目的探讨维生素D受体（VDR）基因多态性与T1DM易感性的关系。方法通过检索PubMed、Web of Science、WanFang等数据库获得相关文献,计算相关基因位点的OR值和95%CI。结果共纳入文献28条。分析结果发现,BsmI和ApaI多态性是亚洲T1DM人群的...目的探讨维生素D受体（VDR）基因多态性与T1DM易感性的关系。方法通过检索PubMed、Web of Science、WanFang等数据库获得相关文献,计算相关基因位点的OR值和95%CI。结果共纳入文献28条。分析结果发现,BsmI和ApaI多态性是亚洲T1DM人群的易感基因[B vs b：OR（95%CI）=1.53（1.06-2.20）,P=0.024;AAvs aa：OR（95%CI）=1.60（1.06-2.40）,P=0.023]。结论 BsmI和ApaI多态性可能是亚洲T1DM人群的易感基因。展开更多
An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism.Hepatic fibrosis is characterized by activated hepatic stellate cells(aHSCs)with an excessive productio...An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism.Hepatic fibrosis is characterized by activated hepatic stellate cells(aHSCs)with an excessive production of extracellular matrix.Although promoted activation of HSCs by M2 macrophages has been demonstrated,the molecular mechanism involved remains ambiguous.Herein,we propose that the vitamin D receptor(VDR)involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes.We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation.The exosomes derived from M2 macrophages can promote HSC activation,while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes.Smooth muscle cell-associated protein 5(SMAP-5)was found to be the key effector protein in promoting HSC activation by regulating autophagy flux.Building on these results,we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect.In this study,we aim to elucidate the association between VDR and macrophages in HSC activation.The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis,and provide potential therapeutic targets for its treatment.展开更多
Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,...Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,serum 25-hydroxy vitamin D,metabolic and inflammatory biomarkers in Egyptian obese women.The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels.Their age ranged between 25 and 35 years.Inflammatory biomarkers(interleukin-6 and C-reactive protein)and serum 25(OH)D were measured by enzyme-linked immunosorbent assay.Insulin resistance(IR)was determined by the homeostasis model assessment of insulin resistance(HOMA-IR).Vitamin D receptor(VDR)gene polymorphisms of FokI,ApaI,and TaqI were studied by PCR using the restriction fragment length polymorphism(RFLP)technique.Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls.Multivariable-logistic regression showed associations between 25(OH)D deficiency and metabolic components when comparing cases with controls.Moreover,cases carrying polymorphic alleles showed significant lower levels of serum 25(OH)D and higher HOMA-IR,blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency.Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers.Moreover,VDR polymorphisms play important role in immune and inflammation status.展开更多
文摘目的探讨维生素D受体（VDR）基因多态性与T1DM易感性的关系。方法通过检索PubMed、Web of Science、WanFang等数据库获得相关文献,计算相关基因位点的OR值和95%CI。结果共纳入文献28条。分析结果发现,BsmI和ApaI多态性是亚洲T1DM人群的易感基因[B vs b：OR（95%CI）=1.53（1.06-2.20）,P=0.024;AAvs aa：OR（95%CI）=1.60（1.06-2.40）,P=0.023]。结论 BsmI和ApaI多态性可能是亚洲T1DM人群的易感基因。
基金supported by the National Natural Science Foundation of China(Nos.81930099,81773664,82130102,92159304,81703585,and 81903651)the Natural Science Foundation of Jiangsu Province(Nos.BK20212011 and BK20180565)+4 种基金the Technology Innovation Project of Nucleic Acid Drug from National Center of Technology Innovation for Biopharmaceuticals(No.NCTIB2022HS01014)the“Double First-Class”University Project(No.CPU2022QZ05)the 111 Project from the Ministry of Education of China and the State Administration of Foreign Expert Affairs of China(Nos.111-2-07 and B17047)the Fundamental Research Funds for the Central Universities of China(No.2632022ZD11)the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZ202017),China.
文摘An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism.Hepatic fibrosis is characterized by activated hepatic stellate cells(aHSCs)with an excessive production of extracellular matrix.Although promoted activation of HSCs by M2 macrophages has been demonstrated,the molecular mechanism involved remains ambiguous.Herein,we propose that the vitamin D receptor(VDR)involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes.We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation.The exosomes derived from M2 macrophages can promote HSC activation,while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes.Smooth muscle cell-associated protein 5(SMAP-5)was found to be the key effector protein in promoting HSC activation by regulating autophagy flux.Building on these results,we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect.In this study,we aim to elucidate the association between VDR and macrophages in HSC activation.The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis,and provide potential therapeutic targets for its treatment.
基金This work was supported by grant from National Research Centre,Egypt(16361).
文摘Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,serum 25-hydroxy vitamin D,metabolic and inflammatory biomarkers in Egyptian obese women.The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels.Their age ranged between 25 and 35 years.Inflammatory biomarkers(interleukin-6 and C-reactive protein)and serum 25(OH)D were measured by enzyme-linked immunosorbent assay.Insulin resistance(IR)was determined by the homeostasis model assessment of insulin resistance(HOMA-IR).Vitamin D receptor(VDR)gene polymorphisms of FokI,ApaI,and TaqI were studied by PCR using the restriction fragment length polymorphism(RFLP)technique.Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls.Multivariable-logistic regression showed associations between 25(OH)D deficiency and metabolic components when comparing cases with controls.Moreover,cases carrying polymorphic alleles showed significant lower levels of serum 25(OH)D and higher HOMA-IR,blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency.Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers.Moreover,VDR polymorphisms play important role in immune and inflammation status.
