In 2015,liposomal formulation of irinotecan(ONIVYDE)has been approved by FDA and widely applied in the treatment of pancreatic cancer.ONIVYDE is a novel liposome formulation,entrapping CPT-11 in the aqueous core of ve...In 2015,liposomal formulation of irinotecan(ONIVYDE)has been approved by FDA and widely applied in the treatment of pancreatic cancer.ONIVYDE is a novel liposome formulation,entrapping CPT-11 in the aqueous core of vesicles using a modified gradient loading method.Due to toxicity concerns,it is essential to explore a rapid and reliable method to effectively isolate and quantify the non-liposomal,namely,free CPT-11and total CPT-11 in plasma.This study focuses on separation of non-liposomal CPT-11,evaluation of the pharmacokinetics of free CPT-11 and total CPT-11 and bio-distribution after intravenous administration of CPT-11 liposome.Free CPT-11 in plasma was separated by solid-phase extraction(SPE).The amount of total CPT-11 and main metabolite 7-ethyl-10-hydroxycamptothecin(SN-38)in plasma was quantified by ultra-performance liquid chromatography–MS/MS.The calibration curves fitted well and lower limit of quantitation for SN-38,free CPT-11,total CPT-11 and CPT-11 in tissue and were 5 ng/ml,10 ng/ml,4.44 ng/ml and 25 ng/ml respectively.The recoveries,precision and accuracy of the method appear satisfactory.Using this method,the pharmacokinetics and bio-distribution of CPT-11 liposome formulation after an intravenous dose of 2.5 mg/kg were then investigated.展开更多
Purple-leafed plants not only have a higher resistance to biotic and abiotic stresses,but also have higher ornamental value.Anthocyanins are vital for leaf color formation,growth and development of purple leaves.Howev...Purple-leafed plants not only have a higher resistance to biotic and abiotic stresses,but also have higher ornamental value.Anthocyanins are vital for leaf color formation,growth and development of purple leaves.However,the molecular mechanism underlying purple leaf formation in Lagerstroemia indica remains unclear.Metabolomic and transcriptomic analysis of purple-leafed cultivar‘Ebony Embers’and greenleafed cultivar‘Arapahoe’showed that the high expression of anthocyanin structure genes induced hyperaccumulation of cyanidin and pelargonidin derivatives,making the leaves purple.LfiHY5,LfiMYB75 and LfibHLH1 were identified using correlation analysis and weighted gene co-expression network analysis.In‘Arapahoe’‘Ebony Embers’population,LfiHY5 and LfiMYB75 showed significant positive correlation with leaf anthocyanin content.Transient expression of LfiMYB75 and LfiHY5 in tobacco and purple-leafed crape myrtle indicated that the two genes activated anthocyanin synthesis.Yeast two-hybrid analysis showed that LfiMYB75 and LfibHLH1 could form a complex that enhanced anthocyanin synthesis.Yeast monohybrid and dual-luciferase assays confirmed that LfiHY5 activated the expression of LfiMYB75,to activate the transcription of anthocyanin structural genes LfiCHS and LfiANS.Moreover,there were three alleles of LfiHY5 in crape myrtle,and the different sequences had different activation effects on LfiMYB75.In conclusion,the results showed that LfiHY5 led to upregulate the transcription of LfiMYB75,and LfiMYB75 formed a complex with LfibHLH1,which increased the transcription level of LfiCHS and LfiANS to affect anthocyanin synthesis in crape myrtle.展开更多
文摘In 2015,liposomal formulation of irinotecan(ONIVYDE)has been approved by FDA and widely applied in the treatment of pancreatic cancer.ONIVYDE is a novel liposome formulation,entrapping CPT-11 in the aqueous core of vesicles using a modified gradient loading method.Due to toxicity concerns,it is essential to explore a rapid and reliable method to effectively isolate and quantify the non-liposomal,namely,free CPT-11and total CPT-11 in plasma.This study focuses on separation of non-liposomal CPT-11,evaluation of the pharmacokinetics of free CPT-11 and total CPT-11 and bio-distribution after intravenous administration of CPT-11 liposome.Free CPT-11 in plasma was separated by solid-phase extraction(SPE).The amount of total CPT-11 and main metabolite 7-ethyl-10-hydroxycamptothecin(SN-38)in plasma was quantified by ultra-performance liquid chromatography–MS/MS.The calibration curves fitted well and lower limit of quantitation for SN-38,free CPT-11,total CPT-11 and CPT-11 in tissue and were 5 ng/ml,10 ng/ml,4.44 ng/ml and 25 ng/ml respectively.The recoveries,precision and accuracy of the method appear satisfactory.Using this method,the pharmacokinetics and bio-distribution of CPT-11 liposome formulation after an intravenous dose of 2.5 mg/kg were then investigated.
基金the National Key R and D Program of China(Grant Nos.2019YFD1000402,2019YFD1001004)the World-Class Discipline Construction and Characteristic Development Guidance Funds for Beijing Forestry University(Grant No.2019XKJS0323).
文摘Purple-leafed plants not only have a higher resistance to biotic and abiotic stresses,but also have higher ornamental value.Anthocyanins are vital for leaf color formation,growth and development of purple leaves.However,the molecular mechanism underlying purple leaf formation in Lagerstroemia indica remains unclear.Metabolomic and transcriptomic analysis of purple-leafed cultivar‘Ebony Embers’and greenleafed cultivar‘Arapahoe’showed that the high expression of anthocyanin structure genes induced hyperaccumulation of cyanidin and pelargonidin derivatives,making the leaves purple.LfiHY5,LfiMYB75 and LfibHLH1 were identified using correlation analysis and weighted gene co-expression network analysis.In‘Arapahoe’‘Ebony Embers’population,LfiHY5 and LfiMYB75 showed significant positive correlation with leaf anthocyanin content.Transient expression of LfiMYB75 and LfiHY5 in tobacco and purple-leafed crape myrtle indicated that the two genes activated anthocyanin synthesis.Yeast two-hybrid analysis showed that LfiMYB75 and LfibHLH1 could form a complex that enhanced anthocyanin synthesis.Yeast monohybrid and dual-luciferase assays confirmed that LfiHY5 activated the expression of LfiMYB75,to activate the transcription of anthocyanin structural genes LfiCHS and LfiANS.Moreover,there were three alleles of LfiHY5 in crape myrtle,and the different sequences had different activation effects on LfiMYB75.In conclusion,the results showed that LfiHY5 led to upregulate the transcription of LfiMYB75,and LfiMYB75 formed a complex with LfibHLH1,which increased the transcription level of LfiCHS and LfiANS to affect anthocyanin synthesis in crape myrtle.
