Controlling postprandial glucose levels for diabetic patients is critical to achieve the tight glycemic control that decreases the risk for developing long-term micro- and macrovascular complications.Herein,we report ...Controlling postprandial glucose levels for diabetic patients is critical to achieve the tight glycemic control that decreases the risk for developing long-term micro- and macrovascular complications.Herein,we report a glucose-responsive oral insulin delivery system based on Fc receptor (FcRn)-targeted liposomes with glucose-sensitive hyaluronic acid (HA) shell for postprandial glycemic regulation.After oral administration,the HA shell can quickly detach in the presence of increasing intestinal glucose concentration due to the competitive binding of glucose with the phenylboronic acid groups conjugated with HA.The exposed Fc groups on the surface of liposomes then facilitate enhanced intestinal absorption in an FcRn-mediated transport pathway.In vivo studies on chemically-induced type 1 diabetic mice show this oral glucose-responsive delivery approach can effectively reduce postprandial blood glucose excursions.This work is the first demonstration of an oral insulin delivery system directly triggered by increasing postprandial glucose concentrations in the intestine to provide an on-demand insulin release with ease of administration.展开更多
Background How the transcriptional factors regulated the innate and adaptive immune system in pregnancy and preeclampsia are less understood.Nevertheless,what the plasma work in the development of this disease was not...Background How the transcriptional factors regulated the innate and adaptive immune system in pregnancy and preeclampsia are less understood.Nevertheless,what the plasma work in the development of this disease was not sure.The present study was design to evaluate what the transcriptional factors change in innate and adaptive immune system and what the plasma do in this filed.Methods Peripheral blood mononuclear cells （PBMC） from non-pregnant women （n=18）,women with clinically normal pregnancies （n=23） and women with pre-eclampsia （n=20） were separated from peripheral blood to isolate monocytes and T cells.The purity of monocytes and T cells were analysed by flow cytometry.Monocytes and T cells were stimulated in either lipopolysaccharides （LPS） or phorbol-myristate-acetate （PMA）,respectively.Transcription Factor Arrays were used to screen the transcription factors of interest in comparing of different groups.PBMC were isolated from another 8 nonpregnant samples were co-incubated with different groups of plasma.Polymerase chain reaction （PCR） was performed using whole cell extractions of the samples.Results Nuclear factor of activated T-cells-1 （NFAT-1）,signal transducers and activators of transcription-1 （STAT-1） and activator protein-1 （AP-1） are up-regulated in monocytes in pregnancy and more so in pre-eclampsia.On the the contrary,NFAT-1,STAT-1 and AP-1 are down-regulated in T cells in pregnancy and more so in pre-eclampsia.A reduction was observed in interferon （IFN）-y,interleukin （IL）-12 and IL-4 expression in T cells incubated with pre-eclamptic plasma.An elevation was observed in tumor necrosis factor （TNF）-α,IL-1 and IL-12 expression in monocytes incubated with preeclamptic plasma.Conclusions Innate immunity is over activated and adaptive immunity is over suppressed in the development of preeclampsia.NFAT-1,STAT-1 and AP-1 might be the central transcription factors in the pathogenesis of pre-eclampsia.They induced some changes in plasma and ＂educate＂ the monocytes and T cells for relevant cytokine production.Successful completion of this study will enhance our understanding of pre-eclampsia and will discover new knowledge beyond pregnancy.The work will inform future therapies for the treatment of a wide range of condition such as transplantation immunology and a wide range of immune and inflammatory conditions.展开更多
基金supported by the grants from NC TraCS,NIHs Clinical and Translational Science Awards (CTSA,NIH grant 1UL1TR001111)the use of the Analytical Instrumentation Facility (AIF) at NC State,which is supported by the State of North Carolina and the National Science Foundation (NSF).
文摘Controlling postprandial glucose levels for diabetic patients is critical to achieve the tight glycemic control that decreases the risk for developing long-term micro- and macrovascular complications.Herein,we report a glucose-responsive oral insulin delivery system based on Fc receptor (FcRn)-targeted liposomes with glucose-sensitive hyaluronic acid (HA) shell for postprandial glycemic regulation.After oral administration,the HA shell can quickly detach in the presence of increasing intestinal glucose concentration due to the competitive binding of glucose with the phenylboronic acid groups conjugated with HA.The exposed Fc groups on the surface of liposomes then facilitate enhanced intestinal absorption in an FcRn-mediated transport pathway.In vivo studies on chemically-induced type 1 diabetic mice show this oral glucose-responsive delivery approach can effectively reduce postprandial blood glucose excursions.This work is the first demonstration of an oral insulin delivery system directly triggered by increasing postprandial glucose concentrations in the intestine to provide an on-demand insulin release with ease of administration.
文摘Background How the transcriptional factors regulated the innate and adaptive immune system in pregnancy and preeclampsia are less understood.Nevertheless,what the plasma work in the development of this disease was not sure.The present study was design to evaluate what the transcriptional factors change in innate and adaptive immune system and what the plasma do in this filed.Methods Peripheral blood mononuclear cells （PBMC） from non-pregnant women （n=18）,women with clinically normal pregnancies （n=23） and women with pre-eclampsia （n=20） were separated from peripheral blood to isolate monocytes and T cells.The purity of monocytes and T cells were analysed by flow cytometry.Monocytes and T cells were stimulated in either lipopolysaccharides （LPS） or phorbol-myristate-acetate （PMA）,respectively.Transcription Factor Arrays were used to screen the transcription factors of interest in comparing of different groups.PBMC were isolated from another 8 nonpregnant samples were co-incubated with different groups of plasma.Polymerase chain reaction （PCR） was performed using whole cell extractions of the samples.Results Nuclear factor of activated T-cells-1 （NFAT-1）,signal transducers and activators of transcription-1 （STAT-1） and activator protein-1 （AP-1） are up-regulated in monocytes in pregnancy and more so in pre-eclampsia.On the the contrary,NFAT-1,STAT-1 and AP-1 are down-regulated in T cells in pregnancy and more so in pre-eclampsia.A reduction was observed in interferon （IFN）-y,interleukin （IL）-12 and IL-4 expression in T cells incubated with pre-eclamptic plasma.An elevation was observed in tumor necrosis factor （TNF）-α,IL-1 and IL-12 expression in monocytes incubated with preeclamptic plasma.Conclusions Innate immunity is over activated and adaptive immunity is over suppressed in the development of preeclampsia.NFAT-1,STAT-1 and AP-1 might be the central transcription factors in the pathogenesis of pre-eclampsia.They induced some changes in plasma and ＂educate＂ the monocytes and T cells for relevant cytokine production.Successful completion of this study will enhance our understanding of pre-eclampsia and will discover new knowledge beyond pregnancy.The work will inform future therapies for the treatment of a wide range of condition such as transplantation immunology and a wide range of immune and inflammatory conditions.
