Miscibility of the fibroin, which was soluble in CaCl\-2\|H\-2O\|C\-2H\-5OH aqueous solution, mixed with chitosan was investigated, and its microspheres were prepared. The chitosan (CS)/fibroin (FB) microsphere inclus...Miscibility of the fibroin, which was soluble in CaCl\-2\|H\-2O\|C\-2H\-5OH aqueous solution, mixed with chitosan was investigated, and its microspheres were prepared. The chitosan (CS)/fibroin (FB) microsphere inclusion fenoprofen calcium (CS\|FB\|FC) was prepared, and its structure was analyzed by FTIR, X\|ray and SEM. The results indicated that blend of chitosan, fibroin and fenoprofen calcium in aqueous solution is miscible, and strong interaction caused by intermolecular hydrogen bonding exits in CS\|FB\|FC. It was indicated that approximately 77% of fenoprofen from the microsphere were released in phosphate\|buffered saline(pH=7.4) within the initial 6h, and with increasing the glutaraldehyde concentration, the release of fenoprofen decreased.展开更多
Ryanodine receptors are ion channels that allow for the release of Ca2+ from the endoplasmic or sarcoplasmic reticulum.They are expressed in many different cell types but are best known for their predominance in skele...Ryanodine receptors are ion channels that allow for the release of Ca2+ from the endoplasmic or sarcoplasmic reticulum.They are expressed in many different cell types but are best known for their predominance in skeletal and cardiac myocytes,where they are directly involved in excitation-contraction coupling.With molecular weights exceeding 2 MDa,Ryanodine Receptors are the largest ion channels known to date and present major challenges for structural biology.Since their discovery in the 1980s,significant progress has been made in understanding their behaviour through multiple structural methods.Cryo-electron microscopy reconstructions of intact channels depict a mushroom-shaped structure with a large cytoplasmic region that pre-sents many binding sites for regulatory molecules.This region undergoes significant motions during opening and closing of the channel,demonstrating that the Ryanodine Receptor is a bona fide allosteric protein.High-resolution structures through X-ray crystallography and NMR currently cover~11% of the entire protein.The combination of high-and low-resolution methods allows us to build pseudo-atomic models.Here we present an overview of the electron microscopy,NMR,and crystallographic analyses of this membrane protein giant.展开更多
The acidic microenvironments of tumor tissue and cells provide an opportunity for the development of pHresponsive drug delivery systems in cancer therapy.In this work,we designed a calcium carbonate(CaCO3)-corecrossli...The acidic microenvironments of tumor tissue and cells provide an opportunity for the development of pHresponsive drug delivery systems in cancer therapy.In this work,we designed a calcium carbonate(CaCO3)-corecrosslinked nanoparticle of methoxy poly(ethylene glycol)-block-poly(L-glutamic acid)through mineralization for intracellular delivery of doxorubicin(DOX),referred to as CaNP/DOX.CaNP/DOX exhibited high drug loading capability,uniform nanoparticle size,and pH-dependent DOX release.In the meantime,the enhanced cell uptake,superior cytotoxicity toward mouse osteosarcoma K7 cells,extended circulation half-life,and improved accumulation of DOX in K7 allograft tumor from CaNP/DOX were also demonstrated.More interestingly,CaNP/DOX displayed improved antitumor effect and reduced side effects against the K7 osteosarcoma-allografted mouse model and the 143B orthotopic osteosarcoma mouse model.Given the superior properties of Ca-mineralized polypeptide nanoparticle for intracellular drug delivery,the smart drug delivery system showed strong competitiveness in clinical chemotherapy of cancers.展开更多
文摘Miscibility of the fibroin, which was soluble in CaCl\-2\|H\-2O\|C\-2H\-5OH aqueous solution, mixed with chitosan was investigated, and its microspheres were prepared. The chitosan (CS)/fibroin (FB) microsphere inclusion fenoprofen calcium (CS\|FB\|FC) was prepared, and its structure was analyzed by FTIR, X\|ray and SEM. The results indicated that blend of chitosan, fibroin and fenoprofen calcium in aqueous solution is miscible, and strong interaction caused by intermolecular hydrogen bonding exits in CS\|FB\|FC. It was indicated that approximately 77% of fenoprofen from the microsphere were released in phosphate\|buffered saline(pH=7.4) within the initial 6h, and with increasing the glutaraldehyde concentration, the release of fenoprofen decreased.
基金funded by the CIHR(operating grant 84350)the Heart and Stroke Foundation of Canadaa CIHR new investigator and a Michael Smith Foundation for Health Research Scholar
文摘Ryanodine receptors are ion channels that allow for the release of Ca2+ from the endoplasmic or sarcoplasmic reticulum.They are expressed in many different cell types but are best known for their predominance in skeletal and cardiac myocytes,where they are directly involved in excitation-contraction coupling.With molecular weights exceeding 2 MDa,Ryanodine Receptors are the largest ion channels known to date and present major challenges for structural biology.Since their discovery in the 1980s,significant progress has been made in understanding their behaviour through multiple structural methods.Cryo-electron microscopy reconstructions of intact channels depict a mushroom-shaped structure with a large cytoplasmic region that pre-sents many binding sites for regulatory molecules.This region undergoes significant motions during opening and closing of the channel,demonstrating that the Ryanodine Receptor is a bona fide allosteric protein.High-resolution structures through X-ray crystallography and NMR currently cover~11% of the entire protein.The combination of high-and low-resolution methods allows us to build pseudo-atomic models.Here we present an overview of the electron microscopy,NMR,and crystallographic analyses of this membrane protein giant.
基金financially supported by the National Natural Science Foundation of China(Grant No.51803006)the Scientific Development Program of Liaoning Province(Grant No.20170541058)the China Postdoctoral Science Foundation(Grant No.2019M650297).
文摘The acidic microenvironments of tumor tissue and cells provide an opportunity for the development of pHresponsive drug delivery systems in cancer therapy.In this work,we designed a calcium carbonate(CaCO3)-corecrosslinked nanoparticle of methoxy poly(ethylene glycol)-block-poly(L-glutamic acid)through mineralization for intracellular delivery of doxorubicin(DOX),referred to as CaNP/DOX.CaNP/DOX exhibited high drug loading capability,uniform nanoparticle size,and pH-dependent DOX release.In the meantime,the enhanced cell uptake,superior cytotoxicity toward mouse osteosarcoma K7 cells,extended circulation half-life,and improved accumulation of DOX in K7 allograft tumor from CaNP/DOX were also demonstrated.More interestingly,CaNP/DOX displayed improved antitumor effect and reduced side effects against the K7 osteosarcoma-allografted mouse model and the 143B orthotopic osteosarcoma mouse model.Given the superior properties of Ca-mineralized polypeptide nanoparticle for intracellular drug delivery,the smart drug delivery system showed strong competitiveness in clinical chemotherapy of cancers.