Ligand based 3D-QSAR model, pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors.

The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer. In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors. Forty eight known inhibitors were collected to establish 3 D-QSAR models and pharmacophore models, investigate the relationship between the activity and conformation of compounds, and verify the efficiency of pharmacophore. In Accelrys Discovery Studio 2016, the ZINC database was filtered by Lipinski's Rule of Five and SMART's filtration. Then, Hypo01 was used for virtual screening of ZINC database. Compounds with predicted activity values less than 1 µM were molecularly docked with FGFR1 protein crystals, the docking results were observed, and the interaction between compounds and targets was studied. The absorption, distribution, metabolism and excretion (ADME) and toxicity of potential inhibitors were studied, and a compound with new structural scaffolds were obtained. It could be further studied to explore their better therapeutic effects. Communicated by Ramaswamy H. Sarma.

Dragon fruit-kiwi fermented beverage: In vitro digestion, untargeted metabolome analysis and anti-aging activity in Caenorhabditis elegans.

The research on the development of dragon fruit and kiwi fruit through LAB-yeast compound fermentation is very limited, and there are few related fermentation products on the market. The purpose of this study was to evaluate the stability of the antioxidant capacity of fermented beverages (FB) through in vitro simulated digestion, to evaluate the changes in metabolites of juice after fermentation through untargeted metabolomics, and used Caenorhabditis elegans as a model to evaluate its anti-aging activity. The results showed that FB not only has good in vitro antioxidant activity, but also the total phenol content (TPC), total flavonoid content (TFC), ABTS scavenging ability, and hydroxyl radical scavenging ability of FB were significantly increased during gastric digestion and intestinal digestion. Metabolomics showed that the contents of phenols and flavonoids related to antioxidant increased after fermentation, and fermentation had a significant effect on organic acids and amino acids in FB. Finally, compared with the control group, although the original concentration of FB has a side-toxic effect on nematodes, the mean lifespan of C. elegans fed with 1.56% FB increased by 18.01%, SOD activity significantly increased by 96.16% and MDA content significantly decreased by 40.62%. FB has good antioxidant activity in vitro and in vivo, and the antioxidant activity is stable during the simulated digestion process.

Diversity, Chemical Constituents, and Biological Activities of Endophytic Fungi Isolated From Ligusticum chuanxiong Hort.

The objective of this study was to evaluate the diversity of endophytic fungi of different parts of Ligusticum chuanxiong Hort (CX) and further characterize their biological activities and identify chemical compounds produced by these endophytic fungi. A total of 21 endophytic fungi were isolated and identified from CX. Penicillium oxalicum, Simplicillium sp., and Colletotrichum sp. were identified as promising strains by the color reaction. Comparing different organic extracts of the three strains, it was observed that the ethyl acetate extract of Penicillium oxalicum and Simplicillium sp. and the n-butanol extract of Colletotrichum sp. showed significant antioxidant and antibacterial activities. The ethyl acetate extracts of Penicillium oxalicum had outstanding antioxidant and antibacterial effects, and its radical scavenging rates for ABTS and DPPH were 98.43 ± 0.006% and 90.11 ± 0.032%, respectively. At the same time, their IC50 values were only 0.18 ± 0.02 mg/mL and 0.04 ± 0.003 mg/mL. The ethyl acetate extract of Penicillium oxalicum showed MIC value of only 0.5 mg/mL against Escherichia coli and Staphylococcus aureus. By liquid chromatography-mass spectrometry (LC-MS), we found that Penicillium oxalicum could produce many high-value polyphenols, such as hesperidin (36.06 µmol/g), ferulic acid (1.17 µmol/g), and alternariol (12.64 µmol/g), which can be a potential resource for the pharmaceutical industry. In conclusion, these results increase the diversity of CX endophytic fungi and the antioxidant and antibacterial activities of their secondary metabolites.

Evaluation of a strawberry fermented beverage with potential health benefits.

BACKGROUND: Functional fermented beverages are popular worldwide due to their potential to promote health. Starter culture is the main determinant of the final quality and flavor of fermented beverages. The co-cultivation of lactic acid bacteria (LAB) and yeast makes a significant contribution to the safe flavor of fermented beverages. However, the research on the potential of antioxidant, antimicrobial, and anti-biofilm formation of strawberry fermented beverage obtained by combining the LAB and yeast as starter cultures has not been well explored. METHODS: In this study, LAB and yeast were combined as starter culture to obtain strawberry fermented beverage. Fourier transform infrared (FTIR ) spectroscopy was used for the qualitative analysis of the fresh strawberry juice and fermented beverage. From the changes in antioxidant content, free radical scavenging ability, total superoxide dismutase (T-SOD) activity and total antioxidant capacity (T-AOC) to evaluate the antioxidant capacity of fermented beverage in vitro. The antibacterial ability was tested by the Oxford cup method. The biofilms of Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538 under fermented beverages treatment was observed by Fluorescence microscope. In addition, sensory analysis was conducted in this study. RESULTS: In this study, the absorption peaks of Fourier transform infrared between 1,542 cm-1 and 976 cm-1, suggest the existence of organic acids, sugars and ethanol. The total phenols and total flavonoids content decreased by 91.1% and 97.5%, respectively. T-SOD activity increased by 33.33%.The scavenging ability of fermented beverage on superoxide anion free radicals was enhanced, and the scavenging ability on DPPH free radicals, hydroxyl free radicals, and ABTS free radicals was weakened. However, the T-AOC increased from 4.15 ± 0.81 to 8.43 ± 0.27 U/mL. Fermented beverage shows antibacterial activity against four pathogens. The minimum inhibitory concentration (MIC) values of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 6538 were 0.05 mL/mL and 0.025 mL/mL, respectively, and the minimum bactericidal concentration (MBC) were both 0.2 mL/mL. It was observed by fluorescence microscope that the green fluorescence area of the two biofilms is greatly reduced after being treated with fermented beverage. Sensory analysis results show that the average scores of fermented beverage in color, appearance and taste were increased. The overall impression and flavor were decreased. CONCLUSION: These results demonstrated that strawberry fermented beverage has potential benefits such as an antioxidant, antibacterial, and anti-biofilm formation, providing the potential for the fermented beverage to become promising candidates for natural antioxidants, antibacterial agents and anti-biofilm agents.

SnRK2.6 interacts with phytochrome B and plays a negative role in red light-induced stomatal opening.

Light is an important environmental factor for plant growth and development. Phytochrome B (phyB), a classical red/far-red light receptor, plays vital role in controlling plant photomorphogenesis and light-induced stomatal opening. Phytohormone abscisic acid (ABA) accumulates rapidly and triggers a series of physiological and molecular events during the responses to multiple abiotic stresses. Recent studies showed that phyB mutant synthesizes more ABA and exhibits improved tolerance to salt and cold stress, suggesting that a crosstalk exists between light and ABA signaling pathway. However, whether ABA signaling components mediate responses to light remains unclear. Here, we showed that SnRK2.6 (Sucrose Nonfermenting 1-Related Protein Kinase 2.6), a key regulator in ABA signaling, interacts with phyB and participates in light-induced stomatal opening. First, we checked the interaction between phyB and SnRK2s, and found that SnRK2.2/2.3/2.6 kinases physically interacted with phyB in yeast and in vitro. We also performed co-IP assay to support that SnRK2.6 interacts with phyB in plant. To investigate the role of SnRK2.6 in red light-induced stomatal opening, we obtained the snrk2.6 mutant and overexpression lines, and found that snrk2.6 mutant exhibited a significantly larger stomatal aperture under red light treatment, while the two independent overexpression lines showed significantly smaller stomatal aperture, indicative of a negative role for SnRK2.6 in red light-induced stomatal opening. The interaction of SnRK2.6 with red light receptor and the negative role of SnRK2.6 in red light-induced stomatal opening provide new evidence for the crosstalk between ABA and red light in guard cell signaling.

Optimal extraction, purification and antioxidant activity of total flavonoids from endophytic fungi of Conyza blinii H. Lév.

BACKGROUND: Flavonoids are widely used in the market because of their antibacterial, antiviral, and antioxidant activities. But the production speed of flavonoids is limited by the growth of plants. CBL9 (Chaetomium cruentum) is a flavonoid-producing endophytic fungi from Conyza blinii H. Lév, which has potential to produce flavonoids. METHODS: In this study, we isolated total flavonoids from endophytic fungus CBL9 of Conyza blinii H. Lév using macroporous resin D101. The process was optimized by response surface and the best extraction process was obtained. The antioxidant activities of total flavonoids were analyzed in vitro. RESULTS: It was found that the best parameters were 25 °C pH 2.80, 1.85 h, and the adsorption ratio reached (64.14 ± 0.04)%. A total of 60% ethanol was the best elution solvent. The elution ratio of total flavonoid reached to (81.54 ± 0.03)%, and the purity was 7.13%, which was increased by 14.55 times compared with the original fermentation broth. Moreover its purity could rise to 13.69% after precipitated by ethanol, which is very close to 14.10% prepared by ethyl acetate extraction. In the antioxidant research, the clearance ratio of L9F-M on DPPH, ABTS, •OH, •O2-, (96.44 ± 0.04)% and (75.33 ± 0.03)%, (73.79 ± 0.02)%, (31.14 ± 0.01)% at maximum mass concentration, was higher than L9F. CONCLUSION: The result indicated using macroporous resin in the extraction of total flavonoid from endophytic fungus is better than organic solvents with higher extraction ratio, safety and lower cost. In vitro testing indicated that the flavonoid extracted by macroporous resin have good antioxidant activity, providing more evidence for the production of flavonoid by biological fermentation method.