目的探讨SOX2基因对人骨关节炎(OA)软骨细胞凋亡的影响及机制。方法以正常软骨组织作为对照,通过Western blotting检测OA软骨组织SOX2蛋白表达。从人OA中分离软骨细胞,参照Lipofectamine^(TM)2000说明将重组体pcDNA3.1-SOX2及空载体pcDN...目的探讨SOX2基因对人骨关节炎(OA)软骨细胞凋亡的影响及机制。方法以正常软骨组织作为对照,通过Western blotting检测OA软骨组织SOX2蛋白表达。从人OA中分离软骨细胞,参照Lipofectamine^(TM)2000说明将重组体pcDNA3.1-SOX2及空载体pcDNA3.1转染软骨细胞,并设置空白对照组。AG490作为JAK2/STAT3信号通路抑制剂,各组细胞处理48 h,通过流式细胞术、ROS试剂盒分别检测各组细胞凋亡率及ROS水平。Western blotting检测JAK2、p-JAK2、STAT3和p-STAT3的蛋白相对表达量。结果人OA软骨组织SOX2表达明显低于在正常软骨组织表达(0.065±0.009 vs 0.313±0.028,P<0.05)。转染pcDNA3.1-SOX2的OA软骨细胞SOX2表达明显高于空白组(0.556±0.048 vs 0.122±0.013,P<0.05)。pcDNA3.1-SOX2可明显降低OA软骨细胞凋亡率(3.11±0.42 vs 8.54±0.68)及ROS水平(23.46±2.15 vs 52.67±4.41),上调p-JAK2(0.142±0.013 vs 0.065±0.009)和p-STAT3表达(0.218±0.020 vs 0.126±0.015)(P<0.05),AG490(15.23±1.13 vs 8.15±0.62)可诱导OA软骨细胞凋亡,而pcDNA3.1-SOX2可减弱AG490对OA软骨细胞凋亡促进作用(P<0.05)。结论SOX2可抑制OA软骨细胞凋亡,其机制可能与激活JAK2/STAT3信号通路有关。展开更多
Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The ...Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs,thereby leading to CSC-mediated clinical relapse.Accumulating evidence suggests that transcription factor SOX2,a master regulator of embryonic and induced pluripotent stem cells,drives cancer stemness,fuels tumor initiation,and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition,ATP-binding cassette drug transporters,anti-apoptotic and/or pro-survival signaling,lineage plasticity,and evasion of immune surveillance.Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.展开更多
High energy density and low-cost lithium-sulfur batteries have been considered as one of the most promising candidates for next-generation energy storage systems.However,the intrinsic problems of the sulfur cathode se...High energy density and low-cost lithium-sulfur batteries have been considered as one of the most promising candidates for next-generation energy storage systems.However,the intrinsic problems of the sulfur cathode severely restrict their further practical application.Here,a unique double-shell architecture composed of hollow carbon spheres@interlayer-expanded and sulfur-enriched MoS2+x nanocoating composite has been developed as an efficient sulfur host.A uniform precursor coating derived from heteropolyanions-induced polymerization of pyrrole leads to space confinement effect during the in-situ sulfurization process,which generates the interlayer-expanded and sulfur-enriched MoS2+x nanosheets on amorphous carbon hollow spheres.This new sulfur host possesses multifarious merits including sufficient voids for loading sulfur active materials,high electronic conductivity,and fast lithium-ion diffusive pathways.In addition,additional active edge sites of MoS2+x accompanied by the nitrogen-doped carbon species endow the sulfur host with immobilizing and catalyzing effects on the soluble polysulfide species,dramatically accelerating their conversion kinetics and re-utilization.The detailed defect-induced interface catalytic reaction mechanism is firstly proposed.As expected,the delicately-designed sulfur host exhibits an outstanding initial discharge capacity of 1,249 mAh·g^−1 at 0.2 C and a desirable rate performance(593 mAh·g^−1 at 5.0 C),implying its great prospects in achieving superior electrochemical performances for advanced lithium sulfur batteries.展开更多
文摘目的探讨SOX2基因对人骨关节炎(OA)软骨细胞凋亡的影响及机制。方法以正常软骨组织作为对照,通过Western blotting检测OA软骨组织SOX2蛋白表达。从人OA中分离软骨细胞,参照Lipofectamine^(TM)2000说明将重组体pcDNA3.1-SOX2及空载体pcDNA3.1转染软骨细胞,并设置空白对照组。AG490作为JAK2/STAT3信号通路抑制剂,各组细胞处理48 h,通过流式细胞术、ROS试剂盒分别检测各组细胞凋亡率及ROS水平。Western blotting检测JAK2、p-JAK2、STAT3和p-STAT3的蛋白相对表达量。结果人OA软骨组织SOX2表达明显低于在正常软骨组织表达(0.065±0.009 vs 0.313±0.028,P<0.05)。转染pcDNA3.1-SOX2的OA软骨细胞SOX2表达明显高于空白组(0.556±0.048 vs 0.122±0.013,P<0.05)。pcDNA3.1-SOX2可明显降低OA软骨细胞凋亡率(3.11±0.42 vs 8.54±0.68)及ROS水平(23.46±2.15 vs 52.67±4.41),上调p-JAK2(0.142±0.013 vs 0.065±0.009)和p-STAT3表达(0.218±0.020 vs 0.126±0.015)(P<0.05),AG490(15.23±1.13 vs 8.15±0.62)可诱导OA软骨细胞凋亡,而pcDNA3.1-SOX2可减弱AG490对OA软骨细胞凋亡促进作用(P<0.05)。结论SOX2可抑制OA软骨细胞凋亡,其机制可能与激活JAK2/STAT3信号通路有关。
基金This work is supported by the National Key Scientific Program of China(2016YFA0100502)M.A.M.is a recipient of the CASTWAS President’s Fellowship.X.S.is a recipient of the 1000 Talents Plan Professorship for Young Talents(KJ2070000026).
文摘Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs,thereby leading to CSC-mediated clinical relapse.Accumulating evidence suggests that transcription factor SOX2,a master regulator of embryonic and induced pluripotent stem cells,drives cancer stemness,fuels tumor initiation,and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition,ATP-binding cassette drug transporters,anti-apoptotic and/or pro-survival signaling,lineage plasticity,and evasion of immune surveillance.Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.
基金The work was financially supported by the National Natural Science Foundation of China(Nos.51672146 and 21805157)the Natural Science Foundation of Shandong Province(No.ZR2018BEM011).
文摘High energy density and low-cost lithium-sulfur batteries have been considered as one of the most promising candidates for next-generation energy storage systems.However,the intrinsic problems of the sulfur cathode severely restrict their further practical application.Here,a unique double-shell architecture composed of hollow carbon spheres@interlayer-expanded and sulfur-enriched MoS2+x nanocoating composite has been developed as an efficient sulfur host.A uniform precursor coating derived from heteropolyanions-induced polymerization of pyrrole leads to space confinement effect during the in-situ sulfurization process,which generates the interlayer-expanded and sulfur-enriched MoS2+x nanosheets on amorphous carbon hollow spheres.This new sulfur host possesses multifarious merits including sufficient voids for loading sulfur active materials,high electronic conductivity,and fast lithium-ion diffusive pathways.In addition,additional active edge sites of MoS2+x accompanied by the nitrogen-doped carbon species endow the sulfur host with immobilizing and catalyzing effects on the soluble polysulfide species,dramatically accelerating their conversion kinetics and re-utilization.The detailed defect-induced interface catalytic reaction mechanism is firstly proposed.As expected,the delicately-designed sulfur host exhibits an outstanding initial discharge capacity of 1,249 mAh·g^−1 at 0.2 C and a desirable rate performance(593 mAh·g^−1 at 5.0 C),implying its great prospects in achieving superior electrochemical performances for advanced lithium sulfur batteries.
