Background:Autologous platelet-rich plasma(PRP)has been suggested to be effective for wound healing.However,evidence for its use in patients with acute and chronic wounds remains insufficient.The aims of this study we...Background:Autologous platelet-rich plasma(PRP)has been suggested to be effective for wound healing.However,evidence for its use in patients with acute and chronic wounds remains insufficient.The aims of this study were to comprehensively examine the effectiveness,synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair.Methods:Full-thickness wounds were made on the back of C57/BL6 mice.PRP or saline solution as a control was administered to the wound area.Wound healing rate,local inflammation,angiogenesis,re-epithelialization and collagen deposition were measured at days 3,5,7 and 14 after skin injury.The biological character of epidermal stem cells(ESCs),which reflect the potential for re-epithelialization,was further evaluated in vitro and in vivo.Results:PRP strongly improved skin wound healing,which was associated with regulation of local inflammation,enhancement of angiogenesis and re-epithelialization.PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β.An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1.Moreover,PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs,and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14.Conclusion:PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization.However,the underlying regulatory mechanism needs to be investigated in the future.Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.展开更多
Ferroptosis and autophagy, playing significant roles in tumor treatment, are two typical forms of the programmed cell death. However, the rational combination of ferroptosis and autophagy for synergistic tumor therapy...Ferroptosis and autophagy, playing significant roles in tumor treatment, are two typical forms of the programmed cell death. However, the rational combination of ferroptosis and autophagy for synergistic tumor therapy is still highly challenging. Herein, we report on an intriguing nanomedicine strategy for achieving autophagy-enhanced ferroptosis on efficiently combating cancer, which was based on the construction of trehalose-loaded mSiO_(2)@MnO_(x)-mPEG(Tre MMM) nanoparticles with satisfactory biocompatibility. The nanoparticles are endowed with high glutathione(GSH) consumption efficiency, thereby inducing cancer-cell ferroptosis via inactivating glutathione peroxidases 4(GPX4). Subsequently, the Tre MMM degradation due to the GSH depletion and p H sensitivity contributed to the trehalose release for inducing autophagy, promoting/enhancing ferroptosis by NCOA4-mediated degradation of ferritin.A substantial in vitro and in vivo antitumor effect was achieved by such an intriguing autophagyenhanced ferroptosis. Therefore, the rational combination of GSH-consumption-induced ferroptosis and trehalose-induced autophagy by nanomedicine design provides an alternative but effective strategy for tumor treatment.展开更多
Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approach...Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.展开更多
Background:Epidermal stem cells(EpSCs)that reside in cutaneous hair follicles and the basal layer of the epidermis are indispensable for wound healing and skin homeostasis.Little is known about the effects of photoche...Background:Epidermal stem cells(EpSCs)that reside in cutaneous hair follicles and the basal layer of the epidermis are indispensable for wound healing and skin homeostasis.Little is known about the effects of photochemical activation on EpSC differentiation,proliferation and migration during wound healing.The present study aimed to determine the effects of photodynamic therapy(PDT)on wound healing in vivo and in vitro.Methods:We created mouse full-thickness skin resection models and applied 5-aminolevulinic acid(ALA)for PDT to the wound beds.Wound healing was analysed by gross evaluation and haematoxylin–eosin staining in vivo.In cultured EpSCs,protein expression was measured using flow cytometry and immunohistochemistry.Cell migration was examined using a scratch model;apoptosis and differentiation were measured using flow cytometry.Results:PDT accelerated wound closure by enhancing EpSC differentiation,proliferation and migration,thereby promoting re-epithelialization and angiogenesis.PDT inhibited inflammatory infiltration and expression of proinflammatory cytokines,whereas the secretion of growth factors was greater than in other groups.The proportion of transient amplifying cells was significantly greater in vivo and in vitro in the PDT groups.EpSC migration was markedly enhanced after ALAinduced PDT.Conclusions:Topical ALA-induced PDT stimulates wound healing by enhancing re-epithelialization,promoting angiogenesis as well as modulating skin homeostasis.This work provides a preliminary theoretical foundation for the clinical administration of topical ALA-induced PDT in skin wound healing.展开更多
In the present study,a numerical model is first calibrated against the crack networks and pressure attenuation data in laboratory blasting test.Then,based on the calibrated numerical model,two-hole plane models are de...In the present study,a numerical model is first calibrated against the crack networks and pressure attenuation data in laboratory blasting test.Then,based on the calibrated numerical model,two-hole plane models are developed and used to perform a series of sim-ulations of smoothwall blasting in deep tunnelling subjected to in-situ stress.The evolutions of rock fracture and excavation damage zone in the roof/floor and sidewalls under different far-field hydrostatic pressure and anisotropic in-situ stress conditions are numerically investigated.The findings in numerical modelling are also analytically interpreted with the stress distributions around the designed tunnel perimeter and perimeter borehole.The numerical and analytical results show that the variations of rock cracking and excavation dam-aged zone induced by smoothwall blasting with in-situ stress are mainly attributed to the high tangential compressive stress concentration around the remaining rock after inner primary blasts and the tensile stress acting on the wall of perimeter hole,which control the crack propagation and initiation respectively.At last,the implications of findings for practical smoothwall blasting in deep tunnelling are discussed.展开更多
Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nev...Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nevertheless,how P311 regulates the differentiation and function of fibroblasts to affect granulation tissue formation remains unclear.In this work,we studied the underlying mechanisms via which P311 affects fibroblasts and promotes acute skin wound repair.Methods:To explore the role of P311,both in vitro and in vivo wound-healing models were used.Full-thickness skin excisional wounds were made in wild-type and P311−/−C57 adult mice.Wound healing rate,re-epithelialization,granulation tissue formation and collagen deposition were measured at days 3,6 and 9 after skin injury.The biological phenotypes of fibroblasts,the expression of target proteins and relevant signaling pathways were examined both in vitro and in vivo.Results:P311 could promote the proliferation and differentiation of fibroblasts,enhance the ability of myofibroblasts to secrete extracellular matrix and promote cell contraction,and then facilitate the formation of granulation tissue and eventually accelerate skin wound closure.Importantly,we discovered that P311 acts via up-regulating the expression of type II transforming growth factor-βreceptor(TGF-βRII)in fibroblasts and promoting the activation of the TGF-βRII-Smad signaling pathway.Mechanistically,the mammalian target of rapamycin signaling pathway is closely implicated in the regulation of the TGF-βRII-Smad pathway in fibroblasts mediated by P311.Conclusions:P311 plays a critical role in activation of the TGF-βRII-Smad pathway to promote fibroblast proliferation and differentiation as well as granulation tissue formation in the process of skin wound repair.展开更多
Background:Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury.However,the systematic and detailed evaluation of the scald burn...Background:Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury.However,the systematic and detailed evaluation of the scald burn injury,including second-degree deep scald(SDDS)and thirddegree scald(TDS),is still unclear.The present study aims to analyze the wound-healing speed,the formation of granulation tissue,and the healing quality after cutaneous damage.Methods:In order to assess SDDS and TDS,the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice.Furthermore,an excisional wound was administered on the dorsal surface in mice(Cut group).The wound-healing rate was first analyzed at days 0,3,5,7,15 and 27,with the Cut group as a control.Then,on the full-thickness wounds,hematoxylin and eosin(H&E)staining,Masson staining,Sirius red staining,Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization,the formation of granulation tissue,vascularization,inflammatory infiltration and the healing quality at different time points in the Cut,SDDS and TDS groups.Results:The presented data revealed that the wound-healing rate was higher in the Cut group,when compared with the SDDS and TDS groups.H&E staining showed that re-epithelialization,formation of granulation tissue and inflammatory infiltration were greater in the Cut group,when compared with the SDDS and TDS groups.Immunohistochemistry revealed that the number of CD31,vascular endothelial growth factor A,transforming growth factor-βandα-smooth muscle actin reached preferential peak in the Cut group,when compared with other groups.In addition,Masson staining,Sirius red staining,Victoria blue staining,Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III,reticular fibers,failure stress,Young’s modulus and failure length in the SDDS group were similar to those in the normal group,suggesting that healing quality was better in the SDDS group,when compared with the Cut and TDS groups.Conclusion:Overall,the investigators first administered a comprehensive analysis in the Cut,SDDS and TDS groups through in vivo experiments,which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.展开更多
Great efforts have been made in investigating the neurotoxicity of dopamine(DA)in the presence of manganous ions.In contrast,here,we probe the possibility of DA-based cancer chemotherapy by leveraging intratumoral red...Great efforts have been made in investigating the neurotoxicity of dopamine(DA)in the presence of manganous ions.In contrast,here,we probe the possibility of DA-based cancer chemotherapy by leveraging intratumoral redox reactions of DA for producing cytotoxic species in situ.For this purpose,we have constructed a Mn-engineered,DA-loaded nanomedicine.Based on the unique size effect of the nanocarrier,this nanomedicine will not enter the central nervous system but can effectively accumulate in the tumor region,after which the nanocarrier can degrade to release Mn^(2+)and DA in response to the mild acidic intracelluar microenvironment of cancer cells.DA can chelate Mn^(2+)to form a binary coordination complex,where the strong metal-ligand interaction significantly promotes electron delocalization and elevates the reducibility of Mn center,favoring two sequential one-electron oxygen reduction reactions forming H_(2)O_(2),which can be further converted into highly oxidizing ·OH under the cocatalysis by Mn^(2+)and intracellular Fe^(2+).Additionally,as a twoelectron oxidation product of DA ligand,DA-oquinone is potent in exhausting cellular sulfhydryl and depleting reduced glutathione,inhibiting the intrinsic antioxidative mechanism of cancer cells,finally triggering severe oxidative damages in a synergistic manner.It is expected that such a strategy of nanotechnology-mediated metal-ligand coordination and subsequent nontoxicity-to-toxicity transition of DA in tumor may provide a promising prospect for future chemotherapy design.展开更多
基金supported by the National Key Research and Development Plan of China(No.2017YFC1103301)Military Medical Innovation Special Projects(No.18CXZ029)+2 种基金National Natural Science Foundation of China(31872742)Top-notch Talent Training Plan(SWH2018BJKJ-04)MilitaryMedical Science and Technology Youth Training Plan(20QNPY024).
文摘Background:Autologous platelet-rich plasma(PRP)has been suggested to be effective for wound healing.However,evidence for its use in patients with acute and chronic wounds remains insufficient.The aims of this study were to comprehensively examine the effectiveness,synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair.Methods:Full-thickness wounds were made on the back of C57/BL6 mice.PRP or saline solution as a control was administered to the wound area.Wound healing rate,local inflammation,angiogenesis,re-epithelialization and collagen deposition were measured at days 3,5,7 and 14 after skin injury.The biological character of epidermal stem cells(ESCs),which reflect the potential for re-epithelialization,was further evaluated in vitro and in vivo.Results:PRP strongly improved skin wound healing,which was associated with regulation of local inflammation,enhancement of angiogenesis and re-epithelialization.PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β.An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1.Moreover,PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs,and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14.Conclusion:PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization.However,the underlying regulatory mechanism needs to be investigated in the future.Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.
基金This work was supported by the National Key R&D Program of China(2016YFA0203700)the National Natural Science Foundation of China(51722211,51672303,and 51902334)+1 种基金Program of Shanghai Academic Research Leader(18XD1404300)the National Science Foundation for Young Scientists of China(81903178)。
文摘Ferroptosis and autophagy, playing significant roles in tumor treatment, are two typical forms of the programmed cell death. However, the rational combination of ferroptosis and autophagy for synergistic tumor therapy is still highly challenging. Herein, we report on an intriguing nanomedicine strategy for achieving autophagy-enhanced ferroptosis on efficiently combating cancer, which was based on the construction of trehalose-loaded mSiO_(2)@MnO_(x)-mPEG(Tre MMM) nanoparticles with satisfactory biocompatibility. The nanoparticles are endowed with high glutathione(GSH) consumption efficiency, thereby inducing cancer-cell ferroptosis via inactivating glutathione peroxidases 4(GPX4). Subsequently, the Tre MMM degradation due to the GSH depletion and p H sensitivity contributed to the trehalose release for inducing autophagy, promoting/enhancing ferroptosis by NCOA4-mediated degradation of ferritin.A substantial in vitro and in vivo antitumor effect was achieved by such an intriguing autophagyenhanced ferroptosis. Therefore, the rational combination of GSH-consumption-induced ferroptosis and trehalose-induced autophagy by nanomedicine design provides an alternative but effective strategy for tumor treatment.
基金supported by the National Natural Science Foundation of China(NO.81570675,NO.31872742)Clinical Innovation Foundation of Southwest Hospital(SWH2017JCZD-06)Top Talent Training Programme Foundation of Southwest Hospital(SWH2018BJKJ-04).
文摘Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.
基金supported by National Natural Science Foundation of China(grant No.81571902,31872742).
文摘Background:Epidermal stem cells(EpSCs)that reside in cutaneous hair follicles and the basal layer of the epidermis are indispensable for wound healing and skin homeostasis.Little is known about the effects of photochemical activation on EpSC differentiation,proliferation and migration during wound healing.The present study aimed to determine the effects of photodynamic therapy(PDT)on wound healing in vivo and in vitro.Methods:We created mouse full-thickness skin resection models and applied 5-aminolevulinic acid(ALA)for PDT to the wound beds.Wound healing was analysed by gross evaluation and haematoxylin–eosin staining in vivo.In cultured EpSCs,protein expression was measured using flow cytometry and immunohistochemistry.Cell migration was examined using a scratch model;apoptosis and differentiation were measured using flow cytometry.Results:PDT accelerated wound closure by enhancing EpSC differentiation,proliferation and migration,thereby promoting re-epithelialization and angiogenesis.PDT inhibited inflammatory infiltration and expression of proinflammatory cytokines,whereas the secretion of growth factors was greater than in other groups.The proportion of transient amplifying cells was significantly greater in vivo and in vitro in the PDT groups.EpSC migration was markedly enhanced after ALAinduced PDT.Conclusions:Topical ALA-induced PDT stimulates wound healing by enhancing re-epithelialization,promoting angiogenesis as well as modulating skin homeostasis.This work provides a preliminary theoretical foundation for the clinical administration of topical ALA-induced PDT in skin wound healing.
基金the financial support from the National Natural Science Foundation of China(Grant no.51974360)for carrying out this research work.
文摘In the present study,a numerical model is first calibrated against the crack networks and pressure attenuation data in laboratory blasting test.Then,based on the calibrated numerical model,two-hole plane models are developed and used to perform a series of sim-ulations of smoothwall blasting in deep tunnelling subjected to in-situ stress.The evolutions of rock fracture and excavation damage zone in the roof/floor and sidewalls under different far-field hydrostatic pressure and anisotropic in-situ stress conditions are numerically investigated.The findings in numerical modelling are also analytically interpreted with the stress distributions around the designed tunnel perimeter and perimeter borehole.The numerical and analytical results show that the variations of rock cracking and excavation dam-aged zone induced by smoothwall blasting with in-situ stress are mainly attributed to the high tangential compressive stress concentration around the remaining rock after inner primary blasts and the tensile stress acting on the wall of perimeter hole,which control the crack propagation and initiation respectively.At last,the implications of findings for practical smoothwall blasting in deep tunnelling are discussed.
基金National Natural Sciences Foundation of China(No.31872742 to W.F.H.and No.81630055 to G.X.L.)Military Medical Science and Technology Youth Training Program of Army Military Medical University(Third Military Medical University)(No.20QNPY024 to W.F.H.)the Special Project for Enhancing Science and Technology Innovation Ability(frontier exploration)of Army Military Medical University(Third Military Medical University)(No.2019XQY12 to W.F.H.).
文摘Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nevertheless,how P311 regulates the differentiation and function of fibroblasts to affect granulation tissue formation remains unclear.In this work,we studied the underlying mechanisms via which P311 affects fibroblasts and promotes acute skin wound repair.Methods:To explore the role of P311,both in vitro and in vivo wound-healing models were used.Full-thickness skin excisional wounds were made in wild-type and P311−/−C57 adult mice.Wound healing rate,re-epithelialization,granulation tissue formation and collagen deposition were measured at days 3,6 and 9 after skin injury.The biological phenotypes of fibroblasts,the expression of target proteins and relevant signaling pathways were examined both in vitro and in vivo.Results:P311 could promote the proliferation and differentiation of fibroblasts,enhance the ability of myofibroblasts to secrete extracellular matrix and promote cell contraction,and then facilitate the formation of granulation tissue and eventually accelerate skin wound closure.Importantly,we discovered that P311 acts via up-regulating the expression of type II transforming growth factor-βreceptor(TGF-βRII)in fibroblasts and promoting the activation of the TGF-βRII-Smad signaling pathway.Mechanistically,the mammalian target of rapamycin signaling pathway is closely implicated in the regulation of the TGF-βRII-Smad pathway in fibroblasts mediated by P311.Conclusions:P311 plays a critical role in activation of the TGF-βRII-Smad pathway to promote fibroblast proliferation and differentiation as well as granulation tissue formation in the process of skin wound repair.
文摘Background:Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury.However,the systematic and detailed evaluation of the scald burn injury,including second-degree deep scald(SDDS)and thirddegree scald(TDS),is still unclear.The present study aims to analyze the wound-healing speed,the formation of granulation tissue,and the healing quality after cutaneous damage.Methods:In order to assess SDDS and TDS,the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice.Furthermore,an excisional wound was administered on the dorsal surface in mice(Cut group).The wound-healing rate was first analyzed at days 0,3,5,7,15 and 27,with the Cut group as a control.Then,on the full-thickness wounds,hematoxylin and eosin(H&E)staining,Masson staining,Sirius red staining,Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization,the formation of granulation tissue,vascularization,inflammatory infiltration and the healing quality at different time points in the Cut,SDDS and TDS groups.Results:The presented data revealed that the wound-healing rate was higher in the Cut group,when compared with the SDDS and TDS groups.H&E staining showed that re-epithelialization,formation of granulation tissue and inflammatory infiltration were greater in the Cut group,when compared with the SDDS and TDS groups.Immunohistochemistry revealed that the number of CD31,vascular endothelial growth factor A,transforming growth factor-βandα-smooth muscle actin reached preferential peak in the Cut group,when compared with other groups.In addition,Masson staining,Sirius red staining,Victoria blue staining,Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III,reticular fibers,failure stress,Young’s modulus and failure length in the SDDS group were similar to those in the normal group,suggesting that healing quality was better in the SDDS group,when compared with the Cut and TDS groups.Conclusion:Overall,the investigators first administered a comprehensive analysis in the Cut,SDDS and TDS groups through in vivo experiments,which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.
基金the National Natural Science Foundation of China(grant no.21835007)Key Research Program of Frontier Sciences,Chinese Academy of Sciences(grant no.ZDBS-LY-SLH029)Shanghai Municipal Government S&T Project(grant no.17JC1404701).
文摘Great efforts have been made in investigating the neurotoxicity of dopamine(DA)in the presence of manganous ions.In contrast,here,we probe the possibility of DA-based cancer chemotherapy by leveraging intratumoral redox reactions of DA for producing cytotoxic species in situ.For this purpose,we have constructed a Mn-engineered,DA-loaded nanomedicine.Based on the unique size effect of the nanocarrier,this nanomedicine will not enter the central nervous system but can effectively accumulate in the tumor region,after which the nanocarrier can degrade to release Mn^(2+)and DA in response to the mild acidic intracelluar microenvironment of cancer cells.DA can chelate Mn^(2+)to form a binary coordination complex,where the strong metal-ligand interaction significantly promotes electron delocalization and elevates the reducibility of Mn center,favoring two sequential one-electron oxygen reduction reactions forming H_(2)O_(2),which can be further converted into highly oxidizing ·OH under the cocatalysis by Mn^(2+)and intracellular Fe^(2+).Additionally,as a twoelectron oxidation product of DA ligand,DA-oquinone is potent in exhausting cellular sulfhydryl and depleting reduced glutathione,inhibiting the intrinsic antioxidative mechanism of cancer cells,finally triggering severe oxidative damages in a synergistic manner.It is expected that such a strategy of nanotechnology-mediated metal-ligand coordination and subsequent nontoxicity-to-toxicity transition of DA in tumor may provide a promising prospect for future chemotherapy design.
