Blood Vascular Endothelial Growth Factor Research Articles

CD133+ Stem Cell Therapy Effects on Myocardial Regeneration Through Increased Vascular Endothelial Growth Factor Correlate with Cardiac Magnetic Resonance Imaging Results in Coronary Artery Bypass Graft Surgery Patients with Low Ejection Fraction.

Stem cell implantation has become a promising therapy for heart failure due to coronary heart disease (CHD). CD133+ stem cell therapy, together with increases of vascular endothelial growth factor (VEGF) and other growth hormones, can induce myocardial repair. To prove that VEGF plays a role in cardiac regeneration. Twenty-six patients with CHD and ejection fractions <35% from Harapan Kita Heart and Vascular Center, Jakarta, Indonesia, from 2016 to 2018 were randomized into 2 groups. The treatment group underwent coronary artery bypass graft (CABG) + CD133+ implantation, and the control group underwent CABG only. Six months later, perfusion and myocardial function were assessed by ejection fraction, wall motion score index (WMSI), ventricular dimensions, and scar size using cardiovascular magnetic resonance imaging. VEGF was assessed with enzyme-linked immunosorbent assay. There was significant improvement in ejection fraction (8.69% ± 9.49% versus 1.43% ± 7.87%, P = .04), WMSI (0.51 ± 0.48 versus -0.01 ± 0.21, P = .003), and scar size (25.46 ± 12.91 versus 27.32 ± 12.92 mm, P = .047) and a significant increase in blood VEGF levels (61.05 ± 63.01 versus 19.88 ± 33.78 pg/mL, P = .01). Improvements in perfusion defects (13.69 ± 5.03 versus 11.53 ± 5.81 P = .32) and ventricular dimensions (-27.59 ± 84.48 versus -19.08 ± 36.79 mm, P = .06) were not statistically significant. CD133+ stem cell implantation improves myocardial function. The increase in VEGF levels is expected to continue improving restoration of myocardial function when myocardial perfusion improvement is still not optimal.

Relationship between levels of vascular endothelial growth factor in blood and severity of diabetic retinopathy

Aim: The aim of the study was to establish the relationship between levels of vascular endothelial growth factor (VEGF) in blood and severity of diabetic retinopathy (DR). Background: The importance of VEGF in the pathogenesis of DR is evident from numerous studies demonstrating a significant increase in VEGF levels in samples obtained from the eye. However, a correlation between blood levels of VEGF and DR has not been conclusively proven or disproven. In this article, we demonstrate the relationship between blood levels of VEGF and the severity of DR. Materials and Methods: This is a hospital-based descriptive analytic study. The study population consisted of 75 Type 2 diabetic patients attending outpatient department for routine DR screening. After obtaining informed consent, 5 ml of blood was drawn from each patient and estimated for the levels of serum VEGF. The data thus obtained were correlated with the grade of DR. Additional parameters studied were duration of diabetes mellitus (DM), hemoglobin levels, blood urea, serum creatinine, fasting blood sugar (FBS) and random blood sugar (RBS), and hemoglobin A1c (HBA1c) levels. Statistical analysis used in this study was Chi-square test, Student's t-test, independent one sample t-test, and analysis of variance using SPSS software version. 19. Results: Overall mean VEGF levels for the study population of 75 diabetic patients were 577.01 ± 291.13 pg/ml. The average duration of DM in the study population was 7.2 years. The average hemoglobin level in the study population was 11.53 ± 2.00 g/dl. The mean urea levels in mg/dl of the whole population were 35.47 ± 25.80 mg/dl. The mean creatinine levels for the population were 1.42 ± 1.55 mg/dL. The mean RBS levels for the whole population were 228.95 ± 74.499 mg/dL. The mean FBS levels for the 75 patients were 165.87 ± 59.04 mg/dl. The mean HBA1c levels were 9.49 ± 2.37%. Conclusion: Levels of blood VEGF are elevated in diabetic patients regardless of whether they have DR or not. There is no statistically significant relationship between blood levels of VEGF and the severity of DR. Even though severe grades of DR showed more anemia, there is no statistically significant relationship between anemia and DR. The levels of urea and creatinine were elevated in the more severe grade of DR. VEGF, therefore, could present a potential treatment and preventive strategy for not only DR but also DM and its complications in general.

Features of the course of the nephropathy in patients with type 2 diabetes mellitus: genetic aspects and angiogenesis

Objective — to determine serum level of vascular endothelial growth factor (VEGF) in patients with diabetic nephropathy (DN) — carriers of different genotypes of Klotho gene polymorphism in different stages of the disease and in the treatment dynamics.Materials and methods. The examinations involved 84 patients (38 men and 46 women) with type 2 diabetes mellitus (DM 2). Depending on the functional state of kidneys, patients were divided into two groups: Group I — patients with normal glomerular filtration rate (GFR) and albuminuria (n = 46), group II — patients with the reduced GFR and albuminuria (n = 38). The control group consisted of 40 healthy individuals. DNA amplification and genotyping of the Klotho gene polymorphism were performed by real-time PCR. VEGF concentration was determined by enzyme-linked immunosorbent assay before and after 6 months of pathogenetic therapy, which included: antidiabetic drugs, ACE inhibitor or angiotensin II receptor blocker and coenzyme A reductase inhibitor.Results. In patients with DN, a significant increase of serum VEGF levels was determined, which was closely related to the functional state of the kidneys. The VEGF level was 162.63 ± 0.31 pg/ml in DN with albuminuria and normal GFR, 367.43 ± 36.15 pg/ml in DN with decreased GFR. The highest response to pathogenetic treatment was observed in the group with the initial stages of nephropathy — the level of VEGF decreased by 28 %, while in the group with low GFR — only by 16 %.Conclusions. It has been established that carriers of the heterozygous genotype of the F352V polymorphism of the Klotho gene had significantly lower serum VEGF levels when compared to the common F352F genotype. Blood VEGF levels in patients with DN can serve as an integral marker of endothelial dysfunction and pathological angiogenesis. After 6 months of pathogenetic nephroprotective therapy serum VEGF levels decreased significantly in all groups of patients with DN.

The effect of fibrin clot and C vitamin on the surgical treatment of Achilles tendon injury in the rat model✰

BackgroundThis study aimed to determine the histological, biochemical, and biomechanical efficacy of fibrin clot and vitamin C in the healing of Achilles tendon ruptures (ATR) in a rat model. Methods52 adult Wistar-Albino rats (300–450 g) were used in the study. 12 rats were divided into four groups as Monitor (Group I), Control (Group II), Fibrin Clot (Group III), Fibrin Clot with vitamin C (Group IV). Four rats were used for fibrin clot preparation. Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) were measured on the 3rd, 7th, 14th, and 21st days. Four rats were sacrificed on the 21st day from each group for histological evaluation. The rest of the rats were sacrificed at 42nd day, half for biomechanical and a half for histological evaluation. ResultsThe 42nd-day HSS score of group IV was significantly lower than those of group I, group II and group III (p = 0.036, p = 0.019, and p = 0.036, respectively). Group IV showed a significantly higher Maximum force N value than those of group I, group II and group III (p = 0.034, p = 0.034 and, p = 0.025, respectively). The blood FGF and VEGF levels of group III and group IV on the 3rd, 7th, 14th, and 21st days were higher than those of group I and group II (p < 0.05). ConclusionFibrin clot and vitamin C produced a stronger tendon structure in terms of biomechanics while providing histological and biochemically better quality tendon healing in the surgical treatment of ATR. This model can be used to accelerate high-quality tendon healing after ATR. Level of EvidenceLevel II, experimental study.

Effects of ozone autohemotherapy on blood VEGF, TGF-β and PDGF levels after finger replantation.

The study aimed to confirm the important role of ozone autologous blood therapy (autohemotherapy) in promoting successful finger replantation and its possible influence mechanism. A total of 150 patients with severed finger replantation admitted to our hospital from March 2018 to March 2019 were selected. Patients were divided into observation group and control group according to different treatment methods. The observation group received additional ozone autologous blood treatment in the control group. We compared the number of white blood cells, visual analogue scale (VAS) scores, and the expression levels of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet-derived growth factor (PDGF) in the two groups of patients before and after intervention. We also assessed the hospitalization time and survival time of the replanted finger in the two groups, as well as blood flow values (Vbcf). Compared with the observation group on the 1st day after the operation and the control group on the 7th day after the operation, the average white blood cell count of the observation group on the 7th day after the operation was significantly increased (P<0.05), and the VAS score was significantly decreased (P<0.05).48 hours after the operation, the average Vbcf value of the replanted finger was lower than that of the contralateral healthy finger (P<0.05). Compared with the control group, the Vbcf value of the replanted fingers in the observation group was higher, and the hospitalization time and finger survival time were shorter (P<0.05). At 7 days after operation, the serum VEGF, TGF-β and PDGF levels in the observation group were significantly higher than the 1 day after operation, before the operation and the control group (P<0.05). Intervention with ozone autohemotherapy after severed finger replantation can significantly increase the number of white blood cells, relieve postoperative pain, and improve the survival rate of the finger body. Ozone autohemotherapy also improves the microcirculation after anastomosis of the severed finger by up-regulating the expression of VEGF, TGF-β and PDGF in blood.

Vascular endothelial growth factor in major depressive disorder, schizophrenia, and bipolar disorder: A network meta-analysis

The peripheral levels of vascular endothelial growth factor (VEGF) have been studied in major psychiatric diseases compared with healthy controls (HCs), but the results were inconsistent. Moreover, few studies have compared VEGF levels between these psychiatric diseases. The aim of the present study was to compare blood VEGF levels in major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder either in a manic episode, a depressive episode, or a euthymic state, and HC. We supposed that VEGF levels may be elevated in some of these diseases as a potential biomarker. In this study, forty-four studies with 6343 participants were included, and network meta-analysis was used to synthesize evidence from both direct and indirect comparisons. The main analysis showed that no significant differences were found between these groups. Subgroup analysis found that patients with MDD may have higher blood VEGF levels than patients with SCZ when the levels were measured through ELISA, and VEGF levels were increased in medication-treated MDD patients compared with HCs. Taken together, blood VEGF levels may be unaltered in these psychiatric disorders, while detection of VEGF in blood by ELISA may a feasible way to distinguish MDD and SCZ. Further replicated studies with larger samples are needed.

Chronic neurogenic pain activates growth factors in the blood of patients with cutaneous melanoma.

e22082 Background: Clusters of tumor cells in blood vessels secrete VEGF family factors necessary for the formation of premetastatic niches. TGF-β activates the epidermal-mesenchymal transition (EMT). The purpose of the study was to analyze levels of angiogenesis and EMT factors in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of VEGF-A, VEGF-C, VEGFR-1, VEGFR-3, TGF-β1 and TGF-βR2 were measured by ELISA in patients with Т3-4NxM0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: VEGF-A in women and men with M+CNP was higher than in controls by 2.7 and 24.9 times respectively; VEGFR-1 was decreased in women by 1.8 times and increased in men by 1.8 times. VEGF-С was unchanged in women and 1.5 times higher in men, and VEGFR-3 was increased by 2.2 times in women and unchanged in men. TGF-β1 was elevated in women and men with M+CNP by 1.4 and 1.8 times, compared to controls, TGF-βR2 – by 1.9 and 2 times respectively. Conclusions: In the blood of women with M+CNP, CNP activates the blood vascular endothelial growth factor VEGF-A and the factor of epidermal-mesenchymal transition TGF-β, while in the blood of men with M+CNP it activates the blood vascular endothelial growth factor VEGF-A, the lymphatic vascular endothelial growth factor VEGF-C and the factor of epidermal-mesenchymal transition TGF-β. VEGF mediates vascular permeability and is associated with the mobilization of endothelial progenitor cells from the bone marrow into premetastatic niches. Activation of TGF-β signaling promotes the induction of the epidermal-mesenchymal transition and supports the properties of cancer stem cells.

Expression of vascular endothelial growth factor and its receptors in infertile men with varicocele

ObjectivesAn enlargement of the spermatic vein is known as a varicocele. Research studies suggest that immune system mediators such as vascular endothelial growth factor (VEGF) and its receptors including VEGFR1, VEGFR2, and VEGFR3 can play a role in angiogenesis and inhibition of endothelial cell apoptosis and correspondingly suppress spermatogenesis. Thus, the purpose of this study was to measure the expression of VEGF and its receptors in infertile men with varicocele. Materials & MethodsTo meet the research objectives, a total number of 30 infertile male patients affected with varicocele (Grade 3) and 30 healthy fertile male subjects without any varicocele or urogenital tract disorder were enrolled in the study. The varicose and normal veins were obtained from the patients along with the blood flowing in these spermatic veins during surgery. Also, peripheral blood samples were collected from the mentioned patients and healthy subjects. The serum levels of VEGF were also measured via enzyme-linked immunosorbent assay (ELISA) and subsequently mRNA level of VEGFR1, VEGFR2, VEGFR3, B Cell Lymphoma-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes were measured using the real-time polymerase chain reaction (RT-PCR) technique. ResultsThe findings of this study revealed that VEGFR2 gene expression in varicose veins was significantly increased compared with normal veins in varicocele patients (P < 0.001) and Bax/Bcl2 ratio reduced in varicose veins when compared to normal veins of the patients (P < 0.05). Our findings also showed a significant rise in the serum levels of VEGF in the peripheral blood and varicose vein bloodstream compared with those in healthy subjects (P < 0.0001). Moreover, a significant difference was observed in the serum levels of VEGF in the peripheral blood and varicose vein blood of patients suffering from varicocele (P < 0.001). ConclusionAccording to the results of this study, VEGF/VEGFR2 axis might act in the survival of endothelial cells of varicocele vein through inhibition of apoptosis and stimulation of angiogenesis. Additionally, increased VEGF in the testis can probably play a role in suppressing spermatogenesis and varicocele-based infertility.

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study.

This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR < 30 mg/g, n = 136, NA), microalbuminuria (UACR at 30-300 mg/g, n = 132, MA), and clinical albuminuria (UACR > 300 mg/g, n = 122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects (P < 0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR (P < 0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.

Efficacy of combined medication of nifedipine and magnesium sulfate on gestational hypertension and the effect on PAPP-A, VEGF, NO, Hcy and vWF.

ObjectiveTo investigate the effects of combined medication of nifedipine and magnesium sulfate on the blood pressure, pregnancy-associated plasma protein A (PAPP-A), vascular endothelial growth factor (VEGF), nitric oxide (NO), homocysteine (Hcy) and von Willebrand factor (vWF) in gestational hypertension patients.MethodsA total of 220 gestational hypertension patients were enrolled as the subjects, and divided into two groups randomly, i.e. the observation group and the control group. In observation group, patients took combined medication of nifedipine and magnesium sulfate, while those in the control group only took magnesium sulfate for treatment. Clinical efficacy, and the changes in blood pressure, PAPP-A, VEGF, NO, Hcy and vWF before and after treatment were compared between two groups.ResultsIn the observation group and the control group, total effectiveness rates were 92.7% and 70.9%, respectively (p < 0.05). After treatment, we found significant decreases in PAPP-A, VEGF, NO, Hcy and vWF in patients of two groups, with more significant decreases in the observation group (p < 0.05). Incidence rates of the adverse reactions in two groups were 5.5% and 6.4%, respectively, without any statistically significant differences (p > 0.05). In the observation group, patients had fewer complications (p < 0.05).ConclusionCombined medication of magnesium sulfate and nifedipine can decrease the levels of PAPP-A, VEGF, NO, Hcy and vWF in serum as well as the blood pressure of patients with gestational hypertension, with a reduction in incidence rate of complications and improvement in efficacy.

Effects and mechanism of urinary kallidinogenase in the survival of random skin flaps in rats

ObjectiveThis study explored the effects of urinary kallidinogenase (UK) on ischemia and necrosis of random skin flaps in rats, and the mechanisms thereof. MethodologyIschemia and necrosis of random skin flaps were induced by constructing a modified McFarlane flap model on the dorsa of rats. UK (0.016 PNA/kg) or normal saline (10 ml/kg, control) was administered through the tail vein immediately after flap ischemia model construction and then daily for 7 days. After sacrifice, the flap tissue was harvested and stained with hematoxylin and eosin (H&E), and histopathological changes were observed. Lead oxide/gelatin angiography and laser Doppler imaging were performed to demonstrate angiogenesis and changes in blood flow. Immunohistochemical analysis of the H&E-stained slices was performed to detect the expression of vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). The TNF-α and IL-6 levels were also detected by enzyme-linked immunosorbent assays. The activity of superoxide dismutase (SOD) and the malondialdehyde (MDA) content were measured to represent the oxidative damage level. ResultsUK significantly alleviated ischemia and necrosis of random skin flaps, as evidenced by improved general results and histopathological manifestations, and markedly increased the mean survival area. UK prompted angiogenesis, increased blood flow and VEGF expression. The levels of TNF-α, IL-6, and IL-1β were declined. Furthermore, UK increased SOD activity and decreased MDA content, suggesting that it has the capacity to alleviate oxidative damage. ConclusionThese findings suggest that UK sufficiently attenuated flap ischemia and increased the survival of random skin flaps in rats.

Can IL-33 and Endocan be New Markers for Retinopathy of Prematurity?

Retinopathy of Prematurity (ROP) is a pathophysiologic condition of the retina due to abnormal proliferation of retinal vessels. The study aimed too ascertain the importance of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), interleukin-33 (IL-33) and endocan in the diagnosis and follow-up of ROP. This prospective cohort study was conducted in the neonatal intensive care unit (NICU) of Health Science University, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey, between February 2017 and August 2018. Preterm infants (gestational age (GA) of ≤32 weeks and birth weight of ≤1500 gr), diagnosed ROP were included in the study. VEGF, IGF-1, IL-33 and endocan levels were evaluated in the cord blood and in the serum before and after treatment of infants in the ROP and control groups. A final number of 146 infants were included in the study. During the study period, 73 infants were identified as the ROP group, and 73 infants were allocated as the control group. In the ROP group, the cord blood VEGF value was higher than the control group (p <0.05). However, IGF-1 levels in the cord blood were lower in the ROP group than control (P<0.05). IL-33 and endocan values in the cord blood were similar in both control and ROP groups (p>0.05). Although serum levels of IL-33, VEGF and endocan were higher before laser treatment, these biomarkers decreased significantly after laser treatment (p <0.05). We determined that serum IL-33 and endocan levels might be suggested as sensitive novel markers for the prediction of severe ROP.

Ultrasound-targeted microbubble destruction improved the antiangiogenic effect of Endostar in triple-negative breast carcinoma xenografts.

Ultrasound-targeted microbubble destruction (UTMD) has been reported to be a meritorious technique for drug targeting delivery. In this study, we aimed to evaluate the synergistic antiangiogenic effect of UTMD combined with Endostar on triple-negative breast carcinoma tumors. The lipid-shelled microbubbles (MBs) conjugated with Endostar were constructed using a biotin-avidin bridging chemistry method, and the morphological characteristics and drug-conjugating content were determined. MBs were administered intravenously to nude mice bearing MDA-MB-231 breast carcinoma xenografts and ultrasound exposure followed. The tumor microcirculation was observed by contrast-enhanced ultrasonography (CEUS) and the Endostar biodistribution was detected by enzyme-linked immunosorbent assay. Twenty-four breast carcinoma-bearing nude mice were divided into four groups. After treatment, every 3days for 15days the in vivo antitumor effects were assessed by calculating the tumor growth inhibition rate (TGIR). The tumor microcirculation was observed by CEUS, the tumor microvessel density (MVD) was calculated by immunohistochemistry under a microscope, and the vascular endothelial growth factor (VEGF) gene expression was detected by real-time quantitative polymerase chain reaction. The prepared Endostar-conjugated MBs were round and well-dispersed with a mean size of 2.8 ± 0.7µm and a drug conjugating content of 800.72 ± 70.53µg/108MBs. UTMD blocked the tumor microcirculation, and improved Endostar release in the targeted tumor tissue with a drug content of 1.12 ± 0.43µg/gram protein, which was about three times higher than that in Endostar group or Endostar conjugated MBs group. Endostar-conjugated MBs combined with UTMD treatment achieved the optimal antitumor effects in vivo with a TGIR of 46.29%, and apparent antiangiogenic effects with minimal tumor blood perfusion, MVD and VEGF gene expression level. UTMD can improve Endostar delivery in the targeting tumor tissue and mediate synergistic antiangiogenetic and antitumor effects, which may be a potential therapeutic strategy for refractory breast cancer.

The level of vascular endothelial growth factor in peripheral blood of type 2 diabetic patients depending on kidney functional state

Abstract. The aim of the study was to assess a serum level of vascular endothelial growth factor (VEGF) in type 2 diabetic patients depending on kidney function.&#x0D; Methods: we examined 66 type 2 diabetic patients and 20 healthy control subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR) level, patients with diabetes mellitus (DM) were divided into the following groups: group I - patients with type 2 DM without signs of nephropathy – normal GFR without albuminuria (n = 26); group ІІ - patients with type 2 DM with normal GFR and albuminuria (n = 22); group III - patients with type 2 DM with reduced GFR and albuminuria (n = 18). ІV group - patients with acute coronary syndrome (n = 26).&#x0D; The concentration of the VEGF was determined by enzyme-linked immunosorbent assay. The glomerular filtration rate (GFR) was calculated using the CKD EPI formula (KDIGO 2012).&#x0D; Results: serum VEGF level in patients with diabetic nephropathy (DN) was significantly increased depending on kidney function.&#x0D; VEGF positively correlated with urine albumin and serum creatinine levels and the negative correlation with GFR was found. These findings prove the undeniable role of kidneys in the development of renocardial syndrome in patients with DN. VEGF levels positively correlated with glycosylated hemoglobin and total cholesterol, indicating an unconditional dependence of endothelial dysfunction on lipid and glucose metabolism disorders.&#x0D; Conclusions: Increased levels of VEGF in type 2 diabetic patients without clinical signs of kidney damage may indicate the development of subclinical renal dysfunction. Blood VEGF in patients with DN may be an integral marker of endothelial dysfunction and pathological angiogenesis. Our findings suggest that determination of serum VEGF level in patients with DN may have practical use as an early predictor of cardiac disruption, estimation of the prognosis, as well as improvement of cardionephroprotective strategy.

SYNTHESIS, CHARACTERIZATION, AND IN VIVO IMMUNOMODULATION OF CCR2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR ANTAGONISTS-LOADED PEGYLATED NANOPARTICLES

Objective: Chemokine (C-C motif) ligand 2 (CCL2), a candidate of cytokines, orchestrates immune cell recruitment to inflamed organs. CCL2 has been shown to have direct angiogenic effects, so providing an anti-angiogenic agent, Avastin (AV), to be combined with the CCR2 antagonist (concentration ratio [CR]) plays an essential role in the hemostatic strategy for immunomodulation. Lack of targetability and the adverse effects of chemical treatments are the main obstacles led scientists to develop novel strategies using nano-delivery approaches such as pegylated nanoparticles (NPs) which exhibits reduced drug clearance rates. The rationale of the current study is to test the in vivo immunomodulatory effects of AV and/or CR in their NPs or free counterparts.Methods: These NPs were synthesized and characterized using different physicochemical techniques. Males Wistar rats (n=114) were used and divided into 7 groups treated with vehicle, AV, AVNP, CCR2 antagonist (CR), CCR2 antagonist NPs (CRNP), AV-CCR2 antagonist (AVCR), and AV-CCR2 antagonist NPs (AVCRNP). Groups were subdivided into three subgroups according to the administrated dose. Blood was taken from rats for differential leukocyte and platelet profile measurements. Sera were collected to test vascular endothelial growth factor (VEGF) levels. Autopsy samples from liver were taken for histopathological investigation.Results: The morphology of the NPs was spherical and had sizes ranging from 89.89 nm to 146 nm. Monocytes and lymphocytes accumulated in the blood circulation and VEGF levels were inhibited after AV and CR administrations. In addition, large platelets concentration ratio was elevated in the blood circulation.Conclusion: We concluded that AV ad CR therapeutic regimens have an immunomodulatory role through induction of monocyte-platelet aggregation and inhibition of VEGF.

SYNTHESIS, CHARACTERIZATION, AND IN VIVO IMMUNOMODULATION OF CCR2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR ANTAGONISTS-LOADED PEGYLATED NANOPARTICLES

Objective: Chemokine (C-C motif) ligand 2 (CCL2), a candidate of cytokines, orchestrates immune cell recruitment to inflamed organs. CCL2 has been shown to have direct angiogenic effects, so providing an anti-angiogenic agent, Avastin (AV), to be combined with the CCR2 antagonist (concentration ratio [CR]) plays an essential role in the hemostatic strategy for immunomodulation. Lack of targetability and the adverse effects of chemical treatments are the main obstacles led scientists to develop novel strategies using nano-delivery approaches such as pegylated nanoparticles (NPs) which exhibits reduced drug clearance rates. The rationale of the current study is to test the in vivo immunomodulatory effects of AV and/or CR in their NPs or free counterparts.Methods: These NPs were synthesized and characterized using different physicochemical techniques. Males Wistar rats (n=114) were used and divided into 7 groups treated with vehicle, AV, AVNP, CCR2 antagonist (CR), CCR2 antagonist NPs (CRNP), AV-CCR2 antagonist (AVCR), and AV-CCR2 antagonist NPs (AVCRNP). Groups were subdivided into three subgroups according to the administrated dose. Blood was taken from rats for differential leukocyte and platelet profile measurements. Sera were collected to test vascular endothelial growth factor (VEGF) levels. Autopsy samples from liver were taken for histopathological investigation.Results: The morphology of the NPs was spherical and had sizes ranging from 89.89 nm to 146 nm. Monocytes and lymphocytes accumulated in the blood circulation and VEGF levels were inhibited after AV and CR administrations. In addition, large platelets concentration ratio was elevated in the blood circulation.Conclusion: We concluded that AV ad CR therapeutic regimens have an immunomodulatory role through induction of monocyte-platelet aggregation and inhibition of VEGF.

Comparative characteristic of the effect of anti-inflammatory therapy on the blood and urine levels of growth factors in patients with rheumatoid arthritis

The purpose of our work was to compare the effect of aceclofenac and meloxicam on the level of transforming growth factor-β1 (TGFβ1) and vascular endothelial growth factor in the blood and urine in chronic kidney disease (CKD) patients with rheumatoid arthritis (RA).&#x0D; Methods. RA patients were allocated into three groups: I group included the patients with RA without CKD presence (n = 47), group II – patients with RA with CKD stage 1 (n = 46), group III – patients suffered from RA with CKD stage 2 (n = 45). To form the group of comparison 20 healthy persons of appropriate age category were examined. Complex clinical-laboratory examination of all patients was performed during the period of extensive clinical manifestations (before nonsteroid anti-inflammatory drug (NAIP) administration), in a week and in 2 weeks during carrying out therapy with NAIP. Treatment was also carried out in accordance with the existing principles of therapy RA and of the revealed nephrologic diseases. In a complex of patients’ therapy aceclofenac was included. Influence of aceclofenac was compared with meloxicam. Concentrations of TGFβ1 and vascular endothelial growth factor (VEGF) in the blood and urine were studied using an immunofermental method.&#x0D; Results. In a week of anti-inflammatory therapy, a significantly decrease in the levels&#x0D; of the studied factors was found in all patients’ groups. The blood VEGF level was lower by 11.90% in the aceclofenac group compared to the meloxicam group. Urine VEGF and TGFβ1 levels were decreased by 5.53% and 39.40%, respectively, in patients with aceclofenac therapy compared with the meloxicam group. After two weeks of the aceclofenac therapy a significant decrease of TGFβ1 and VEGF in the blood (p&lt;0.05) and urine (p &lt;0.001) of the CKD patients with RA were determined.&#x0D; Conclusion. The use of aceclofenac as a new generation of NSAIDs for the complex&#x0D; treatment of patients with RА and comorbid CKD improves the therapy efficiency due to reducing the blood and urine levels of growth factors.

Involvement of stromal cell-derived factor-1α (SDF-1α), stem cell factor (SCF), fractalkine (FKN) and VEGF in TSG protection against intimal hyperplasia in rat balloon injury

BackgroundIntimal hyperplasia is the major therapeutic concern after percutaneous coronary intervention. The aim of this study is to investigate effects of 2,3,4′,5-tetrahydroxystilbene-2-O-β-D glucoside (TSG) on intimal hyperplasia and the underling mechanisms through attenuating the expressions of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1, and through promoting re-endothelialization with vascular endothelial growth factor (VEGF). MethodRats were operated with carotid artery balloon injury. The treatment groups were gavaged with 50 and 100 mg/kg/d of TSG. After 10 days of treatment, carotid artery pathological changes were evaluated by histology. Serum levels of SDF-1α, SCF, FKN and VEGF were detected by enzyme linked immunosorbent assay. The protein expressions of the receptors c-kit, CXCR4, CX3CR1, as well as CD34 and proliferating cell nuclear antigen (PCNA) were detected by immunochemistry. ResultsTSG dose-dependently inhibited balloon injury-induced intimal hyperplasia, as evidenced by reducing neointima area (NIA), neointima area/media area (NIA/MA), neointima area/internal elastic area (NIA/IELA), and by decreasing the protein expression of PCNA. TSG reduced serum levels of SDF-1α, SCF and FKN, and it also decreased the expressions of the corresponding receptors c-kit, CXCR4, CX3CR1 in neointima. Importantly, the level of VEGF in peripheral blood and the expression of CD34 in vascular walls were increased to promote re-endothelialization. ConclusionsThis study clearly demonstrated that TSG was effective in inhibiting intimal hyperplasia, and this effect was mediated, at least in part, through the SCF/c-kit, SDF-1α/CXCR4 and FKN/CX3CR1 axes. Importantly, TSG could increase VEGF and CD34 to promote endothelial repair.

Role of vascular endothelial growth factor in children's hydrocephalus

Objective To analyze the level of vascular endothelial growth factor (VEGF) of peripheral blood and cerebrospinal fluid (CSF) in patients with hydrocephalus and to explore the clinical significance of VEGF in evaluating hydrocephalus and its prognosis. Methods A retrospective study was conducted on 29 children of hydrocephalus (experimental group), including 1 case of mild hydrocephalus, 14 cases of moderate hydrocephalus, and 14 cases of severe hydrocephalus, who received treatment at Neurosurgery Department, Children’s Hospital of Fudan University from March 2015 to December 2016. A total of 24 children with tethered spinal cord treated during the same period were enrolled into this study as well and served as controls. All the children in this series underwent surgical treatment, and the prognosis was evaluated according to the Salmon standard. The Luminex technology was used to measure the levels of VEGF in peripheral blood and CSF collected in all cases, and correlation analysis was further conducted to explore the relationship of VEGF levels to the conditions and prognosis of hydrocephalus. Results In the experimental group of hydrocephalus, the VEGF levels in peripheral blood and CSF (132.04±69.85 and 82.72±42.84 pg/ml, respectively) were significantly higher than those in control group (69.20±35.69 and 52.76±45.69 pg/ml, respectively, both P<0.05), and they demosntrated significant correlation (r=0.732, P<0.01). In the experimental group, the blood and CSF VEGF level of cases with severe hydrocephalus (184.07±65.55 and 89.40±28.23 pg/ml, respectively) were significantly higher than those of cases with moderate hydrocephalus (103.38±70.73 and 56.16±28.69 pg/ml, respectively, both P<0.05). Among the 27 patients with postoperative follow-up, 11(40.7%) cases obtained significantly improvement, 10(37.0%) were moderately improved, 4(14.8%) were slightly better, and 2(7.4%) deteriorated. The single factor variance analysis showed that the content of VEGF in blood and CSF decreased with the improvement of the prognosis of children with hydrocephalus (both P<0.05). Conclusions VEGF content is increased in the blood and CSF of the children with hydrocephalus. Measurement of VEGF level could help evaluate the conditions and prognosis of pediatric hydrocephalus, which serves as an index of laboratory assessment. Key words: Hydrocephalus; Child; Vascular endothelial growth factor; Prognosis

Antiangiogenesis activity test of tin leaf (Ficus carica L.) on the number of blood vessels and VEGF expression of chorioallantoic membrane of embryonated chicken eggs

Abstract This research has been conducted on the antiangiogenesis activity test of the tin leaf (Ficus carica L.) on the number of blood vessels and vascular endothelial growth factor (VEGF) expression of chorioallantoic membrane (CAM) of embryonated chicken eggs. The general objective of this study is the use of natural products from the F. carica L. as chemopreventive in cancer through the mechanism of inhibition of angiogenesis. Inhibition of angiogenesis, supply of nutrients and oxygen to cancer cells will also be inhibited, so that indirectly cancer cells will be stunted. This study used 25 embryonated chicken eggs that divided into 5 treatments and each treatment has 5 repetitions. This treatment includes placebo negative controls, celecoxib-positive controls, and 3 treatment groups were given a water extract of F. carica L. which was divided into several doses of 75, 90, and 110 μg. The result found a significant difference (P &lt; .05) in the macroscopic observation of the number of blood vessels in the CAM loaded with the paper dish. Observation of VEGF expression in vascular endothelial cells in the CAM also had a significant difference (P &lt; .05). The optimal dose of water extract of F. carica L. of 90 μg has been able to inhibit the formation of new blood vessels by 65.51% and reduce VEGF expression by 45% in the chorioallantoic membrane. Thus, it can be concluded that the administration of water extract of F. carica L. can inhibit the formation of new blood vessels and inhibit VEGF expression.