The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,sp...The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.展开更多
目的探讨mi R-26a在乳腺癌组织和细胞中表达量的改变及其对人乳腺癌细胞增殖和侵袭的影响。方法采用实时荧光定量PCR(Real-time PCR)法检测20例患者乳腺癌组织及对应的癌旁组织、人乳腺癌细胞MCF-7、BT474及健康者乳腺细胞MCF-10A中mi R...目的探讨mi R-26a在乳腺癌组织和细胞中表达量的改变及其对人乳腺癌细胞增殖和侵袭的影响。方法采用实时荧光定量PCR(Real-time PCR)法检测20例患者乳腺癌组织及对应的癌旁组织、人乳腺癌细胞MCF-7、BT474及健康者乳腺细胞MCF-10A中mi R-26a的表达,用Western bolt法检测COX-2的表达。MCF-7及BT474细胞分别转染mi R-NC和mi R-26a,采用Western blot法检测转染后细胞中COX-2的表达水平,同时采用CCK-8和克隆形成实验检测转染后细胞的增殖和侵袭情况。结果mi R-26a在乳腺癌组织中的表达明显低于癌旁组织(t=20.33,P=0.001),在MCF-7和BT474细胞中的表达明显低于MCF-10A细胞(Dunnett t test I-J=-0.031,P=0.001)。COX-2在乳腺癌组织和细胞中的表达明显高于癌旁组织(t=18.01,P=0.002)和健康者乳腺细胞(Dunnett t test I-J=-0.028,P=0.000)。转染mi R-26a后,乳腺癌细胞内COX-2的表达量显著下调。CCK-8和克隆形成实验结果显示,过表达mi R-26a能明显抑制乳腺癌细胞的增殖(F=6.032,P=0.013)和侵袭(Dunnett t test I-J=-0.21,P=0.037)。结论过表达mi R-26a可以通过下调乳腺癌细胞中COX-2的表达,抑制乳腺癌细胞的增殖和侵袭。展开更多
基金the Natural Science Foundation of China(Grant Nos.82072413,82101649)National Key Research and Development Program of China(Grant Nos.2021YFE0105400).
文摘The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.
文摘目的探讨mi R-26a在乳腺癌组织和细胞中表达量的改变及其对人乳腺癌细胞增殖和侵袭的影响。方法采用实时荧光定量PCR(Real-time PCR)法检测20例患者乳腺癌组织及对应的癌旁组织、人乳腺癌细胞MCF-7、BT474及健康者乳腺细胞MCF-10A中mi R-26a的表达,用Western bolt法检测COX-2的表达。MCF-7及BT474细胞分别转染mi R-NC和mi R-26a,采用Western blot法检测转染后细胞中COX-2的表达水平,同时采用CCK-8和克隆形成实验检测转染后细胞的增殖和侵袭情况。结果mi R-26a在乳腺癌组织中的表达明显低于癌旁组织(t=20.33,P=0.001),在MCF-7和BT474细胞中的表达明显低于MCF-10A细胞(Dunnett t test I-J=-0.031,P=0.001)。COX-2在乳腺癌组织和细胞中的表达明显高于癌旁组织(t=18.01,P=0.002)和健康者乳腺细胞(Dunnett t test I-J=-0.028,P=0.000)。转染mi R-26a后,乳腺癌细胞内COX-2的表达量显著下调。CCK-8和克隆形成实验结果显示,过表达mi R-26a能明显抑制乳腺癌细胞的增殖(F=6.032,P=0.013)和侵袭(Dunnett t test I-J=-0.21,P=0.037)。结论过表达mi R-26a可以通过下调乳腺癌细胞中COX-2的表达,抑制乳腺癌细胞的增殖和侵袭。
