按我院与美国OIR(organization For Industrial Research)公司签订的成组技术软件引进合同的规定,我方于1987年8月派员去美国波斯顿(Boston),OIR公司总部所在地接受培训,最后两周我们访问了该公司的三个用户厂。在此作一简介,以期读者...按我院与美国OIR(organization For Industrial Research)公司签订的成组技术软件引进合同的规定,我方于1987年8月派员去美国波斯顿(Boston),OIR公司总部所在地接受培训,最后两周我们访问了该公司的三个用户厂。在此作一简介,以期读者能从中了解到一些有关成组技术及其软件在美国的应用情况。展开更多
Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide...Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.展开更多
AIM: To investigate the expression of FLT4 in retina with oxygen induced retinopathy (OIR) and in brain endothelial cell lines (bEnd3) under hypoxia conditions in mice. METHODS: Fifty-two one-week-old C57BL/6J mice we...AIM: To investigate the expression of FLT4 in retina with oxygen induced retinopathy (OIR) and in brain endothelial cell lines (bEnd3) under hypoxia conditions in mice. METHODS: Fifty-two one-week-old C57BL/6J mice were divided into control group and hypoxia group. The mice of hypoxia group were exposed to 75% oxygen for 5 days and then returned to the room air to induce retinal neovascularization. Mice in control group were raised in the environment of room air at the same time. The expressions of FLT4 mRNA and protein were checked with RT-PCR and Western Blot analysis at postnatal day 14, 17 and 21 (P14, P17 and P21) respectively. 125mmol/L CoCl(2) were added to the culture medium of bEnd3 cell, proteins were extracted in 12, 24, 48 and 72 hours and FLT4 levels were examined by Western Blot analysis. RESULTS: The mRNA and protein level of FLT4 Expressed in P14 and P17 OIR mice retina statistically up-regulated as compared with those in control group, but there was no statistical difference between OIR group and control group at P21. FLT4 levels increased significantly in 12, 24 and 48 hours hypoxia intervened bEnd3 cells, its levels in 72 hours raised mildly but showed no significance. CONCLUSION: FLT4 levels increase in OIR mice retinas and bEnd3 cells in hypoxia. It may play an important role in endothelial cells proliferation in hypoxia and retinal neovascularization in OIR mice.展开更多
文摘按我院与美国OIR(organization For Industrial Research)公司签订的成组技术软件引进合同的规定,我方于1987年8月派员去美国波斯顿(Boston),OIR公司总部所在地接受培训,最后两周我们访问了该公司的三个用户厂。在此作一简介,以期读者能从中了解到一些有关成组技术及其软件在美国的应用情况。
基金supported by the National Natural Science Foundation of China(Nos.82200379 and 82300309)the Shanghai Sailing Program(No.22YF1443100)+1 种基金the Academy Talent Special Fund of The First Affiliated Hospital of Nanjing Medical University(Nos.YNRCQN0312 and MXJL202208)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB592),China.
文摘Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.
基金National Natural Science Foundation of China(No. 30872822)
文摘AIM: To investigate the expression of FLT4 in retina with oxygen induced retinopathy (OIR) and in brain endothelial cell lines (bEnd3) under hypoxia conditions in mice. METHODS: Fifty-two one-week-old C57BL/6J mice were divided into control group and hypoxia group. The mice of hypoxia group were exposed to 75% oxygen for 5 days and then returned to the room air to induce retinal neovascularization. Mice in control group were raised in the environment of room air at the same time. The expressions of FLT4 mRNA and protein were checked with RT-PCR and Western Blot analysis at postnatal day 14, 17 and 21 (P14, P17 and P21) respectively. 125mmol/L CoCl(2) were added to the culture medium of bEnd3 cell, proteins were extracted in 12, 24, 48 and 72 hours and FLT4 levels were examined by Western Blot analysis. RESULTS: The mRNA and protein level of FLT4 Expressed in P14 and P17 OIR mice retina statistically up-regulated as compared with those in control group, but there was no statistical difference between OIR group and control group at P21. FLT4 levels increased significantly in 12, 24 and 48 hours hypoxia intervened bEnd3 cells, its levels in 72 hours raised mildly but showed no significance. CONCLUSION: FLT4 levels increase in OIR mice retinas and bEnd3 cells in hypoxia. It may play an important role in endothelial cells proliferation in hypoxia and retinal neovascularization in OIR mice.
