PDF(Pubmed)
Abstract：
UNASSIGNED: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively.
UNASSIGNED: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined.
UNASSIGNED: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 μM H2O2 and 200 μg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2.
UNASSIGNED: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.
UNASSIGNED: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined.
UNASSIGNED: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 μM H2O2 and 200 μg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2.
UNASSIGNED: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.
摘要：
■抑制ROS过度产生被认为是治疗周围神经损伤的非常有效的策略，硒具有显著的抗氧化作用；然而，由于硒的有效浓度和毒性剂量之间的差异不大，我们合成了一种可以缓慢释放Se的纳米材料，从而可以更有效地使用。
■Se@SiO2NPs是使用Cu2-xSe纳米晶体的混合物合成的，通过测序初步探索了Se@SiO2NPs的作用机理，细胞实验的免疫荧光染色和蛋白质印迹。Se@SiO2NPs的作用机制通过在动物实验后进行行为测定和通过对材料取样进行组织学染色来进一步确定,免疫荧光染色，和ELISA。的影响，确定了Se@SiO2NPs用于周围神经再生的机制和生物相容性。
■成功合成了多孔Se@SiO2，具有良好的颗粒性质，并能缓慢释放Se。CCK-8实验表明，最佳实验剂量为100μMH2O2和200μg/mLSe@SiO2，RNA-seq表明多孔Se@SiO2与细胞增殖有关，凋亡，和PI3K/AKT途径。WB显示多孔Se@SiO2可以增加细胞增殖抗原（PCNA和S100）和抗凋亡蛋白（Bcl-2）的表达，降低促凋亡蛋白（Bax）的表达，并增加抗氧化应激蛋白（Nrf2，HO-1和SOD2）的表达。EdU细胞增殖和ROS荧光检测显示多孔Se@SiO2促进细胞增殖并降低ROS水平。LY294002(PI3K/AKT途径抑制剂)的治疗效果显著降低,并且当它与多孔Se@SiO2同时添加时,其效果丧失。动物实验表明，再生神经纤维密度，髓鞘厚度,轴突区,腓肠肌湿重比，肌纤维面积,坐骨神经功能指数（SFI），CMAP,凋亡细胞比率，多孔Se@SiO2给药后，抗氧化应激蛋白和抗炎因子水平升高。Se@SiO2组氧化应激蛋白和抗炎因子水平显著高于PNI组,当与多孔Se@SiO2同时添加时，LY294002的效果显着降低，并且消失。
■Se@SiO2NPs很有希望，经济有效的硒释放纳米材料，可以有效减少ROS的产生，通过PI3K/AKT通路抑制神经损伤后细胞凋亡，促进细胞增殖，最终加速神经再生.这些发现可以用来设计新的，有希望的治疗周围神经损伤的药物。
■Se@SiO2NPs是使用Cu2-xSe纳米晶体的混合物合成的，通过测序初步探索了Se@SiO2NPs的作用机理，细胞实验的免疫荧光染色和蛋白质印迹。Se@SiO2NPs的作用机制通过在动物实验后进行行为测定和通过对材料取样进行组织学染色来进一步确定,免疫荧光染色，和ELISA。的影响，确定了Se@SiO2NPs用于周围神经再生的机制和生物相容性。
■成功合成了多孔Se@SiO2，具有良好的颗粒性质，并能缓慢释放Se。CCK-8实验表明，最佳实验剂量为100μMH2O2和200μg/mLSe@SiO2，RNA-seq表明多孔Se@SiO2与细胞增殖有关，凋亡，和PI3K/AKT途径。WB显示多孔Se@SiO2可以增加细胞增殖抗原（PCNA和S100）和抗凋亡蛋白（Bcl-2）的表达，降低促凋亡蛋白（Bax）的表达，并增加抗氧化应激蛋白（Nrf2，HO-1和SOD2）的表达。EdU细胞增殖和ROS荧光检测显示多孔Se@SiO2促进细胞增殖并降低ROS水平。LY294002(PI3K/AKT途径抑制剂)的治疗效果显著降低,并且当它与多孔Se@SiO2同时添加时,其效果丧失。动物实验表明，再生神经纤维密度，髓鞘厚度,轴突区,腓肠肌湿重比，肌纤维面积,坐骨神经功能指数（SFI），CMAP,凋亡细胞比率，多孔Se@SiO2给药后，抗氧化应激蛋白和抗炎因子水平升高。Se@SiO2组氧化应激蛋白和抗炎因子水平显著高于PNI组,当与多孔Se@SiO2同时添加时，LY294002的效果显着降低，并且消失。
■Se@SiO2NPs很有希望，经济有效的硒释放纳米材料，可以有效减少ROS的产生，通过PI3K/AKT通路抑制神经损伤后细胞凋亡，促进细胞增殖，最终加速神经再生.这些发现可以用来设计新的，有希望的治疗周围神经损伤的药物。
