High Vascular Endothelial Growth Factor Research Articles

Dental pulp stem cells regenerate neural tissue in degenerative disorders and stroke rehabilitation: A scope systematic review

BackgroundDental Pulp Stem Cells (DPSCs) possess a remarkable ability for tissue differentiation, making them highly efficient in tissue regeneration and inflammation regulation. This systematic study proposes to find an answer to the question, “Do DPSCs have the ability to regenerate and rehabilitate nerve tissue?" MethodsThis systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of non-bias was respected. All the articles from 2014 to 2024 were extracted from the Web of Science, PubMed, and Scopus databases. This study extracted the antigens and pro-inflammatory factors associated with DPSCs' involvement and how they affect the CNS's neural tissue regeneration. ResultsTwo persons of researchers searched the database. After screening the full texts, they included 11 articles in their study. DPSCs control the following antigens: CD73, CD34, CD90, CD105, CD14, CD45, CD19Oct-4, CD73, CD31, CD34CD29CD44. Even though hematopoietic markers did not change much, OCT-4 and CD-73 were increased by DPSCs. DPSC-derived exosomes suppressed the expression of IL-6, IL-1β, TNF-α, and TGF, key mediators of nerve tissue inflammation. Additionally, DPSCs show high Vascular Endothelial Growth Factor (VEGF) expression in mice brain tissue cultures. DPSCs reduce Subarachnoid Hemorrhage (SAH), a condition in which blood collects in the subarachnoid space and causes ischemia. DiscussionDPSCs showed the ability to regenerate nerve tissue and brain ganglia, stimulating angiogenesis by expressing cell markers and controlling growth factors in mice, and high therapeutic potential in neurodegenerative disorders. The present study invites further research in neurological disorders, specifically strokes, to prescribe these stem cells to the human population.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis.

Acute myeloid leukemia (AML) is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand, inhibiting hematopoiesis. The treatment and prognosis of this disease have always been unsatisfactory. To investigate the correlation between vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGFβ1) expression and prognosis in older adults with AML. This study enrolled 80 patients with AML (AML group), including 36 with complete response (AML-CR), 23 with partial response (AML-PR), and 21 with no response (AML-NR). The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls. Kaplan-Meier analysis was performed to assess overall survival (OS) and progression- or disease-free survival (DFS). Prognostic risk factors were analyzed using a Cox proportional hazards model. The AML group showed a VEGF level of 2.68 ± 0.16. VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR (P < 0.05). TGFβ1 expression in the AML group was 0.33 ± 0.05. Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR (P < 0.05). VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes, platelets, hemoglobin, and peripheral blood immature cells (P < 0.05); Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression (P < 0.05), whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels (P < 0.05). VEGF, TGFβ1, and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS (P < 0.05), while VEGF, TGFβ1, and white blood cell count were independent risk factors for DFS (P < 0.05). Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Radiomic analysis based on magnetic resonance imaging for the prediction of VEGF expression in hepatocellular carcinoma patients.

The purpose of this study was to investigate the ability of radiomic characteristics of magnetic resonance images to predict vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) patients. One hundred and twenty-four patients with HCC who underwent fat-suppressed T2-weighted imaging (FS-T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) one week before surgical resection were enrolled in this retrospective study. Immunohistochemical analysis was used to evaluate the expression level of VEGF. Radiomic features were extracted from the axial FS-T2WI, DCE-MRI (arterial phase and portal venous phase) images of axial MRI. Least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses were performed to select the best radiomic features. Multivariate logistic regression models were constructed and validated using tenfold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models. Our results show that there were 94 patients with high VEGF expression and 30 patients with low VEGF expression among the 124 HCC patients. The FS-T2WI, DCE-MRI and combined MRI radiomics models had AUCs of 0.8713, 0.7819, and 0.9191, respectively. There was no significant difference in the AUC between the FS-T2WI radiomics model and the DCE-MRI radiomics model (p > 0.05), but the AUC for the combined model was significantly greater than the AUCs for the other two models (p < 0.05) according to the DeLong test. The combined model had the greatest net benefit according to the DCA results. The radiomic model based on multisequence MR images has the potential to predict VEGF expression in HCC patients. The combined model showed the best performance.

HIF1A protein expression is correlated with clinical features in gastric cancer: an updated systematic review and meta-analysis

To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science for studies on GC and HIF1A, covering studies published until January 31st, 2022. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for clinical characteristics based on high and low HIF1A protein levels. We used random-effects and fixed-effects meta-analysis methods to determine mean effect sizes of ORs and evaluated publication heterogeneity with τ2, I2, and Q values. Additionally, we generated funnel plots to inspect publication bias. Our meta-analysis included 20 publications with 3416 GC patients to estimate the association between high or low HIF1A expression and clinical characteristics. Positive HIF1A expression was significantly associated with T stage progression (OR: 2.46; 95% CI 1.81–3.36; P < 0.01), TNM stage progression (OR: 2.50; 95% CI 1.61–3.87; P < 0.01), lymph node metastasis (OR: 2.06; 95% CI 1.44–2.94; P < 0.01), undifferentiated status (OR: 1.83; 95% CI 1.45–2.32; P < 0.01), M stage progression (OR: 2.34; 95% CI 1.46–3.77; P < 0.01), Borrmann stage progression (OR: 1.48; 95% CI 1.02–2.15; P = 0.04), larger tumor size (OR: 1.27; 95% CI 1.06–1.52; P < 0.01), vascular invasion (OR: 1.94; 95% CI 1.38–2.72; P < 0.01), and higher vascular endothelial growth factor (VEGF) protein expression (OR: 2.61; 95% CI 1.79–3.80; P < 0.01) in our meta-analysis. GC Patients highly expressing HIF1A protein might be prone to tumor progression, poorly differentiated GC cell types, and a high VEGF expression.

Longitudinal prospective study of Sturge–Weber syndrome urine angiogenic factors and neurological outcome

AbstractObjectiveThis study identified biomarkers of neurological outcome in Sturge‐Weber syndrome (SWS) via urine angiogenic factors and captured longitudinally derived natural history data within an SWS cohort.MethodsThis longitudinal, prospective, multicentered study of 61 people with SWS aged 0.4–55 years reports port‐wine birthmark score, Neuroscore, Neuro‐Quality of Life, and urine angiogenic factors over a two‐year period.ResultsCognitive Neuroscore worsened over time for children aged 0–2 years. Male sex was associated with worsening Cognitive Function Neuroscore during the study. Age of seizure onset before 2 years was strongly associated with worse Neuroscore. Children with SWS had low Neuro‐Quality of Life related to cognitive function. Seizure severity, male sex, and earlier age of seizure onset were associated with worse Neuro‐Quality of Life in school‐aged children. Children with SWS have elevated basic fibroblast growth factor in their urine compared with controls, whereas higher vascular endothelial growth factor was associated with better Neuroscore.InterpretationThis study is the first multicenter, prospective, and longitudinal study of people with SWS. It identifies significant clinical prognostic factors such as age of seizure onset and male sex, informs symptom progression over time by age group, and suggests that further study of angiogenic mechanisms and potential biomarkers are needed.

Predicting chemotherapy toxicity in multiple myeloma: the prognostic value of pre-treatment serum cytokine levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor

IntroductionMultiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events.MethodsWe conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia.ResultsOur findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414).ConclusionsPre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.

Association of Neurotrophic Factors at Midlife With In Vivo Measures of β-Amyloid and Tau Burden 15 Years Later in Dementia-Free Adults.

Neurotrophic factors (NTFs) play an important role in Alzheimer disease (AD) pathophysiology. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are important NTFs. However, a direct link of BDNF and VEGF circulating levels with in vivo measures of amyloid-β (Aβ) and tau burden remains to be elucidated. We explored the relationship of BDNF and VEGF serum levels with future brain Aβ and tau pathology in a cohort of cognitively healthy, predominantly middle-aged adults and tested for possible effect modifications by sex and menopausal status. This cross-sectional analysis was conducted using data from the Framingham Heart Study (FHS), a community-based cohort study. The study sample included cognitively healthy participants from the FHS Offspring and Third-generation cohorts. BDNF and VEGF were measured in the third-generation cohort during examination cycles 2 (2005-2008) and 1 (2002-2005), respectively, and in the offspring cohort during examination cycle 7 (1998-2001). Participants underwent 11C-Pittsburgh compound B amyloid and 18F-Flortaucipir tau-PET imaging (2015-2021). Linear regression models were used to assess the relationship of serum BDNF and VEGF levels with regional tau and global Aβ, adjusting for potential confounders. Interactions with sex and menopausal status were additionally tested. The sample included 414 individuals (mean age = 41 ± 9 years; 51% female). Continuous measures of BDNF and VEGF were associated with tau signal in the rhinal region after adjustment for potential confounders (β = -0.15 ± 0.06, p = 0.018 and β = -0.19 ± 0.09, p = 0.043, respectively). High BDNF (≥32,450 pg/mL) and VEGF (≥488 pg/mL) levels were significantly related to lower rhinal tau (β = -0.27 ± 0.11, p = 0.016 and β = -0.40 ± 0.14, p = 0.004, respectively) and inferior temporal tau (β = -0.24 ± 0.11, p = 0.028 and β = -0.26 ± 0.13, p = 0.049, respectively). The BDNF-rhinal tau association was observed only among male individuals. Overall, BDNF and VEGF were not associated with global amyloid; however, high VEGF levels were associated with lower amyloid burden in postmenopausal women (β = -1.96 ± 0.70, p = 0.013, per 1 pg/mL). This study demonstrates a robust association between BDNF and VEGF serum levels with in vivo measures of tau almost 2 decades later. These findings add to mounting evidence from preclinical studies suggesting a role of NTFs as valuable blood biomarkers for AD risk prediction.

DYNAMICS OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN HEMORRHAGIC STROKE DEPENDING ON THE DISEASE SEVERITY

Introduction. The results of experimental studies indicate the growth factors, in particular the vascular endothelial growth factor, around the hematoma already at the beginning of hemorrhagic stroke.&#x0D; The aim of the study: to find out the features of vascular endothelial growth factor expression in patients with hemorrhagic stroke depending on the disease severity.&#x0D; Research metods. 53 patients with hemorrhagic stroke were examined. The control group - 25 people with hypertension without dyscirculatory disorders of cerebral circulation.&#x0D; The level of neurological deficit was assessed using the National Institute of Health Stroke Scale (NIHSS).&#x0D; Vascular endothelial growth factor (VEGF) in the blood was determined on the 1st, 5th and 21st days of the acute stroke period by enzyme-linked immunosorbent assay (ELISA) (test kits of the company "Biosourse" (USA)). The research results were analyzed by the method of variational statistics using the program "STATISTICA 6.0" (StatSoft, USA).&#x0D; Results and discussion. With a mild degree of severity, the content of VEGF in the blood is significantly lower on the 1st and 5th days of the acute period compared to the control group. This may be one of the factors contributing to the development of a hemorrhagic stroke. An increase in VEGF in the first days of the disease can be a marker of the serious condition of patients with hemorrhagic stroke. VEGF levels on the 5th and 21st days are highest in mild cases, and lowest in severe cases. The increased synthesis of VEGF in case of a mild stroke indicates a more adequate response of the endothelium to damage.&#x0D; Conclusions. A marker of a mild hemorrhagic stroke can be low VEGF levels in the first days of the disease and their significant increase at the end of the previous period. High VEGF in the blood at the beginning of the disease, and relatively lower indicators (compared to a mild course) at the end of the previous period are associated with the severe condition of patients with hemorrhagic stroke.

Whole brain morphologic features improve the predictive accuracy of IDH status and VEGF expression levels in gliomas.

Glioma is a systemic disease that can induce micro and macro alternations of whole brain. Isocitrate dehydrogenase and vascular endothelial growth factor are proven prognostic markers and antiangiogenic therapy targets in glioma. The aim of this study was to determine the ability of whole brain morphologic features and radiomics to predict isocitrate dehydrogenase status and vascular endothelial growth factor expression levels. This study recruited 80 glioma patients with isocitrate dehydrogenase wildtype and high vascular endothelial growth factor expression levels, and 102 patients with isocitrate dehydrogenase mutation and low vascular endothelial growth factor expression levels. Virtual brain grafting, combined with Freesurfer, was used to compute morphologic features including cortical thickness, LGI, and subcortical volume in glioma patient. Radiomics features were extracted from multiregional tumor. Pycaret was used to construct the machine learning pipeline. Among the radiomics models, the whole tumor model achieved the best performance (accuracy 0.80, Area Under the Curve 0.86), while, after incorporating whole brain morphologic features, the model had a superior predictive performance (accuracy 0.82, Area Under the Curve 0.88). The features contributed most in predicting model including the right caudate volume, left middle temporal cortical thickness, first-order statistics, shape, and gray-level cooccurrence matrix. Pycaret, based on morphologic features, combined with radiomics, yielded highest accuracy in predicting isocitrate dehydrogenase mutation and vascular endothelial growth factor levels, indicating that morphologic abnormalities induced by glioma were associated with tumor biology.

Neuropilin-1 and placental growth factor as prognostic factors in metastatic breast cancer

BackgroundAngiogenesis is crucial for tumor development, progression, and metastasizing. The most important regulator of angiogenesis is the vascular endothelial growth factor (VEGF) family, which is involved in multiple pathways in tumor microenvironment. The objective of this study was to investigate the prognostic value of the VEGF family in patients treated for metastatic breast cancer. The emphasis was on neuropilin-1 (NRP-1) and placental growth factor (PlGF).Materials and methodsAn analysis of eight members of the VEGF family was performed using baseline plasma samples of 65 patients treated for metastatic HER2 negative breast cancer in a phase II first-line bevacizumab plus chemotherapy trial. The patients were divided into two groups, high or low, according to the median for each VEGF family member. Progression-free survival (PFS) and overall survival (OS) were determined for each VEGF family member.ResultsThe patients with low plasma levels of NRP-1 and PlGF had a longer OS than those with high plasma levels [multivariable adjusted hazard ratios (HRs) 2.54 (95% confidence interval (CI) 1.11–5.82, p = 0.02) and 3.11 (95% CI 1.30–7.47, p = 0.01), respectively]. The patients with low levels of both NRP-1 and PlGF had a remarkably long OS with HR of 6.24, (95% CI 1.97–19.76, p = 0.002). In addition, high baseline NRP-1 level was associated with a significantly shorter PFS [multivariable adjusted HR 2.90 (95% CI 1.02–8.28, p = 0.04)] than that in the low-level group, and a high baseline vascular endothelial growth factor receptor-2 level was associated with a longer PFS [multivariable adjusted HR 0.43 (95% CI 0.19–0.98, p = 0.04)].ConclusionEspecially NRP-1 and PlGF have prognostic potential in metastatic breast cancer patients treated with a bevacizumab-taxane combination. Patients with low plasma levels of NRP-1 or PlGF have longer OS than patients with high levels. Patients with both low NRP-1 and PlGF levels appear to have excellent long-term survival.Trial registrationClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008.

Long-term day-by-day tracking of microvascular networks sprouting in fibrin gels: From detailed morphological analyses to general growth rules.

Understanding and controlling of the evolution of sprouting vascular networks remains one of the basic challenges in tissue engineering. Previous studies on the vascularization dynamics have typically focused only on the phase of intense growth and often lacked spatial control over the initial cell arrangement. Here, we perform long-term day-by-day analysis of tens of isolated microvasculatures sprouting from endothelial cell-coated spherical beads embedded in an external fibrin gel. We systematically study the topological evolution of the sprouting networks over their whole lifespan, i.e., for at least 14 days. We develop a custom image analysis toolkit and quantify (i) the overall length and area of the sprouts, (ii) the distributions of segment lengths and branching angles, and (iii) the average number of branch generations-a measure of network complexity. We show that higher concentrations of vascular endothelial growth factor (VEGF) lead to earlier sprouting and more branched networks, yet without significantly affecting the speed of growth of individual sprouts. We find that the mean branching angle is weakly dependent on VEGF and typically in the range of 60°-75°, suggesting that, by comparison with the available diffusion-limited growth models, the bifurcating tips tend to follow local VEGF gradients. At high VEGF concentrations, we observe exponential distributions of segment lengths, which signify purely stochastic branching. Our results-due to their high statistical relevance-may serve as a benchmark for predictive models, while our new image analysis toolkit, offering unique features and high speed of operation, could be exploited in future angiogenic drug tests.

Prospective Observational Study of Ramucirumab Plus Docetaxel After Combined Chemoimmunotherapy in Patients With Non-Small-Cell Lung Cancer.

A history of pre-administration of immune checkpoint inhibitors has been reported to be associated with good outcomes of ramucirumab (RAM) plus docetaxel (DOC) combination therapy for advanced non-small-cell lung cancer (NSCLC). However, existing knowledge on the clinical significance of RAM and DOC following combined chemoimmunotherapy is limited. Therefore, we evaluated the efficacy and safety of RAM plus DOC therapy after combined chemoimmunotherapy and attempted to identify the predictors of its outcomes. This multicenter, prospective study investigated the efficacy and safety of RAM plus DOC after combined chemoimmunotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. An exploratory analysis measured serum cytokine levels at the start of treatment. Overall, 44 patients were enrolled from 10 Japanese institutions between April 2020 and June 2022. The median PFS and OS were 6.3 and 22.6 months, respectively. Furthermore, the ORR and DCR were 36.4% and 72.7%, respectively. The high vascular endothelial growth factor D (VEGF-D) group had a significantly shorter PFS and OS. A combination of high VEGF-A and low VEGF-D levels was associated with a longer PFS. Our results showed that RAM plus DOC after combined chemoimmunotherapy might be an effective and relatively feasible second-line treatment for patients with advanced NSCLC in a real-world setting.

RORα inhibits gastric cancer proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity

BackgroundGlycolysis is critical for harvesting abundant energy to maintain the tumor microenvironment in malignant tumors. Retinoic acid-related orphan receptor α (RORα) has been identified as a circadian gene. However, the association of glycolysis with RORα in regulating gastric cancer (GC) proliferation remains poorly understood.MethodsBioinformatic analysis and retrospective study were utilized to explore the role of RORα in cell cycle and glycolysis in GC. The mechanisms were performed in vitro and in vivo including colony formation, Cell Counting Kit-8 (CCK-8), Epithelial- mesenchymal transition (EMT) and subcutaneous tumors of mice model assays. The key drives between RORα and glycolysis were verified through western blot and chip assays. Moreover, we constructed models of high proliferation and high glucose environments to verify a negative feedback and chemoresistance through a series of functional experiments in vitro and in vivo.ResultsRORα was found to be involved in the cell cycle and glycolysis through a gene set enrichment analysis (GSEA) algorithm. GC patients with low RORα expression were not only associated with high circulating tumor cells (CTC) and high vascular endothelial growth factor (VEGF) levels. However, it also presented a positive correlation with the standard uptake value (SUV) level. Moreover, the SUVmax levels showed a positive linear relation with CTC and VEGF levels. In addition, RORα expression levels were associated with glucose 6 phosphate dehydrogenase (G6PD) and phosphofructokinase-2/fructose-2,6-bisphosphatase (PFKFB3) expression levels, and GC patients with low RORα and high G6PD or low RORα and high PFKFB3 expression patterns had poorest disease-free survival (DFS). Functionally, RORα deletion promoted GC proliferation and drove glycolysis in vitro and in vivo. These phenomena were reversed by the RORα activator SR1078. Moreover, RORα deletion promoted GC proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity in vitro and in vivo. Mechanistically, RORα was recruited to the G6PD and PFKFB3 promoters to modulate their transcription. Next, high proliferation and high glucose inhibited RORα expression, which indicated that negative feedback exists in GC. Moreover, RORα deletion improved fluorouracil chemoresistance through inhibition of glucose uptake.ConclusionRORα might be a novel biomarker and therapeutic target for GC through attenuating glycolysis.

Serum Vitamin D Levels and Vascular Endothelial Growth Factor in Patients with Type 2 Diabetes Mellitus: A Cross-sectional Study

Introduction: Diabetes Mellitus (DM) is the most common noncommunicable disease and the fifth leading cause of death worldwide. Recent research has demonstrated that low Vitamin D levels and high Vascular Endothelial Growth Factor (VEGF) in middle-aged and elderly populations represent a risk factor for Type 2 Diabetes Mellitus (T2DM). Aim: To estimate the Vitamin D and VEGF levels in study subjects with T2DM and healthy controls and to correlate the Vitamin D level and VEGF with HbA1c % in study subjects with T2DM. Materials and Methods: A cross-sectional study was undertaken from October 2014 to November 2016 at the Department of Medicine in collaboration with the Department of Biochemistry, Bangalore Medical College and Research Institute, Bangalore. The study included 50 T2DM subjects on oral hypoglycaemic agents for five years and 50 age and sexmatched healthy controls selected randomly from the general population. In all the study subjects, Random Blood Glucose (RBG), LFT, Renal Function Test (RFT), HBA1c, serum Vitamin D, and serum VEGF were estimated. Student t-test and Chisquare/Fisher-Exact test were used to find the significance of study parameters between cases and controls. Multivariate logistic regression analysis was done to assess the risk factors for DM. Results: The mean age of the cases was 50.9±9.7 years and of controls was 49.76±7.7 years. Among the 50 cases, 19 (38%) were men and 31 (62%) were women. Among the 50 controls, 27 (54%) were men and 23 (46%) were women. The mean Body Mass Index (BMI) among cases was 27.21±4.59 and in controls was 24.82±2.63 (p-value=0.0016). The mean serum 25(OH) Vitamin D levels in cases were 11.39±3.32 ng/mL and in controls were 28.06±11.14 ng/mL (p-value &lt;0.001). The mean serum VEGF levels in cases were 97.52±16.96 pg/mL and in controls were 56.37±17.74 pg/mL (p-value &lt;0.001). Conclusion: The present study found that subjects with T2DM have lower serum 25(OH) Vitamin D levels and higher serum VEGF levels than those without T2DM. Serum Vitamin D decreases and serum VEGF-A levels increase with increasing HbA1c%, correlating with vascular complications.

Эндотелиальная дисфункция сосудов как возможный предиктор тяжелого течения COVID-19

Objective. To study the role of the main marker of endothelial dysfunction VEGF-A as a possible predictor of severe COVID-19 formation. Patients and methods. On the basis of the clinic of the Republican Specialized Scientific and Practical Medical Center of Epidemiology, Microbiology, Infectious and Parasitic Diseases (RSSPMCEMIPD) and Samarkand Regional Specialized Medical Center, 210 patients with coronavirus infection were examined during 2020–2022. Patients were divided into 2 groups comparable by main characteristics: I consisted of 98 (47%) patients with a moderate form of COVID-19, II – 112 (53%) with a severe form of the disease. All patients were fully examined at admission to the hospital and at discharge from it. The level of medium molecular peptides (MMP) in blood plasma was determined by the method of N.I.Gabrielyan on spectrophotometer SF-46 in ultraviolet spectrum; the levels of vascular endothelial growth factor (VEGF-A) – in 163 patients – and interleukins 1 and 6 (IL-1, IL-6) in blood serum – by enzyme immunoassay (test systems of Cytokin LLC and Vector-Best JSC). The level of C-reactive protein (CRP) was determined using the immunoenzyme analyzer "MINDRAY MR-96A"; procalcitonin and D-dimer values were determined using an automatic ELISA analyzer mini-VIDAS. The obtained results were processed by methods of descriptive and variation statistics. Differences were considered reliable at (p &lt; 0.05). Results. The clinical picture of COVID-19 complicated by pneumonia was characterized by pronounced symptoms of intoxication, respiratory tract damage, respiratory failure. In group II patients, such comorbidities as ischemic heart disease (23.5 vs. 41.1%), arterial hypertension (9.2 vs. 25.4%), and diabetes mellitus (2.0 vs. 12.5%) were recorded significantly more often. In 119 (56.7%) cases (mostly in the group with severe coronavirus infection), there was a combination of several comorbidities. In 36 (17.1%) patients with elevated blood sugar level before hospitalization for COVID-19 neither clinical nor laboratory signs of diabetes ellitus were present; in group II stable elevated blood sugar level against the background of therapy of the main disease was recorded 2 times more often (23.2 vs. 10.2%, respectively). In the same group, the level of CPR was 1.5 times higher. A significant correlation (p &lt; 0.05) of elevated levels of CRP and D-dimer with the severity of COVID-19 course was established. In 163 patients the mean values of VEGF-A on admission were elevated; in patients from group II this index was significantly (p &lt; 0.01) higher: 303.02 ± 21.47 vs. 390.52 ± 29.05 pg/mL. At discharge, this index increased to 466.56 ± 37.59 pg/mL in group II patients and decreased to 237.60 ± 17.03 pg/mL in group I patients (differences were significant; p &lt; 0.01). In group I, this index returned to normal after 1 month, and in group II, it decreased to 205.05 ± 15.90 pg/mL only 2 months after discharge. A reliable correlation (p &lt; 0.05) of elevated levels of D-dimer, CRP, MMP with high VEGF-A levels, as well as with the severity of the disease and increasing respiratory failure was established. Positive results of bacteriologic study of upper respiratory tract secretions were found in 63 (64.3%) patients of group I and in 78 (69.6%) patients of group II; Staphylococcus aureus predominated in patients from group II (11.1 vs. 38.5%) and Candida spp (85.7 vs. 28.2%) from group I. Conclusion. The relationship between blood levels of VEGF-A and standard inflammatory markers allows us to propose this factor of endothelial dysfunction as a predictor of inflammation and disease progression, as well as to use it to assess the efficacy of therapy. Key words: bacterial pneumonia, novel coronavirus infection, procalcitonin, C-reactive protein, vascular endothelial growth factor, endothelial dysfunction

Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury

Nonsurgical treatment and surgical repairment of injured Achilles tendons seldom restore the wounded tendon to its original elasticity and stiffness. Therefore, we hypothesized that the surgically repaired Achilles tendon can achieve satisfactory regeneration by applying multi-drug encapsulated hydrogels. In this study, a novel bupivacaine-eluting carbon dioxide-encapsulated Pluronic F127 hydrogel (BC-hydrogel) was developed for the treatment of Achilles tendon injuries. The rheological properties of BC-hydrogel were measured. A high-performance liquid chromatography assay was used to assess the release characteristics of bupivacaine in both in vitro and in vivo settings. Furthermore, the effectiveness of BC-hydrogel in treating torn tendons was examined in a rat model, and histological analyses were conducted. Evidently, the degradable hydrogels continuously eluted bupivacaine for more than 14 days. The animal study results revealed that the BC-hydrogel improved the post-surgery mobility of the animals compared with pristine hydrogels. Histological assay results demonstrated a significant reaction to high vascular endothelial growth factor in the surrounding tissues and expression of collagen I within the repaired tendon. This demonstrates the potential of this novel BC-hydrogel as an effective treatment method for Achilles tendon injuries.

The possible dual role of Ang-2 in the prognosis of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, which raises the intratumoral interstitial pressure leading to vascular collapse and hypoxia, inducing angiogenesis. Vascular growth factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), increase in PDAC. A high VEGF and a high circulating Ang-2 associate with shorter survival in PDAC. In addition to the circulatory Ang-2, PDAC endothelial and epithelial cells express Ang-2. No correlation between tumor epithelial nor endothelial cell Ang-2 expression and survival has been published. We aimed to examine Ang-2 expression and survival. This study comprised PDAC surgical patients at Helsinki University Hospital in 2000–2013. Ang-2 immunohistochemistry staining was completed on 168 PDAC patient samples. Circulating Ang-2 levels were measured using ELISA in the sera of 196 patients. Ang-2 levels were assessed against clinical data and patient outcomes. A low tumor epithelial Ang-2 expression predicted shorter disease-specific survival (DSS) compared with a high expression (p = 0.003). A high serum Ang-2 associated with shorter DSS compared with a low circulating Ang-2 (p = 0.016). Ang-2 seemingly plays a dual role in PDAC survival. Further studies are needed to determine the mechanisms causing tumor cell Ang-2 expression and its positive association with survival.

Serum VEGF levels as a predictor of recurrence in patients with advanced‑stage esophageal squamous cell carcinoma following curative esophagectomy followed by chemotherapy or concurrent radiotherapy.

The present study evaluated serum levels of vascular endothelial growth factor (VEGF) as a predictor of recurrence in patients with advanced-stage esophageal squamous cell carcinoma (ESCC) following curative esophagectomy followed by chemotherapy or concurrent radiotherapy. Patients with locally advanced resectable ESCC underwent R0 esophagectomy followed by chemotherapy or concurrent radiotherapy as an adjuvant. Serum VEGF levels in 173 patients, including 57 patients with recurrent disease, and 183 healthy controls were determined using a Luminex assay. The results demonstrated that the serum VEGF levels were significantly higher in 57 patients with locally advanced resectable ESCC at recurrence compared with the levels at pre-treatment (P<0.001). The patients with recurrence exhibited significantly higher serum VEGF levels during chemotherapy or concurrent radiotherapy than patients with no recurrence (P<0.05). Patients with low serum VEGF levels had a significantly longer survival time than those with high serum VEGF levels prior to treatment (P<0.01). The median survival times were 70 and 25 months in patients with locally advanced resectable ESCC with serum VEGF levels <161.75 and ≥161.75 pg/ml following treatment, respectively (P<0.01). Compared with patients with VEGF levels <147 pg/ml following treatment, patients with locally advanced resectable ESCC with VEGF levels ≥147 pg/ml had a significantly higher risk of recurrence (P<0.01). Patients with low serum VEGF levels (<147 pg/ml) had significantly higher recurrence-free survival rates than those with high serum VEGF levels (≥147 pg/ml) following treatment (P<0.01). The findings of the present study demonstrate that serum VEGF levels are a potential predictor of recurrence and of the treatment outcomes of chemotherapy or concurrent radiotherapy in patients with locally advanced resectable ESCC.

VEGFR-2 adhesive nanoprobes reveal early diabetic retinopathy in vivo

Diabetic retinopathy (DR) is a debilitating organ manifestation of diabetes. Absent of early diagnosis and intervention, vision tends to drastically and irreversibly decline. Previously, we showed higher vascular endothelial growth factor receptor 2 (VEGFR-2) expression in diabetic microvessels, and the suitability of this molecule as a biomarker for early DR diagnosis. However, a hurdle to translation remained generation of biodegradable nanoprobes that are sufficiently bright for in vivo detection. Here, an adhesive fluorescent nanoprobe with high brightness was developed using biodegradable materials. To achieve that, a fluorophore with bulky hydrophobic groups was encapsulated in the nanoparticles to minimize fluorophore π-π stacking, which diminishes brightness at higher loading contents. The nanoprobe selectively targeted the VEGFR-2 under dynamic flow conditions. Upon systemic injection, the nanoprobes adhered in the retinal microvessels of diabetic mice and were visualized as bright spots in live retinal microscopy. Histology validated the in vivo results and showed binding of the nanoprobes to the microvascular endothelium and firmly adhering leukocytes. Leukocytes were found laden with nanoprobes, indicating the potential for payload transport across the blood-retinal barrier. Our results establish the translational potential of these newly generated nanoprobes in early diagnosis of DR.

High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner.

We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway modulates VEGF-induced fibrosis. We determined cross-linked actin network (CLAN) formation using TM cells. Changes in fibrotic and ECM protein expression were determined. High VEGF concentrations (10 and 30 ng/mL) increased TAZ and decreased p-TAZ/TAZ expression in TM cells. Western blotting and real-time PCR revealed no YAP expression changes. Fibrotic and ECM protein expression decreased at low VEGF concentrations (1 and 10 ρg/mL) and significantly increased at high VEGF concentrations (10 and 30 ng/mL). CLAN formation increased in TM cells treated with high VEGF concentrations. Moreover, TAZ inhibition by verteporfin (1 μM) rescued TM cells from high-VEGF-concentration-induced fibrosis. Low VEGF concentrations reduced fibrotic changes, whereas high VEGF concentrations accelerated fibrosis and CLAN formations in TM cells in a TAZ-dependent manner. These findings reflect the dose-dependent influences of VEGF on TM cells. Moreover, TAZ inhibition might be a therapeutic target for VEGF-induced TM dysfunction.