Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological ...Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared(NIR) fluorescent probe(DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered fromherbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.展开更多
A novel Diels-Alder adduct possesses a 6/6/6/5/6/6/6/6 octacyclic skeleton featured with bicyclo[2.2.2]octane moiety,biseupyiheoid A(1),along with another decacyclic 6/6/6/3/5/6/5/6/6/6 fused diterpenoid dimer,bisfisc...A novel Diels-Alder adduct possesses a 6/6/6/5/6/6/6/6 octacyclic skeleton featured with bicyclo[2.2.2]octane moiety,biseupyiheoid A(1),along with another decacyclic 6/6/6/3/5/6/5/6/6/6 fused diterpenoid dimer,bisfischoid C(2),were isolated from Euphorbia fischeriana.Their structures were determined by spectroscopic,X-ray crystallographic approaches,and quantum mechanical calculations.The structural features of 1 and 2 were hypothesized to involve intramolecular Diels-Alder reactions with different coupling patterns.Dimer 1 showed antiproliferative activity through apoptosis activation in LoVo cells.展开更多
基金financially supported by National Natural Science Foundation of China(Nos.81930112 and 82004211)State Key Laboratory of Fine Chemicals KF1912,Distinguished professor of Liaoning Province,Dalian Science and Technology Leading Talents Project(2019RD15,China)the Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University(2021YB07)。
文摘Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared(NIR) fluorescent probe(DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered fromherbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.
基金the National Natural Science Foundation of China(No.81930112)Distinguished Professor Program of Liaoning Province(No.XLYC2002008)+1 种基金Natural Science Foundation of Liaoning Province(Nos.2020-BS-203 and 2020-MS-256)Natural Science Foundation of Fujian Province(No.2021J01509).
文摘A novel Diels-Alder adduct possesses a 6/6/6/5/6/6/6/6 octacyclic skeleton featured with bicyclo[2.2.2]octane moiety,biseupyiheoid A(1),along with another decacyclic 6/6/6/3/5/6/5/6/6/6 fused diterpenoid dimer,bisfischoid C(2),were isolated from Euphorbia fischeriana.Their structures were determined by spectroscopic,X-ray crystallographic approaches,and quantum mechanical calculations.The structural features of 1 and 2 were hypothesized to involve intramolecular Diels-Alder reactions with different coupling patterns.Dimer 1 showed antiproliferative activity through apoptosis activation in LoVo cells.
