Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells.

BACKGROUND: With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. METHODS: Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. RESULTS: With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. CONCLUSIONS: The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Effect of parenteral glutamine supplementation combined with enteral nutrition on Hsp90 expression and Peyer's patch apoptosis in severely burned rats.

OBJECTIVES: The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation combined with enteral nutrition (EN) on heat shock protein (Hsp) 90 expression and Peyer's patch (PP) apoptosis in severely burned rats. METHODS: Male Sprague-Dawley (SD) rats were randomly assigned to four groups: Sham burn + EN + GLN-free amino acid (AA; n = 10), sham burn + EN + GLN (n = 10), burn + EN + AA (n = 10), and burn + EN + GLN (n = 10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back, burned rats in two of the experimental groups (burn + EN + AA and burn + EN + GLN groups) were fed with a conventional EN solution by oral gavage for 7 d. Simultaneously, rats in the burn + EN + GLN group were given 0.35 g GLN/kg body weight/d once via a tail vein injection for 7 d and rats in the burn + EN + AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. Rats in two sham burn control groups (sham burn + EN + AA and sham burn + EN + GLN groups) were treated in the same manner except for the burn injury. All rats in the four groups were given 175 kcal/kg body wt/d. There was isonitrogenous, isovolumic, and isocaloric intake among the four groups. At the end of the seventh day after completion of the nutritional program, all rats were anesthetized and samples were collected for further analysis. PP apoptosis was measured by terminal deoxyuridine nick-end labeling (TUNEL). The expression of Hsp90 in PPs was analyzed by western blotting. Caspase-3 activity of PPs was also assessed. Levels of proinflammatory cytokines of gut tissues were evaluated by enzyme-linked immunosorbent assay (ELISA). The intestinal immunoglobulin A (IgA) content was also determined by ELISA. RESULTS: The results revealed that intestinal IgA content in rats of the burn + EN + GLN group were significantly increased compared with those in the burn + EN + AA group (P < 0.05). The expression of Hsp90 of PPs in rats in the burn + EN + GLN group was significantly upregulated compared with those in the burn + EN + AA group (P < 0.05). On the other hand, levels of proinflammatory cytokines of gut tissues, caspase-3 activity, and the number of TUNEL-stained cells of PPs in rats of the burn + EN + GLN group were markedly decreased compared with those of the burn + EN + AA group (P < 0.05). CONCLUSIONS: The results of this study show that parenteral glutamine supplementation combined with EN may upregulate the expression of Hsp90, reduce caspase-3 activity, lessen the release of proinflammatory cytokines, attenuate PP apoptosis, and improve intestinal IgA response in burned rats. Clinically, therapeutic efforts to improve intestinal immunity may contribute to a favorable outcome in severely burned patients.

[Comparative study on the infrared fingerprint of Abrus cantoniensis based on the methods of sequential analysis of dual-indexes and cluster analysis].

The methods of sequential analysis of dual-indexes and cluster analysis were utilized to investigate the infrared fingerprints of A. cantoniensis planted in different years and different places in Guangxi, China. The results showed that 6 samples were able to be completely separated only through 13 point smoothing, when the dual-indexes analysis was applied in the present research, and the accurate relationship between these samples could be inspected and expressed by quantitative relationships under 6-dimensional spaces; however, the effect of cluster was bad only through 13 point smoothing of raw spectra, and it was very difficult to find out the regular sequences while the cluster analysis was applied. Furthermore, the 6 samples were able to be completely separated if raw spectra were dealed with 1st derivative after 13 point smoothing, and the clustering effects were more obvious and 6 samples of A. cantoniensis were completely separated. The above two methods could be used to evaluate the quality of Chinese medicinal materials easily when the sample was not excessive quantitatively, but the method of dual-indexes analysis was more difficult than the clustering analysis if the sample size was too large, since a mass of data such as common peak ratio and variation peak ratio of the IR fingerprint spectra were processed and analyzed statistically, while this method could accurately find out the closest relationship between any samples through comparing the quantitative relationships of common peak ratio and variation peak ratio of each sample under 6-dimensional space; the precision of cluster analysis was less than dual-indexes analysis, but it was more convenient than dual-indexes analysis when large sample data were analysed. Finally the above two methods all showed that the chemical composition of the A. cantoniensis was similar in the same cultivated area, but the difference in chemical composition of A. cantoniensis in different years was distinct even they were in the same place.