Following injury,tissue autonomously initiates a complex repair process,resulting in either partial recovery or regeneration of tissue architecture and function in most organisms.Both the repair and regeneration proce...Following injury,tissue autonomously initiates a complex repair process,resulting in either partial recovery or regeneration of tissue architecture and function in most organisms.Both the repair and regeneration processes are highly coordinated by a hierarchy of interplay among signal transduction pathways initiated by different growth factors,cytokines and other signaling molecules under normal conditions.However,under chronic traumatic or pathological conditions,the reparative or regenerative process of most tissues in different organs can lose control to different extents,leading to random,incomplete or even flawed cell and tissue reconstitution and thus often partial restoration of the original structure and function,accompanied by the development of fibrosis,scarring or even pathogenesis that could cause organ failure and death of the organism.Ample evidence suggests that the various combinatorial fibroblast growth factor(FGF)and receptor signal transduction systems play prominent roles in injury repair and the remodeling of adult tissues in addition to embryonic development and regulation of metabolic homeostasis.In this review,we attempt to provide a brief update on our current understanding of the roles,the underlying mechanisms and clinical application of FGFs in tissue injury repair.展开更多
Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult ne...Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.展开更多
Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in allevia...Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart diseases.However,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity.Here,an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction(MI)model.As shown in our echocardiographic results,a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI.It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment.Furthermore,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells.However,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long term.On another hand,FGF10 coacervate also increased the expression of cardiac-associated the mRNA(cTnT,Cx43 and α-SMA),angiogenic factors(Ang-1 and VEGFA)and decreased the level of inflammatory factor(tumor necrosis factor-α).The downstream signaling of the FGF10 was also investigated,with the western blot results showing that FGF10 coacervate activated the p-FGFR,PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10.In general,it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.展开更多
Adsorption of low-density lipoprotein from plasma is vital for the treatment of dyslipidemia.Appropriate adsorbent material for efficient and selective adsorption of low-density lipoprotein is highly desired.In this w...Adsorption of low-density lipoprotein from plasma is vital for the treatment of dyslipidemia.Appropriate adsorbent material for efficient and selective adsorption of low-density lipoprotein is highly desired.In this work,we developed pollens-derived magnetic porous particles as adsorbents for this purpose.The natural pollen grains were modified to obtain high surface porosity,a large inner cavity,magnet responsiveness,and specific wettability.The resultant particles exhibited satisfying performance in the adsorption of a series of oils and organic solvents out of water.Besides,the particles were directly utilized to the adsorption of low-density lipoprotein in plasma,which showed high selectivity,and achieved an outstanding adsorption capacity as high as 34.9%within 2 h.Moreover,their salient biocompatibility was demonstrated through simulative hemoperfusion experiments.These features,together with its abundant source and facile fabrication,makes the pollens-derived magnetic porous particles excellent candidate for low-density lipoprotein-apheresis and water treatment applications.展开更多
基金supported by start-up funds from Wenzhou Medical University and The First Affiliated Hospital to YL,and Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2019-I2M-5-028)to XL.
文摘Following injury,tissue autonomously initiates a complex repair process,resulting in either partial recovery or regeneration of tissue architecture and function in most organisms.Both the repair and regeneration processes are highly coordinated by a hierarchy of interplay among signal transduction pathways initiated by different growth factors,cytokines and other signaling molecules under normal conditions.However,under chronic traumatic or pathological conditions,the reparative or regenerative process of most tissues in different organs can lose control to different extents,leading to random,incomplete or even flawed cell and tissue reconstitution and thus often partial restoration of the original structure and function,accompanied by the development of fibrosis,scarring or even pathogenesis that could cause organ failure and death of the organism.Ample evidence suggests that the various combinatorial fibroblast growth factor(FGF)and receptor signal transduction systems play prominent roles in injury repair and the remodeling of adult tissues in addition to embryonic development and regulation of metabolic homeostasis.In this review,we attempt to provide a brief update on our current understanding of the roles,the underlying mechanisms and clinical application of FGFs in tissue injury repair.
基金This study was partly funded by a grant the National Natural Science Foundation of China(81802235,81871503),Zhejiang Medical and Health Science and Technology Plan Project(2021KY212),and Wenzhou Basic Science Research Plan Project(Y2020050),Advanced Postdoctoral Programs of Zhejiang(zj2019030),China Postdoctoral Science Foundation(2019M662015),CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).
文摘Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.
基金This work was supported by grants from Advanced Postdoctoral Programs of Zhejiang(zj2019030)China Postdoctoral Science Foundation(2019M662015)+1 种基金Research Unit of Research and Clinical Translation of Cell Growth Factors and Diseases,Chinese Academy of Medical Science(No.2019RU010 to X.L.)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028),China.
文摘Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart diseases.However,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity.Here,an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction(MI)model.As shown in our echocardiographic results,a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI.It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment.Furthermore,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells.However,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long term.On another hand,FGF10 coacervate also increased the expression of cardiac-associated the mRNA(cTnT,Cx43 and α-SMA),angiogenic factors(Ang-1 and VEGFA)and decreased the level of inflammatory factor(tumor necrosis factor-α).The downstream signaling of the FGF10 was also investigated,with the western blot results showing that FGF10 coacervate activated the p-FGFR,PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10.In general,it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060,22002018,81800567 and 61927805)+2 种基金the Natural Science Foundation of Jiangsu(BE2018707)the Launching Funds from Fudan University(JIH1340032 and JIH1340038)the affiliated Zhongshan-Xuhui Hospital(KJK04202000021).
文摘Adsorption of low-density lipoprotein from plasma is vital for the treatment of dyslipidemia.Appropriate adsorbent material for efficient and selective adsorption of low-density lipoprotein is highly desired.In this work,we developed pollens-derived magnetic porous particles as adsorbents for this purpose.The natural pollen grains were modified to obtain high surface porosity,a large inner cavity,magnet responsiveness,and specific wettability.The resultant particles exhibited satisfying performance in the adsorption of a series of oils and organic solvents out of water.Besides,the particles were directly utilized to the adsorption of low-density lipoprotein in plasma,which showed high selectivity,and achieved an outstanding adsorption capacity as high as 34.9%within 2 h.Moreover,their salient biocompatibility was demonstrated through simulative hemoperfusion experiments.These features,together with its abundant source and facile fabrication,makes the pollens-derived magnetic porous particles excellent candidate for low-density lipoprotein-apheresis and water treatment applications.