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
AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was i...AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.展开更多
We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be class...We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be classified roughly into four different states.Type-C quasi-periodic oscillations(QPOs)observed by NICER(about 0.1-6 Hz)and Insight-HXMT(about 0.7-8 Hz)are also reported in this work.Meanwhile,we study various physical quantities related to QPO frequency.The QPO rms-frequency relationship in the energy band 1-10 keV indicates that there is a turning pointing in frequency around2 Hz,which is similar to that of GRS 1915+105.A possible hypothesis for the relationship above may be related to the inclination of the source,which may require a high inclination to explain it.The relationships between QPO frequency and QPO rms,hardness,total fractional rms and count rate have also been found in other transient sources,which can indicate that the origin of type-C QPOs is non-thermal.展开更多
The LE is the low energy telescope that is carried on Insight-HXMT.It uses swept charge devices(SCDs)to detect soft X-ray photons.LE’s time response is caused by the structure of the SCDs.With theoretical analysis an...The LE is the low energy telescope that is carried on Insight-HXMT.It uses swept charge devices(SCDs)to detect soft X-ray photons.LE’s time response is caused by the structure of the SCDs.With theoretical analysis and Monte Carlo simulations we discuss the influence of LE time response(LTR)on the timing analysis from three aspects:the power spectral density,the pulse profile and the time lag.After the LTR,the value of power spectral density monotonously decreases with the increasing frequency.The power spectral density of a sinusoidal signal reduces by a half at frequency 536 Hz.The corresponding frequency for quasi-periodic oscillation(QPO)signals is 458 Hz.The root mean square(RMS)of QPOs holds a similar behaviour.After the LTR,the centroid frequency and full width at half maxima(FWHM)of QPOs signals do not change.The LTR reduces the RMS of pulse profiles and shifts the pulse phase.In the time domain,the LTR only reduces the peak value of the cross-correlation function while it does not change the peak position;thus it will not affect the result of the time lag.When considering the time lag obtained from two instruments and one among them is LE,a 1.18 ms lag is expected caused by the LTR.The time lag calculated in the frequency domain is the same as that in the time domain.展开更多
We investigate high time resolution data obtained by the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)during the flare event on 2022 April 21 at 01:52 UT.Several subpeaks with durat...We investigate high time resolution data obtained by the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)during the flare event on 2022 April 21 at 01:52 UT.Several subpeaks with durations of 4-6 s have been detected in the hard X-ray precursor phase,and the key feature is that they appear in pairs and seem like double-peak struc-tures.These subpeaks are rarely observed in hard X-ray band and confirmed by the microwave obtained by Nobeyama Radio Polarimeters(NoRP)and Radio Solar Telescope Network(RSTN).While an exponential function can describe the continuum component of the time profile from the precursor to part of the impulsive phase.The periods of quasi-periodic pulsations(QPPs)are detected to be about 7.3 and 12.8 s for the precursor and impulsive phase,respectively,with at least 95%confidence level.The paired QPPs are assumed to be double-peak QPPs and then the scenario of current loop coalescence model is found to be in good agreement with our observation.The precursor phase can be interpreted as the oscillating coalescence of two islands,while the impulsive phase can be interpreted as more islands to coalesce one by one to form larger islands.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Supported partially by National Natural Science Foundation of China(No.81271033,81470621)
文摘AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.
基金the HXMT mission,a project funded by China National Space Administration(CNSA)and the Chinese Academy of Sciences(CAS)supported by the National Key R&D Program of China(2016YFA0400800)the National Natural Science Foundation of China(Grant Nos.11673023,U1838201,U1838115,U1838111,U1838202,11733009 and U1838108)。
文摘We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846-031 during its outburst in 2019 with the observations of Insight-HXMT,NICER and MAXI.This outburst can be classified roughly into four different states.Type-C quasi-periodic oscillations(QPOs)observed by NICER(about 0.1-6 Hz)and Insight-HXMT(about 0.7-8 Hz)are also reported in this work.Meanwhile,we study various physical quantities related to QPO frequency.The QPO rms-frequency relationship in the energy band 1-10 keV indicates that there is a turning pointing in frequency around2 Hz,which is similar to that of GRS 1915+105.A possible hypothesis for the relationship above may be related to the inclination of the source,which may require a high inclination to explain it.The relationships between QPO frequency and QPO rms,hardness,total fractional rms and count rate have also been found in other transient sources,which can indicate that the origin of type-C QPOs is non-thermal.
基金the National Key R&D Program of China(2016YFA0400800)the National Natural Science Foundation of China(Grant Nos.U1838201,U1838202,U1838101 and U1938109)the Insight-HXMT mission,a project funded by China National Space Administration(CNSA)and the Chinese Academy of Sciences(CAS)。
文摘The LE is the low energy telescope that is carried on Insight-HXMT.It uses swept charge devices(SCDs)to detect soft X-ray photons.LE’s time response is caused by the structure of the SCDs.With theoretical analysis and Monte Carlo simulations we discuss the influence of LE time response(LTR)on the timing analysis from three aspects:the power spectral density,the pulse profile and the time lag.After the LTR,the value of power spectral density monotonously decreases with the increasing frequency.The power spectral density of a sinusoidal signal reduces by a half at frequency 536 Hz.The corresponding frequency for quasi-periodic oscillation(QPO)signals is 458 Hz.The root mean square(RMS)of QPOs holds a similar behaviour.After the LTR,the centroid frequency and full width at half maxima(FWHM)of QPOs signals do not change.The LTR reduces the RMS of pulse profiles and shifts the pulse phase.In the time domain,the LTR only reduces the peak value of the cross-correlation function while it does not change the peak position;thus it will not affect the result of the time lag.When considering the time lag obtained from two instruments and one among them is LE,a 1.18 ms lag is expected caused by the LTR.The time lag calculated in the frequency domain is the same as that in the time domain.
基金supported by the National Natural Science Foundation of China (Grant Nos. U1938102, and 11973092)the National Program on Key Research and Development Project (Grant No. 2016YFA0400802)supported by the Surface Project of Jiangsu Province (Grant No. BK20211402)
文摘We investigate high time resolution data obtained by the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)during the flare event on 2022 April 21 at 01:52 UT.Several subpeaks with durations of 4-6 s have been detected in the hard X-ray precursor phase,and the key feature is that they appear in pairs and seem like double-peak struc-tures.These subpeaks are rarely observed in hard X-ray band and confirmed by the microwave obtained by Nobeyama Radio Polarimeters(NoRP)and Radio Solar Telescope Network(RSTN).While an exponential function can describe the continuum component of the time profile from the precursor to part of the impulsive phase.The periods of quasi-periodic pulsations(QPPs)are detected to be about 7.3 and 12.8 s for the precursor and impulsive phase,respectively,with at least 95%confidence level.The paired QPPs are assumed to be double-peak QPPs and then the scenario of current loop coalescence model is found to be in good agreement with our observation.The precursor phase can be interpreted as the oscillating coalescence of two islands,while the impulsive phase can be interpreted as more islands to coalesce one by one to form larger islands.
