The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatme...The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of diseases.thioesterase superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding proteins.Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation.Initially,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous findings.Considering these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially cancer.This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.展开更多
Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace...Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.展开更多
Induced pluripotent stem cells(iPSCs)can be personalized and differentiated into neural stem cells(NSCs),thereby effectively providing a source of transplanted cells for spinal cord injury(SCI).To further improve the ...Induced pluripotent stem cells(iPSCs)can be personalized and differentiated into neural stem cells(NSCs),thereby effectively providing a source of transplanted cells for spinal cord injury(SCI).To further improve the repair efficiency of SCI,we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold(LOCS).We confirmed that transplantation of this tissue regenerated neurons and synapses,improved the microenvironment of the injured area,enhanced remodeling of the extracellular matrix,and promoted functional recovery of the hind limbs in a rat SCI model with complete transection.RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI.Together,we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time.This tissue can effectively improve the therapeutic effect of SCI,thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.展开更多
Since the acceptance and publication of this article1,the authors opted to change the order of authors in the author group.The correct order of authors is:Yuanbo Kang,Weihan He,Caiping Ren,Jincheng Qiao,Qiuyong Guo,Ca...Since the acceptance and publication of this article1,the authors opted to change the order of authors in the author group.The correct order of authors is:Yuanbo Kang,Weihan He,Caiping Ren,Jincheng Qiao,Qiuyong Guo,Caiping Ren,Jingyu Hu,Hongjuan Xu,Xingjun Jiang1 and Lei Wang This has been corrected in the original version.展开更多
Nasopharyngeal carcinoma(NPC)is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus.Bas...Nasopharyngeal carcinoma(NPC)is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus.Based on epidemiological data,both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region,in particular,with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy(IMRT)which profoundly contributes to the cure rate of NPC patients.To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment,we discussed the implication of using targeted therapy against critical molecules in various signal pathways,and how they synergize with chemoradiotherapy in the NPC treatment.Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options,which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82071399 and 81773179)the Key Research and Development Program of Hunan Province(No.2022SK2055)the Natural Science Foundation of Hunan Province(No.2023JJ30733),China.
文摘The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of diseases.thioesterase superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding proteins.Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation.Initially,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous findings.Considering these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially cancer.This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.
基金supported by the National Natural Science Foundation of China(81891002 and 81971178)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16040700)the National Key Research and Development Program of China(2017YFA0104701,2017YFA0104704,2016YFC1101501 and 2016YFC1101502)。
文摘Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.
基金supported by the National Natural Science Foundation of China(82071399)National Key Research and Development Program of China(2023YFC2412504,2016YFC1101502)Key Research and Development Program of Hunan Province(2021DK2003,2021SK2016).
文摘Induced pluripotent stem cells(iPSCs)can be personalized and differentiated into neural stem cells(NSCs),thereby effectively providing a source of transplanted cells for spinal cord injury(SCI).To further improve the repair efficiency of SCI,we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold(LOCS).We confirmed that transplantation of this tissue regenerated neurons and synapses,improved the microenvironment of the injured area,enhanced remodeling of the extracellular matrix,and promoted functional recovery of the hind limbs in a rat SCI model with complete transection.RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI.Together,we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time.This tissue can effectively improve the therapeutic effect of SCI,thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.
文摘Since the acceptance and publication of this article1,the authors opted to change the order of authors in the author group.The correct order of authors is:Yuanbo Kang,Weihan He,Caiping Ren,Jincheng Qiao,Qiuyong Guo,Caiping Ren,Jingyu Hu,Hongjuan Xu,Xingjun Jiang1 and Lei Wang This has been corrected in the original version.
基金supported by the National Natural Science Foundation of China(grant nos.81773179 and 81272972(C.R.),and grant no.81472355(X.J.))the Provincial Natural Science Foundation of Hunan(grant nos.2020JJ4771,2016JJ2172(W.L.))+3 种基金the National Basic Research Program of China(2010CB833605(C.R.))the Program for New Century Excellent Talents in University(NCET-10-0790(C.R.))the Hunan Provincial Science and Technology Department(grant nos.2016JC2049(C.R.),2014FJ6006(X.J.))the Undergraduate Training Programs for Innovation and Entrepreneurship(UTPIE,S2020105330083(Y.K.)).
文摘Nasopharyngeal carcinoma(NPC)is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus.Based on epidemiological data,both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region,in particular,with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy(IMRT)which profoundly contributes to the cure rate of NPC patients.To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment,we discussed the implication of using targeted therapy against critical molecules in various signal pathways,and how they synergize with chemoradiotherapy in the NPC treatment.Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options,which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.
