Identification of the Molecular Mechanisms of Peimine in the Treatment of Cough Using Computational Target Fishing.

Peimine (also known as verticine) is the major bioactive and characterized compound of Fritillariae Thunbergii Bulbus, a traditional Chinese medicine that is most frequently used to relieve a cough. Nevertheless, its molecular targets and mechanisms of action for cough are still not clear. In the present study, potential targets of peimine for cough were identified using computational target fishing combined with manual database mining. In addition, protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using, GeneMANIA and Database for Annotation, Visualization and Integrated Discovery (DAVID) databases respectively. Finally, an interaction network of drug-targets-pathways was constructed using Cytoscape. The results identified 23 potential targets of peimine associated with cough, and suggested that MAPK1, AKT1 and PPKCB may be important targets of pemine for the treatment of cough. The functional annotations of protein targets were related to the regulation of immunological and neurological function through specific biological processes and related pathways. A visual representation of the multiple targets and pathways that form a network underlying the systematic actions of peimine was generated. In summary, peimine is predicted to exert its systemic pharmacological effects on cough by targeting a network composed of multiple proteins and pathways.

Carbon and hydrogen isotope fractionation during aerobic biodegradation of quinoline and 3-methylquinoline.

Compound-specific isotope analysis has been used extensively to investigate the biodegradation of various organic pollutants. To date, little isotope fractionation information is available for the biodegradation of quinolinic compounds. In this study, we report on the carbon and hydrogen isotope fractionation during quinoline and 3-methylquinoline aerobic microbial degradation by a Comamonas sp. strain Q10. Degradation of quinoline and 3-methylquinoline was accompanied by isotope fractionation. Large hydrogen and small carbon isotope fractionation was observed for quinoline while minor carbon and hydrogen isotope fractionation effects occurred for 3-methylquinoline. Bulk carbon and hydrogen enrichment factors (ε bulk) for quinoline biodegradation were -1.2 ± 0.1 and -38 ± 1‰, respectively, while -0.7 ± 0.1 and -5 ± 1‰ for 3-methylquinoline, respectively. This reveals a potential advantage for employing quinoline as the model compound and hydrogen isotope analysis for assessing aerobic biodegradation of quinolinic compounds. The apparent kinetic isotope effects (AKIEC) values of carbon were 1.008 ± 0.0005 for quinoline and 1.0048 ± 0.0005 for 3-methylquinoline while AKIEH values of hydrogen of 1.264 ± 0.011 for quinoline and 1.0356 ± 0.0103 for 3-methylquinoline were obtained. The combined evaluation of carbon and hydrogen isotope fractionation yields Λ values (Λ = Δδ2H/Δδ13C ≈ ÎµHbulk/εCbulk) of 29 ± 2 for quinoline and 8 ± 2 for 3-methylquinoline. The results indicate that the substrate specificity may have a significant influence on the isotope fractionation for the biodegradation of quinolinic compounds. The substrate-specific isotope enrichment factors would be important for assessing the behavior and fate of quinolinic compounds in the environment.

Systematic Understanding of the Mechanism of Salvianolic Acid A via Computational Target Fishing.

Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A systematic overview of its mechanism of action is yet to be performed. In the present study, the druggability of SAA was measured using the TCMSP server, and potential targets of SAA were identified by PharmMapper and DRAR-CPI. Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and drug-target-pathway networks were constructed to give a visual view. The results showed that SAA has good druggability, and 13 putative protein targets were identified. Network analysis showed that these targets were associated with cancer, metabolism and other physiological processes. In summary, SAA is predicted to target multiple proteins and pathways to form a network that exerts systematic pharmacological effects.

[Identification of alkaloids and flavonoids in all parts of Fritillaria thunbergii using LC-LTQ-Orbitrap MSn].

Alkaloids and flavonoids in flowers, flower buds, stems, leaves, and bulbs of Fritillaria thunbergii were identified by LC-LTQ-Orbitrap MSn.Alkaloids were identified by ACQUITY UPLC BEH C18（2.1 mm×50 mm, 1.7 µm ) chromatographic column with a mobile phase of 10 mmol•L⁻¹ ammonium formate-acetonitrile and gradient elution in positive MS scan mode.Meanwhile, flavonoids were analyzed by Agilent-Zorbax SB C18 (4.6 mm×250 mm, 5 µm) chromatographic column with a mobile phase of 0.2% acetic acid-acetonitrile and gradient elution in negative MS scan mode.Combined with literature reports, chemical constituents were identified and determined by accurate molecular weights and fragment ion peaks in the ESI-MS/MS spectra based on high resolution mass spectrometer.In all parts of F.thunbergii, 37 alkaloids including 7 alkaloids (zhebeininoside, peimisine, peimine, peiminine, ebeiedinone/puqiedinone, ebeiedine/ puqiedine, peimisine-N-oxide) were simultaneously analyzed.Moreover, 16 flavonoids including quercetin, kaempferol and their glycosides were identified.The results indicated that the aerial parts had the similar alkaloids as the bulbs on the whole.Meanwhile, it had a series of flavonoids undetected in the bulbs.Our results provided the scientific basis for the development and utilization of aerial parts of F.thunbergii.

Airborne spread and infection of a novel swine-origin influenza A (H1N1) virus.

BACKGROUND: The novel swine-origin influenza A (H1N1) virus (S-O 2009 IV) can cause respiratory infectious diseases in humans and pigs, but there are few studies investigating the airborne spread of the virus. In January 2011, a swine-origin H1N1 epidemic emerged in eastern China that rapidly spread to neighboring farms, likely by aerosols carried by the wind. METHODS: In this study, quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect viruses in air samples from pig farms. Based on two aerosol infection models (Pig and guinea pig), we evaluated aerosol transmission and infection of the novel S-O 2009 IV isolate. RESULTS: Three novel S-O 2009 IV were isolated from the diseased pig. The positive rate and viral loads of air samples were 26.1% and 3.14-5.72 log10copies/m³ air, respectively. In both pig and guinea pig infection models, the isolate (A/swine/Shandong/07/2011) was capable of forming aerosols and infected experimental animals at a range of 2.0-4.2 m by aerosols, but aerosol route was less efficient than direct contact. CONCLUSIONS: The results indicated that S-O 2009 IV is able to be aerosolized by infected animals and to be transmitted to susceptible animals by airborne routes.

Analysis of CT imaging changes of psoas major muscles in patients with lumbar disc herniation mainly based on low back pain and lower limb pain.

Background: The study aimed to compare the area changes of CT (computed tomograghy) imaging of psoas major muscle (PM) in patients with lumbar disc herniation (LDH) mainly based on low back pain (LBP) and lower limb pain (LLP), and to analyze the correlation among them. Methods: We retrospectively analyzed the lumbar CT imaging data of 120 patients with LDH and 60 healthy control people in our hospital from July 2017 to August 2019. They were divided into LBP group (60 cases), LLP group (60 cases) and healthy controls group (60 cases). According to the pain duration and pain degree, LBP group and LLP group were divided into three subgroups respectively. The maximum cross-sectional area (CSA) of PM and the CSA of L5 vertebral body were calculated by Image J software, and the ratio of them was the maximum CSA index of PM. The maximum CSA indices of PM among three groups and three subgroups were compared, respectively. Results: The baseline data among the three groups weren't significantly different (P > 0.05), yet the maximum CSA index of PM did (P < 0.05). In the LBP group, the maximum CSA indices of PM among the three subgroups (short, medium and long) according to the pain duration were significantly different (P < 0.05), and those among the three subgroups (light, medium and heavy) according to pain degree did (P < 0.05). In the LLP group, the maximum CSA indices of PM among the three subgroups (short, medium and long) were compared, but there was not statistical difference among the three subgroups (P > 0.05). No statistical difference in terms of the maximum CSA indices of PM among the three subgroups (light, medium and heavy) was observed (P > 0.05). Conclusion: The atrophy and thinning of PM may be related to LDH. The correlation between the atrophy of PM and LBP was greater than that of LLP. The atrophy of PM in LDH patients with LBP increased with the prolongation of pain duration and aggravation of pain degree.

Mechanisms of Fritillariae Thunbergii Flos in lung cancer treatment from a systems pharmacology perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae Thunbergii Flos (FTF) included in the Chinese Pharmacopoeia (1977 Edition) is a Chinese medicinal herb traditionally used to treat bronchitis. In recent years, it has been applied in the treatment of lung cancer. However, the molecular mechanism remains largely unknown. METHODS: The screening of bioactive compounds, acquisition of drug targets, network construction, and experimental validation in vivo were combined to explored the mechanism of FTF in the treatment of lung carcinoma with regards to systems pharmacology. RESULTS: The network Lung Cancer Pathway consisted of 114 nodes (44 compounds and 70 potential targets) and 361 edges, as well as modules that included inflammatory response, angiogenesis, negative regulation of the apoptotic process, and positive regulation of cell proliferation and migration. It was examined by conducting experiments that involved the administration of ethanol-based extracts of FTF in Lewis lung carcinoma mice. The extracts exerted excellent anti-lung cancer effects in vivo by significantly inhibiting tumor proliferation, thereby extending the survival period of tumor-bearing mice. Moreover, FTF induced the downregulation of PIK3CG, Bcl-2, eNOS, VEGF, p-STAT3, and STAT3 genes in tumor-bearing mice. CONCLUSIONS: The findings of the present study verify the therapeutic effects and mechanism of FTF on lung cancer and provide a theoretical basis to support the comprehensive utilization of FTF resources.

Simultaneous determination of four amides in Saururus chinensis by matrix solid phase dispersion and high-performance liquid chromatography method.

A rapid and simple analytical method was established for the determination of four amides (N-p-trans-coumaroyltyramine, aristolactam AⅡ, sauristolactam and aristolactam BⅡ) in Saururus chinensis by matrix solid phase dispersion (MSPD) and high-performance liquid chromatography-diode array detector (HPLC-DAD). In the optimized MSPD, 0.2 g S. chinensis powder was blended with 0.4 g silica gel, and 5 mL methanol was selected as elution solvent. The MSPD extraction achieved higher extraction recovery of four amides, and required less sample, solvent and preparation time, comparing with the conventional methods (Soxhlet and ultrasonic extraction). The assay was performed on a TSK gel ODS-100Z column (4.6 mm × 250 mm, 5 µm) at 30 °C. Acetonitrile and 0.4% acetic acid aqueous solution was used as mobile phase by gradient elution at the flow rate of 1.0 mL/min. The detection wavelength was 280 nm. All the analytes showed good linear regression (R2 ≥ 0.9998) within the concentration ranges. The validated method showed good precision and stability with relative standard deviations (RSDs) ≤ 3.18%. The recoveries were in the range of 96.57-99.65%, with RSDs less than 2.74%.

Associations Between IL-10 Polymorphisms and Susceptibility to Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma: A Meta-Analysis.

BACKGROUND: According to relevant reports, interleukin-10 (IL-10), as a multifunctional anti-inflammatory cytokine, has a critical influence in cancer development. A meta-analysis was carried out regarding the relationships among the -592 A/C, -1082 G/A, and -819 T/C polymorphisms as well as the susceptibility to skin squamous cell carcinoma (sSCC), melanoma, and basal cell carcinoma (BCC). MATERIALS AND METHODS: A meta-analysis was carried out on the inter-relationships among the -592 A/C, IL-10-1082 G/A, and -819 T/C polymorphisms as well as the susceptibility to sSCC, melanoma, and BCC. RESULTS: In this analysis, a total of 11 researches, involving 2149 controls and 2128 cases, were included. No association was found between skin cancer risk and the -592A/C or IL-10-1082G/A polymorphisms in any of the analyses. However, a moderately decreased skin cancer risk was found in the -819 TC versus CC model (odds ratio [OR] = 0.81 and 95% confidence interval [CI] = 0.67-0.99, p = 0.04). From the subgroup analysis, a decreased risk was found between the studies of nonmelanoma skin cancers and IL-10-819T/C in the dominant model (OR = 0.60, 95% CI = 0.43-0.85, p = 0.004 for TT+TC vs. CC). Egger's and Begg's tests demonstrated that there was no significant publication bias. CONCLUSION: This meta-analysis showed that the -592A/C and 1082G/A IL-10 polymorphisms might not be risk factors for melanoma or for BCC and sSCC patients, but we obtained a correlation between skin cancer risk and the IL-10 -819T/C polymorphism.

Metabolic profiling investigation of Fritillaria thunbergii Miq. by gas chromatography-mass spectrometry.

Thunberg fritillary bulb (the dry bulbs of Fritillaria thunbergii Miq.), a traditional Chinese Medicine, is widely applied as an expectorant and antitussive. In this investigation, the primary metabolites of bulbs, flowers, leaves, and stems of F. thunbergii were analyzed by gas chromatography-mass spectrometry. Principal component analysis, partial least squares-discriminate analysis, orthogonal projection to latent structures-discriminate analysis, and heat map analysis showed that there were dissimilar metabolites, and a negative correlation between amino acids and saccharides in different analytes. Furthermore, carbodiimide, tryptophan, glucose-6-phosphate, xylose, 2-piperidinecarboxylic acid, monoamidomalonic acid, phenylalanine, and histidine were found to play an important role in the plant metabolism net of F. thunbergii.

Photochemical degradation performance of quinoline aqueous solution in the presence of hydrogen peroxide.

Photochemical degradation performance of quinoline aqueous solution in the presence of H2O2 was carried out, and some intermediates produced during quinoline degradation were also identified tentatively. The experimental results showed that the advanced oxidation of quinoline by UV/H2O2 process accorded well with the pseudo first order kinetics, and the dependence of concentrations of H2O2 and quinoline, and pH value on the photodegradation kinetics has been investigated in detail. It is found that the concentrations of hydrogen peroxide and quinoline have opposite effect on photodegradation kinetics. That means the photodegradation rate of quinoline increased significantly as the hydrogen peroxide concentration increasing, while the photodegradation rate decreased critically as the initial concentration of quinoline increasing. It also concluded that the photodegradation of quinoline by H2O2/UV process is more favorable under alkali solution than acid solution.