Expression Of Vascular Endothelial Growth Factor In Tissues Research Articles

Design, synthesis, and evaluation of antitumor activity in Pseudolaric acid B Azole derivatives: Novel and potent angiogenesis inhibitor via regulation of the PI3K/AKT and MAPK mediated HIF-1/VEGF signaling pathway

Tumor proliferation and metastasis are intricately linked to blood vessel formation, with vascular endothelial growth factor (VEGF) playing a pivotal role in orchestrating angiogenesis throughout tumor progression. Pseudolaric acid B (PAB) has emerged as a potent inhibitor of tumor cell proliferation, migration, and angiogenesis. In efforts to enhance its efficacy, 37 derivatives of PAB were synthesized and assessed for their capacity to suppress VEGF secretion in SiHa cells under hypoxic conditions. Notably, majority of these derivatives exhibited significant inhibition of VEGF protein secretion without inducing cytotoxicity. Among them, compound M2 displayed the most potent inhibitory activity, with an IC50 value of 0.68 μM, outperforming the lead compound PAB (IC50 = 5.44 μM). Compound M2 not only curbed the migration and angiogenesis of HUVECs under hypoxic conditions but also hindered the invasion of SiHa cells. Mechanistic investigations unveiled that compound M2 may impede the accumulation and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) in SiHa cells, thereby downregulating VEGF expression. This inhibitory effect on HIF-1α was corroborated by experiments utilizing the protease inhibitor MG-132 and protein synthesis inhibitor CHX, indicating that compound M2 diminishes HIF-1α levels by reducing its synthesis. Furthermore, compound M2 was observed to modulate the PI3K/AKT/mTOR and MAPK signaling pathways in tumor cells, thereby regulating HIF-1α translation and synthesis. In vivo studies demonstrated that compound M2 exhibited low toxicity and effectively curbed tumor growth. Immunohistochemistry analyses validated that compound M2 effectively suppressed the expression of HIF-1α and VEGF in tumor tissues, underscoring its potential as a promising therapeutic agent for targeting tumor angiogenesis.

The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.

The aim of our study was to investigate an association between polymorphisms of either the VEGF (vascular endothelial growth factor) gene (rs6921438) or the KDR (kinase insert domain receptor) gene (rs2071559, rs2305948) and DN (diabetic nephropathy) in Caucasians with T2DM (type 2 diabetes mellitus). The second aim was to investigate the effect of either the VEGF gene (rs6921438) or the KDR gene (rs2071559, rs2305948) on the immune expression of either VEGF or KDR in the renal tissues of T2DM subjects (to test the functional significance of tested polymorphisms). The study included 897 Caucasians with T2DM for at least ten years (344 patients with DN and 553 patients without DN). Each subject was genotyped and analyzed for KDR (rs1617640, rs2305948) and VEGF (rs6921438) polymorphisms. Kidney tissue samples taken from 15 subjects with T2DM (autopsy material) were immunohistochemically stained for the expression of VEGF and KDR. We found that the rs2071559 KDR gene was associated with an increased risk of DN. In addition, the GG genotype of the rs6921438 VEGF gene had a protective effect. We found a significantly higher numerical area density of VEGF-positive cells in T2DM subjects with the A allele of the rs6921438-VEGF compared to the homozygotes for wild type G allele (7.0 ± 2.4/0.1 mm2 vs. 1.24 ± 0.5/0.1 mm2, respectively; p < 0.001). Moreover, a significantly higher numerical area density of KDR-positive cells was found in T2DM subjects with the C allele of rs2071559 (CC + CT genotypes) compared to the homozygotes for wild type T allele (9.7± 3.2/0.1 mm2 vs. 1.14 ± 0.5/0.1 mm2, respectively; p < 0.001) To conclude, our study showed that the presence of the C allele of the rs2071559 KDR gene was associated with a higher risk of DN, while the G allele of the rs6921438-VEGF conferred protection against DN in Slovenian T2DM subjects.

VEGF, HIF-1α, and Metabolic Indicators in Esophageal Squamous Cell Carcinoma

Objective: To explore and analyze the expression and clinical significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α), and metabolic indicators in esophageal squamous cell carcinoma (ESCC). Methods: Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group. Sixty normal healthy patients from the same period were chosen as the control group. Their serum samples and tissue samples were collected. Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission. RT-PCR was utilized to detect the expression of VEGF and HIF-1α in ESCC tissues. Results: The expression of VEGF and HIF-1α in the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ (Tis) group, T1+T2 group, and control group. Furthermore, the expression of HIF-1α was found to be related to the expression of VEGF, showing a significant correlation between the quantities. Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group (P &lt; 0.05). Conclusion: Metabolic indicators are associated with the onset of ESCC in patients. Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors. The expression of VEGF and HIF-1α in ESCC tissues significantly correlates with the tumor stage, providing a new reference for the diagnosis and treatment of ESCC.

Preparation of Chitosan Nanoparticles Loaded with Vascular Endothelial Growth Factor and Its Application in the Treatment of Skin Injury

This research was aimed to explore the application of chitosan (CS) nanoparticles (NPs) loaded with vascular endothelial growth factor (VEGF) in rat skin injury. Method: the VEGF-loaded CS NPs (VEGF/CS-NPs) were prepared, and a skin injury model on the back skin of rats was established. The VEGF/CS-NPs were applied to the injury model to observe the skin changes in the wound area of each group, compare the healing rate, the number of micro-vessels, and VEGF expression in each group of rats, so as to explore the intervention effect of VEGF/CS-NPs in skin injury. Results: the prepared VEGF/CS-NPs were spherical or quasi-spherical in morphology, uniformly dispersed, with smooth surfaces and relatively uniform size. The average particle size (PS) of the blank CS-NPs was 267.5 nm± 25.3 nm, while that of the drug-loaded CS-NPs was 298.6 nm ±44.7 nm, and the PS distribution was also very concentrated. The genipin cross-linked NPs could effectively prevent the degradation of the spherical wall and achieve the slow release of VEGF. After VEGF was applied to rats in the form of NPs, its healing rate and micro-vessel count were markedly superior to those of VEGF injection alone and blank group (P &lt; 0.05), and VEGF expression in skin injury tissues was also greatly increased (P &lt; 0.05). Conclusion: VEGF/CS-NPs could improve the bioavailability of VEGF and promote the healing of rat skin injuries.

Expression and distribution of erythropoietin, vascular endothelial growth factor (VEGF) and VEGF receptor 2 in small intestine of yaks at different ages.

This study aimed to detect the expression and distribution of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2), and erythropoietin (EPO) proteins in small intestinal tissues of 50-day-old, newborn, and adult yaks. The results provide basic data for the study of the relationship between adaptability and age of plateau yak. Small intestine tissues from healthy adult, 50-day-old, and newborn yak were collected and embedded in paraffin sections. Histological features were observed by haematoxylin and eosin staining. The expression of VEGF, VEGFR-2, and EPO proteins were detected by immunohistochemical staining. Immunohistochemical results showed that of the expression VEGF, VEGFR-2, and EPO were detected in the small intestinal villi of yaks at all ages. The EPO expression level in the jejunum and duodenal villous epithelial cells of newborn yaks was significantly higher than that of 50-day-old and adult yaks. The EPO expression level in ileum villous epithelial cells of 50-day-old yaks was significantly higher than that of newborn and adult yaks. VEGF expression in newborn yak ileum and jejunum epithelial cells of the intestinal villus were significantly higher than in the 50-day-old and adult. In the 50-day-old yaks, the duodenal intestinal villus epithelial cells expression levels were higher than in the adult and newborn yaks. The expression level of VEGFR-2 in the ileum, jejunum and duodenal villous epithelial cells of 50-day-old yak was significantly higher than in that of adult and newborn yak. The expression and distribution characteristics of EPO, VEGF, and VEGFR-2 in yak intestinal tissues of different ages indicate that these proteins may be involved in the physiological regulation of yak intestines in hypoxic environments. It may be an important regulatory protein in yak adaptation to a high altitude and low oxygen environment.

Expression of endocan and vascular endothelial growth factor and their correlation with histopathological prognostic parameters in pheochromocytoma.

Endocan and vascular endothelial growth factor (VEGF) are markers expressed in various cancer types that are highly vascular, and they have prognostic significance for these cancers. In this study, we aimed to show the expression of endocan and VEGF in pheochromocytoma tumor tissues and to evaluate their correlations with histopathological parameters. Thirty-eight patients who had been operated for pheochromocytoma were included in the study. As the control group, 28 subjects whose specimens contained normal adrenal medulla tissue were included. The formalin-fixed paraffin-embedded specimens of pheochromocytoma patients were evaluated for Pheochromocytoma of the Adrenal gland Scaled Score (PASS). Sections were then stained for immunohistochemical analysis. The degree of endocan and VEGF positivity was determined by the proportion of stained cells on a negative to strong scale. Endocan (p < 0.001) and VEGF (p = 0.004) expressions were found to be significantly higher in the pheochromocytoma group than in the control group. In the pheochromocytoma group, total PASS score (r = 0.714; p < 0.001) and most of the PASS score components were positively correlated with the level of endocan expression. Median Ki-67 index (p = 0.010), total PASS score (p < 0.001), tumor cell spindling (p = 0.048), and nuclear pleomorphism (p = 0.030) were higher in pheochromocytoma with VEGF expression than in those without. If our findings are supported by studies with a larger sample size, we think that endocan has the potential to be used both as a tumor marker and in predicting malignancy potential in patients with pheochromocytoma, and that the detection of VEGF expression in these tumors is also associated with an increase in malignancy potential.

Anti-Fibrotic Efficacy of Apigenin in a Mice Model of Carbon Tetrachloride-Induced Hepatic Fibrosis by Modulation of Oxidative Stress, Inflammation, and Fibrogenesis: A Preclinical Study.

Hepatic fibrosis is a major health problem all over the world, and there is no effective treatment to cure it. Hence, the current study sought to assess the anti-fibrotic efficacy of apigenin against CCl4-induced hepatic fibrosis in mice. Forty-eight mice were put into six groups. G1: Normal Control, G2: CCl4 Control, G3: Silymarin (100 mg/kg), G4 and G5: Apigenin (2 &20 mg/Kg), G6: Apigenin alone (20 mg/Kg). Groups 2, 3, 4, and 5 were given CCl4 (0.5 mL/kg. i.p.) twice/week for six weeks. The level of AST, ALT, TC, TG, and TB in serum and IL-1β, IL-6, and TNF-α in tissue homogenates were assessed. Histological studies by H&E staining and Immunostaining of liver tissues were also performed. The CCl4-challenged group showed increased serum AST (4-fold), ALT (6-fold), and TB (5-fold). Both silymarin and apigenin treatments significantly improved these hepatic biomarkers. The CCl4-challenged group showed reduced levels of CAT (89%), GSH (53%), and increased MDA (3-fold). Both silymarin and apigenin treatments significantly altered these oxidative markers in tissue homogenates. The CCl4-treated group showed a two-fold increase in IL-1β, IL-6, and TNF-α levels. Silymarin and apigenin treatment considerably decreased the IL-1β, IL-6, and TNF-α levels. Apigenin treatment inhibited angiogenic activity, as evidenced by a decrease in VEGF (vascular endothelial growth factor) expression in liver tissues, and a decline in vascular endothelial cell antigen expression (CD34). Finally, these data collectively imply that apigenin may have antifibrotic properties, which may be explained by its anti-inflammatory, antioxidant, and antiangiogenic activities.

Research Progress of Serum VEGF and FAS in Prognosis of Gastric Cancer

Vascular endothelial growth factor (VEGF) is an important factor to promote endothelial cell division and angiogenesis. In physiological conditions, the expression level of VEGF in human tissues is very low. Ischemia, hypoxia and many tumors can promote the synthesis and secretion of VEGF, and its expression level is related to the degree of vascularization of tumors, the proliferation, growth and metastasis of tumor cells. Fatty acid synthase (FAS) is a key enzyme for endogenous fatty acid synthesis, which is expressed at a low level in normal tissue cells, while FASN in a variety of tumor cells is continuously highly expressed to meet the energy needs of cell proliferation and the excessive demand for rapid proliferation of tumor cells to form cell membrane lipids. A large amount of research shows that VEGF and FAS play an important role in the development and development of many tumors, and the abnormally high expression in tumor tissue cells is positively correlated with serum VEGF and FAS levels, which is closely related to the prognosis of tumors. Gastric cancer (GC) is one of the most common clinical malignant tumors of the digestive tract, and its incidence and mortality have shown an increasing trend in recent years, and the prognosis is poor, seriously endangering human health. The biological properties of GC are related to the level of VEGF and FAS expression in tissues and serum. This article reviews the research progress of VEGF and FAS, their expression in GC and their prognosis.

Placental micro blood perfusion for isolated single umbilical artery foetuses and VEGF protein expression in the placenta

Microblood perfusion of isolated single umbilical artery (ISUA) foetus placenta was evaluated using three-dimensional power Doppler ultrasound (3D-PDU). Vascular endothelial growth factor (VEGF) protein expression in the placenta was also semi-quantitative and qualitatively analysed. Differences between ISUA and control groups were compared. 3D-PDU was used to detect placental blood flow parameters, including vascularity index (VI), flow index, and vascularity flow index (VFI), in 58 foetuses in the ISUA group and 77 normal foetuses in the control group. Immunohistochemistry and polymerase chain reaction were employed to analyse the VEGF expression in placental tissues of 26 foetuses in the ISUA group and 26 foetuses in the control group. The control group exhibited higher VI and VFI than the ISUA group (p < 0.05). Meanwhile, the ISUA group showed a higher positivity rate of VEGF protein expression than the control group (χ 2=28.013, p˂0.001). The ISUA group also presented a higher VEGF mRNA protein expression than the control group (p˂0.001). 3D-PDU can be used to quantitatively analyse microblood perfusion of the placenta and provide an objective assessment of ISUA foetuses. Impact statement What is already known on this subject? Colour Doppler flow can be used to evaluate placental and maternal circulation and remains an ideal method for evaluating high-risk placental function. Three-dimensional power Doppler ultrasound (3D-PDU) can be used to quantify blood vessels and blood flow in placental parenchyma via the measurement of the amplitude of blood vessels and blood flow in normal foetuses, respectively. What do the results of this study add? 3D-PDU can be used to quantitatively analyse micro blood perfusion of the placenta and conduct an objective assessment of isolated single umbilical artery foetuses. The isolated single umbilical artery foetuses exhibited a higher positivity rate of vascular endothelial growth factor (VEGF) protein expression and higher VEGF mRNA protein expression than the normal foetuses. What are the implication of these findings for clinical practice and/or further research? The study provides a reliable basis for maternal-foetal monitoring during pregnancy in the isolated single umbilical artery foetuses. Objective assessment of the occurrence and development of foetuses with isolated single umbilical artery was performed.

Expression of EPO and related factors in the liver and kidney of plain and Tibetan sheep.

Erythropoietin (EPO), hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), and vascular endothelial growth factor (VEGF) are key factors in the regulation of hypoxia, and can transcriptionally activate multiple genes under hypoxic conditions, thereby initiating large hypoxic stress in the network. The liver and kidneys are important metabolic organs of the body. We assessed the expression of EPO, HIF-1α, HIF-2α, and VEGF in liver and kidney tissues of plain and Tibetan sheep using hematoxylin and eosin staining, immunohistochemistry, and RT-qPCR. The results showed that EPO, HIF-1α, HIF-2α, and VEGF were expressed in tubular epithelial cells, collecting duct epithelial cells, mural epithelial cells, and the glomerular cytoplasm of Tibetan sheep, and their expression was significantly higher in Tibetan sheep than in plain sheep (P<0.05). EPO, HIF-1α, HIF-2α, and VEGF are expressed in hepatocytes, interlobular venous endothelial cells, and interlobular bile duct epithelial cells. In plain sheep, positive signals for EPO, HIF-1α, HIF-2α, and VEGF were localized mainly in interlobular venous endothelial cells, whereas VEGF and HIF-2α were negatively expressed in interlobular bile duct epithelial cells and positively expressed in EPO and HIF-1α. The differences in EPO, HIF-1α, and HIF-2α in Tibetan sheep were significantly higher than those in plain sheep (P<0.001). In the liver and kidney tissues of Tibetan sheep, EPO was associated with HIF-1α, HIF-2α, and VEGF (P<0.05). RT-qPCR results showed that EPO was not expressed, and HIF-1α, HIF-2α, and VEGF were expressed (P<0.05). The results showed that the expression of EPO, HIF-1α, HIF-2α, and VEGF in the kidney and liver of Tibetan sheep was higher than that in of plain sheep. Therefore, EPO, HIF-1α, HIF-2α, and VEGF may be involved in the adaptive response of plateau animals, which provides theoretical clarity to further explore the adaptive mechanism of plateau hypoxia in Tibetan sheep.

Potato Alkaloids α-Solanine and α-Chaconine Promote bFGF and VEGF Expression in Vein and Adjacent Tissues in the Rabbit Model of Phlebitis

Objectives: To investigate the therapeutic effect of mashed potato and its alkaloids α-solanine and α-chaconine on basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression in ear venous vessels and adjacent tissues in a rabbit model of phlebitis. Materials and Methods: Japanese white rabbits were randomly allocated into control, vaseline cream (model), magnesium sulfate, mashed potato, α-solanine cream 100 mg/kg or 200 mg/kg, and α-chaconine cream 100 mg/kg or 200 mg/kg groups. The phlebitis model was established by intravenous infusion of vincristine in the rabbit ears. Group A received physiological saline. Group B−F was applied treatment 3 times/day, for 2 days along the ears vein. The alkaloid contents in α-solanine and α-chaconine were analyzed with HPLC. The bFGF, protein kinase C alpha (PKC-α), and VEGF expression in the ear vessels and nearby tissues were analyzed using immunohistochemistry, polymerase chain reaction (PCR), and Western blot analysis, respectively. Results: After phlebitis modeling, the vascular endothelium of the rabbit ear vein was damaged or layered, the lumen was swollen and deformed to an oval or round shape, and the proportion of bFGF and VEGF positive areas in the vascular endothelium and adjacent tissues was higher than the control group. The phlebitis score shows that various treatments have certain effects, among which magnesium sulfate wet gauze and mashed potatoes are more effective. The application of α-solanine and α-chaconine cream promotes the expression of bFGF and VEGF, as well as PKC-α in the venous blood vessels and adjacent tissues, but mashed potatoes had little effect. Conclusion: α-solanine and α-chaconine cream can promote the expression of bFGF and VEGF in venous blood vessels and adjacent tissues, which may contribute to the recovery of blood vessels in phlebitis.

Role of progesterone on dexamethasone-induced alterations in placental vascularization and progesterone receptors in rats†.

Intrauterine growth restriction (IUGR) is manifested by lower maternal progesterone levels, smaller placental size, and decreased placental vascularity indicated by lower expression of vascular endothelial growth factor (VEGF). Studies showed that progesterone increases angiogenesis and induces VEGF expression in different tissues. Therefore, the aim of the present study is to evaluate the effect of progesterone on placental vascular bed and VEGF expression and the modulation of nuclear and membranous progesterone receptors (PR) in dexamethasone-induced rat IUGR model. Pregnant Sprague-Dawley rats were allocated into four groups and given intraperitoneal injections of either saline, dexamethasone, dexamethasone, and progesterone or progesterone. Injections started on gestation day (DG) 15 and lasted until the days of euthanization (19 and 21 DG). Enzyme-linked immunosorbent assay was used to evaluate plasma progesterone levels. Real-time PCR and western blotting were used to evaluate gene and protein expressions of VEGF, and PR in labyrinth and basal placental zones. Immunohistochemistry was used to locate VEGF and different PRs in placental cells. Immunofluorescence was used to monitor the expression of blood vessel marker (αSMA). Dexamethasone decreased the vascular bed fraction and the expression of VEGF in both placental zones. Progesterone co-treatment with dexamethasone prevented this reduction. Nuclear and membrane PRs showed tissue-specific expression in different placental zones and responded differently to both dexamethasone and progesterone. Progesterone treatment improves the outcomes in IUGR pregnancy. Progesterone alleviated DEX-induced IUGR probably by promoting placental VEGF and angiogenesis.

VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway.

Diabetic retinopathy (DR) is a common microvascular complication in patients with diabetes mellitus. DR is caused by chronic hyperglycemia and is characterized by progressive loss of vision because of damage to the retinal microvasculature. In this study, we investigated the regulatory role and clinical significance of the vascular endothelial growth factor (VEGF)/protein kinase C (PKC)/endothelin (ET)/nuclear factor-κB (NF-κB)/intercellular adhesion molecule 1 (ICAM-1) signaling pathway in DR using a rat model. Intraperitoneal injections of the VEGF agonist, streptozotocin (STZ) were used to generate the DR model rats. DR rats treated with the VEGF inhibitor (DR+VEGF inhibitor) were used to study the specific effects of VEGF on DR pathology and the underlying mechanisms. DR and DR+VEGF agonist rats were injected with the PKCβ2 inhibitor, GF109203X to determine the therapeutic potential of blocking the VEGF/PKC/ET/NF-κB/ICAM-1 signaling pathway. The body weights and blood glucose levels of the rats in all groups were evaluated at 16 weeks. DR-related retinal histopathology was analyzed by hematoxylin and eosin staining. ELISA assay was used to estimate the PKC activity in the retinal tissues. Western blotting and RT-qPCR assays were used to analyze the expression levels of PKC-β2, VEGF, ETs, NF-κB, and ICAM-1 in the retinal tissues. Immunohistochemistry was used to analyze VEGF and ICAM-1 expression in the rat retinal tissues. Our results showed that VEGF, ICAM-1, PKCβ2, ET, and NF-κB expression levels as well as PKC activity were significantly increased in the retinal tissues of the DR and DR+VEGF agonist rat groups compared to the control and DR+VEGF inhibitor rat groups. DR and DR+VEGF agonist rats showed significantly lower body weight and significantly higher retinal histopathology scores and blood glucose levels compared to the control and DR+VEGF inhibitor group rats. However, treatment of DR and DR+VEGF agonist rats with GF109203X partially alleviated DR pathology by inhibiting the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway. In summary, our data demonstrated that inhibition of the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway significantly alleviated DR-related pathology in the rat model. Therefore, VEGF/PKC/ET/NF-κB/ICAM-1 signaling axis is a promising therapeutic target for DR.

Tissue concentration of vascular endothelial growth factor is not related to the depth of trophoblastic invasion in ampullary pregnancies-A pilot study.

Introduction: The factors that modulate trophoblastic invasion into the tubal wall remain uncertain. Moreover, it is known that the concentration of vascular endothelial growth factor (VEGF) is increased in cases of deeper trophoblastic invasion in the fallopian tubes. Objective: This study aimed to assess if there is a correlation between VEGF tissue expression and the depth of trophoblastic infiltration into the tubal wall in patients with ampullary pregnancy. Methods: A cross-sectional study was conducted in patients with a diagnosis of tubal pregnancy in the ampullary region who underwent salpingectomy. Inclusion criteria were spontaneously conceived singleton pregnancies, diagnosis of tubal pregnancy in the ampullary region, and radical surgical treatment. A lack of agreement regarding the location of the tubal pregnancy and impossibility of either anatomopathological or tissue VEGF analysis were the exclusion criteria. Histologically, trophoblastic invasion into the tubal wall was classified as grade I when limited to the tubal mucosa, grade II when it reached the muscle layer, and grade III when it comprised the full thickness of the tubal wall. A total of 42 patients fulfilled the inclusion criteria and were selected to participate in the study. Eight patients were excluded. After surgery, tissue VEGF expression was measured by immunohistochemistry and the point counting technique. Results: Histological analysis revealed that eight patients had stage I tubal infiltration, seven had stage II, and 19 had stage III. The difference between the percentage of VEGF expression in the trophoblastic tissue was not significant in relation to the degree of trophoblastic invasion (p = 0.621) (ANOVA). Trophoblastic tissue VEGF showed no statistical difference for prediction of both degrees of trophoblastic invasion (univariate multinomial regression). Conclusion: The depth of trophoblastic penetration into the tubal wall in ampullary pregnancies is not associated with tissue VEGF expression.

Muscle-derived Stem Cells Combined With Nerve Growth Factor Transplantation in the Treatment of Stress Urinary Incontinence

To investigate the efficacy of muscle-derived stem cells (MDSCs) combined with nerve growth factor (NGF) in the treatment of stress urinary incontinence (SUI) METHODS: MDSCs were isolated and extracted from 90 SD rats, and the stem cell characteristics of the cells were identified using flow cytometry. NGF overexpression (oe-NGF) plasmid was coated with adenovirus and qRT-PCR was applied to verify adenovirus transfection efficiency. The rat models of SUI were constructed and randomly divided into 5 groups: control group, phosphate buffer (PBS) group, MDSCs+oe-NGF group, MDSCs+vector group, and MDSCs group. After 8 weeks of feeding, the leakage point pressure (LPP) rats, and Masson staining of rat urethral sections were detected. The expression of NGF and vascular endothelial growth factor (VEGF) was detected by western blot and IHC staining. Compared with the control group, the LPP and the ratio of muscle fibers/collagen fibers were significantly increased in the MDSCs treated groups, with the highest increase in the MDSCs+oe-NGF group. Western blot and IHC results showed that the expression of NGF and VEGF in the urethral tissues in the MDSCs treated groups were significantly up-regulated comparing with the control group, with the highest increase in the MDSCs+oe-NGF group. MDSCs alone can relieve SUI, while MDSCs combined with NGF is more effective, which may be related to the up-regulating of VEGF.

Expression and Relationship of Netrin-1, DCC, UNC5B, and VEGF in Villous Tissues of Patients with Delayed Abortion.

In order to investigate the correlation between neuroaxon-guiding factor (Netrin-1), deleted in colorectal cancer (DCC), uncoordinated 5B (UNC5B), and vascular endothelial growth factor (VEGF) expression machine in villus tissues of delayed abortion in colorectal cancer, a total of 120 pregnant women are selected from February 2019 to August 2021. The two groups of subjects improve the relevant examinations before surgery and the underwent negative pressure induces abortion hysterectomy guided by abdominal ultrasound under intravenous anesthesia. The mRNA and protein expressions of netrin-1, DCC, UNC5B, and VEGF in the villi of the two groups are detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), and the correlation of the four indicators is analyzed by Pearson's test.

VEGF Family Gene Expression as Prognostic Biomarkers for Alzheimer's Disease and Primary Liver Cancer.

Background To analyze the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and cognitive impairment, explore the relationship between the expression of VEGF family genes and prognosis of patients with HCC, and evaluate the predictive ability of VEGF in cognitive impairment using computerized methods. Methods VEGF expression in liver cancer tissues and normal tissues was analyzed using bioinformatics methods. The Kaplan-Meier survival analysis method was also used to analyze the relationship between VEGF expression and the prognosis of patients with HCC. Furthermore, immune infiltration assessment and gene set enrichment analysis were performed. Meanwhile, the differential expression of VEGF family genes between patients with Alzheimer's disease (AD) and healthy controls was also checked. Results Based on The Cancer Genome Atlas (TCGA) database, the VEGF family genes (VEFGA, VEGFB, VEGFC, and VEGFD) were highly expressed in cancer tissues and were significantly associated with poor prognosis in HCC. In HCC, the VEGF family genes showed significant heterogeneity in their functional and immune infiltration characteristics. Finally, VEGF family genes were identified as prognostic biomarkers in AD and risk prediction markers in HCC. Conclusions VEGF is highly expressed in patients with HCC and lowly expressed in patients with AD. VEGF has opposite opposing roles in the treatment of tumors and cognitive impairment.

Vascular endothelial growth factor promotes cancer stemness of triple-negative breast cancer via MAPK/ERK pathway

To investigate the role of vascular endothelial growth factor (VEGF) in regulating triple-negative breast cancer (TNBC) stem cells and the possible pathways involved in this regulatory mechanism. The Oncomine database, UALCAN database and Human Protein Atlas (HPA) database were used to analyze the expression of VEGF in breast cancer and its association with the molecular subtypes and prognosis of breast cancer. Sphere formation assay was carried out to examine the effects of hVEGF165 on sphere formation ability of TNBC MDA-MB-231 cell line; Western blotting and RT-qPCR were performed to detect the expression of the tumor stem cell markers including CD44, c-Myc, Nanog, and ALDH1 and the activation of the related pathways. Data from the online databases all showed a significant increase of VEGF expression in breast cancer tissues than in the adjacent tissues (P < 0.0001), and its expression level was associated with the molecular subtypes of breast cancer. Specifically, the expression of VEGF was markedly higher in TNBC than in other subtypes of breast cancer. Survival analysis showed that breast cancer patients with a high VEGF expression had a significantly shortened overall survival (P < 0.0001). In the cell experiments, the sphere formation ability of MDA-MB-231 cells was significantly enhanced after treatment with hVEGF165 (P=0.0029). Compared with the monolayer cells, MDA-MB-231 spheres showed significantly increased expressions of VEGF, NRP-1, CD44, Nanog and c-Myc. Treatment with hVEGF165 resulted in significant time-dependent up-regulation of the expressions of CD44, c-Myc, Nanog and ALDH1 and down-regulation of CD24 expression in the cells. The results of Western blotting demonstrated that treatment with hVEGF165 caused significant activation of the ERK/MAPK pathway in MDA-MB-231 cells. VEGF promotes cancer stemness of triple-negative breast cancer possibly through the ERK/MAPK pathway.

Expression of VEGF, EGF and HGF in early- and late-stage colorectal cancer.

The heterogenous nature of colorectal cancer (CRC) highlights the need for a better understanding of the growth factors that affect tumour growth and cancer progression. The aim of the present study was to evaluate the role of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in the early (I and II) and late (III and IV) stages of CRC. The serum levels and mRNA expression (n=30) of the aforementioned growth factors were measured and immunohistochemistry (n=20) was performed in patients with CRC. Histological examination revealed comparable distribution of early-stage [I: 8 (26.7%) and II: 7 (23.3%)] and late-stage [III: 8 (26.7%) and IV: 7 (23.3%)] CRC. The mean serum concentrations of VEGF during the early (152.9±14.5 vs. 88.39±3.99 pg/ml; P=0.001) and late (182.7±25.8 vs. 88.39±3.99 pg/ml; P=0.002) stages were significantly higher compared with those in controls. Similarly, the mean serum concentrations of EGF in the early (409.4±7.96 vs. 153.7±13.8 pg/ml; P=0.05) and HGF in the late (90.4±17.4 vs. 56.9±4.97 pg/ml; P=0.05) stages were significantly higher compared with those in controls. The serum concentrations of VEGF, EGF and HGF were comparable between the early and late stages of CRC. Compared to normal tissues, the mRNA expression of both VEGF (P<0.001) and HGF (P<0.01) was upregulated in early-stage and downregulated in late-stage CRC. The expression of EGF remained significantly elevated during both the early and late stages of CRC (P<0.01). Histopathological analyses confirmed increased expression of VEGF in cancerous tissues compared with that in normal tissues. The present study emphasized the need for monitoring the serum levels and tissue expression of growth factors to fully elucidate their role in patients with CRC.

Nrf2/HO-1 Axis Regulates the Angiogenesis of Gastric Cancer via Targeting VEGF.

PurposeGastric cancer (GC) is one of the most fatal digestive tumors worldwide. Abnormal activation or accumulation of the nuclear factor-erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) axis is a malignant event in numerous solid tumors. However, its involvement in angiogenesis of GC remains unknown. This study investigated the role of the Nrf2/HO-1 axis in angiogenesis of GC.MethodsThe expression of Nrf2, HO-1, and vascular endothelial growth factor (VEGF) in BGC-823 cells under hypoxia was analyzed using immunocytochemistry, immunofluorescence, Western blotting, and quantitative polymerase chain reaction. The effects of brusatol (Nrf2 inhibitor) and tert-butylhydroquinone (Nrf2 inducer) on these factors and angiogenesis were examined using immunofluorescence, Western blotting, quantitative polymerase chain reaction, and tube formation assay. Moreover, immunohistochemistry and Western blotting were used to determine these factors and microvessel density in tumor and normal tissues of tumor-bearing and tumor-free mice, respectively. Immunohistochemistry and Western blotting were employed to examine these factors and microvessel density in human paracancerous tissues, well-differentiated GC, and poorly differentiated GC. The correlations between Nrf2, HO-1, and VEGF gene expression in 375 patients with GC from The Cancer Genome Atlas cohort were analyzed.ResultsThe expression of Nrf2, HO-1, and VEGF was increased in hypoxic BGC-823 cells (P<0.05). Although brusatol decreased their expression and angiogenesis (P<0.05), tert-butylhydroquinone had the opposite effect (P<0.05). Moreover, the expression of Nrf2, HO-1, and VEGF, and microvessel density in tumor tissues was higher than that recorded in normal tissues of nude mice (P<0.05). Similarly, these parameters were low in paracancerous tissues, but high in GC tissues (P<0.05). Also, they were weak in well-differentiated GC, but strong in poorly differentiated GC (P<0.05). In addition, there was a significant correlation between Nrf2, HO-1, and VEGF (P<0.05).ConclusionThe Nrf2/HO-1 axis may regulate the angiogenesis of GC via targeting VEGF. These findings provide a promising biomarker and potential treatment target for GC.