Molecular Mechanism of Berberine in the Treatment of Calcified Aortic Valve Disease Based on AGE-RAGE Signal Pathway.

Objective: We aimed to explore the molecular mechanism of berberine in the treatment of calcified aortic valve disease through the network pharmacology-molecular docking method. Methods: The targets of berberine and calcified aortic valve disease were retrieved, the interactions between the targets were analyzed, Cytoscape software was used to build a "target-path" network, R language was used to conduct enrichment analysis of GO and KEGG pathways, and AutoDock Vina was used to verify the binding force of the target protein and small molecules. Results: 96 targets for berberine and 4293 disease targets were screened through multiple databases, and 56 targets were identified through veen analysis. The enrichment of PPI, GO, and KEGG pathways suggests that berberine may act on PIK3CD, PIK3CB, PIK3R1, MAPK14, MAPK10, and other targets, and regulate the role of calcified aortic valve disease through AGE-RAGE signaling pathway, Chemokine signaling pathway, Lipid and atherosclerosis, and other pathways. The docking results showed that berberine has good binding activity with the target on the key pathway AGE-RAGE signaling pathway. Conclusion: The network pharmacology preliminarily revealed the mechanism of berberine in the treatment of calcified aortic valve disease by regulating vascular calcification, inflammatory reaction, oxidative stress, and other effects, providing the basis for follow-up experimental research, and also providing the basis for clinical medication.

Cinnamic Acid (CINN) Induces Apoptosis and Proliferation in Human Nasopharyngeal Carcinoma Cells.

BACKGROUND/AIMS: CINN is the main ingredient of the traditional Chinese medicine cinnamon. The purpose of the present study was to investigate the effects of CINN on the proliferation and apoptosis of NPC cells and to elucidate the underlying molecular mechanisms. MATERIALS AND METHODS: CNE2 human NPC cells were treated with various CINN concentrations. The effects of CINN on the proliferation and apoptosis of CNE2 NPC cells were examined using the MTT assay and flow cytometric analysis. Additionally, western blotting was performed to analyze the expression of a number of cell cycle- and apoptosis-related proteins. RESULTS: The proliferation of CNE2 cells was significantly inhibited after treatment with different CINN concentrations for various lengths of time. The inhibitory effect of CINN was concentration-and time-dependent. Flow cytometric analysis showed that 2 mmol/L CINN displayed a significant apoptosis-inducing effect. The western blot analysis results showed that KLF6, Fas-L, Bax, P53 and caspase-3 protein expression was drastically increased in the CNE2 cells after treatment with 2 mmol/L CINN, whereas Bcl-2 and cyclin D1 protein expression was markedly reduced. CONCLUSION: CINN inhibits the proliferation and induces the apoptosis of CNE2 cells. Therefore, CINN possesses a potential anti-tumor effect.

Functional characterization of the copper-transporting P-type ATPase gene of Penicillium janthinellum strain GXCR.

Copper (Cu)-transporting P-type ATPase (CTPA) genes have been documented to play an important role in resistance to heavy metals. However, our understanding of roles of CTPA genes of the filamentous fungi was based only on sequence similarity prediction before. In a previous study, we isolated a Penicillum janthinellum strain GXCR of higher tolerance to Cu (200 mM). In this study, we cloned the partial cDNA of CTPA gene, named PcpA, from the strain GXCR. Sequence alignment indicated that the cloned cDNA sequence has the highest identity (94.4%) with a predictive CTPA gene of Aspergillus clavatus. The PcpA-encoded protein, termed PcpA, has classical functional domains of CTPAs, and shows differences from reported CTPAs in some specific sequence motifs and transmembrane regions. Expression of the PcpA was induced by extracellular Cu, cadmium (Cd), and silver (Ag). PcpA RNA interference (RNAi) mutants with a reduced level of PcpA mRNA were more sensitive to Cu, iron, Cd, and Ag than the wild-type (WT) strain GXCR. When grown in the presence of Cu, iron, and Cd, intracellular Cu and iron contents in the PcpA RNAi mutant were significantly (P<0.05) lower than those in the WT; However, intracellular Cd content in the mutant was significantly (P<0.05) higher than that in the WT. Taken together, it can be concluded that the PcpA functions in Cu uptake and homeostasis, iron uptake, and Cd export from the cytosol to the extracytosol.