Mechanism of Taxanes in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Docking.

Taxanes are natural compounds for the treatment of lung cancer, but the molecular mechanism behind the effects is unclear. In the present study, through network pharmacology and molecular docking, the mechanism of the target and pathway of taxanes in the treatment of lung cancer was studied. The taxanes targets were determined by PubChem database, and an effective compounds-targets network was constructed. The GeneCards database was used to determine the disease targets of lung cancer, and the intersection of compound targets and disease targets was obtained. The Protein-Protein Interaction (PPI) network of the intersection targets was analyzed, and the PPI network was constructed by Cytoscape 3.6.0 software. The hub targets were screened according to the degree value, and the binding activity between taxanes and hub targets was verified by molecular docking. The results showed that eight taxane-active compounds and 444 corresponding targets were screened out, and 131 intersection targets were obtained after mapping with lung cancer disease targets. The hub targets obtained by PPI analysis were TP53, EGFR, and AKT1. Gene Ontology (GO) biological function enrichment analysis obtained 1795 biological process (BP) terms, 101 cellular component (CC) terms, and 164 molecular function (MF) terms. There were 179 signaling pathways obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Twenty signaling pathways were screened out, mainly pathways in cancer, proteoglycans in cancer pathway, microRNAs in cancer pathway, and so on. Molecular docking shows that the binding energies of eight taxanes with TP53, EGFR, and AKT1 targets were less than -8.8 kcal/mol, taxanes acts on TP53, EGFR, and AKT1 targets through pathways in cancer, proteoglycans in cancer pathway and microRNAs in cancer pathway, and plays a role in treating lung cancer in biological functions such as protein binding, enzyme binding, and identical protein binding.

Parameter Optimization of Ultrasonic-Microwave Synergistic Extraction of Taxanes from Taxus cuspidata Needles.

Taxanes are the best-known compounds in Taxus cuspidata owing to their strong anticancer effects. However, the traditional taxanes extraction method is the solid-liquid extraction method, which is limited by a large energy consumption and low yield. Therefore, it is urgent to find an efficient method for taxanes extraction. The ultrasonic microwave synergistic extraction (UME) method integrates the cavitation effect of ultrasound and the intensifying heat transfer (ionic conduction and dipole rotation of molecules) effect of microwave to accelerate the release of intracellular compounds and is used in active ingredient extractions. This study aimed to evaluate the performance of UME in extracting taxanes from T. cuspidata needles (dichloromethane-ethanol as extractant). A single-factor experiment, Plackett-Burman design, and the response surface method showed that the optimal UME parameters for taxanes extraction were an ultrasonic power of 300 W, a microwave power of 215 W, and 130 sieve meshes. Under these conditions, the taxanes yield was 570.32 µg/g, which increased by 13.41% and 41.63% compared with the ultrasound (US) and microwave (MW) treatments, respectively. The reasons for the differences in the taxanes yield were revealed by comparing the physicochemical properties of T. cuspidata residues after the UME, US, and MW treatments. The cell structures were significantly damaged after the UME treatment, and numerous tiny holes were observed on the surface. The absorption peaks of cellulose, hemicellulose, and lignin increased significantly in intensity, and the lowest peak temperature (307.40 °C), with a melting enthalpy of -5.19 J/g, was found after the UME treatment compared with the US and MW treatments. These results demonstrate that UME is an effective method (570.32 µg/g) to extract taxanes from T. cuspidata needles by destroying cellular structures.

Storage impact on egg white powder's physical and functional properties.

BACKGROUND: Changes in storage temperature and time alter the functional properties of egg white powder (EWP) and determine its quality and shelf-life, finally affecting the consumer acceptance of the products made from EWP. In the present study, the EWP samples were stored at four different temperatures (-20, 4, 25 and 37 °C) for 60 days, and then the protein structural, physical and functional properties of EWP were measured and assessed further for correlation with storage conditions using heatmap. RESULTS: The viscosity of the EWP solution increased after 30 days. Foaming ability and rheological properties increased first and then decreased compared to untreated samples with the prolonged storage time. Correlation analysis results indicated that the gel hardness, water holding capacity, foaming ability, emulsifying ability, particle size, dispersibility and viscosity of EWP were significantly related to storage time (P < 0.05). Only the gelation properties of EWP stored at 37 °C for 60 days changed significantly and were negatively related to its moisture content (P < 0.05). Additionally, the random coil content of EWP was positively correlated with particle size, moisture content, solubility and gel properties, whereas ß-sheet was negatively correlated with them. CONCLUSION: Compared to other temperatures, the functional properties of EWP were relatively stable under 4 °C. Therefore, the low temperature (4 °C) was selected as the most suitable storage temperature for EWP. The results of the present study could provide a theoretical basis for the shelf-life extension of EWP. © 2022 Society of Chemical Industry.

Computer-Aided Screening and Revealing Action Mechanism of Food-Derived Tripeptides Intervention in Acute Colitis.

Food-derived tripeptides can relieve colitis symptoms; however, their alleviation mode has not been systematically evaluated as an alternative nutritional compound. This study aimed to reveal the potential mechanism of 8000 food-derived tripeptides against acute colitis using a computer-aided screening strategy. Forty-one potential hub targets related to colitis with a Fit score > 4.0 were screened to construct the protein-protein and protein-tripeptide network based on the PharmMapper database and STRING software (Ver. 11.5). In addition, 30 significant KEGG signaling pathways with p-values < 0.001 that the 41 hub targets mainly participated in were identified using DAVID software (Ver. 6.8), including inflammatory, immunomodulatory, and cell proliferation and differentiation-related signaling pathways, particularly in the Ras- and PI3K-Akt signaling pathways. Furthermore, molecular docking was performed using the Autodock against majorly targeted proteins (AKT1, EGFR, and MMP9) with the selected 52 tripeptides. The interaction model between tripeptides and targets was mainly hydrogen-bonding and hydrophobic interactions, and most of the binding energy of the tripeptide target was less than −7.13 kcal/mol. This work can provide valuable insight for exploring food-derived tripeptide mechanisms and therapeutic indications.

Transcriptomics and Physiological Analyses Reveal Changes in Paclitaxel Production and Physiological Properties in Taxus cuspidata Suspension Cells in Response to Elicitors.

In this research, the cell growth, physiological, and biochemical reactions, as well as the paclitaxel production, of Taxus cuspidata suspension cells after treatment with polyethylene glycol (PEG), cyclodextrin (CD), or salicylic acid (SA) (alone or in combination) were investigated. To reveal the paclitaxel synthesis mechanism of T. cuspidata suspension cells under elicitor treatment, the transcriptomics of the Control group and P + C + S group (PEG + CD + SA) were compared. The results show that there were no significant differences in cell biomass after 5 days of elicitor treatments. However, the content of hydrogen peroxide (H2O2) and malondialdehyde (MDA), and the activities of phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO) after elicitor combination treatments were decreased compared with the single-elicitor treatment. Meanwhile, the antioxidant enzyme activity (superoxide dismutase (SOD), catalase (CAT), and peroxidase (PO)) and the contents of soluble sugar and soluble protein were increased after combination elicitor treatments. Additionally, the paclitaxel yield after treatment with the combination of all three elicitors (P + C + S) was 6.02 times higher than that of the Control group, thus indicating that the combination elicitor treatments had a significant effect on paclitaxel production in T. cuspidata cell suspension culture. Transcriptomics analysis revealed 13,623 differentially expressed genes (DEGs) between the Control and P + C + S treatment groups. Both GO and KEGG analyses showed that the DEGs mainly affected metabolic processes. DEGs associated with antioxidant enzymes, paclitaxel biosynthesis enzymes, and transcription factors were identified. It can be hypothesized that the oxidative stress of suspension cells occurred with elicitor stimulation, thereby leading to a defense response and an up-regulation of the gene expression associated with antioxidant enzymes, paclitaxel synthesis enzymes, and paclitaxel synthesis transcription factors; this ultimately increased the production of paclitaxel.

In vivo and in silico studies on the mechanisms of egg white peptides in relieving acute colitis symptoms.

Active peptides, as an alternative nutrition supplement, have been confirmed to have beneficial efficacy against acute colitis. Herein, egg white peptides (EWPs) were used as a nutritional supplement to relieve dextran sulfate sodium-induced acute colitis symptoms. The potential multi-component synergetic pharmacological intervention mechanism of EWPs was investigated on the basis of in silico pharmacology, bioinformatics analysis, and molecular docking. In vitro experiments demonstrated that the migration rate of HSF cells was enhanced 5.30-fold upon treatment with EWPs relative to the control group. After administration with EWPs, colitis symptoms were alleviated in a dose-dependent manner and the serum amino acid content was significantly enhanced, especially for Ala, Leu, Ser, Thr, and Met. Four peptides identified from EWPs showed a total of 52 acute colitis-related potential targets (Fit score >3.8) with network pharmacology analysis, and the targets participated in 31 signaling pathways (p < 0.001). Among these pathways, PI3K-Akt, VEGF, Ras, TNF, and MAPK signaling pathways may exert essential anti-inflammatory effects and accelerate repairing intestinal mucosa. Molecular docking showed that the majority binding energy of peptides-targets was between -10.35 kcal mol-1 and -18.72 kcal mol-1, and peptides mainly interacted with the core targets (Btk, Gstm1, and Rac1) by hydrogen-bonding interactions. The current study confirmed that EWPs as supplementary nutrition can alleviate acute colitis.