Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as ...Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.展开更多
目的探讨小鼠心肌梗死进程中巨噬细胞亚群的动态变化与CD59、P2X7表达的动态变化。方法将成年雄性C57BL/6J小鼠36只随机分为对照组(不做任何处理,6只)和心肌梗死组(30只)。通过冠状动脉左前降支结扎建立小鼠急性心肌梗死模型,心肌梗死...目的探讨小鼠心肌梗死进程中巨噬细胞亚群的动态变化与CD59、P2X7表达的动态变化。方法将成年雄性C57BL/6J小鼠36只随机分为对照组(不做任何处理,6只)和心肌梗死组(30只)。通过冠状动脉左前降支结扎建立小鼠急性心肌梗死模型,心肌梗死组30只小鼠又随机分为A、B、C、D、E组,分别在心肌梗死后1、3、5、7、14 d取材。收取小鼠的外周血和心脏组织,采用流式细胞术检测巨噬细胞亚群的动态变化与CD59和P2X7的表达情况。结果心肌梗死后1、3 d外周血中单核细胞数量均高于对照组[(9.5±1.7)、(10.3±3.7)×10^(4)/ml比(3.2±3.1)×10^(4)/ml](均P<0.05)。心肌梗死后1、3、5 d心脏组织白细胞计数、巨噬细胞计数均高于对照组(均P<0.05)。心脏组织中Ly6C^(high)巨噬细胞计数在心肌梗死后3 d达到高峰,而Ly6C^(low)亚群在心肌梗死后5 d达到高峰,均高于对照组(均P<0.05)。心肌梗死后1 d P2X7^(-)CD59^(-)巨噬细胞占Ly6C^(high)巨噬细胞百分比高于对照组,而P2X7^(+)CD59^(+)巨噬细胞占比低于对照组(均P<0.05)。心肌梗死后1、3、5 d P2X7^(+)CD59^(+)巨噬细胞占Ly6C^(low)巨噬细胞百分比均低于对照组,而P2X7^(-)CD59^(+)巨噬细胞占比均高于对照组(均P<0.05)。结论在小鼠急性心肌梗死的不同阶段,心脏组织巨噬细胞的亚群呈现动态变化,同时伴随CD59和P2X7表达的动态变化。展开更多
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean Government(the Ministry of Science and ICT(MSIT))(No.2021R1A2C2006013)the Bio&Medical Technology Development Program of the NRF funded by the Korean government(MSIT)(No.RS-2023-00223591)the Korea Medical Device Development Fund grant funded by the Korean government(the MSIT,the MOTIE,the Ministry of Health and Welfare,the Ministry of Food and Drug Safety)(NTIS Number:9991006781,KMDF_PR_(2)0200901_0108)。
文摘Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.
文摘目的探讨小鼠心肌梗死进程中巨噬细胞亚群的动态变化与CD59、P2X7表达的动态变化。方法将成年雄性C57BL/6J小鼠36只随机分为对照组(不做任何处理,6只)和心肌梗死组(30只)。通过冠状动脉左前降支结扎建立小鼠急性心肌梗死模型,心肌梗死组30只小鼠又随机分为A、B、C、D、E组,分别在心肌梗死后1、3、5、7、14 d取材。收取小鼠的外周血和心脏组织,采用流式细胞术检测巨噬细胞亚群的动态变化与CD59和P2X7的表达情况。结果心肌梗死后1、3 d外周血中单核细胞数量均高于对照组[(9.5±1.7)、(10.3±3.7)×10^(4)/ml比(3.2±3.1)×10^(4)/ml](均P<0.05)。心肌梗死后1、3、5 d心脏组织白细胞计数、巨噬细胞计数均高于对照组(均P<0.05)。心脏组织中Ly6C^(high)巨噬细胞计数在心肌梗死后3 d达到高峰,而Ly6C^(low)亚群在心肌梗死后5 d达到高峰,均高于对照组(均P<0.05)。心肌梗死后1 d P2X7^(-)CD59^(-)巨噬细胞占Ly6C^(high)巨噬细胞百分比高于对照组,而P2X7^(+)CD59^(+)巨噬细胞占比低于对照组(均P<0.05)。心肌梗死后1、3、5 d P2X7^(+)CD59^(+)巨噬细胞占Ly6C^(low)巨噬细胞百分比均低于对照组,而P2X7^(-)CD59^(+)巨噬细胞占比均高于对照组(均P<0.05)。结论在小鼠急性心肌梗死的不同阶段,心脏组织巨噬细胞的亚群呈现动态变化,同时伴随CD59和P2X7表达的动态变化。
文摘【目的】研究连翘叶提取物(Forsythia suspensa leaves extract,FSLE)对孕马血清促性腺激素(pregnant mare serum gonadotropin,PMSG)在肝脏中代谢的影响,改善在畜牧生产中因PMSG代谢缓慢而造成的氧化应激。【方法】采用半仿生酶醇法提取连翘叶有效成分,给予昆明雌鼠不同含量的FSLE进行动物体内试验;收集小鼠血清,进行酶联免疫吸附试验,检测各组小鼠血清中PMSG的质量浓度;采集小鼠肝脏组织,检测氧化应激指标谷胱甘肽、超氧化物歧化酶、丙二醛和过氧化氢的水平;采用Western-blot检测小鼠肝脏组织孕烷X受体(pregnane X receptor,PXR)和细胞色素酶P45017A1(cytochrome P45017A1,CYP17A1)蛋白的表达水平。【结果】FSLE可显著降低小鼠血清中PMSG的质量浓度,且可以减缓PMSG代谢引起的氧化应激。Western-blot结果显示:FSLE可显著下调小鼠肝组织中PXR和CYP17A1蛋白的表达。【结论】连翘叶提取物可能是通过下调肝脏中PXR和CYP17A1的表达减缓PMSG代谢引起的氧化应激。
