The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic.Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure.The pathoph...The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic.Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure.The pathophysiologic states of hypertension,including obesity,are regulated by the production of adipocytederived factors.Increased body mass index was closely linked to elevated blood pressure.Mostly the hypertensive subjects were obese as well as overweight.There are numerous adipokines,however,this review article only focuses on the major adipokines including chemerin,visfatin,retinol-binding protein 4,plasminogen activator inhibitor-1,monocyte chemotactic protein-1,omentin-1,lipocalin-2,vaspin,progranulin,complement c1q tumor necrosis factor-related protein,and nesfatin-1 role in the pathogenesis of hypertension.This review article concludes the significant association of major adipokines in the pathogenesis of hypertensives.New research should be focused on other newly reported adipokine roles in hypertensive subjects and the management of these adipokines in hypertensive subjects.The discovery of this information could result in the creation of antihypertensive medications,particularly those that focus on obesity-related hypertension.展开更多
Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequ...Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy.There is no single gold standard test that accurately reflects the presence of liver disease,or that can be used to monitor fibrosis progression,particularly in conditions such as cystic fibrosis.This has lead to controversy over how suspected liver disease in children is detected and diagnosed.This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease.In addition,the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.展开更多
Background： Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein- 1 （MCP- 1）. Oxidized low-density lipoprotein （oxLDL） participates in the local chronic in...Background： Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein- 1 （MCP- 1）. Oxidized low-density lipoprotein （oxLDL） participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinftammatory function of αLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L 1 adipocytes induced by oxLDL and to elucidate the possible mechanisms. Methods： Fully differentiated 3T3-L 1 adipocytes were incubated in the medium containing various concentration of L-4F （0-50 gg/ml） with oxLDL （50 Lag/ml） stimulated, with/without protein kinase A （PKA） inhibitor H-89 （10 gmol/L） preincubated. The concentrations of MCP- 1 in the supematant, the mRNA expression of MCP- 1, the levels of CCAAT/enhancer binding protein α （C/EBPα）, and CCAAT/ enhancer binding protein 13 （C/EBPβ） were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber. Results： OxLDL stimulation induced a significant increase ofMCP-1 expression and secretion in 3T3-L 1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F （50 μg/ml） （P 〉 0.05）. OxLDL stimulation showed no significant effect on C/EBPa protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPI3 protein level in oxLDL-induced 3T3-L1 adipocytes. Conclusions： OxLDL induces C/EBPI3 protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L 1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBP-β signaling pathway may participate in it.展开更多
Background Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy...Background Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia. Methods Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay. Results Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preec^ampsia patients. In particular, intedeukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients. Conclusions Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.展开更多
文摘The incidence and prevalence of hypertension are increasing as a consequence of the obesity epidemic.Adipocytes and their variety of factors make contributions to the long-term regulation of blood pressure.The pathophysiologic states of hypertension,including obesity,are regulated by the production of adipocytederived factors.Increased body mass index was closely linked to elevated blood pressure.Mostly the hypertensive subjects were obese as well as overweight.There are numerous adipokines,however,this review article only focuses on the major adipokines including chemerin,visfatin,retinol-binding protein 4,plasminogen activator inhibitor-1,monocyte chemotactic protein-1,omentin-1,lipocalin-2,vaspin,progranulin,complement c1q tumor necrosis factor-related protein,and nesfatin-1 role in the pathogenesis of hypertension.This review article concludes the significant association of major adipokines in the pathogenesis of hypertensives.New research should be focused on other newly reported adipokine roles in hypertensive subjects and the management of these adipokines in hypertensive subjects.The discovery of this information could result in the creation of antihypertensive medications,particularly those that focus on obesity-related hypertension.
基金Supported by a Project Grant from the National Health and Medical Research Council of Australia(NHMRC#496602 to GAR and PJL)Dr.Tamara Pereira is Supported by the Phillip Bushell Foundation Post-Doctoral Research Fellowship from the Gastroenterological Society of AustraliaAssociate Professor Grant A Ramm is Supported by a NHMRC Senior Research Fellowship(NHMRC#552409)
文摘Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy.There is no single gold standard test that accurately reflects the presence of liver disease,or that can be used to monitor fibrosis progression,particularly in conditions such as cystic fibrosis.This has lead to controversy over how suspected liver disease in children is detected and diagnosed.This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease.In addition,the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30470705 and No. 81270154）.
文摘Background： Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein- 1 （MCP- 1）. Oxidized low-density lipoprotein （oxLDL） participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinftammatory function of αLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L 1 adipocytes induced by oxLDL and to elucidate the possible mechanisms. Methods： Fully differentiated 3T3-L 1 adipocytes were incubated in the medium containing various concentration of L-4F （0-50 gg/ml） with oxLDL （50 Lag/ml） stimulated, with/without protein kinase A （PKA） inhibitor H-89 （10 gmol/L） preincubated. The concentrations of MCP- 1 in the supematant, the mRNA expression of MCP- 1, the levels of CCAAT/enhancer binding protein α （C/EBPα）, and CCAAT/ enhancer binding protein 13 （C/EBPβ） were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber. Results： OxLDL stimulation induced a significant increase ofMCP-1 expression and secretion in 3T3-L 1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F （50 μg/ml） （P 〉 0.05）. OxLDL stimulation showed no significant effect on C/EBPa protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPI3 protein level in oxLDL-induced 3T3-L1 adipocytes. Conclusions： OxLDL induces C/EBPI3 protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L 1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBP-β signaling pathway may participate in it.
基金This study was supported by grants from the National Natural Science Foundation of China，Science and Technology Bureau of Sichuan Province，Science and Technology Development of Chengdu City
文摘Background Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia. Methods Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay. Results Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preec^ampsia patients. In particular, intedeukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients. Conclusions Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.
