondria, while reducing the expression of the mitochondrial gene MT-CO1 and the activity of mitochondrial respiratory chain complex IV in macrophages. In addition, DEX administration increased mtROS levels, mitochondrial permeability transition pore opening, and mitochondrial cytochrome C release in macrophages, which promoted their apoptosis. We found that Tubastatin-A inhibited mitochondrial GR translocation and reversed the DEX-induced increase in GR levels within the mitochondria. Furthermore, Tubastatin-A mitigated various mitochondrial changes induced by DEX, including reducing the efflux of mitochondrial cytochrome C and inhibiting macrophage apoptosis. Similarly, MitoQ exerted its effects on macrophage apoptosis by reducing mtROS levels through the mitochondrial pathway. The DEX-mediated translocation of GR into mitochondria disrupts the mitochondrial function of macrophages, which induces their apoptosis. By inhibiting mitochondrial translocation of GR and reducing mtROS levels, Tubastatin-A and MitoQ can effectively attenuate macrophage apoptosis, which has clinical implications for reducing the notable side effects associated with glucocorticoid use. [ABSTRACT FROM AUTHOR]

The solution of SUMApHMP model has a certain difficulty while not considering the transit corridor(TC) basic network in air battlefield, so a hybrid taboo search algorithm based on Floyd shortest path algorithm is proposed to control the airspace in battlefield effectively, and ensure the safe, efficient and orderly process of military transportation. According to the solution result of SUMApHMP model, the TC basic network without considering the restricted airspace is designed. The flow matrix and distance matrix between 10 airports in the air battlefield are used to test the hybrid taboo search algorithm, and the result obtained by the proposed algorithm is compared with the results optimized by Lingo 9.0 software. The results show that the proposed hybrid taboo search algorithm has short solution time and correct solution results.