Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alve-olar bone defects remains a great challenge.Macrophages are necessary for alveolar bone regeneration via their polari...Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alve-olar bone defects remains a great challenge.Macrophages are necessary for alveolar bone regeneration via their polarization and paracrine actions.Our previous studies showed that Cu-bearing Ti6AI4V alloys are capable of regulating macrophage responses.When considering the complexity of oral microenvir-onments,the influences of Cu-bearing Ti6AI4V alloys on osteoporotic macrophages in infectious microenvironments are worthy of further investigations.In this study,we fabricated Ti6AI4V-Cu alloy by selective laser melting technology and used Porphyromonas gingivalis lipopolysaccharide(P.g-LPS)to imitate oral pathogenic bacterial infections.Then,we evaluated the impacts of T6AI4V-Cu on osteoporotic macrophages in infectious microenvironments.Our results indicated that Ti6AI4V-Cu not only inhibited the P.g-LPS-induced M1 polarization and pro-inflammatory cytokine production of osteoporotic macrophages but also shifted polarization towards the pro-regenerative M2 phenotype and remarkably promoted antinflammatory cytokine release.In addition,T6AI4V-Cu effectively promoted the actity of COMMD1 to potentially repress NF-κB-mediated transcription.It is concluded that the Cubearing Ti6AI4V alloy results in ameliorated osteoporotic macrophage responses to create a favourable microenvironment under infectious conditions,which holds promise to develop a GBR-barrier membrane for alveolar bone regeneration of osteoporosis patients.展开更多
文摘寨卡病毒(Zika virus,ZIKV)是一种蚊媒黄病毒,也可通过性传播,同时还能感染睾丸组织并导致损伤.探究寨卡病毒在睾丸内持续复制过程中病毒基因的变化规律,发现潜在的睾丸适应性突变位点,可为寨卡病毒变异的风险评估提供重要参考.为此,本研究以寨卡病毒株FSS13025为研究对象,通过将其在A129小鼠睾丸中连续传代10轮后获得适应性传代毒株,将原始株(WT)、第5代(P5)和第10代(P10)病毒经腹腔接种A129小鼠后发现,睾丸中P5和P10的RNA载量较WT分别提高4.6和3.8倍;进一步通过深度测序分析P5和P10的基因组变异情况,结果显示二者的包膜蛋白(envelope,E)和非结构蛋白1(nonstructural protein 1,NS1)分别出现H401Y和K146E突变.在此基础上,以寨卡病毒FSS13025株为基因骨架,利用反向遗传学技术构建拯救携带上述突变的重组病毒H401Y+K146E,并评价其在细胞和小鼠体内的复制能力,结果显示病毒感染睾丸细胞15P-1和TM3后第48 h,细胞培养上清中的重组病毒RNA含量分别是WT的5.2和2.1倍;经腹腔途径感染A129小鼠后的第3和6天,睾丸中重组病毒RNA载量较WT分别提高97.5和58.4倍.上述结果表明,H401Y+K146E联合突变显著增强了寨卡病毒在睾丸细胞中的复制能力,同时明显提升了其对睾丸的嗜性和侵袭力,上述位点可作为寨卡病毒变异风险预警的监测靶点.
基金This study was supported by National Natural Science Foundation of China(Grant No.81870766,51801198)the Science Foundation of Fujian Province(Grant No.2017J01805)+1 种基金Joint Funds for the Innovation of Sciences and Technology,Fujian Province(Grant No.2016Y9023)Startup Fund for scientific research,Fujian Medical University(Grant No.2019QH2041).
文摘Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alve-olar bone defects remains a great challenge.Macrophages are necessary for alveolar bone regeneration via their polarization and paracrine actions.Our previous studies showed that Cu-bearing Ti6AI4V alloys are capable of regulating macrophage responses.When considering the complexity of oral microenvir-onments,the influences of Cu-bearing Ti6AI4V alloys on osteoporotic macrophages in infectious microenvironments are worthy of further investigations.In this study,we fabricated Ti6AI4V-Cu alloy by selective laser melting technology and used Porphyromonas gingivalis lipopolysaccharide(P.g-LPS)to imitate oral pathogenic bacterial infections.Then,we evaluated the impacts of T6AI4V-Cu on osteoporotic macrophages in infectious microenvironments.Our results indicated that Ti6AI4V-Cu not only inhibited the P.g-LPS-induced M1 polarization and pro-inflammatory cytokine production of osteoporotic macrophages but also shifted polarization towards the pro-regenerative M2 phenotype and remarkably promoted antinflammatory cytokine release.In addition,T6AI4V-Cu effectively promoted the actity of COMMD1 to potentially repress NF-κB-mediated transcription.It is concluded that the Cubearing Ti6AI4V alloy results in ameliorated osteoporotic macrophage responses to create a favourable microenvironment under infectious conditions,which holds promise to develop a GBR-barrier membrane for alveolar bone regeneration of osteoporosis patients.
