BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced gly...BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced glycation end products(AGEs)and their cell toxicity can be a useful therapeutic strategy in the prevention of diabetic retinopathy(DR).Gardenia jasminoides Ellis(GJE)fruit is a selective inhibitor of AGEs.Genipin is an active compound of GJE fruit,which can be employed to treat diabetes.AIM To confirm the effect of genipin,a vital component of GJE fruit,in preventing human retinal microvascular endothelial cells(hRMECs)from AGEs damage in DR,to investigate the effect of genipin in the down-regulation of AGEs expression,and to explore the role of the CHGA/UCP2/glucose transporter 1(GLUT1)signal pathway in this process.METHODS In vitro,cell viability was tested to determine the effects of different doses of glucose and genipin in hRMECs.Cell Counting Kit-8(CCK-8),colony formation assay,flow cytometry,immunofluorescence,wound healing assay,transwell assay,and tube-forming assay were used to detect the effect of genipin on hRMECs cultured in high glucose conditions.In vivo,streptozotocin(STZ)induced mice were used,and genipin was administered by intraocular injection(IOI).To explore the effect and mechanism of genipin in diabetic-induced retinal dysfunction,reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose(2-NBDG)assays were performed to explore energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas.Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines[vascular endothelial growth factor(VEGF),SCG3,tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-18,and nucleotide-binding domain,leucine-rich-containing family,pyrin domain-containing 3(NLRP3)].The protein expression of the receptor of AGEs(RAGE)and the mitochondria-related signal molecules CHGA,GLUT1,and UCP2 in high glucose-induced hRMECs and STZ mouse retinas were measured and compared with the genipin-treated group.RESULTS The results of CCK-8 and colony formation assay showed that genipin promoted cell viability in high glucose(30 mmol/L D-Glucose)-induced hRMECs,especially at a 0.4μmol/L dose for 7 d.Flow cytometry results showed that high glucose can increase apoptosis rate by 30%,and genipin alleviated cell apoptosis in AGEs-induced hRMECs.A high glucose environment promoted ATP,ROS,MMP,and 2-NBDG levels,while genipin inhibited these phenotypic abnormalities in AGEs-induced hRMECs.Furthermore,genipin remarkably reduced the levels of the pro-inflammatory cytokines TNF-α,IL-1β,IL-18,and NLRP3 and impeded the expression of VEGF and SCG3 in AGEs-damaged hRMECs.These results showed that genipin can reverse high glucose induced damage with regard to cell proliferation and apoptosis in vitro,while reducing energy metabolism,oxidative stress,and inflammatory injury caused by high glucose.In addition,ROS levels and glucose uptake levels were higher in the retina from the untreated eye than in the genipin-treated eye of STZ mice.The expression of inflammatory cytokines and pathway protein in the untreated eye compared with the genipin-treated eye was significantly increased,as measured by Western blot.These results showed that IOI of genipin reduced the expression of CHGA,UCP2,and GLUT1,maintained the retinal structure,and decreased ROS,glucose uptake,and inflammation levels in vivo.In addition,we found that SCG3 expression might have a higher sensitivity in DR than VEGF as a diagnostic marker at the protein level.CONCLUSION Our study suggested that genipin ameliorates AGEs-induced hRMECs proliferation,apoptosis,energy metabolism,oxidative stress,and inflammatory injury,partially via the CHGA/UCP2/GLUT1 pathway.Control of advanced glycation by IOI of genipin may represent a strategy to prevent severe retinopathy and vision loss.展开更多
BACKGROUND Optical coherence tomography angiography(OCTA)is a new and reliable machine used to evaluate retinal structure and macular perfusion in children.The use of OCTA under bad condition such as high altitude,low...BACKGROUND Optical coherence tomography angiography(OCTA)is a new and reliable machine used to evaluate retinal structure and macular perfusion in children.The use of OCTA under bad condition such as high altitude,low atmospheric oxygen,and low humidity,in children is rarely.AIM To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo.METHODS Design:Prospective cross-sectional,school-based study.Three hundred and fortyseven normal students from 9 schools in 4 different areas in Qamdo were included.OCTA was performed on a 3 mm×3 mm area centered on the macular region and macular cube 512×128 showed details in macular.Early treatment of diabetic retinopathy study Vessel Flow Density(VD)of the macular central vascular plexus density(CVD),inner vascular plexus density(IVD),full vascular plexus density(FVD),and the size of the foveal avascular zone(FAZ)were measured.All these results corrected by t/s=3.382×0.01306×(axial length-1.82).The differences were compared among various ages,sexes and living environments.RESULTS The mean FAZ area in all eyes was 0.27 mm^(2)±0.12 mm^(2).The mean foveal thickness(MFT)in the macular cube was 227.64μm±23.51μm.Compared with girls,boys had a lager FAZ(P=0.0029).Among the different age groups,MFT(P<0.001)and FVD(P<0.0001),IVD(P<0.0001),and CVD(P=0.0050)increased with age.FAZ areas were not correlated with age(P=0.8853)or others(MFT,area).CONCLUSION OCTA can use to evaluate macular perfusion in children.Our data bridge the gap between structural OCT and perfusion density in children in high altitude.Even though these were not a longitudinal study,it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.展开更多
Three-dimensional(3D)artificial metacrystals host rich topological phases,such as Weyl points,nodal rings,and 3D photonic topological insulators.These topological states enable a wide range of applications,including 3...Three-dimensional(3D)artificial metacrystals host rich topological phases,such as Weyl points,nodal rings,and 3D photonic topological insulators.These topological states enable a wide range of applications,including 3D robust waveguides,one-way fiber,and negative refraction of the surface wave.However,these carefully designed metacrystals are usually very complex,hindering their extension to nanoscale photonic systems.Here,we theoretically proposed and experimentally realized an ideal nodal ring in the visible region using a simple 1D photonic crystal.The TT-Berrry phase around the ring is manifested by a 2π reflection phase's winding and the resultant drumhead surface states.By breaking the inversion symmetry,the nodal ring can be gapped and the n-Berry phase would diffuse into a toroidal-shaped Berry flux,resulting in photonic ridge states(the 3D extension of quantum valley Hall states).Our results provide a simple and feasible platform for exploring 3D topological physics and its potential applications in nanophotonics.展开更多
基金the National Natural Science Foundation of China,No.81870650,No.81570832,and No.81900885Science and Technology Program Chongqing,No.2018GDRC008 and No.XKTS049。
文摘BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced glycation end products(AGEs)and their cell toxicity can be a useful therapeutic strategy in the prevention of diabetic retinopathy(DR).Gardenia jasminoides Ellis(GJE)fruit is a selective inhibitor of AGEs.Genipin is an active compound of GJE fruit,which can be employed to treat diabetes.AIM To confirm the effect of genipin,a vital component of GJE fruit,in preventing human retinal microvascular endothelial cells(hRMECs)from AGEs damage in DR,to investigate the effect of genipin in the down-regulation of AGEs expression,and to explore the role of the CHGA/UCP2/glucose transporter 1(GLUT1)signal pathway in this process.METHODS In vitro,cell viability was tested to determine the effects of different doses of glucose and genipin in hRMECs.Cell Counting Kit-8(CCK-8),colony formation assay,flow cytometry,immunofluorescence,wound healing assay,transwell assay,and tube-forming assay were used to detect the effect of genipin on hRMECs cultured in high glucose conditions.In vivo,streptozotocin(STZ)induced mice were used,and genipin was administered by intraocular injection(IOI).To explore the effect and mechanism of genipin in diabetic-induced retinal dysfunction,reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose(2-NBDG)assays were performed to explore energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas.Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines[vascular endothelial growth factor(VEGF),SCG3,tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-18,and nucleotide-binding domain,leucine-rich-containing family,pyrin domain-containing 3(NLRP3)].The protein expression of the receptor of AGEs(RAGE)and the mitochondria-related signal molecules CHGA,GLUT1,and UCP2 in high glucose-induced hRMECs and STZ mouse retinas were measured and compared with the genipin-treated group.RESULTS The results of CCK-8 and colony formation assay showed that genipin promoted cell viability in high glucose(30 mmol/L D-Glucose)-induced hRMECs,especially at a 0.4μmol/L dose for 7 d.Flow cytometry results showed that high glucose can increase apoptosis rate by 30%,and genipin alleviated cell apoptosis in AGEs-induced hRMECs.A high glucose environment promoted ATP,ROS,MMP,and 2-NBDG levels,while genipin inhibited these phenotypic abnormalities in AGEs-induced hRMECs.Furthermore,genipin remarkably reduced the levels of the pro-inflammatory cytokines TNF-α,IL-1β,IL-18,and NLRP3 and impeded the expression of VEGF and SCG3 in AGEs-damaged hRMECs.These results showed that genipin can reverse high glucose induced damage with regard to cell proliferation and apoptosis in vitro,while reducing energy metabolism,oxidative stress,and inflammatory injury caused by high glucose.In addition,ROS levels and glucose uptake levels were higher in the retina from the untreated eye than in the genipin-treated eye of STZ mice.The expression of inflammatory cytokines and pathway protein in the untreated eye compared with the genipin-treated eye was significantly increased,as measured by Western blot.These results showed that IOI of genipin reduced the expression of CHGA,UCP2,and GLUT1,maintained the retinal structure,and decreased ROS,glucose uptake,and inflammation levels in vivo.In addition,we found that SCG3 expression might have a higher sensitivity in DR than VEGF as a diagnostic marker at the protein level.CONCLUSION Our study suggested that genipin ameliorates AGEs-induced hRMECs proliferation,apoptosis,energy metabolism,oxidative stress,and inflammatory injury,partially via the CHGA/UCP2/GLUT1 pathway.Control of advanced glycation by IOI of genipin may represent a strategy to prevent severe retinopathy and vision loss.
基金Supported by the National Natural Science Foundation of China,No.81870650,No.81570832,and No.81300794Science and Technology Program Chongqing,China,No.2018GDRC008.
文摘BACKGROUND Optical coherence tomography angiography(OCTA)is a new and reliable machine used to evaluate retinal structure and macular perfusion in children.The use of OCTA under bad condition such as high altitude,low atmospheric oxygen,and low humidity,in children is rarely.AIM To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo.METHODS Design:Prospective cross-sectional,school-based study.Three hundred and fortyseven normal students from 9 schools in 4 different areas in Qamdo were included.OCTA was performed on a 3 mm×3 mm area centered on the macular region and macular cube 512×128 showed details in macular.Early treatment of diabetic retinopathy study Vessel Flow Density(VD)of the macular central vascular plexus density(CVD),inner vascular plexus density(IVD),full vascular plexus density(FVD),and the size of the foveal avascular zone(FAZ)were measured.All these results corrected by t/s=3.382×0.01306×(axial length-1.82).The differences were compared among various ages,sexes and living environments.RESULTS The mean FAZ area in all eyes was 0.27 mm^(2)±0.12 mm^(2).The mean foveal thickness(MFT)in the macular cube was 227.64μm±23.51μm.Compared with girls,boys had a lager FAZ(P=0.0029).Among the different age groups,MFT(P<0.001)and FVD(P<0.0001),IVD(P<0.0001),and CVD(P=0.0050)increased with age.FAZ areas were not correlated with age(P=0.8853)or others(MFT,area).CONCLUSION OCTA can use to evaluate macular perfusion in children.Our data bridge the gap between structural OCT and perfusion density in children in high altitude.Even though these were not a longitudinal study,it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.
基金This work was supported by National Natural Science Foundation of China(Grant Nos.11874435,62035016,12074443,and 11904421)Guangdong Basic and Applied Basic Research Foundation(Grant No.20198151502036)+2 种基金Natural Science Foundation of Guangdong Province(Grant No.20188030308005)Guangzhou Science,Technology and Innovation Commission(Grant Nos.201904010223 and 202102020693)Fundamental Research Funds for the Central Universities(Grant No.20lgzd29,20lgjc05,and 2021qntd27).
文摘Three-dimensional(3D)artificial metacrystals host rich topological phases,such as Weyl points,nodal rings,and 3D photonic topological insulators.These topological states enable a wide range of applications,including 3D robust waveguides,one-way fiber,and negative refraction of the surface wave.However,these carefully designed metacrystals are usually very complex,hindering their extension to nanoscale photonic systems.Here,we theoretically proposed and experimentally realized an ideal nodal ring in the visible region using a simple 1D photonic crystal.The TT-Berrry phase around the ring is manifested by a 2π reflection phase's winding and the resultant drumhead surface states.By breaking the inversion symmetry,the nodal ring can be gapped and the n-Berry phase would diffuse into a toroidal-shaped Berry flux,resulting in photonic ridge states(the 3D extension of quantum valley Hall states).Our results provide a simple and feasible platform for exploring 3D topological physics and its potential applications in nanophotonics.
