This article summarized the research progress on the antidepressant mechanism of icariin II,mainly elaborating on its mechanism from five aspects:GABAergic nervous system,inflammatory response,oxidative stress,neurotr...This article summarized the research progress on the antidepressant mechanism of icariin II,mainly elaborating on its mechanism from five aspects:GABAergic nervous system,inflammatory response,oxidative stress,neurotrophic factors,and neurotransmitters in the brain.Its clinical application value was further explored to provide a theoretical basis for the development and utilization of icariin II in treating depression.展开更多
Articular cartilage injury induced by collision or trauma is a common sports-related condition that may progress to pain,dysfunction,and secondary osteoarthritis(OA).Limited by self-renewal potential,cartilage regener...Articular cartilage injury induced by collision or trauma is a common sports-related condition that may progress to pain,dysfunction,and secondary osteoarthritis(OA).Limited by self-renewal potential,cartilage regeneration faces a quandary while bio-inspired novel strategies are urgently required.In this study,by a soft freezing method and surface modification technique,a multi-functional silk fibroin(SF)plus gelatin methacrylate(GelMA)scaffold laden with melatonin(MT)was prepared.SF-GelMA@MT scaffold demonstrated enhanced biomechanical characteristics and long-acting melatonin release.In vitro treatment with SF-GelMA@MT induced the synthesis of cartilage extracellular matrix(ECM)components.Mechanistically,sustained release of melatonin yielded robust chondroprotective effects via improving mitochondrial polarization and antioxidant properties.SF-GelMA@MT implantation boosted cartilage renascence in a full-thickness cartilage defect model via mitochondria-associated sirtuins 1(SIRT1)-superoxide dismutase 2(SOD2)signaling pathway in vivo.In summary,this research proposed a welldesigned bionic composite scaffold that promotes cartilage regeneration via mitochondrial function enhancement,which is of tremendous potential for cartilage tissue engineering.展开更多
Neuroendocrine carcinoma(NEC)of the gallbladder(GB-NEC)is a rare but extremely malignant subtype of gallbladder cancer(GBC).The genetic and molecular signatures of GB-NEC are poorly understood;thus,molecular targeting...Neuroendocrine carcinoma(NEC)of the gallbladder(GB-NEC)is a rare but extremely malignant subtype of gallbladder cancer(GBC).The genetic and molecular signatures of GB-NEC are poorly understood;thus,molecular targeting is currently unavailable.Inthe present study,we applied whole-exome sequencing(WES)technology to detect gene mutations and predicted somatic singlenucleotide variants(SNVs)in 15 cases of GB-NEC and 22 cases of general GBC.in 15 GB-NECs,the C>T mutation was predominantamong the 6 types of SNVs.TP53 showed the highest mutation frequency(73%,11/15).Compared with neuroendocrine carcinomasof other organs,signifcantly mutated genes(SMGs)in GB-NECs were more similar to those in pulmonary large-cell euroendocrinecarcinomas(LCNECs),with drver roles for TP53 and RB1.Iin the COSMIC database of cancer-related genes,211 genes were mutated.Strikingly,RB1(4/15,27%)and NAB2(3/15,20%)mutations were found specifically in GB-NECs;in contrast,mutations in 29 genes,including ERB82 and ERBB3,were identified exclusively in GBC.Mutations in RB1 and NAB2 were significanty related to downregulation of the RB1 and NAB2 proteins,respectively,according to immunohistochemical(IHC)data(p values=0.0453 and0.0303).Clinically actionable genes indicated 23 mutated genes,including ALK,BRCA1,and BRCA2.Iin addition,potential somaticSNVs predicted by ISowN and SomVarlUS constituted 6 primary coSMIC mutation signatures(1,3,30,6,7,and 13)in GB-NEC.Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch,WNT,Hippo,and RTK-RASpathways.In summary,we have systematically identified the mutation landscape of GB-NEC,and these findings may providemechanistic insights into the specifc pathogenesis of this deadly disease.展开更多
Reconstruction of osteochondral(OC)defects represents an immense challenge due to the need for synchronous regeneration of special stratified tissues.The revolutionary innovation of bioprinting provides a robust metho...Reconstruction of osteochondral(OC)defects represents an immense challenge due to the need for synchronous regeneration of special stratified tissues.The revolutionary innovation of bioprinting provides a robust method for precise fabrication of tissue-engineered OCs with hierarchical structure;however,their spatial living cues for simultaneous fulfilment of osteogenesis and chondrogenesis to reconstruct the cartilage-bone interface of OC are underappreciated.Here,inspired by natural OC bilayer features,anisotropic bicellular living hydrogels(ABLHs)simultaneously embedding articular cartilage progenitor cells(ACPCs)and bone mesenchymal stem cells(BMSCs)in stratified layers were precisely fabricated via two-channel extrusion bioprinting.The optimum formulation of the 7%GelMA/3%AlgMA hydrogel bioink was demonstrated,with excellent printability at room temperature and maintained high cell viability.Moreover,the chondrogenic ability of ACPCs and the osteogenic ability of BMSCs were demonstrated in vitro,confirming the inherent differential spatial regulation of ABLHs.展开更多
文摘This article summarized the research progress on the antidepressant mechanism of icariin II,mainly elaborating on its mechanism from five aspects:GABAergic nervous system,inflammatory response,oxidative stress,neurotrophic factors,and neurotransmitters in the brain.Its clinical application value was further explored to provide a theoretical basis for the development and utilization of icariin II in treating depression.
基金supported by the National Natural Science Foundation of China(Nos.82072410,82072476 and 82072442)the Natural Science Foundation of Jiangsu Province(No.BK20220046)+1 种基金the Major Science and Technology Project of Changzhou Health Commission(No.ZD202001)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Articular cartilage injury induced by collision or trauma is a common sports-related condition that may progress to pain,dysfunction,and secondary osteoarthritis(OA).Limited by self-renewal potential,cartilage regeneration faces a quandary while bio-inspired novel strategies are urgently required.In this study,by a soft freezing method and surface modification technique,a multi-functional silk fibroin(SF)plus gelatin methacrylate(GelMA)scaffold laden with melatonin(MT)was prepared.SF-GelMA@MT scaffold demonstrated enhanced biomechanical characteristics and long-acting melatonin release.In vitro treatment with SF-GelMA@MT induced the synthesis of cartilage extracellular matrix(ECM)components.Mechanistically,sustained release of melatonin yielded robust chondroprotective effects via improving mitochondrial polarization and antioxidant properties.SF-GelMA@MT implantation boosted cartilage renascence in a full-thickness cartilage defect model via mitochondria-associated sirtuins 1(SIRT1)-superoxide dismutase 2(SOD2)signaling pathway in vivo.In summary,this research proposed a welldesigned bionic composite scaffold that promotes cartilage regeneration via mitochondrial function enhancement,which is of tremendous potential for cartilage tissue engineering.
基金supported by the National Natural Science Foundation of China(Nos.81902361,31620103910,81874181,91940305,and 81702381)the Shanghai Sailing Program(19YF1433000)+5 种基金the Shanghai Artificial Intelligence Innovation and Development Project(2019-RGZN-01096)the Medical Science and Technology Project of Zhejiang Provincial Health Commission(No.2019334001)the Medical Science and Technology Program of Ningbo(No.2019Y06)the Natural Science Foundation of Ningbo(No.2019A610208)the Shanghai Key Laboratory of Biliary Tract Disease Research Foundation(17DZ2260200)appreciate the support from the Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine(JYKCGZS04).
文摘Neuroendocrine carcinoma(NEC)of the gallbladder(GB-NEC)is a rare but extremely malignant subtype of gallbladder cancer(GBC).The genetic and molecular signatures of GB-NEC are poorly understood;thus,molecular targeting is currently unavailable.Inthe present study,we applied whole-exome sequencing(WES)technology to detect gene mutations and predicted somatic singlenucleotide variants(SNVs)in 15 cases of GB-NEC and 22 cases of general GBC.in 15 GB-NECs,the C>T mutation was predominantamong the 6 types of SNVs.TP53 showed the highest mutation frequency(73%,11/15).Compared with neuroendocrine carcinomasof other organs,signifcantly mutated genes(SMGs)in GB-NECs were more similar to those in pulmonary large-cell euroendocrinecarcinomas(LCNECs),with drver roles for TP53 and RB1.Iin the COSMIC database of cancer-related genes,211 genes were mutated.Strikingly,RB1(4/15,27%)and NAB2(3/15,20%)mutations were found specifically in GB-NECs;in contrast,mutations in 29 genes,including ERB82 and ERBB3,were identified exclusively in GBC.Mutations in RB1 and NAB2 were significanty related to downregulation of the RB1 and NAB2 proteins,respectively,according to immunohistochemical(IHC)data(p values=0.0453 and0.0303).Clinically actionable genes indicated 23 mutated genes,including ALK,BRCA1,and BRCA2.Iin addition,potential somaticSNVs predicted by ISowN and SomVarlUS constituted 6 primary coSMIC mutation signatures(1,3,30,6,7,and 13)in GB-NEC.Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch,WNT,Hippo,and RTK-RASpathways.In summary,we have systematically identified the mutation landscape of GB-NEC,and these findings may providemechanistic insights into the specifc pathogenesis of this deadly disease.
基金This work was supported by grants from the National Key R&D Program of China(Grant Nos.2018YFA0703100 and 2022YFC2502902)the National Nature Science Foundation of China(Grant Nos.82072442,82272494,82072082,32122046,32101102)+3 种基金the Orthopaedic Medical Innovation Center of Jiangsu(CXZX202209)Key Laboratory of Orthopaedics of Suzhou(SZS2022017)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Shenzhen Fundamental Research Foundation(Grant Nos.JSGG20210629144537007,JCYJ20210324115814040,and JCYJ20210324113001005).
文摘Reconstruction of osteochondral(OC)defects represents an immense challenge due to the need for synchronous regeneration of special stratified tissues.The revolutionary innovation of bioprinting provides a robust method for precise fabrication of tissue-engineered OCs with hierarchical structure;however,their spatial living cues for simultaneous fulfilment of osteogenesis and chondrogenesis to reconstruct the cartilage-bone interface of OC are underappreciated.Here,inspired by natural OC bilayer features,anisotropic bicellular living hydrogels(ABLHs)simultaneously embedding articular cartilage progenitor cells(ACPCs)and bone mesenchymal stem cells(BMSCs)in stratified layers were precisely fabricated via two-channel extrusion bioprinting.The optimum formulation of the 7%GelMA/3%AlgMA hydrogel bioink was demonstrated,with excellent printability at room temperature and maintained high cell viability.Moreover,the chondrogenic ability of ACPCs and the osteogenic ability of BMSCs were demonstrated in vitro,confirming the inherent differential spatial regulation of ABLHs.
