Brain tissues that are severely damaged by traumatic brain injury(TBI)is hardly regenerated,which leads to a cavity or a repair with glial scarring.Stem-cell therapy is one viable option to treat TBI-caused brain tiss...Brain tissues that are severely damaged by traumatic brain injury(TBI)is hardly regenerated,which leads to a cavity or a repair with glial scarring.Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage,whose use is,whereas,limited by the low survival rate and differentiation efficiency of stem cells.To approach this problem,we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate(GelMA-imid).In addition,polydopamine(PDA)nanoparticles were used as carrier for stromal-cell derived factor-1(SDF-1α).GelMA-imid hydrogel loaded with PDA@SDF-1αnanoparticles and human amniotic mesenchymal stromal cells(hAMSCs)were injected into the damaged area in an in-vivo cryogenic injury model in rats.The hydrogel had low module and its average pore size was 204.61±41.41 nm,which were suitable for the migration,proliferation and differentiation of stem cells.In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1αcould promote the migration of hAMSCs to injury site and their differentiation into nerve cells.The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model.Additionally,histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells.In summary,the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells,and showed great application potential for the physiological recovery of TBI.展开更多
The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities tha...The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.展开更多
Ti-6Al-4V(TC4)used in dentistry and orthopedics as implant biomaterial faces the risk of microbiologically influenced corrosion(MIC)owing to the residence of diverse oral microorganisms.Hereinto,Streptococcus mutans i...Ti-6Al-4V(TC4)used in dentistry and orthopedics as implant biomaterial faces the risk of microbiologically influenced corrosion(MIC)owing to the residence of diverse oral microorganisms.Hereinto,Streptococcus mutans is a critical pathogenic microorganism that causes dental caries.This work investigated the corrosive effects of S.mutans on TC4 and functional gradient TC4/TC4-5Cu coupons fabricated by selective laser melting(SLM)through various electrochemical measurements,surface examination,observation of biofilm and corrosion analysis.The results indicated that the Cu-bearing alloy showed an inhibitory effect on the biofilms due to the release of Cu element,thereby reducing the corrosion rate of MIC.The corrosion current density(icorr)of TC4(11.7±0.8)nA cm−2 is higher than that of TC4/TC4-5Cu(7.4±0.4)nA cm−2 in the presence of S.mutans,while the maximum pit depth of TC4 is 1.6 times that of TC4/TC4-5Cu.Therefore,metal modification through Cu alloying is an effective strategy to improve the MIC resistance.展开更多
Dear Editor,The skin barrier can be impaired by acute skin wounds,which may lead to a series of complications.It is essential to accelerate wound healing and rapidly restore the structural integrity and functionality ...Dear Editor,The skin barrier can be impaired by acute skin wounds,which may lead to a series of complications.It is essential to accelerate wound healing and rapidly restore the structural integrity and functionality of skin.One of the promising bioactive agents is human salivary histatin 1(Hst1),a 38-amino acid histidine-rich peptide that functions to maintain the homeostasis of oral mucosa with a cellular mechanism of promoting the adhesion,spreading,migration of epithelial cells and thus re-epithelialization[1].In recent years,Hst1 has been shown to be effective against various skin-related cell types,such as fibroblasts,myo-fibroblasts,keratinocytes and endothelial cells.In our latest in-vivo study,Hst1 not only promotes angiogenesis,re-epithelialization and collagen production,but also suppresses inflammation,thereby significantly accelerating acute skin wound healing in mice[2].All these studies show that Hst1 is a potent bioactive agent for accelerating acute skin wound healing.展开更多
基金financially supported by the Science and Technology Project of Guangdong Province(No.2015A020212021)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2020KY625)+4 种基金Zhejiang Provincial Department of Education(No.Y201636248)Natural Science Foundation of Zhejiang Province(No.LQY17H140023)Science Technology Department of Zhejiang Province(No.2017C33168)Zhejiang Provincial Basic Public Welfare Research Project(No.GJ19H140001)China's National Key R&D Programs(No.2018YFB0407204).
文摘Brain tissues that are severely damaged by traumatic brain injury(TBI)is hardly regenerated,which leads to a cavity or a repair with glial scarring.Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage,whose use is,whereas,limited by the low survival rate and differentiation efficiency of stem cells.To approach this problem,we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate(GelMA-imid).In addition,polydopamine(PDA)nanoparticles were used as carrier for stromal-cell derived factor-1(SDF-1α).GelMA-imid hydrogel loaded with PDA@SDF-1αnanoparticles and human amniotic mesenchymal stromal cells(hAMSCs)were injected into the damaged area in an in-vivo cryogenic injury model in rats.The hydrogel had low module and its average pore size was 204.61±41.41 nm,which were suitable for the migration,proliferation and differentiation of stem cells.In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1αcould promote the migration of hAMSCs to injury site and their differentiation into nerve cells.The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model.Additionally,histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells.In summary,the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells,and showed great application potential for the physiological recovery of TBI.
基金supported by the National Natural Science Foundations of China(82273554,82073470)the Shandong Provincial Key R&D Program(ZR2019ZD36).
文摘The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.
基金supported by the National Natural Science Foundation of China(No.52301091)the Medical Engineering Intersection Joint Funds of the Natural Science Foundation of Liaoning Province of China(No.2022-YGJC-01).
文摘Ti-6Al-4V(TC4)used in dentistry and orthopedics as implant biomaterial faces the risk of microbiologically influenced corrosion(MIC)owing to the residence of diverse oral microorganisms.Hereinto,Streptococcus mutans is a critical pathogenic microorganism that causes dental caries.This work investigated the corrosive effects of S.mutans on TC4 and functional gradient TC4/TC4-5Cu coupons fabricated by selective laser melting(SLM)through various electrochemical measurements,surface examination,observation of biofilm and corrosion analysis.The results indicated that the Cu-bearing alloy showed an inhibitory effect on the biofilms due to the release of Cu element,thereby reducing the corrosion rate of MIC.The corrosion current density(icorr)of TC4(11.7±0.8)nA cm−2 is higher than that of TC4/TC4-5Cu(7.4±0.4)nA cm−2 in the presence of S.mutans,while the maximum pit depth of TC4 is 1.6 times that of TC4/TC4-5Cu.Therefore,metal modification through Cu alloying is an effective strategy to improve the MIC resistance.
基金funded by the National Natural Science Foundation of China(82172223)the National Key Research and Development Plan of China(2017YFC1103301)+1 种基金the Military Medical Innovation Special Projects(18CXZ029)the Key Research and Development Plan of Zhejiang Province(2021C04013).
文摘Dear Editor,The skin barrier can be impaired by acute skin wounds,which may lead to a series of complications.It is essential to accelerate wound healing and rapidly restore the structural integrity and functionality of skin.One of the promising bioactive agents is human salivary histatin 1(Hst1),a 38-amino acid histidine-rich peptide that functions to maintain the homeostasis of oral mucosa with a cellular mechanism of promoting the adhesion,spreading,migration of epithelial cells and thus re-epithelialization[1].In recent years,Hst1 has been shown to be effective against various skin-related cell types,such as fibroblasts,myo-fibroblasts,keratinocytes and endothelial cells.In our latest in-vivo study,Hst1 not only promotes angiogenesis,re-epithelialization and collagen production,but also suppresses inflammation,thereby significantly accelerating acute skin wound healing in mice[2].All these studies show that Hst1 is a potent bioactive agent for accelerating acute skin wound healing.
