Formation of advanced glycation end products (AGEs), which are associated with diabetes mellitus, contributes to prominent features of osteoarthritis, i.e., inflammation-mediated destruction of articular cartilage. Among the phytochemicals which play a role in anti-inflammatory effects, anthocyanins have also been demonstrated to have anti-diabetic properties. Purple corn is a source of three major anthocyanins: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside and peonidin-3-O-glucoside. Purple corn anthocyanins have been demonstrated to be involved in the reduction of diabetes-associated inflammation, suggesting that they may have a beneficial effect on diabetes-mediated inflammation of cartilage. This investigation of the chondroprotective effects of purple corn extract on cartilage degradation found a reduction in glycosaminoglycans released from AGEs induced cartilage explants, corresponding with diminishing of uronic acid loss of the cartilage matrix. Investigation of the molecular mechanisms in human articular chondrocytes showed the anti-inflammatory effect of purple corn anthocyanins and the metabolite, protocatechuic acid (PCA) on AGEs induced human articular chondrocytes via inactivation of the NFκb and MAPK signaling pathways. This finding suggests that purple corn anthocyanins and PCA may help ameliorate AGEs mediated inflammation and diabetes-mediated cartilage degradation.
The coronavirus disease 2019 (COVID-19) pandemic causes many morbidity and mortality cases. Despite several developed vaccines and antiviral therapies, some patients experience severe conditions that need intensive care units (ICU); therefore, precision medicine is necessary to predict and treat these patients using novel biomarkers and targeted drugs. In this study, we proposed a multi-level biological network analysis framework to identify key genes via protein–protein interaction (PPI) network analysis as well as survival analysis based on differentially expressed genes (DEGs) in leukocyte transcriptomic profiles, discover novel biomarkers using microRNAs (miRNA) from regulatory network analysis, and provide candidate drugs targeting the key genes using drug–gene interaction network and structural analysis. The results show that upregulated DEGs were mainly enriched in cell division, cell cycle, and innate immune signaling pathways. Downregulated DEGs were primarily concentrated in the cellular response to stress, lysosome, glycosaminoglycan catabolic process, and mature B cell differentiation. Regulatory network analysis revealed that hsa-miR-6792-5p, hsa-let-7b-5p, hsa-miR-34a-5p, hsa-miR-92a-3p, and hsa-miR-146a-5p were predicted biomarkers. CDC25A, GUSB, MYBL2, and SDAD1 were identified as key genes in severe COVID-19. In addition, drug repurposing from drug–gene and drug–protein database searching and molecular docking showed that camptothecin and doxorubicin were candidate drugs interacting with the key genes. In conclusion, multi-level systems biology analysis plays an important role in precision medicine by finding novel biomarkers and targeted drugs based on key gene identification.
Obesity is a global health concern. Physical activities and eating nutrient-rich functional foods can prevent obesity. In this study, nano-liposomal encapsulated bioactive peptides (BPs) were developed to reduce cellular lipids. The peptide sequence NH2-PCGVPMLTVAEQAQ-CO2H was chemically synthesized. The limited membrane permeability of the BPs was improved by encapsulating the BPs with a nano-liposomal carrier, which was produced by thin-layer formation. The nano-liposomal BPs had a diameter of ~157 nm and were monodispersed in solution. The encapsulation capacity was 61.2 ± 3.2%. The nano-liposomal BPs had no significant cytotoxicity on the tested cells, keratinocytes, fibroblasts, and adipocytes. The in vitro hypolipidemic activity significantly promoted the breakdown of triglycerides (TGs). Lipid droplet staining was correlated with TG content. Proteomics analysis identified 2418 differentially expressed proteins. The nano-liposomal BPs affected various biochemical pathways beyond lipolysis. The nano-liposomal BP treatment decreased the fatty acid synthase expression by 17.41 ± 1.17%. HDOCK revealed that the BPs inhibited fatty acid synthase (FAS) at the thioesterase domain. The HDOCK score of the BPs was lower than that of orlistat, a known obesity drug, indicating stronger binding. Proteomics and molecular docking analyses confirmed that the nano-liposomal BPs were suitable for use in functional foods to prevent obesity.
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