AIM:To evaluate chronic ocular sequelae in patients with symblepharon caused by ocular burns and propose an objective grading system.METHODS:This was a retrospective,single-center clinical study.Patients with symbleph...AIM:To evaluate chronic ocular sequelae in patients with symblepharon caused by ocular burns and propose an objective grading system.METHODS:This was a retrospective,single-center clinical study.Patients with symblepharon caused by ocular burns at least six months later were assessed.Chronic ocular sequelae were classified into 3 categories(eyelid,conjunctiva,and cornea)and 9 chronic ocular sequelae[friction factors,exposure factors,conjunctival hyperemia,length of symblepharon,scope of adhesion,lacrimal area adhesion,loss of the palisades of Vogt(POV),corneal neovascularization,and corneal opacification].Each ocular sequela was graded from 0 to 3,depending on the increasing severity.The 9 ocular sequelae were evaluated to obtain the total severity score for each eye.The total severity score was defined as Grade I(1-9),Grade II(10-18),and Grade III(19-27).Moreover,the correlation between the severity of chronic ocular sequelae and visual acuity,surgical strategy,and the prognosis was analyzed,respectively.RESULTS:Cases of 79 eyes with symblepharon caused by ocular burns were included in this study.Of these,20(25.32%)were defined as Grade I,43(54.43%)as Grade II,and 16(20.25%)as Grade III.Eyes with a high total severity score had reduced visual acuity,required complicated surger y strategies,and poor prognosis(P<0.001).Multivariate regression analysis showed that the scope of adhesion,corneal opacification,and corneal neovascularization significantly affected visual acuity,surgical strategy,and prognosis(all P<0.001).CONCLUSION:The evaluation of chronic ocular sequelae enabled the development of an objective grading system for patients with symblepharon caused by ocular burns.This grading system can be applied to guide the treatment and predict the prognosis.展开更多
Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a signifi...Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge.Inspired by metalloenzymes with well-defined coordination structures,a series of MOFs containing halogen-coordinated copper nodes(Cu-X MOFs,X=Cl,Br,I)are employed to elucidate their structure–activity relationship.Intriguingly,experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center.The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes.More importantly,by performing enzyme-mimicking catalysis,the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress,thus effectively relieving ocular chemical burns.Mechanistically,the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways.Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and,more significantly,demonstrating their potential therapeutic effect in ophthalmic disease.展开更多
AIM:To explore the effects of alarmins produced by necrotic human conjunctival fibroblasts on the release of matrix metalloproteinases(MMPs)by human corneal fibroblasts(HCFs).METHODS:A necrotic cell supernatant(NHCS)w...AIM:To explore the effects of alarmins produced by necrotic human conjunctival fibroblasts on the release of matrix metalloproteinases(MMPs)by human corneal fibroblasts(HCFs).METHODS:A necrotic cell supernatant(NHCS)was prepared by subjecting human conjunctival fibroblasts to three cycles of freezing and thawing.The amounts of interleukin(IL)-1βand tumor necrosis factor(TNF)-αin NHCS were determined by enzyme-linked immunosorbent assays.HCFs exposed to NHCS or other agents in culture were assayed for the release of MMPs as well as for intracellular signaling by immunoblot analysis.The abundance of MMP m RNAs in HCFs was examined by reverse transcription and real-time polymerase chain reaction analysis.RESULTS:NHCS increased the release of MMP-1 and MMP-3 by HCFs as well as the amounts of the corresponding m RNAs in the cells.NHCS also induced activation of mitogen-activated protein kinase(MAPK)signaling pathways mediated by extracellular signal-regulated kinase(ERK),p38,and c-Jun NH2-terminal kinase(JNK)as well as elicited that of the nuclear factor(NF)-κB signaling pathway by promoting phosphorylation of the endogenous NF-κB inhibitor IκB-α.Inhibitors of MAPK and NF-κB signaling as well as IL-1 and TNF-αreceptor antagonists attenuated the NHCS-induced release of MMP-1 and MMP-3 by HCFs.Furthermore,IL-1βand TNF-αwere both detected in NHCS,and treatment of HCFs with these cytokines induced the release of MMP-1 and MMP-3 in a concentration-dependent manner.CONCLUSION:Alarmins,including IL-1βand TNF-α,produced by necrotic human conjunctival fibroblasts triggered MMP release in HCFs through activation of MAPK and NF-κB signaling.IL-1βand TNF-αare therefore potential therapeutic targets for the amelioration of corneal stromal degradation in severe ocular burns.展开更多
基金Supported by the National Natural Science Foundation of China(No.81770888)the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(No.20161421)+2 种基金the Shanghai Municipal Science and Technology Commission the Commercialization and Industrialization of Research Findings Project(No.17411963800)Shanghai Pujiang Program(No.18PJD025)Shanghai Jiao Tong University School of Medicine Two-hundred Talent(No.20191914)。
文摘AIM:To evaluate chronic ocular sequelae in patients with symblepharon caused by ocular burns and propose an objective grading system.METHODS:This was a retrospective,single-center clinical study.Patients with symblepharon caused by ocular burns at least six months later were assessed.Chronic ocular sequelae were classified into 3 categories(eyelid,conjunctiva,and cornea)and 9 chronic ocular sequelae[friction factors,exposure factors,conjunctival hyperemia,length of symblepharon,scope of adhesion,lacrimal area adhesion,loss of the palisades of Vogt(POV),corneal neovascularization,and corneal opacification].Each ocular sequela was graded from 0 to 3,depending on the increasing severity.The 9 ocular sequelae were evaluated to obtain the total severity score for each eye.The total severity score was defined as Grade I(1-9),Grade II(10-18),and Grade III(19-27).Moreover,the correlation between the severity of chronic ocular sequelae and visual acuity,surgical strategy,and the prognosis was analyzed,respectively.RESULTS:Cases of 79 eyes with symblepharon caused by ocular burns were included in this study.Of these,20(25.32%)were defined as Grade I,43(54.43%)as Grade II,and 16(20.25%)as Grade III.Eyes with a high total severity score had reduced visual acuity,required complicated surger y strategies,and poor prognosis(P<0.001).Multivariate regression analysis showed that the scope of adhesion,corneal opacification,and corneal neovascularization significantly affected visual acuity,surgical strategy,and prognosis(all P<0.001).CONCLUSION:The evaluation of chronic ocular sequelae enabled the development of an objective grading system for patients with symblepharon caused by ocular burns.This grading system can be applied to guide the treatment and predict the prognosis.
基金the National Key R&D Program of China(Grant No.2020YFA0908100)the National Nature Science Foundation(Grant Nos.12274356,82070931,and 82271045)+1 种基金Fundamental Research Funds for the Central Universities(20720220022)the 111 Project(B16029)。
文摘Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge.Inspired by metalloenzymes with well-defined coordination structures,a series of MOFs containing halogen-coordinated copper nodes(Cu-X MOFs,X=Cl,Br,I)are employed to elucidate their structure–activity relationship.Intriguingly,experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center.The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes.More importantly,by performing enzyme-mimicking catalysis,the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress,thus effectively relieving ocular chemical burns.Mechanistically,the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways.Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and,more significantly,demonstrating their potential therapeutic effect in ophthalmic disease.
基金Supported by the National Natural Science Foundation of China(No.81770889)the Natural Science Foundation of Guangdong Province(No.2018A030313428)。
文摘AIM:To explore the effects of alarmins produced by necrotic human conjunctival fibroblasts on the release of matrix metalloproteinases(MMPs)by human corneal fibroblasts(HCFs).METHODS:A necrotic cell supernatant(NHCS)was prepared by subjecting human conjunctival fibroblasts to three cycles of freezing and thawing.The amounts of interleukin(IL)-1βand tumor necrosis factor(TNF)-αin NHCS were determined by enzyme-linked immunosorbent assays.HCFs exposed to NHCS or other agents in culture were assayed for the release of MMPs as well as for intracellular signaling by immunoblot analysis.The abundance of MMP m RNAs in HCFs was examined by reverse transcription and real-time polymerase chain reaction analysis.RESULTS:NHCS increased the release of MMP-1 and MMP-3 by HCFs as well as the amounts of the corresponding m RNAs in the cells.NHCS also induced activation of mitogen-activated protein kinase(MAPK)signaling pathways mediated by extracellular signal-regulated kinase(ERK),p38,and c-Jun NH2-terminal kinase(JNK)as well as elicited that of the nuclear factor(NF)-κB signaling pathway by promoting phosphorylation of the endogenous NF-κB inhibitor IκB-α.Inhibitors of MAPK and NF-κB signaling as well as IL-1 and TNF-αreceptor antagonists attenuated the NHCS-induced release of MMP-1 and MMP-3 by HCFs.Furthermore,IL-1βand TNF-αwere both detected in NHCS,and treatment of HCFs with these cytokines induced the release of MMP-1 and MMP-3 in a concentration-dependent manner.CONCLUSION:Alarmins,including IL-1βand TNF-α,produced by necrotic human conjunctival fibroblasts triggered MMP release in HCFs through activation of MAPK and NF-κB signaling.IL-1βand TNF-αare therefore potential therapeutic targets for the amelioration of corneal stromal degradation in severe ocular burns.