Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive ...Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive peptides contain a great deal of development potential.More specifically,food-derived bioactive peptides have the advantages of a wide variety of sources,unique structures,high efficiency and safety,so they have broad development prospects.This review provides an overview of the current advances regarding the preparation,functional characteristics,and structure–activity relationships of food-derived bioactive peptides.Moreover,the prospects for the future development and application of food-derived bioactive peptides are discussed.This review may provide a better understanding of foodderived bioactive peptides,and some constructive inspirations for further research and applications in the food industry.展开更多
Bioactive components are partially responsible for the nutritional and health benefits of soybeans. Four major bioactive components: isoflavones, oligosaccharides, phospholipids,and saponins, were quantified in 763 so...Bioactive components are partially responsible for the nutritional and health benefits of soybeans. Four major bioactive components: isoflavones, oligosaccharides, phospholipids,and saponins, were quantified in 763 soybean samples collected from widely distributed regions across China from 2010 to 2013. A majority of the tested bioactive components showed generally declining trends from the north(high latitude) to the south(low latitude).A positive relationship between total oligosaccharides(TO) and altitude was observed. Total isoflavones(TI), phospholipids(TP) and TO were negatively correlated with cumulative temperature above or equal to 15 °C(AT15) and mean daily temperature(MDT), but positively correlated with diurnal temperature range(DTR) and hours of sunshine(HS).Total saponins(TS) were negatively correlated with MDT but positively correlated with rainfall(RF), whereas TO were negatively correlated with RF. Path-coefficient analysis showed that, besides genotype differences, temperature and HS during the reproductive period influenced TI and TP contents, while temperature and RF influenced TS and TO. The effects of weather factors on soybean bioactive components in diverse regions of China were characterized. These findings will be helpful in promoting soybean production for functional food purposes.展开更多
Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechan...Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation.However,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them.In this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory sites.Even so,literature is conflicted regarding the location and persistence of MSC in the body after transplantation.For this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic acids.Moreover,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms.Taken together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.展开更多
Injury to central nervous system (CNS) tissues in adult mam- mals often leads to neuronal loss, scarring, and permanently lost neurologic functions, and this default healing response is increasingly linked to a pro-...Injury to central nervous system (CNS) tissues in adult mam- mals often leads to neuronal loss, scarring, and permanently lost neurologic functions, and this default healing response is increasingly linked to a pro-inflammatory innate immune response. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling in various tissues and organs, including the CNS.展开更多
Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration ...Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.展开更多
The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration.However,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration w...The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration.However,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose,which limits their clinical benefits.Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth fa ctors and can activate the equivalent receptors but have simplified sequences and structures.In this study,we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth fa ctor mimetic peptides(Chi/PDA-Ps).We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides.In this study,we evaluated the biocompatibility of the Chi/P DA-Ps conduits.Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth fa ctor mimetic peptide synergistically promoted prolife ration of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro.The Chi/P DA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury.We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy.The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and re myelination was further resto red.These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.展开更多
Objective Expressing the human matured brain-derived neurotrophic factor (mBDNF) gene in E. Coli and determining its bioactivity. Methods The resulting gene of mBDNF was subcloned into the EcoRI-BamHI site or the expr...Objective Expressing the human matured brain-derived neurotrophic factor (mBDNF) gene in E. Coli and determining its bioactivity. Methods The resulting gene of mBDNF was subcloned into the EcoRI-BamHI site or the expression vector plasmid pBV220. The ligation products were used to transform the competent E. Coli DH5a. The proteins or mBDNF were experessed by temperature inducing. The expression products were dealed with solubilizing inclusion bodies and refolding protein. It was introduced into the embryonic chicken DRG to test whether the expressed mBDNF is a biologically active protein. Results The recombinant plasmid pBV/mBDNF was success- fully constructed. By temperature inducing, under the control of the bacteriophage λPL promoter, the experessed mBDNF protein was a 14Kd non-fusion protein,which existed in E. Coli as inclusion bodies. The size or expressed mBDNF is identical to the prediction. Bioactivity of the products was proved that it could support the cell survival and neurite growth in the primary cultures of embryonic 8-day-old chicken DRG neurons as compared to control. Conclusion Tke mBDNF gene can be expressed bioactively in E. Coli.展开更多
It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous s...It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.展开更多
The ability to maintain functional hepatocytes has important implications for bioartificial liver development,cell-based therapies,drug screening,and tissue engineering.Several approaches can be used to restore hepato...The ability to maintain functional hepatocytes has important implications for bioartificial liver development,cell-based therapies,drug screening,and tissue engineering.Several approaches can be used to restore hepatocyte function in vitro,including coating a culture substrate with extracellular matrix(ECM),encapsulating cells within biomimetic gels(Collagen-or Matrigel-based),or co-cultivation with other cells.This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids.These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors.We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes.We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor(HGF)into microcapsules and inhibiting transforming growth factor(TGF)-β1 signaling.Overall,bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering,regenerative medicine,and drug testing applications.展开更多
Human pluripotent stem cells(hPSC)hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure.Some of the challenges that limit the clinical/translational impa...Human pluripotent stem cells(hPSC)hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure.Some of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation protocols.In this paper,we sought to address these challenges through the development of bioactive microcapsules.A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel shell.Importantly,the shell contained heparin moieties for growth factor(GF)binding and release.The aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal differentiation.Specifically,we demonstrated that one-time,1 h long loading of pluripotency signals,fibroblast growth factor(FGF)-2 and transforming growth factor(TGF)-β1,into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble GFs.Furthermore,stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue,Nodal,resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard protocol.Overall,bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.展开更多
Dermal substitutes provide a template for dermal regeneration and reconstruction.They constitutes an ideal clinical treatment for deep skin defects.However,rapid vascularization remains as a major hurdle to the develo...Dermal substitutes provide a template for dermal regeneration and reconstruction.They constitutes an ideal clinical treatment for deep skin defects.However,rapid vascularization remains as a major hurdle to the development and application of dermal substitutes.Several bioactive factors play an important regulatory role in the process of angiogenesis and an understanding of the mechanism of achieving their effective delivery and sustained function is vital.Nanomaterials have great potential for tissue engineering.Effective delivery of bioactive factors(including growth factors,peptides and nucleic acids)by nanomaterials is of increasing research interest.This paper discusses the process of dermal substitute angiogenesis and the roles of related bioactive factors in this process.The application of nanomaterials for the delivery of bioactive factors to enhance angiogenesis and accelerate wound healing is also reviewed.We focus on new systems and approaches for delivering bioactive factors for enhancing angiogenesis in dermal substitutes.展开更多
Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secr...Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.展开更多
The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote stru...The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury.Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue.While amphibians have a pronounced ability to regenerate the spinal cord,few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury.Here we report for the first time the successful identification and isolation of a new polypeptide,VD11(amino acid sequence:VDELWPPWLPC),from the spinal cord of an endemic Chinese amphibian(Odorrana schmackeri).In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide,as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia.In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury,alleviated pathological damage,and promoted axonal regeneration.Furthermore,RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways.In summary,we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.展开更多
基金supported by the National Natural Science Foundation of China(U1905202,31972017,and 31771922)the National Key R&D Program of China(2018YFD0901006)+2 种基金the Fujian Major Project of Provincial Science&Technology Hall,China(2020NZ010008)the Open Project of the Key Laboratory of Refrigeration and Conditioning Aquatic Products Processing,Ministry of Agriculture and Rural Affairs,China(KLRCAPP2021-03)the Quanzhou Science&Technology Project,China(2019C085R)。
文摘Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive peptides contain a great deal of development potential.More specifically,food-derived bioactive peptides have the advantages of a wide variety of sources,unique structures,high efficiency and safety,so they have broad development prospects.This review provides an overview of the current advances regarding the preparation,functional characteristics,and structure–activity relationships of food-derived bioactive peptides.Moreover,the prospects for the future development and application of food-derived bioactive peptides are discussed.This review may provide a better understanding of foodderived bioactive peptides,and some constructive inspirations for further research and applications in the food industry.
基金supported by the National Key Research and Development Program of China(2017YFD0101400)China Agriculture Research System(CARS-04)Agricultural Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences
文摘Bioactive components are partially responsible for the nutritional and health benefits of soybeans. Four major bioactive components: isoflavones, oligosaccharides, phospholipids,and saponins, were quantified in 763 soybean samples collected from widely distributed regions across China from 2010 to 2013. A majority of the tested bioactive components showed generally declining trends from the north(high latitude) to the south(low latitude).A positive relationship between total oligosaccharides(TO) and altitude was observed. Total isoflavones(TI), phospholipids(TP) and TO were negatively correlated with cumulative temperature above or equal to 15 °C(AT15) and mean daily temperature(MDT), but positively correlated with diurnal temperature range(DTR) and hours of sunshine(HS).Total saponins(TS) were negatively correlated with MDT but positively correlated with rainfall(RF), whereas TO were negatively correlated with RF. Path-coefficient analysis showed that, besides genotype differences, temperature and HS during the reproductive period influenced TI and TP contents, while temperature and RF influenced TS and TO. The effects of weather factors on soybean bioactive components in diverse regions of China were characterized. These findings will be helpful in promoting soybean production for functional food purposes.
文摘Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s disease.Although the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation.However,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them.In this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory sites.Even so,literature is conflicted regarding the location and persistence of MSC in the body after transplantation.For this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic acids.Moreover,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms.Taken together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.
文摘Injury to central nervous system (CNS) tissues in adult mam- mals often leads to neuronal loss, scarring, and permanently lost neurologic functions, and this default healing response is increasingly linked to a pro-inflammatory innate immune response. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling in various tissues and organs, including the CNS.
基金supported by the Interdisciplinary Program of Shanghai Jiao Tong University,China,No.YG2021QN60(both to WL)Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,China,No.JYZZ086B(both to WL).
文摘Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.
基金the National Natural Science Foundation of China,Nos.31771322,31571235the Natural Science Foundation of Beijing,No.7212121+3 种基金Beijing Science Technology New Star Cross Subject of China,No.2018019Shenzhen Science and Technology Plan Project of China,No.JCYJ 20190806162205278the Key Laboratory of Trauma and Neural Regeneration(Peking University),Ministry of Educationa grant from National Center for Trauma Medicine,No.BMU2020XY005-01(all to PXZ)。
文摘The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration.However,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose,which limits their clinical benefits.Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth fa ctors and can activate the equivalent receptors but have simplified sequences and structures.In this study,we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth fa ctor mimetic peptides(Chi/PDA-Ps).We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides.In this study,we evaluated the biocompatibility of the Chi/P DA-Ps conduits.Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth fa ctor mimetic peptide synergistically promoted prolife ration of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro.The Chi/P DA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury.We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy.The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and re myelination was further resto red.These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.
文摘Objective Expressing the human matured brain-derived neurotrophic factor (mBDNF) gene in E. Coli and determining its bioactivity. Methods The resulting gene of mBDNF was subcloned into the EcoRI-BamHI site or the expression vector plasmid pBV220. The ligation products were used to transform the competent E. Coli DH5a. The proteins or mBDNF were experessed by temperature inducing. The expression products were dealed with solubilizing inclusion bodies and refolding protein. It was introduced into the embryonic chicken DRG to test whether the expressed mBDNF is a biologically active protein. Results The recombinant plasmid pBV/mBDNF was success- fully constructed. By temperature inducing, under the control of the bacteriophage λPL promoter, the experessed mBDNF protein was a 14Kd non-fusion protein,which existed in E. Coli as inclusion bodies. The size or expressed mBDNF is identical to the prediction. Bioactivity of the products was proved that it could support the cell survival and neurite growth in the primary cultures of embryonic 8-day-old chicken DRG neurons as compared to control. Conclusion Tke mBDNF gene can be expressed bioactively in E. Coli.
基金supported by the National Natural Science Foundation of ChinaNos.82272171 (to ZY),82271403 (to XL),31971279 (to ZY),81941011 (to XL),31730030 (to XL)。
文摘It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.
基金supported in part by the Center for Regenerative Medicine and Cells to Cures Strategic Initiative at Mayo Clinic,J.W.Kieckhefer Foundation,Al Nahyan Foundation,and NIH(DK107255 and P30DK084567).
文摘The ability to maintain functional hepatocytes has important implications for bioartificial liver development,cell-based therapies,drug screening,and tissue engineering.Several approaches can be used to restore hepatocyte function in vitro,including coating a culture substrate with extracellular matrix(ECM),encapsulating cells within biomimetic gels(Collagen-or Matrigel-based),or co-cultivation with other cells.This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids.These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors.We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes.We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor(HGF)into microcapsules and inhibiting transforming growth factor(TGF)-β1 signaling.Overall,bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering,regenerative medicine,and drug testing applications.
基金supported in part by the grants from the Mayo Clinic Center for Regenerative Medicine,J.W.Kieckhefer Foundation and Al Nahyan Foundation,from Regenerative Medicine Minnesota(RMM 101617 TR 004)and from NIH(DK107255).
文摘Human pluripotent stem cells(hPSC)hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure.Some of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation protocols.In this paper,we sought to address these challenges through the development of bioactive microcapsules.A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel shell.Importantly,the shell contained heparin moieties for growth factor(GF)binding and release.The aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal differentiation.Specifically,we demonstrated that one-time,1 h long loading of pluripotency signals,fibroblast growth factor(FGF)-2 and transforming growth factor(TGF)-β1,into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble GFs.Furthermore,stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue,Nodal,resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard protocol.Overall,bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.
基金supported by the National key research and development project(2016YFC1100800,2016YFC1100803)the National Natural Science Foundation of China(81772069,81401591,81801911)the Zhejiang Provincial Basic Public Welfare Research Program(LGF19H150008).
文摘Dermal substitutes provide a template for dermal regeneration and reconstruction.They constitutes an ideal clinical treatment for deep skin defects.However,rapid vascularization remains as a major hurdle to the development and application of dermal substitutes.Several bioactive factors play an important regulatory role in the process of angiogenesis and an understanding of the mechanism of achieving their effective delivery and sustained function is vital.Nanomaterials have great potential for tissue engineering.Effective delivery of bioactive factors(including growth factors,peptides and nucleic acids)by nanomaterials is of increasing research interest.This paper discusses the process of dermal substitute angiogenesis and the roles of related bioactive factors in this process.The application of nanomaterials for the delivery of bioactive factors to enhance angiogenesis and accelerate wound healing is also reviewed.We focus on new systems and approaches for delivering bioactive factors for enhancing angiogenesis in dermal substitutes.
基金supported by Military Medical Science&Technology Youth Training Program,No. 19QNP005President Foundation of Nanfang Hospital,Southern Medical University,No. 2020B028 (both to JY)。
文摘Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.
基金supported by the National Natural Science Foundation of China,Nos.32060212(to YW),81760648(to XWY),81560118(to BYZ)Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation,Nos.202101AY070001-006(to XWY)and 2018FE001(-161)(to JS)+2 种基金Yunnan Applied Basic Research Project Foundation,No.2019FB128(to YW)Project of Yunnan Province Clinical Research Centerfor Chronic Kidney Disease,No.202102AA10060(to BYZ)a grant from Scientific Research Foundation of Department of Education of Yunnan Province,No.2021J0205(to SSL)。
文摘The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury.Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue.While amphibians have a pronounced ability to regenerate the spinal cord,few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury.Here we report for the first time the successful identification and isolation of a new polypeptide,VD11(amino acid sequence:VDELWPPWLPC),from the spinal cord of an endemic Chinese amphibian(Odorrana schmackeri).In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide,as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia.In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury,alleviated pathological damage,and promoted axonal regeneration.Furthermore,RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways.In summary,we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.