AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudativ...AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.展开更多
AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included ...AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group.Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups.· RESULTS： AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness（P =0.01, 0.047, 0.025 and 〈0.001, respectively）. Serum VEGFR-2level revealed a significant decrease in AMD patients compared to controls（26.48 ±6.44 vs 30.42 ±7.92 ng/m L,P 〈0.001）. There was an insignificant increase in serum adropin level in AMD patients（6.17±3.19 vs 5.79±2.71 ng/m L,P =0.4）. Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness（r =-0.226, P =0.025） and a significant positive correlation with subfoveal choroidal thickness（r=0.2, P=0.048）.·CONCLUSION： The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD.展开更多
OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predic...OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular docking.The effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation assays.Analysis of apoptosis was performed by flow cytometry.CD31 levels were examined by immunofluorescence.The abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot analysis.Corneal alkali burn was performed on 40 mice.Animals were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a day.Slitlamp microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and 14.The mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein extraction.RESULTS:Molecular docking confirmed that emodin was able to target VEGFR2.The findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent manner.In mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn.Compared to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated group.Emodin dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated HUVEC.CONCLUSION:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization.Emodin might be a promising new therapeutic option for corneal alkali burns.展开更多
Objective： To observe the effect of Kang＇ai Injection （康艾注射液, KAI） on serum level of soluble interleukin-2 receptor （sIL-2R） and vascular endothelial growth factor （VEGF） in patients with esophageal carci...Objective： To observe the effect of Kang＇ai Injection （康艾注射液, KAI） on serum level of soluble interleukin-2 receptor （sIL-2R） and vascular endothelial growth factor （VEGF） in patients with esophageal carcinoma （EC） during radiotherapy （RT）, and to investigate its synergistic effect with RT and its influence on immunological function of the body. Methods： One hundred and seventy patients with EC, who had missed the chance of surgical operational therapy, were assigned to the treated group （90 cases） and the RT group （80 cases）, and at the same time a control group consisting of 80 inpatients without tumors was set up. Patients in the RT group were treated with RT alone but KAI was given additionally to those in the treated group, with 50 ml given once per day via intravenous dripping, 15 days as one course, and 2 courses administered in total. The immediate therapeutic efficacy and changes of serum slL-2R and VEGF levels were observed, and the effect of KAI on patients＇ quality of life （QOF） was evaluated by Karnofsky scoring. Results： In 16 patients of the treated group it was completely remission （OR）, in 54 partially remission （PR）, in 18 it was stabilized disease （SD） and in 2 progressive disease （PD）, with the total effective rate （CR ＋ PR） as 77.8%, while in those of the control group it was 12, 46, 18, 4 and 72.5%, respectively, the immediate therapeutic efficacy in the treated group was somewhat better than that in the RT group, but showed no statistical significance （P〉0.05）. Serum levels of slL-2R and VEGF in all the patients before treatment were higher than those in the control group, which were decreased after treatment in both groups （P〈0.05）, but the improvement in the treated group was better than that in the RT group, showing significant difference （P〈0.05）, and patients＇ QOF improved more significantly in the former as well （62.2 % vs 40.0%, P〈 0.05）. Conclusion： KAI in combination with RT in treating patients with EC could enhance the immunological function of patients, improve their QOF and enhance their sensitivity to RT.展开更多
Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregna...Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls,and aimed to explore the effect of DBP on endothelial cells(ECs)and the underlying mechanism.Methods::DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry.The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA(siRNA)and DBP-expression vector,respectively.The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC(HUVEC)cultures.Angiogenic effects on HUVECs were assessed by tube formation assays,and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer.The expression of vascular endothelial growth factor(VEGF)and VEGF receptor(VEGFR)-2,as well as the phosphorylation of different residues of VEGFR-2 in HUVECs,were determined by western blotting.Results::DBP expression was significantly increased in the placental tissues collected from PE patients.The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs,in addition to their proliferation and migration.Furthermore,treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996,whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951,996,and 1,175.Conclusions::The expression of DBP is increased in the placentas of PE patients.DBP plays potential roles in endothelial dysfunction,which contributes to PE development,by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.展开更多
OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were r...OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control(group 1). The remaining rats were injected intradermally with emulsified type Ⅱ bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis(CIA), rats were randomly divided into three groups(n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model(saline); group 3, tripterygium polyglycoside(TP; 7.81 mg/kg, positive control);group 4, Huatan Tongluo decoction(HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF) and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS: Compared with the model group, a significantly lower arthritis index was observed in the positive control group(P < 0.05) and HTTL group(P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P < 0.05) in the treatment groups.CONCLUSION: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.展开更多
基金Supported by the National Natural Science Foundation of China(No.81670881)
文摘AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.
文摘AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group.Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups.· RESULTS： AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness（P =0.01, 0.047, 0.025 and 〈0.001, respectively）. Serum VEGFR-2level revealed a significant decrease in AMD patients compared to controls（26.48 ±6.44 vs 30.42 ±7.92 ng/m L,P 〈0.001）. There was an insignificant increase in serum adropin level in AMD patients（6.17±3.19 vs 5.79±2.71 ng/m L,P =0.4）. Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness（r =-0.226, P =0.025） and a significant positive correlation with subfoveal choroidal thickness（r=0.2, P=0.048）.·CONCLUSION： The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD.
基金Fujian Major Research Grants for Young and Middle-aged Health Professionals(No.2021ZQNZD012,Research and Development of Anti-Keratitis Protein Drug Sgp130)National Natural Science Foundation of China(No.81774369,Study on Mechanism of Yijing Decoction in Preventing Microvascular Damage of Early Diabetic Retinopathy based on MMPs/TIMPs)。
文摘OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular docking.The effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation assays.Analysis of apoptosis was performed by flow cytometry.CD31 levels were examined by immunofluorescence.The abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot analysis.Corneal alkali burn was performed on 40 mice.Animals were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a day.Slitlamp microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and 14.The mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein extraction.RESULTS:Molecular docking confirmed that emodin was able to target VEGFR2.The findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent manner.In mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn.Compared to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated group.Emodin dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated HUVEC.CONCLUSION:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization.Emodin might be a promising new therapeutic option for corneal alkali burns.
文摘Objective： To observe the effect of Kang＇ai Injection （康艾注射液, KAI） on serum level of soluble interleukin-2 receptor （sIL-2R） and vascular endothelial growth factor （VEGF） in patients with esophageal carcinoma （EC） during radiotherapy （RT）, and to investigate its synergistic effect with RT and its influence on immunological function of the body. Methods： One hundred and seventy patients with EC, who had missed the chance of surgical operational therapy, were assigned to the treated group （90 cases） and the RT group （80 cases）, and at the same time a control group consisting of 80 inpatients without tumors was set up. Patients in the RT group were treated with RT alone but KAI was given additionally to those in the treated group, with 50 ml given once per day via intravenous dripping, 15 days as one course, and 2 courses administered in total. The immediate therapeutic efficacy and changes of serum slL-2R and VEGF levels were observed, and the effect of KAI on patients＇ quality of life （QOF） was evaluated by Karnofsky scoring. Results： In 16 patients of the treated group it was completely remission （OR）, in 54 partially remission （PR）, in 18 it was stabilized disease （SD） and in 2 progressive disease （PD）, with the total effective rate （CR ＋ PR） as 77.8%, while in those of the control group it was 12, 46, 18, 4 and 72.5%, respectively, the immediate therapeutic efficacy in the treated group was somewhat better than that in the RT group, but showed no statistical significance （P〉0.05）. Serum levels of slL-2R and VEGF in all the patients before treatment were higher than those in the control group, which were decreased after treatment in both groups （P〈0.05）, but the improvement in the treated group was better than that in the RT group, showing significant difference （P〈0.05）, and patients＇ QOF improved more significantly in the former as well （62.2 % vs 40.0%, P〈 0.05）. Conclusion： KAI in combination with RT in treating patients with EC could enhance the immunological function of patients, improve their QOF and enhance their sensitivity to RT.
基金This study was supported by the National Key R and D Program of China(2016YFC1000403)the National Nature Science Foundation of China(81601311 and 81300491).
文摘Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls,and aimed to explore the effect of DBP on endothelial cells(ECs)and the underlying mechanism.Methods::DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry.The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA(siRNA)and DBP-expression vector,respectively.The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC(HUVEC)cultures.Angiogenic effects on HUVECs were assessed by tube formation assays,and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer.The expression of vascular endothelial growth factor(VEGF)and VEGF receptor(VEGFR)-2,as well as the phosphorylation of different residues of VEGFR-2 in HUVECs,were determined by western blotting.Results::DBP expression was significantly increased in the placental tissues collected from PE patients.The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs,in addition to their proliferation and migration.Furthermore,treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996,whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951,996,and 1,175.Conclusions::The expression of DBP is increased in the placentas of PE patients.DBP plays potential roles in endothelial dysfunction,which contributes to PE development,by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.
基金Supported by National Natural Science Foundation of China Funded project:Study on the Relation between Rheumatic Arthralgia Induced by Phlem and Blood Stasis and Joints Angiogenesis of Rheumatoid Arthritis(No.81473574)Internal Project of Xiamen Hospital of Traditional Chinese Medicine Funded Project:Investigating the Therapeutic Effect and Mechanism of Resolving Phlegm and Turbidity Decoction(No.2015003)Nature Science Foundation of Fujian Province Funded Project:Studies on siRNA Drugs by Down-Regulation of both c-FLIPL and MADD for Targeted Ovarian Cancer Therapy(No.2015J01347)
文摘OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control(group 1). The remaining rats were injected intradermally with emulsified type Ⅱ bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis(CIA), rats were randomly divided into three groups(n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model(saline); group 3, tripterygium polyglycoside(TP; 7.81 mg/kg, positive control);group 4, Huatan Tongluo decoction(HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF) and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS: Compared with the model group, a significantly lower arthritis index was observed in the positive control group(P < 0.05) and HTTL group(P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P < 0.05) in the treatment groups.CONCLUSION: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.
