scholarly journals Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlo Gesualdo ◽  
Cornel Balta ◽  
Chiara Bianca Maria Platania ◽  
Maria Consiglia Trotta ◽  
Hildegard Herman ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Drug Repurposing ◽  
Melanocortin Receptors ◽  
Control Group ◽  
Vascular Endothelial ◽  
Diabetic Mice ◽  
Dynamic Simulations ◽  
Endothelial Growth Factor

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.

scholarly journals The Usefulness of Serum Sorbitol and Vascular Endothelial Growth Factor A in Predicting Diabetic Retinopathy as Compared to Optical Coherence Tomography

2019 ◽  
Vol 6 (1) ◽  
pp. 41-49
Author(s):  
Sanaa Gadbaan Hama Almandlawi ◽  
Muhanad Salah Mawlood
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Proliferative Diabetic Retinopathy ◽  
Control Group ◽  
Vascular Endothelial ◽  
Optical Coherence ◽  
Diagnostic Efficiency ◽  
Endothelial Growth Factor

Background: No specific and sufficient diagnostic biomarkers are currently available for predicting diabetic retinopathy (DR). Objectives: This study was conducted to investigate the validity of serum sorbitol and Vascular Endothelial Growth Factor A (VEGF-A) in diagnosing DR and differentiating it from diabetes without retinopathy (DNR). The study also investigated the diagnostic efficiency of these biomarkers when compared to optical coherence tomography OCT. Methods: A cross-sectional study included 164 diabetes mellitus patients: 30 patients with no retinopathy (the control group), 86 patients with non-proliferative diabetic retinopathy (NPDR), and 48 patients with Proliferative Diabetic Retinopathy (PDR). Patients were referred to the Layla Qasim Diabetic Center between November 2016 and October 2017 and an ophthalmologist established a DR diagnosis using OCT. Serum sorbitol and serum VEGF-A were measured for all patients. Results: By using study biomarkers, the cut-off values of VEGF-A (124.7 ng/ml) and sorbitol (0.3112 mg/ml) were established, and their validity parameters. For sorbitol, the values were as follows: specificity was 75.4, the sensitivity was 80 and 68.3% of observed agreement with the results of the OCT technique. For VEGF-A, the specificity was 73.1 the sensitivity was 80 and 76.2% of the observed agreement. The combined parallel test was applied as negative if both the tests were negative or as positive if either of the tests was positive: a highly significant statistical agreement (Kappa test p <0.001) was found with the gold standard diagnosis (OCT), with 85.4% of observed agreement. Conclusion: A combination of serum sorbitol and VEGF-A for diagnosing DR and for differentiating DR from DNR patients exhibits a significant agreement with an OCT diagnosis.

Effect of HylocereusPolyrhizus Rind Extract Toward Interleukin-1β, Vascular Endothelial Growth Factor Expression, Endometriosis Implant Area

2017 ◽  
Vol 9 (08) ◽  
Author(s):  
YanuarEka P. ◽  
Hendy Hendarto ◽  
Widjiati .
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Treatment Group ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Vascular Endothelial ◽  
Mice Model ◽  
Endothelial Growth Factor ◽  
Fruit Rind

Retrograde menstruation lead to I Kappa B Kinase (IKK) fosforilation in peritoneum macrophage and cause secretion of proinflammatory cytokine interleukin1β then stimulate endometriosis cell to produce Vascular Endothelial Growth Factor which lead to increasing of endometriosis lession seen as endometriosis implant area. Cytokine secretion was inhibited through prevention of NF-κB activation by dragon red fruit rind extract (Hylocereuspolyrhizus). The aim of this reserach is to know the effect of dragon red fuit rind extract with 0,25; 0,5; and 1 mg/g bodyweight dosage toward IL-1β, VEGF expression and implant area in endometriosis mice model. The design of this experiment was randomized post test only control group design.Endometrios mice model were made in 14 days and split into two group, positive control group and treatment group after two week negative control group and postive control group were given Na-CMC 0,5% solution consequetively, and treatment group were given dragon red fruit extract with different dosage. Signification number for IL-1β is p>0,05, signification number for VEGF is p>0,05, and implant area signification number is p>0,05. Administration of dragon red fruit rind extract can decrease IL-1β, VEGF, and implant area.

scholarly journals Relationship between Serum Vascular Endothelial Growth Factor Levels and Stages of Diabetic Retinopathy and Other Biomarkers

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Nakhleh E. Abu-Yaghi ◽  
Nafez M. Abu Tarboush ◽  
Ala M. Abojaradeh ◽  
Amal S. Al-Akily ◽  
Esra’a M. Abdo ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Glycosylated Hemoglobin ◽  
Density Lipoprotein ◽  
Significant Negative Correlation ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Dm Type 2

Aim. This study aims to measure serum vascular endothelial growth factor (VEGF) levels in a sample of Jordanian patients and to determine their relationship with the different stages of diabetic retinopathy. It also explores the correlation between VEGF concentrations and different biochemical and demographic findings. Materials and Methods. A total of 167 adults participated in the study. Participants were divided into two main categories: patients with diabetes mellitus (DM) type 2 without diabetic retinopathy (DR) (N = 62) and patients with DM type 2 affected by DR (N = 105). DR patients were further subclassified into nonproliferative (N = 41) and proliferative (N = 64). Basic laboratory tests were measured to correlate with VEGF levels. Irisin, a hormone linked to diabetic retinopathy was also measured and correlated with VEGF. Results. Serum VEGF was found to positively correlate with the severity of diabetic retinopathy. The means of VEGF serum concentrations were 60 pg/mL for controls, 133 pg/mL for nonproliferative DR patients, and 229 pg/mL for proliferative DR patients. We found a significant positive correlation with glycosylated hemoglobin (HbA1c), and a significant negative correlation with high-density lipoprotein (HDL) levels, age, and irisin. Conclusion. In this cohort of Jordanian diabetics, serum VEGF concentrations strongly correlated with the presence and stages of diabetic retinopathy, suggesting it as an appropriate indicator for diabetic retinopathy early detection and management in this society. VEGF levels also significantly correlated with HbA1c, HDL, and irisin levels. Further studies are encouraged to explore these relationships in other ethnic groups and with different diabetic complications.

scholarly journals Vascular endothelial growth factor in prognosis of splenic malignant tumours in dogs

2014 ◽  
Vol 58 (2) ◽  
pp. 255-260
Author(s):  
Aleksandra Sobczyńska-Rak ◽  
Izabela Polkowska ◽  
Adam Brodzki
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Comparative Analysis ◽  
Growth Factor ◽  
Who Classification ◽  
Control Group ◽  
Vascular Endothelial ◽  
Malignant Tumours ◽  
Blood Samples ◽  
Endothelial Growth Factor ◽  
Immunoenzymatic Assays

Abstract The aim of the study was to determine the levels of the vascular endothelial growth factor (VEGF) in the serum of dogs suffering from splenic malignant tumours, prior to splenectomy, as well as three and six months after the surgery. Tumours and blood samples were collected from 10 dogs of various breeds, aged between 7 and 13 years, and from 10 control animals. Tumour sections were fixed in 10% buffered formalin for 24 h. The type of tumour was determined according to the WHO classification. Blood samples were centrifuged and the obtained sera were subjected to immunoenzymatic assays to determine the VEGF levels. The median of VEGF levels in the serum of dogs suffering from splenic malignant tumours was 37.85 pg/mL (15.40-107.18 pg/mL). The highest values were observed in dogs with confirmed metastases (107.18 pg/mL and 65.43 pg/mL). The VEGF values in control group were between 0.1 pg/mL and 13.04 pg/mL. A comparative analysis of the VEGF levels against the animals' survival time indicated that VEGF overexpression may serve as a prognostic factor in cases of malignant tumours of the spleen.

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