Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation.

Influenza is an acute viral respiratory illness with high morbidity rates worldwide. Excessive pulmonary inflammation is the main characteristic of lethal influenza A virus (IAV) infections. Therapeutic options for managing influenza are limited to vaccines and some antiviral medications. Phillyrin is one of the major bioactive components of the Chinese herbal medicine Forsythia suspensa, which has the functions of sterilization, heat clearing and detoxification. In this work, the effect and mechanism of phillyrin on H1N1 influenza (PR8)-induced pneumonia were investigated. We reported that phillyrin (15 mg/kg) treatment after viral challenge significantly improved the weight loss, ameliorated pulmonary inflammation and inhibited the accumulation of multiple cytokines and chemokines in bronchoalveolar lavage fluid on 7 days post infection (dpi). In vitro, phillyrin suppressed influenza viral replication (Matrixprotein and nucleoprotein messenger RNA level) and reduced influenza virus-induced cytopathic effect (CPE). Furthermore,chemokine receptor CXCR2 was confirmed to be markedly inhibited by phillyrin. Surface plasmon resonance results reveal that phillyrin exhibits binding affinity to CXCR2, having a binding affinity constant (KD) value of 1.858e-5 M, suggesting that CXCR2 is a potential therapeutic target for phillyrin. Moreover, phillyrin inhibited the mRNA and protein expression levels of Caspase1, ASC and NLRP3 in the lungs of mice with H1N1-induced pneumonia.This study reveals that phillyrin ameliorates IAV-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation partly.

Mechanism of Erzhiwan in treating osteoporosis based on molecular docking technology and molecular dynamics simulation.

This experiment was a network pharmacology research based on the theoretical system of traditional Chinese medicine. TCMSP database, PubChem database, RCSB database, and SwissTargetPrediction database were used to study the effective chemical constituents of Ligustri lucidi Fructus and Ecliptae Herba in Erzhiwan, a traditional prescription for nourishing the liver and kidney. Then Genecards database, OMIM database, OMIM Gene Map, and Metascape database were used to study the therapeutic targets of osteoporosis. At last, Cytoscape 3.6.0 software, its built-in Bisogenet and CytoNCA, AutoDockTools-1.5.6 software, PYMOL-2.2.0 software, and Gromacs software, by drawing the relationship diagram between chemical components and disease targets, PPI network of disease, semi-flexible molecular docking technology, evaluation and analysis of enrichment pathway, and molecular dynamics simulation, were used to study the therapeutic mechanism of Erzhiwan on osteoporosis. It is found that the intervention and regulation of Erzhiwan on osteoporosis were mainly realized through multiple targets of active ingredients and multiple pathways, which provided support for the continued development of Erzhiwan.

[Electroacupuncture for acute ischemic stroke and its effect on plasma levels of IL-17 and IL-10].

OBJECTIVE: To compare the clinical efficacy on acute ischemic stroke (AIS) between electroacupuncture combined with conventional western medicine therapy and simple conventional western medicine therapy and its effect on plasma levels of interleukin (IL)-17 and IL-10. METHODS: A total of 60 patients with AIS were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 4 cases dropped off). The control group was treated with conventional western medicine therapy i.e neuroprotection and cerebral circulation improvement. On the basis of the treatment in the control group, in the observation group, acupuncture was applied at Baihui (GV 20), Yintang (GV 24+) and Quchi (LI 11), Zusanli (ST 36), Sanyinjiao (SP 6), etc. on the affected side, Baihui (GV 20)-Yintang (GV 24+), Quchi (LI 11)-Hegu (LI 4) and Zusanli (ST 36)-Sanyinjiao (SP 6) were connected with electroacupuncture, with disperse-dense wave, 2 Hz/15 Hz in frequency, once a day for consecutive 10 days. Before and after treatment, the scores of National Institution of Health stroke scale (NIHSS) and modified Barthel index (MBI) were observed, plasma levels of IL-17 and IL-10 were detected by ELISA method. RESULTS: After treatment, NIHSS scores were decreased while MBI scores were increased compared before treatment in both groups (P<0.01); compared with the control group, NIHSS score was decreased while MBI score was increased in the observation group (P<0.05). After treatment, IL-17 levels were decreased while IL-10 levels were increased compared before treatment in both groups (P<0.01); compared with the control group, IL-17 level was decreased while IL-10 level was increased in the observation group (P<0.05). CONCLUSION: Electroacupuncture combined with conventional western medinice therapy can improve the nerve function and activity of daily living in patients with AIS, its clinical efficacy is superior to simple conventional western medicine therapy, the mechanism may relate to the regulation on IL-17/IL-10 imbalance.

Transcriptome sequencing and characterization of Astragalus membranaceus var. mongholicus root reveals key genes involved in flavonoids biosynthesis.

BACKGROUND: Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao is a traditional medicinal herb of Leguminosae since it contains bioactive compounds such as flavonoids, which have significant pharmacological effects on immunity and antioxidant. However, the scanty genomic and transcriptome resources of Astragalus membranaceus have hindered further exploration of its biosynthesis and accumulation mechanism. OBJECTIVE: This project aim to further improve our understanding of the relationship between transcriptional behavior and flavonoids content of A. mongholicus. METHODS: The accumulation of flavonoids and related gene expression in five different developmental stages (A: vegetative, B: florescence, C: fruiting, D: fruit ripening and E: defoliating stages) of A. mongholicus root were studied by combining UV spectrophotometry and transcriptomic techniques. The de novo assembly, annotation and functional evaluation of the contigs were performed with bioinformatics tools. RESULTS: After screening and assembling the raw data, there were a total of 158,123 unigenes with an average length of 644.89 bp were finally obtained, which has 8362 unigenes could be jointly annotated by NR, SwissProt, eggNOG, GO, KEGG and Pfam databases. KEGG enrichment analysis was performed on differentially expressed genes(DEGs)in the four groups (A vs. B, B vs. C, C vs. D, D vs. E). The results showed that many DEGs in each group were significantly enriched to flavonoids biosynthesis related pathways. Among them, a number of 86 were involved in the biosynthesis of isoflavonoid (12), flavonoid (5) and phenylpropanoid (69). Further analysis of these DEGs revealed that the expression levels of key genes such as PAL, 4CL, CCR, COMT, DFR, etc. were all down-regulated at the fruiting stage, and then raised at the fruit ripening stage. This expression pattern was similar to the accumulation trend of total flavonoids content. CONCLUSIONS: In summary, this comprehensive transcriptome dataset allowed the identification of genes associated with flavonoids metabolic pathways. The results laid a foundation for the biosynthesis and regulation of flavonoids. It also provided a scientific basis for the most suitable harvest time and resource utilization of A. mongholicus.

Electroacupuncture Alleviates Cerebral Ischemia/Reperfusion Injury in Rats by Histone H4 Lysine 16 Acetylation-Mediated Autophagy.

Background: Electroacupuncture (EA) treatment in ischemic stroke has been highlighted recently; however, the specific mechanism is still elusive. Autophagy is considered a new target for cerebral ischemia/reperfusion (I/R), but whether it plays a role of protecting or causing rapid cell apoptosis remains unclear. Studies have reported that the reduction in lysine 16 of histone H4 acetylation coheres with autophagy induction. The primary purpose of the study was to explore whether EA could alleviate I/R via autophagy-mediated histone H4 lysine 16 acetylation in the middle cerebral artery occlusion (MCAO) rat model. Methods: One hundred and twenty male Sprague-Dawley rats were divided into five groups: control group, MCAO group, MCAO+EA group, MCAO+EA+hMOF siRNA group, and MCAO+EA+Sirt1 inhibitor group. EA was applied to "Baihui" (Du20) and "Renzhong" (Du26) at 5 min after modeling and 16 h after the first EA intervention. The structure and molecular markers of the rat brain were evaluated. Results: EA significantly alleviated I/R injury by upregulating the expressions of Sirt1, Beclin1, and LC3-II and downregulating the expressions of hMOF and H4K16ac. In contrast, the Sirt1 inhibitor lowered the increase in Sirt1, Beclin1, and LC3-II and enhanced the level of hMOF and H4K16ac expressions associated with EA treatment. Besides, ChIP assay revealed that the binding of H4K16ac in the Beclin1 promoter region of the autophagy target gene was significantly raised in the MCAO+EA group and MCAO+EA+hMOF siRNA group. Conclusions: EA treatment inhibited the H4K16ac process, facilitated autophagy, and alleviated I/R injury. These findings suggested that regulating histone H4 lysine 16 acetylation-mediated autophagy may be a key mechanism of EA at Du20 and Du26 to treat I/R.

Pollutant removal performance of an integrated system that combines a baffled vertical-flow wetland and a scenic water body.

Stormwater treatment requires effective control measures and development of low-cost and high-efficiency technologies. An integrated system is developed by combining a baffled vertical-flow constructed wetland (BVFCW) and a scenic water body for stormwater quality control purpose. The objectives of the study are to compare the pollutant removal performance of the full-scale integrated system with four groups of wetland-to-scenic water body area ratios (WSARs) including 1/11, 2/11, 3/11, 4/11 and investigate its treatment efficiency. Results show that the system performs better in the removal of chemical oxygen demand (COD), total nitrogen (TN), ammonia nitrogen (NH4+-N), nitrate-nitrogen (NO3-N), and total phosphorus (TP) at the WSAR of 4/11 than that at 3/11 in sixteen-day operation, while it reaches the highest total nitrogen (TN) removal efficiency of 74.0% at the WSAR of 2/11 due to relatively rich carbon source and high influent TN concentration. The integrated system may prove the most effective COD removal at the WSAR of 4/11 for four-time aerobic/anaerobic alternating conditions, a longer flow path and more time to contact with substrates, although the influent COD is lower than that at 2/11 and 1/11. After sixteen-day operation, BVFCW achieved COD removal rate of 90.3%, NH4+-N removal rate of 85.7%, NO3-N removal rate of 68.6%, and TP removal rate of 52.5% at the WSAR of 4/11. At the WSAR of 1/11, effluent met the Class IV requirements in Chinese standards after one-week operation, while effluent met the Class III requirements under the rest conditions. Since effluent in all WSARs met the standards, WSARs of 1/11 and 2/11 were recommended.

Properties of pectin extracted from fermented and steeped hawthorn wine pomace: A comparison.

To investigate the characteristics of the pectins from fermented and steeped hawthorn wine pomace (FHP and SHP), they were acid-extracted, respectively, and compared detailedly. The results of esterification degree indicated that these two pectins were both defined as high methoxyl pectin, which was confirmed by Fourier transform infrared spectroscopy analysis. Molecular weight of SHP was higher than that of FHP. Differential scanning calorimetry analysis showed that the melt temperature of SHP was lower than that of FHP, and the molecular arrangement of SHP is more orderly than FHP. FHP and SHP solutions exhibited shear-thinning properties but SHP had a stronger anti-shear ability. FHP tended to be more elastic-solid as the concentration increased, which was not prominent in SHP. This study suggested that FHP and SHP powder could be new sources of pectin and both pectins could be potentially used as a thicker and stabilizer in food processing.