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Objective:To explore the risk factors for the occurrence of preeclampsia (PE) and the predictive value of serum vascular endothelial growth factor receptor-1 (VEGFR-1) and placental growth factor (PLGF) for PE.Methods:A retrospective study was conducted to select 148 pregnant women who underwent prenatal examinations at the First People′s Hospital of Chenzhou from January 2020 to January 2022 and were ultimately diagnosed with PE as the PE group, and 148 healthy pregnant women who underwent prenatal examinations during the same period as the PE group were selected as the control group. The levels of VEGFR-1, PLGF, and VEGFR-1/PLGF were compared between two groups of pregnant women. Logistic regression analysis was performed on the risk factors for PE, and the correlation between VEGFR-1, PLGF, VEGFR-1/PLGF and risk factors was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of VEGFR-1, PLGF, and VEGFR-1/PLGF for PE and obtain cutoff values. The survival curve of pregnant women with PE was plotted based on the cutoff values.Results:The levels of VEGFR-1 and VEGFR-1/PLGF in the PE group were higher than those in the control group (all P<0.05), while the levels of PLGF were lower than those in the control group ( P<0.05). Logistic regression analysis showed that age, body mass index (BMI), pregnancy induced hypertension, pregnancy induced diabetes, family history of hypertension, preeclampsia, VEGFR-1 and VEGFR-1/PLGF were risk factors for PE (all P<0.05), and PLGF was a protective factor for PE ( P<0.05). VEGFR-1, VEGFR-1/PLGF were positively correlated with age, BMI, pregnancy induced hypertension, pregnancy induced diabetes, hypertension family history, and PE (all P<0.001), while PLGF was negatively correlated with age, BMI, pregnancy induced hypertension, pregnancy induced diabetes, hypertension family history, and preeclampsia (all P<0.001). VEGFR-1, PLGF, and VEGFR-1/PLGF had higher predictive value for PE (AUC=0.773, 0.791, 0.825), with cutoff values of 9190.83 ng/L, 508.17 ng/L, and 21.64, respectively. According to the cutoff value, 296 pregnant women were divided into three groups: low, medium, and high risk. The survival analysis results showed that the probabilities of PE occurrence in the three groups were 1.36%, 18.97%, and 66.67%, respectively. Conclusions:VEGFR-1 and PLGF have high predictive value for PE, and clinical monitoring of VEGFR-1/PLGF levels combined with other examination methods can improve the accuracy of PE diagnosis and prediction, and improve pregnancy outcomes.
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Objective:To investigate the expression and diagnostic value of microRNA-335-5p (miR-335-5p) and Human Vascular endothelial growth factor receptor 1 (VEGFR-1, FLT1) in serum exosomal bodies of patients with triple negative breast cancer (TNBC) .Methods:Gene Expression Omnibus database (GEO) analysis was performed and differentially expressed miRNA in breast cancer tissues was screened. From Jan. 2016 to Nov. 2017, the peripheral blood samples of 56 TNBC patients in People’s Hospital Affiliated to Ningbo University were collected, and the exosomes were isolated and identified. FLT1 was selected as the target gene of miR-335-5p by using bioinformatics analysis. Expression levels of miR-335-5p and FLT1 in serum exosome were detected by qRT-PCR. The relationship between miR-335-5p and clinicopathological parameters of TNBC patients was analyzed. The diagnostic value of miR-335-5p was evaluated by receiver operating characteristic (ROC) , and the survival prognosis of miR-335-5p and FLT1 was analyzed by Kaplan Meier survival curve.Results:The expression of miR-335-5p in the serum exosome of TNBC patients was lower than that of the control group, while the expression of FLT1 in the serum exosome was higher than that of the control group ( P<0.05) . The expression of miR-335-5p was related to tissue grade ( χ2=22.02, P<0.000 1) , degree of differentiation ( χ2=20.67, P<0.000 1) and lymph node metastasis ( χ2=4.667, P=0.030 8) in patients with TNBC ( P<0.05) . The area under ROC diagnosed by miR-335-5p was 0.809 8 (95% CI: 0.726 3-0.893 2, P<0.000 1) . Kaplan-Meier survival analysis showed that the overall survival time of patients with low expression of miR-335-5p was significantly shorter than that of patients with high expression of miR-335-5p ( P=0.004 5) . The high expression of its target gene FLT1 was associated with low survival rate ( P=0.048 0) . Conclusion:Serum exosomal miR-335-5p can be used as an important index to predict the prognosis of TNBF and is expected to play a role in diagnosis and treatment of TNBC.
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Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.
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Objective To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)?like mouse models. Methods C57BL/6J mice were randomly subcutaneously injected with N?nitro?L?arginine methyl ester (L?NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE?like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L?NAME+Pra, LPS+Pra, Con+Pra) and saline (L?NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt?1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real?time fluorescence quantitative PCR (RT-PCR). Results (1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50± 4.31) levels were significantly increased in L?NAME+Pra group compared with L?NAME+NS group (all P<0.05). Serum VEGF (202.30 ± 4.90, 144.50 ± 6.71) and PlGF (121.50 ± 3.86, 95.41 ± 4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt?1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt?1 level in L?NAME+Pra group was significantly lower than that in L?NAME+NS group (2.60±0.06, 583.70±9.83;all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66 ± 0.14) in the liver of mice in the L?NAME+Pra group were significantly higher than those in the L?NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L?NAME+Pra group were not significantly different from those of L?NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT?PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L?NAME+Pra group were not significantly different from those in L?NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05). Conclusions Pra has different regulatory effects on vascular endothelial function in different PE?like models. It reveals that different pathogenesis and pathways exist in different PE?like changes.
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Objective • To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods • The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results • Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models(P<0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion • ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.
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Objective@#To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)-like mouse models.@*Methods@#C57BL/6J mice were randomly subcutaneously injected with N-nitro-L-arginine methyl ester (L-NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE-like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L-NAME+Pra, LPS+Pra, Con+Pra) and saline (L-NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt-1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real-time fluorescence quantitative PCR (RT-PCR).@*Results@#(1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50±4.31) levels were significantly increased in L-NAME+Pra group compared with L-NAME+NS group (all P<0.05). Serum VEGF (202.30±4.90, 144.50±6.71) and PlGF (121.50±3.86, 95.41±4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt-1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt-1 level in L-NAME+Pra group was significantly lower than that in L-NAME+NS group (2.60±0.06, 583.70±9.83; all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66±0.14) in the liver of mice in the L-NAME+Pra group were significantly higher than those in the L-NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L-NAME+Pra group were not significantly different from those of L-NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT-PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L-NAME+Pra group were not significantly different from those in L-NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05).@*Conclusions@#Pra has different regulatory effects on vascular endothelial function in different PE-like models. It reveals that different pathogenesis and pathways exist in different PE-like changes.
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Objective To investigate the expression of soluble vascular endothelial growth factor receptor 1 (sFlt1) in human umbilical cord-derived mesenchymal stem cells (HUCMSC) under the condition of inflammatory cytokine and co-culture with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs).Methods ① HUCMSC were cultured alone or stimulated by Tumour necrosis factor (TNF)-αt,interferon (IFN)-γor the combination of TNF-α and IFN-γ.The sFh1 levels of each group were detected by enzyme-linked immunosorbent assay (ELISA) at 24 h,48 h and 72 h respectively.② RA-FLSs and HUCMSC were cocultured in a transwell system with both of them cultured alone as control for 72 hours.ELISA was used to detect sFlt1 levels in each group.T test was used for comparison between two groups,and ANOVA was used to compare multi-group variables.Results ① The sFlt1 levels of TNF-α + IFN-γ group were significantly higher than those of the control group at 24 h and 48 h (24 h (5.4±0.4) ng/ml vs (2.8±1.7) ng/ml,t=0.942,P=0.026;48 h (7.2±0.8) vs (4.3±1.0) ng/ml,t=4.285,P=0.005),while that at 72 h was not significantly different [(9.1±1.7) ng/ml vs (7.0±1.4) ng/ml,t=0.683,P=0.52].And no significant difference in sFlt1 levels between control group and TNF-α group or IFN-γ stimulation group were observed.② Compared with RA-FLSs,the expression of sFlt1 in HUCMSC was significantly higher (8.19±3.64) ng/ml vs (0.19±0.08) ng/ml,t=7.280,P＜0.01].After co-cultured with RA-FLSs and HUCMSC,the sFlt1 concentration of the co-culture group was significantly higher than that of HUCMSC group [(17.26±6.92) ng/ml vs (8.19±3.64) ng/ml,t=3.985,P=0.000 7].Conclusion The sFlt1 expression of HUCMSC is up-regulated by inflammatory cytokine TNF-α combined with IFN-γ.RA FLSs may promote the co-cultured HUCMSC to increase sFlt1 expression by secreting inflammatory factors.
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·The common feature of retinal neovascularization is the formation of pathological neovascularization. The primary one of endogenous retinal neovascularization factor in current research is vascular endothelial growth factor (VEGF). SFlt-1, the soluble form of splicing in mRNA extracellular region of VEGFR - 1, which is short of intracellular tyrosine kinase domain can only encode the extracellular domain. Therefore, it only can bind with ligands but can not transmit signals, thus preventing the formation of neovascularization. SFlt-1,as a hot research topic in recent years, may provide a new gene therapy method for this disease. This review focus on the mechanism and research progress of sFlt-1 in retinal neovascularization.
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Objective To research the correlation between the level of serum brain natriuretic peptide (BNP) ,soluble vascular endothelial growth factor receptor 1 (sFlt-1) and nitric oxide (NO) and the changes of condition in preeclampsia(PE) patients.Methods Totally 89 patients with PE who had prenatal examina-tion and normal delivery in the hospital from May 2014 to January 2017 were enrolled in this study as the PE group ,and 94 healthy pregnant women who underwent normal delivery during the same period were selected as the NP group.The levels of serum BNP ,sFlt-1 and NO in PE patients with different severity and different onset stages were compared and analyzed.Results The levels of serum BNP and sFlt-1 in the PE group were significantly higher than those in the NP group ,and the level of NO was significantly lower than that in the NP group ,and the differences were statistically significant (P＜0.05).The levels of serum BNP and sFlt-1 in the severe PE group were significantly higher than those in the mild PE group ,and the level of NO was signifi-cantly lower than that in the mild PE group ,and the differences were statistically significant (P＜0.05).The levels of serum BNP and sFlt-1 in the early and late onset PE groups were significantly higher than those in the early NP group and the late NP group ,while the NO levels were significantly lower than those in the early NP group and the late NP group ,and the differences were statistically significant (P＜0.05).Conclusion On the occurrence of PE ,the levels of serum BNP and sFlt-1 in pregnant women elevated abnormally ,and the lev-el of NO decreased.The changes of serum BNP ,sFlt-1 and NO levels are closely related to the development of PE ,and can be used as a reference index to detect the changes of PE.
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PURPOSE: We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-GNQWFI, to target tumor cells, and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model.METHODS: TAMRA-GHEG-ECG-GNQWFI was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-GNQWFI with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with U87MG tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy.RESULTS: After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-GNQWFI complexes were prepared in high yield (> 95%). The K(d) of Tc-99m TAMRA-GHEG-ECG-GNQWFI determined by saturation binding was 29.5 ± 4.5 nM. Confocal microscopy images of U87MG cells incubated with TAMRA-GHEG-ECG-GNQWFI showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumors. Tumor uptake was effectively blocked by the co-injection of an excess concentration of GNQWFI. Specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI was assessed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies.CONCLUSION: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumor cells. Tc-99m TAMRA-GHEG-ECG-GNQWFI could be a good candidate dual-modality imaging agent for tumors.
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Cytoplasm , Fluorescence , Immunohistochemistry , In Vitro Techniques , Microscopy, Confocal , Multimodal Imaging , Radionuclide Imaging , Solid-Phase Synthesis TechniquesABSTRACT
Objective: To evaluate the clinical indications of CD151 in patients with lung adenocarcinoma with positive expressions of vascular endothelial growth factor A (VEGFA) or vascular endothelial growth factor receptor (VEGFR). Methods: The expressions of VEGFA, VEGFR1, VEGFR2 and CD151 in 116 specimens of patients with lung adenocarcinoma after surgery were detected by immunohistochemistry. The association of CD151 expression with the clinical features of patients with lung adenocarcinoma with positive expression of VEGFA or VEGFR was analyzed. The effect of CD151 expression on the disease-free survival (DFS) of patients with lung adenocarcinoma with positive expression of VEGFA or VEGFR was evaluated. Results: The positive rates of VEGFA, VEGFR1, VEGFR2 and CD151 in lung adenocarcinoma tissues were 69.83% (81/116), 69.83% (81/116), 44.83% (52/116), and 42.24% (49/116), respectively. For patients with lung adenocarcinoma with positive expression of VEGFA, positive expression of CD151 was positively correlated with clinical TNM stage (r = 0.24, P = 0.04) as well as lymph node metastasis (r = 0.26, P = 0.02). CD151 was an independent factor predicting DFS of patients with lung adenocarcinoma with positive expression of VEGFA [hazard ratio (HR) = 1.80, 95% confidence interval (CI): 1.00 - 3.19, P = 0.048]. The median DFS of CD151-positive patients with positive expression of VEGFA was significantly shorter than that of CD151-negative patients (20 vs 34 months, P < 0.05). For patients with lung adenocarcinoma with positive expression of VEGFR1, positive expression of CD151 was positively correlated with TNM stage (r = 0.28, P = 0.01) and lymph node metastasis (r = 0.31, P < 0.01). Moreover, CD151 was an independent factor predicting DFS of patients with lung adenocarcinoma with positive expression of VEGFR2 (HR = 2.10 C95% CI: 1.02 - 4.33, P = 0.044), and the median DFS of CD151-positive patients with positive expression of VEGFR2 was significantly shorter than that of CD151-negative patients (21 vs 42 months, P < 0.05). Conclusion: CD151 is an independent factor predicting DFS of patients with lung adenocarcinoma with positive expression of VEGFA or VEGFR2.
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Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 years old. Vascular endothelial growth factor (VEGF) plays a critical role in the development of wet AMD. At present, the main treatment is monoclonal antibodies against VEGF, but the maintenance time is short, and it requires frequent and repeated treatment. Recently with the fast development of gene therapy, soluble VEGF receptor -1 (sFlt-1), which may act as one of the biomarkers of AMD, is gaining more attention. sFlt-1 is the unique endogenous VEGF inhibitor. With the development of AMD, serum sFlt-1 decreases markedly. This article reviewed the molecular structure and pathophysiological function of sFlt-1, its role in the advance of AMD, and the preclinical studies as well as clinical studies about it.
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Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 years old. Vascular endothelial growth factor (VEGF) plays a critical role in the development of wet AMD. At present, the main treatment is monoclonal antibodies against VEGF, but the maintenance time is short, and it requires frequent and repeated treatment. Recently with the fast development of gene therapy, soluble VEGF receptor -1 (sFlt-1), which may act as one of the biomarkers of AMD, is gaining more attention. sFlt-1 is the unique endogenous VEGF inhibitor. With the development of AMD, serum sFlt-1 decreases markedly. This article reviewed the molecular structure and pathophysiological function of sFlt-1, its role in the advance of AMD, and the preclinical studies as well as clinical studies about it.
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Objective To investigate the correlation between long non-coding RNA (lncRNA)-LOC391533 and inadequate placental spiral artery remodeling in severe preeclampsia (sPE).Methods Thirty-six gravidas who were admitted to the Third Affiliated Hospital of Zhengzhou University with sPE from January 2016 to December 2016 were enrolled in sPE group.An equal number of healthy gravidas who experienced uneventful pregnancy and were of similar age (difference less than two years) and gestational age (difference less than one week) to those in the sPE group served as controls.Scanning electron microscopy was used to measure the luminal area and vessel wall thickness of placental spiral arteries for all gravidas.Levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sVEGFR-1) in placenta tissues and maternal serum samples were detected by Western blot and ELISA.Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of LOC391533 at mRNA level in placenta tissues of the two groups.Independent two samples t-test,Mann-Whitney U test and Spearman correlation analysis were used for statistical analysis.Results (1) The average luminal area of spiral arteries of the sPE group was smaller than that of the control group [(130.1 22.3) vs (188.1 ±21.5) μ m2,t=10.888,P＜0.05],but the average thickness of spiral artery wall was thicker [(122.619.5) vs (98.9±2.5) μ m,t=-8.812,P＜0.05].(2) Compared with the control group,the sPE group showed increased sVEGFR-1 at protein level in both placenta tissues and serum samples [placenta:0.2±0.0 vs 0.4±0.1,serum:(15.6±2.4) vs (50.8±6.1) ng/L,t=-17.569 and-30.699,both P＜0.05],decreased VEGF at protein level in both placenta tissues and serum samples [placenta:0.6 ± 0.1 vs 0.2±0.0,serum:(40.8±3.2) vs (28.1 ±3.2) ng/L,t=18.013 and 16.200,both P＜0.05],and enhanced expression of LOC391533 at mRNA level in placenta tissues (1.00.2 vs 2.40.5,t=-14.799,P＜0.05).(3) Expression of LOC391533 at mRNA level in placenta tissues of the sPE group was positively correlated with spiral artery wall thickness and levels of sVEGFR-1 protein in placenta tissues and serum (r=0.683,0.759 and 0.857,all P＜0.05),and negatively correlated with luminal area and levels of VEGF protein in placenta tissues and serum (r=-0.702,-0.806 and-0.796,all P＜0.05).Conclusions Abnormal expression of VEGF and sVEGF-1 in placenta and serum of patients with sPE may be related to inadequate placental spiral artery remodeling.
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ABSTRACT Background: Healing is an innate biological phenomenon, and carcinogenesis acquired, but with common humoral and cellular elements. Carcinogenesis interferes negatively in healing. Aim: To evaluate the histological changes in laparotomy scars of healthy Balb/c mice and with an Ehrlich tumor in its various forms of presentation. Methods: Fifty-four mice were divided into three groups of 18 animals. First group was the control; the second had Ehrlich tumor with ascites; and the third had the subcutaneous form of this tumor. Seven days after tumor inoculation, all 54 mice were submitted to laparotomy. All of the animals in the experiment were operated on again on 7th day after surgery, with resection of the scar and subsequent euthanasia of the animal. The scars were sent for histological assessment using immunohistochemical techniques to evaluate Cox-2 (cyclooxygenase 2), VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor). Semi-quantitatively analysis was done in the laparotomy scars and in the abdominal walls far away from the site of the operation. Results: Assessing the weight of the animals, the correct inoculation of the tumor and weight gain in the group with tumoral ascites was observed. The histological studies showed that groups with the tumor showed a statistically significant higher presence of Cox-2 compared to the control. In the Cox-2 analysis of the abdominal wall, the ascites group showed the most significant difference. VEGF did not present any significant differences between the three groups, regardless of the site. The FGF showed a significant increase in animals with the tumor. Conclusion: Histological findings in both laparotomy scar and the abdominal wall showed that with Ehrlich's neoplasia there was an exacerbated inflammatory response, translated by more intense expression of Cox-2 and greater fibroblast proliferation, translated by more intense expression of FGF, that is, it stimulated both the immediate inflammatory reactions, observed with Cox-2 reactions, and late scarring by fibroblasts and FGF.
RESUMO Racional: A cicatrização é fenômeno biológico inato, e a carcinogênese adquirido, mas com elementos humorais e celulares comuns. A carcinogênese interfere de forma negativa na cicatrização. Objetivo: Avaliar as modificações histológicas nas cicatrizes laparotômicas de camundongos Balb/c sadios como controles, e com a neoplasia de Ehrlich, em suas diferentes formas de apresentação. Métodos: Foram utilizados 54 camundongos, divididos em três grupos de 18 animais cada um. O primeiro era controle; o segundo com a neoplasia de Ehrlich em sua forma ascítica; e o terceiro na forma subcutânea. Sete dias após a inoculação do tumor, todos os 54 camundongos foram submetidos à laparotomia e reoperados no sétimo dia de pós-operatório, com ressecção da cicatriz e posterior eutanásia. As cicatrizes foram encaminhadas para estudo histológico com técnicas imunoistoquímicas para avaliar Cox-2 (ciclo-oxigenase 2), VEGF (fator de crescimento do endotélio vascular) e FGF (fator de crescimento dos fibroblastos) e analisadas de forma semiquantitativana tanto na cicatriz laparotômica como na parede abdominal mais distante do local operado. Resultados: Avaliando o peso, observou-se a correta inoculação do tumor e o aumento de peso no grupo com a neoplasia na modalidade ascítica. Os estudos histológicos mostraram que os grupos com a neoplasia apresentaram maior presença da Cox-2 em relação ao controle, estatisticamente significante. No estudo da Cox-2 da parede abdominal foi o local em que o grupo ascítico apresentou a diferença mais expressiva. O VEGF não apresentou diferenças significantes entre os três grupos, independentemente do local estudado. O FGF teve aumento significante nos animais com neoplasia. Conclusão: Os achados histológicos encontrados tanto na cicatriz das laparotomias quanto na parede abdominal mostraram que com a neoplasia de Ehrlich houve resposta inflamatória exacerbada, traduzida por expressão mais intensa da Cox-2 e maior proliferação fibroblástica, traduzida por expressão mais intensa do FGF, ou seja, estimulou tanto as reações inflamatórias imediatas, observadas nas reações da Cox-2, como nas cicatriciais tardias com os fibroblastos e o FGF.
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Animals , Female , Rats , Wound Healing , Intercellular Signaling Peptides and Proteins/physiology , Cyclooxygenase 2/physiology , Carcinoma, Ehrlich Tumor , Cicatrix , Mice, Inbred BALB CABSTRACT
Recurrent spontaneous abortion (RSA) was one of the most difficult infertile diseases which was usually defined as consecutive still birth for more than three times during the first 20 weeks of gestation. Various factors and pathogeneses were thought to play a role in RSA. Recent studies had indicated that the disorders of blood vessel growth and the secondary abnormal blood perfusion may contribute to the occurrence of RSA. However, blood vessel growth was linked with the regulation of angiogenesis related factors. To provide references for the clinical prevention and treatment, the purpose of this paper was to evaluate the association between solubility vascular endothelial growth factor receptor-1(sflt-1), thrombospondin 1(TSP-1) and ovary, endometrial abnormal blood perfusion in cases of RSA.
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Background Age-related macular degeneration (AMD) is a heritable,progressive degenerative disorder that triggers central visual impairment.Research demonstrated that the single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor 1 (VEGFR1) gene is associated with AMD in different population.However,the results varied among diversified ethnic origin composition and distinct regions.Objective This study was to investigate the associations between the SNPs of VEGFR1 genetic variants along with smoking exposure and the risk of AMD in Hui and Han ethnics in the Ningxia population in China.Methods A case-control study was conducted.Four hundreds and thirty-two AMD patients including 325 Han ethnic patients and 107 Hui ethnic patients were recruited from March 2011 to June 2015,and 906 ethnicity-and gender-matched age-related cataract patients were contemporaneously recruited as control group,including 698 Han ethnic patients and 208 Hui ethnic patients.Periphery blood sample of 5 ml was collected from the subjects and genomic DNA was prepared.Eight tagging SNPs loci were acquired to cover rs2281827,rs3936415,rs7337610,rs7981680,rs9554320,rs9554322,rs9582036 and rs9943922,and the genotypes of SNPs were detected by using MassARRAYTM time-of-flight mass spectrometry system.Chi-square test and multi-factor Logistic regression analysis were utilized to estimate the discrepancy of allele frequency and genotype distribution in Hui and Han AMD patients.Moreover,the correlation of AMD with smoking and age statue were further analyzed.This study protocol complied with Helsinki Declaration and was approved by Ethic Committee of Ningxia Eye Hospital.Written informed consent was obtained before any relevant medical examination.Results There were significant differences in the age between AMD group and control group in both Han and Hui ethnicity (Han:P =0.000;Hui:P =0.009).The smoking exposure was significantly different between AMD group and control group in Han ethnicity (P =0.000),and smoking was the independent risk factor of AMD disease in Han ethnicity of N ingxia region (odds ratio [OR] =2.622,95％ confidence interval [CI]:1.899-3.619).The allele frequencies of SNPs were not significantly different in the AMD patients between Han and Hui ethnicity (all at P＞0.05).However,the allele frequencies and genotype distribution of rs7337610 and rs9554322 SNPs were significantly different between the AMD group and control group in both Han and Hui ethnicity (all at P=0.00).The genotype distribution of rs9582036 and rs9943922 SNPs was significantly different between the AMD group and control group in Han ethnicity (P=0.02,0.00).Allelic G of rs7337610 was the protective factor of AMD disease in Han and Hui ethnieity (OR=0.354,95％ CI:0.288-0.435;OR=0.446,95％ CI:0.315-0.632),while allelic C of rs9554322 was the risk factor of AMD disease in Han and Hui ethnicity (OR=1.671,95％ C1:1.234-2.262;OR=3.661,95％ CI:2.156-6.218).Allelic A of rs9582036 was the risk factor of AMD disease in Han ethnicity (OR =1.477,95％ CI:1.124-1.940).Conclusions Smoking is the independent risk component for Han population with AMD.Of the eight SNPs tagged,the genotypes and alleles of rs9554322 and rs7337610 seems to confer susceptibility to AMD in both Han and Hui ethnicity,the genotypes and alleles of rs9582036 and rs9943922 confer susceptibility to AMD in only Han ethnicity.
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Preeclampsia is one of the most common complications of pregnancy that is prevalent worldwide, resulting in substantial maternal and neonatal morbidity and mortality. Although the cause remains unclear, preeclampsia may be initiated by abnormal placentation and reduced placental perfusion, followed by an imbalance of angiogenic and antiangiogenic factors and subsequent systemic endothelial dysfunction. High level of antiangiogenic factors, such as soluble vascular endothelial growth factor (VEGF) receptor 1 (sVEGFR-1, also known as sFlt-1) and soluble endoglin, and low levels of angiogenic factors, such as free maternal VEGF and placental growth factor (PlGF), are associated with preeclampsia. Angiogenic and antiangiogenic factors also play an important role during lung angiogenesis, and an imbalance between the two types of factors triggered by inflammation disrupts angiogenesis in bronchopulmonary dysplasia (BPD). Because preeclampsia represents an antiangiogenic state, preterm infants born to mothers with preeclampsia would be at increased risk of developing BPD due to impaired lung development. Recently, preeclampsia has been shown to be independently associated with a high risk for BPD. I have reviewed recent progress in research concerning the correlation between preeclampsia and BPD in aspect of pathophysiology and epidemiology.
Subject(s)
Humans , Infant, Newborn , Pregnancy , Angiogenesis Inducing Agents , Bronchopulmonary Dysplasia , Epidemiology , Infant, Premature , Inflammation , Lung , Mortality , Mothers , Perfusion , Placentation , Pre-Eclampsia , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-1ABSTRACT
Objective To explore the clinical diagnostic value of joint detection of serum platelet-derived growth factor BB (PDGF-BB), soluble vascular endothelial growth factor receptor -1 (sFlt-1) and urotensinⅡ( U-Ⅱ) in preeclampsia disease.Methods The cases of obstetric patients suffering from preeclampsia in the Third People′s Hospital of Liaocheng , Shandong Province between October 2012 and April 2014 were enrolled , including 96 cases of mild preeclampsia and 81 cases of severe preeclampsia.Totally 68 cases of normal pregnant women with similar age and gestational age were selected as control group.A case-control study was applied for the following investigations.The concentrations of serum PDGF-BB, sFlt-1 and U-Ⅱwere measured using ELISA.The diagnostic value of PDGF-BB, sFlt-1 and U-Ⅱalone or in combination for preeclampsia was analyzed and evaluated with receiver operating characteristic curve ( ROC) and Logistic regression analysis.Results Serum concentrations of PDGF-BB, sFlt-1 and U-Ⅱin mild preeclampsia group were (80.45 ±21.87)ng/L,(23.03 ±6.67)μg/L and(4.54 ± 1.02)ng/L, and those in severe preeclampsia group were (124.91 ±47.54)ng/L,(35.65 ±12.45)μg/L and(6.29 ±2.31) ng/L, while those in control group were (60.89 ±19.38) ng/L,(17.19 ±7.867)μg/L and ( 3.81 ±1.01 ) ng/L, respectively.The three parameters in mild preeclampsia group and severe preeclampsia group were significantly higher than those in control group ( P<0.01; F value was 79.43, 79.28 and 50.72 respectively ).In the same situation , these three indicators in severe preeclampsia group were significantly higher than those in mild group (P<0.01).Moreover, the AUC of serum PDGF-BB, sFlt-1 and U-Ⅱalone or in combination were 0.821, 0.786, 0.772 and 0.933, respectively.The differences between joint detection and three individual detections were statistically significant ( P<0.05 ) , as combined detection having a sensitivity of 95.7% and a specificity of 86.6%.Conclusion The combined detection of Serum PDGF-BB, sFlt-1 and U-Ⅱ had an important value in early assessment and treatment of preeclampsia.
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Objective To investigate the effect of hydrogen-rich saline postconditioning on the expression of vascular endothelial growth factor receptor-1 (VEGFR1) during myocardial ischemiareperfusion (I/R) injury in rats.Methods Thirty-six adult male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 3 groups (n=12 each) using a random number table:sham operation group (group S),group I/R and hydrogen-rich saline group (group H2).Myocardial I/R was induced by 30 min ligation of anterior descending branch of the left coronary artery followed by 2 h reperfusion.In group H2,hydrogen-rich saline 5 ml/kg was injected intravenously at 5 min before reperfusion,while the equal volume of normal saline was given in group I/R.Left ventricular systolic pressure (LVSP),left ventricular enddiastolic pressure (LVEDP) and ± dp/dtmax were measured and recorded during reperfusion and at 120 min of reperfusion.The rats were sacrificed at 120 min of reperfusion,and myocardial specimens were obtained for determination of myocardial infarct size,contents of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (using ELISA),and expression of VEGFR1 (by Western blot).At 120 min of reperfusion,blood samples were collected from the common carotid artery to measure cardiac troponin I (cTnI) concentrations in serum.Results Compared with group S,LVSP and ± dp/dtmax were significantly decreased,LVEDP was increased,the myocardial infarct size was enlarged,cTnI concentrations in serum and contents of IL-6 and TNF-α were increased,and the expression of VEGFR1 was down-regulated at 120 min of reperfusion in H2 and I/R groups.Compared with group I/R,LVSP and ± dp/dtmax were significantly increased,LVEDP and myocardial infarct size were decreased,cTnI concentrations in serum and contents of IL-6 and TNF-α were decreased,and the expression of VEGFR1 was up-regulated at 120 min of reperfusion in group H2.Conclusion Hydrogen-rich saline postconditioning can reduce myocardial I/R injury possibly by upregulating myocardial VEGFR1 expression and inhibiting inflammatory responses in the myocardium of rats.