Major Metabolite Levels of Preoperative Proton Magnetic Resonance Sectroscopy and Intraoperative Fluorescence Intensity in Glioblastoma.

Objective To compare the intraoperative major metabolite level of preoperative proton magnetic resonance spectroscopy(1H-MRS)and fluorescence intensity marked with fluorescein sodium(FLs)in glioblastoma(GBM)and thus provide an objective basis for fluorescence surgical treatment of GBM. Methods All newly diagnosed patients by plain and enhanced magnetic resonance imaging from the April 1,2014 to December 31,2015 were enrolled in this study.All of them received 1H-MRS and marked with FLs.The expression of Ki67 in tumor boundary were confirmed by postoperative pathology and determined by immunostaining assay.The relationship between 1H-MRS metabolite levels and tumor fluorescence intensity was analyzed. Results Totally 33 patients were included in the study.Preoperative 1H-MRS revealed high-grade gliomas in 25 cases.The N-acetylaspartate(NAA)decreased significantly and choline(Cho)increased significantly in high-grade gliomas.The ratios of Cho/NAA,NAA/creatine(Cr),and Cho/Cr significantly differed in different tumor regions(P=0.02,P=0.01,and P=0.00,respectively).Surgical results were marked with FLs intraoperatively.Tissue fluorescence were clearly seen.There were 29 patients undergoing total resection and 4 cases undergoing subtotal resection.No acute encephalocele occured after operation,while 2 patients suffered from epilepsy.Postoperative pathology results included:28 cases were diagnosed as GBM(22 cases consistent with 1H-MRS diagnosis).The results of GBM fluorescence imaging included:the level of fluorescence intensity in tumor parenchyma was significantly higher than that in tumor boundary and peritumoral edema(P=0.01).The result of 1H-MRS metabolite analysis included:The kurtosis of NAA and of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor parenchyma(P=0.01,P=0.02,and P=0.01).While there was no difference in the kurtosis of NAA,the kurtosis of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor boundary(P=0.02, P=0.00).In peritumoral edema,there was no significant different in kurtosis of NAA and of Cho and in the ratio of Cho/NAA(P=0.23,P=0.09,P=0.14).Immunohistochemistry in GBM tumor boundary showed different Ki67 expressions according to different fluorescence imaging(P=0.03). Conclusions The fluorescence intensity in GBM parenchyma is higher than that in other tumor regions,and there are different metabolic levels in different fluorescence intensity.The metabolic information marked by FLs and provided by 1H-MRS before operationis are important,and the correlation between them should be further investigated.

Exploiting Substrate Diversity of NRPS Led to the Generation of New Sansanmycin Analogs.

Further exploration of substrate diversity of the sansaninycin biosynthetic pathway using available halogen- and methyl-phenylalanines led to the generation of diverse sansanmycin derivatives, either at the single C- or N-terminus alone or at both C- and N-termini. The structures of all of these derivatives were determined by MS/MS spectra, and amongst them, the structures of [2-Cl-Phe]-sansanmycin H (1) and [2-Cl-Phe]-sansanmycin A (2) were further identified by NMR. Both the C-terminal derivative I and the N-terminal derivative 2 were assayed for their antibacterial activitiesi and compound 1 exhibited moderate activity against P. aeruginosa and ΔtolC mutant E. coli.

Synthesis, in silico and in vivo blood brain barrier permeability of ginkgolide B cinnamate.

Ginkgolide B, one of the important components of Ginkgo biloba extracts, has been revealed to exhibit great potential in therapy of cerebrovascular diseases. However the lack of permeability greatly limited it from further clinical application. Based on the prediction model for blood brain barrier (BBB) permeation, herein a potential brain-targeting analog ginkgolide B cinnamate (GBC) was successfully synthesized and characterized. After intravenous administration of GBC or GB, liquid chromatography tandem mass spectrometry (LC-MS/MS) was conducted to determine the analog in rat plasma and brain. The results showed that GBC had a significant increase in BBB permeability. A significant 1.61-times increase in half-life was observed for GBC and the drug targeting index (DTI) value was calculated to be 9.91. The experiment results matched well with the predicted one, which revealed that BBB permeability prediction model combined with in vivo study could be used as a quick, feasible and efficient tool for brain-targeting drug design.