Association of Vascular Endothelial Growth Factor Levels with Risk of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative illness that leads to impairment of cognitive functions and memory loss. Even though there is a plethora of research reporting the abnormal regulation of VEGF expression in AD pathogenesis, whether the CSF and serum VEGF are increased in AD is an open question yet. In this study, the association of CSF and serum VEGF concentrations with the risk of Alzheimer's disease was investigated using systematic review and meta-analysis. METHODS: A systematic literature search was carried out using online specialized biomedical databases of Web of Science, Pubmed, Scopus, Embase, and Google Scholar until Feb 2023 without restriction to the beginning time. The meta-analysis was performed using the random-effects model and only case-control publications describing VEGF concentrations in Alzheimer's patients were considered for calculating the pooled effect size. RESULTS: In the systematic literature search, 6 and 13 studies met the inclusion criteria to evaluate CSF and serum VEGF concentrations of Alzheimer's patients, respectively. This meta-analysis retrieved a total number of 2380 Alzheimer's patients and 5368 healthy controls. Under the random-effects model in the meta-analysis, the pooled SMD for CSF and serum VEGF concentrations of Alzheimer's patients were -0.13 (95%CI,-0.42-0.16) and 0.23 (95%CI,-0.27-0.73), respectively. Results of meta-regression analysis showed that the quality scores of papers and female sex ratios of participants did not affect the associations of VEGF concentrations with the risk of Alzheimer's disease. However, the age average of patients significantly affects the associations of CSF VEGF concentrations with the risk of Alzheimer's disease (P=0.051). There was a statistically significant subgroup effect for the disease severity of Alzheimer's patients which modifies the associations of serum VEGF concentrations with the risk of Alzheimer's disease (P<0.01) and subgroup analysis shows that study location modifies the associations of CSF and serum VEGF concentrations with the risk of Alzheimer's disease (P<0.01). CONCLUSION: The results show that the serum VEGF concentrations increased for Alzheimer's patients in accordance with the increased expression of VEGF and the VEGF levels of Alzheimer's patients decreased by increasing their disease severities. Therefore, in addition to detecting AD in the earliest stages of the disease, serum VEGF could be a promising biomarker to follow up on the disease and evaluate the clinical course of the disease.

Comparison of growth factor levels in injectable platelet-rich fibrin obtained from healthy individuals and patients with chronic periodontitis: a pilot study.

BACKGROUND: This study aimed to assess and compare the concentrations of growth factors, white blood cells (WBCs), and platelets in injectable platelet-rich fibrin (i-PRF) derived from people with healthy periodontal conditions and those with chronic periodontitis. METHODS: Venous blood samples were obtained from 30 patients diagnosed with chronic periodontitis (test group) and 30 participants with healthy periodontal conditions (control group). The i-PRF was then acquired from centrifuged blood. The growth factors (VEGF, IGF-1, TGF-ß1, PDGF-BB and EGF) released from the i-PRF samples were compared between groups with ELISA testing. The amounts of WBCs and platelets were also compared. RESULTS: No significant differences in the concentrations of growth factors were found between the groups (the mean values for the control and test groups were, respectively: IGF: 38.82, 42.46; PDGF: 414.25, 466.28; VEGF: 375.69, 412.18; TGF-ß1: 21.50, 26.21; EGF: 138.62, 154.82). The test group exhibited a significantly higher WBC count than the control group (8.80 vs. 6.60, respectively). However, the platelet count did not show a statistically significant difference between the groups (control group 242.0 vs. test group 262.50). No significant correlation was observed between WBC count and growth factor level in either group. CONCLUSIONS: The growth factor levels in i-PRFs did not exhibit significant difference between the two groups. This suggests that the levels of these growth factors may be unaffected by the periodontal disease.

Lidocaine effects on neutrophil extracellular trapping and angiogenesis biomarkers in postoperative breast cancer patients with different anesthesia methods: a prospective, randomized trial.

BACKGROUND: Anesthesia techniques and drug selection may influence tumor recurrence and metastasis. Neutrophil extracellular trapping (NETosis), an immunological process, has been linked to an increased susceptibility to metastasis in individuals with tumors. Furthermore, recurrence may be associated with vascular endothelial growth factor A (VEGF-A), a mediator of angiogenesis. This study investigates the impact of lidocaine (combined with sevoflurane or propofol anesthesia ) during breast cancer surgery inhibits the expression of biomarkers associated with metastasis and recurrence (specifically H3Cit, NE, MPO, MMP-9 and VEGF-A). METHODS: We randomly assigned 120 women undergoing primary or invasive breast tumor resection to receive one of four anesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Blood samples were collected before induction and 3 h after the operation. Biomarkers associated with NETosis (citrullinated histone H3 [H3Cit], myeloperoxidase [MPO], and neutrophil elastase [NE]) and angiogenesis were quantified using enzyme-linked immunosorbent assays. RESULTS: Patient and breast tumor characteristics, along with perioperative management, did not differ between study groups. In intra-group comparisons, S and P groups demonstrated a statistically significant increase in post-operative MPO (S group: 10.39[6.89-17.22] vs. 14.31[8.55-20.87] ng ml-1, P = 0.032; P group: 9.45[6.73-17.37] vs. 14.34[9.87-19.75] ng ml-1, P = 0.035)and NE(S group: 182.70[85.66-285.85] vs. 226.20[91.85-391.65] ng ml-1, P = 0.045; P group: 154.22[97.31-325.30] vs. 308.66[132.36-483.57] ng ml-1, P = 0.037) concentrations compared to pre-operative measurements, whereas SL and PL groups did not display a similar increase. H3Cit, MMP-9, and VEGF-A concentrations were not significantly influenced by the anesthesia techniques and drugs. CONCLUSIONS: Regardless of the specific technique employed for general anesthesia, there was no increase in the postoperative serum concentrations of MPO and NE after perioperative lidocaine infusion compared to preoperative serum concentrations. This supports the hypothesis that intravenous lidocaine during cancer surgery aimed at achieving a cure may potentially decrease the likelihood of recurrence. Further interpretation and discussion of clinical implications are warranted, emphasizing the significance of these findings in the context of cancer surgery and recurrence prevention. CLINICAL TRIAL REGISTRATION: ChiCTR2300068563.

Universal nanocomposite coating with antifouling and redox capabilities for electrochemical affinity biosensing in complex biological fluids.

Electrochemical affinity biosensors have the potential to facilitate the development of multiplexed point-of-care diagnostics in complex biological fluids. However, their commercial viability has been hindered by challenges such as electrode biofouling and the lack of inherent redox properties. To address this unmet need, we have developed a universal nanocomposite coating which is unique in its ability to not only allow oriented conjugation of the biorecognition element but also specific detection directly in complex biological fluids like serum and urine owing to its built-in antifouling and redox capabilities, thus improving suitability for point of care testing. This multifunctional coating comprises a 3D porous crosslinked bovine serum albumin matrix for oriented conjugation and antifouling properties with embedded graphene nanosheets modified with amino-ferrocene for enhanced conductivity and mediator-free biosensing. The coating showed minimal signal degradation despite prolonged exposure to 1% bovine serum albumin, artificial urine and untreated human serum for up to 30 days. To demonstrate its utility, we fabricated and tested proof-of-concept electrochemical immunosensors for bladder cancer protein biomarkers, specifically interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The practical feasibility was highlighted by the excellent sensitivity and specificity observed for IL-8 and VEGF with a limit of detection of 41 pg mL-1 and 67 pg mL-1, respectively. Consequently, this universal nanocomposite-based electrochemical biosensing platform can be extended to the point of care testing of a broad spectrum of biomarkers present in complex biological fluids, thus enabling reliable and early diagnostics.

Effects of Photobiomodulation Therapy on the Expression of Hypoxic Inducible Factor, Vascular Endothelial Growth Factor, and Its Specific Receptor: A Randomized Control Trial in Patients with Diabetic Foot Ulcer.

Background: Impaired angiogenesis is a significant factor contributing to delayed healing in diabetic foot ulcers (DFUs) due to inadequate oxygenation. Objective: This study aimed to investigate the impact of photobiomodulation (PBM) using a Ga-As laser on the release of serum hypoxia-inducible factor 1-α (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2, and nitric oxide (NO) in diabetic patients with DFUs. Materials and methods: In this double-blind RCT, a total of 30 patients with grade II DFUs were enrolled. The patients were randomly divided into two groups: the PBM (n = 15) and the placebo (n = 15). In the PBM group, a Ga-As laser (904 nm, 2 J/cm2, 90 W) was given for 3 days/week for 4 weeks (11 sessions). In the placebo group, the power was turned off. Both groups received similar standard wound care. Before and after interventions, the levels of serum HIF-1α, VEGF, NO, and sVEGFR-2 were measured. In addition, the percentage decrease in the wound surface area (%DWSA) was measured. Results: Following the intervention, the results revealed that the PBM group had significantly lower levels of VEGF than the placebo group (p = 0.005). The %DWSA was significantly higher in the PBM group compared to the placebo group (p = 0.003). Moreover, VEGF showed a significant negative correlation with %DWSA (p < 0.001). Conclusions: The observed decrease in serum levels of VEGF and an increase in %DWSA, compared to the placebo group, suggests that PBM effectively improves angiogenesis. Furthermore, the significant correlation found between VEGF levels and %DWSA emphasizes the importance of evaluating wound surface in patients as a dependable indicator of enhanced wound angiogenesis. Clinical Trial Registration: NCT02452086.

Plasma sPD-L1 and VEGF levels are associated with the prognosis of NSCLC patients treated with combination immunotherapy.

The clinical significance of plasma soluble programmed cell death ligand 1 (sPD-L1) and vascular endothelial growth factor (VEGF) for non-small cell lung cancer (NSCLC) treated with the combination of anti-angiogenic therapy and anti-PD-L1 antibody (Ab) remain unknown. This study aimed to explore the association between plasma sPD-L1 and VEGF levels and the prognosis of NSCLC patients treated with the combination of Envafolimab and Endostar. Peripheral blood samples were collected from 24 NSCLC patients at baseline and after 6 weeks of treatment and were detected for sPD-L1 and VEGF levels. Both baseline and posttreatment sPD-L1 were significantly higher in progressive disease (PD) group than in controlled disease (CD) group (median: 77.5 pg/ml vs. 64.6 pg/ml, P  = 0.036, median: 8451 pg/ml vs. 5563 pg/ml, P  = 0.012). In multivariate analysis, lower baseline sPD-L1 levels were significantly associated with longer progression-free survival (PFS) (HR = 6.834, 95% CI: 1.350-34.592, P  = 0.020). There were significantly higher posttreatment VEGF levels in PD group compared with CD group (median: 323.7 pg/ml vs. 178.5 pg/ml, P  = 0.009). Higher posttreatment VEGF levels were significantly associated with shorter PFS in multivariate analysis (HR = 5.911, 95% CI: 1.391-25.122, P  = 0.016). Plasma sPD-L1 and VEGF levels are associated with the clinical response and prognosis of NSCLC patients treated with the combination of PD-L1 inhibitors and anti-angiogenetic therapy.

Relationship between Changes of Serum Vascular Endothelial Growth Factor and Folate Receptor-α Levels and Clinical Efficacy of Toripalimab in Patients with Bladder Cancer.

OBJECTIVE: This study aims to explore the changes of serum vascular endothelial growth factor (VEGF) and folate receptor-α (FR-α) levels in patients with bladder cancer before and after treatment with toripalimab and to analyse the relationship between the changes of VEFG and FR-α and the clinical efficacy of patients. METHODS: A total of 176 patients with bladder cancer admitted to our hospital from January 2020 to January 2022 were selected as the research subjects. All patients were treated with toripalimab. The clinical efficacy and changes of serum VEGF and FR-α levels before and after treatment were observed. Logistic regression was used to analyse the relationship between serum VEGF and FR-α levels and the therapeutic effect of toripalimab, and receiver operating characteristic curve was used to evaluate the predictive value of serum VEGF and FR-α on the efficacy. RESULTS: The objective response rate and disease control rate after treatment were 31.82% and 70.45%, respectively. The serum VEGF and FR-α levels in patients after treatment were significantly lower than those before treatment (p < 0.001). The patients were divided into an effective group (n = 124) and an ineffective group (n = 52) according to clinical efficacy. The serum VEGF and FR-α levels of patients in the effective group were significantly lower than those of the ineffective group (p < 0.001). Logistic regression analysis showed that the elevated levels of serum VEGF (odds ratio = 1.226) and FR-α (odds ratio = 1.384) were the risk factors affecting the therapeutic effect of toripalimab (p < 0.05). The area under curve of the combined prediction of VEGF and FR-α was 0.920, the Youden index was 0.722, the sensitivity was 89.52%, the specificity was 82.69%, and the predictive value was higher than the single detection of VEGF or FR-α (p = 0.001, p < 0.001). CONCLUSIONS: The changes of serum VEGF and FR-α levels in patients with bladder cancer can predict the therapeutic effect of toripalimab. Before clinical treatment, the detection of the two indicators must be strengthened, and intervention measures must be formulated as early as possible to improve the prognosis of patients.

Predicting clinical progression and cognitive decline in patients with relapsing-remitting multiple sclerosis: a 6-year follow-up study.

INTRODUCTION: Cognitive impairment occurs from the earliest stages of multiple sclerosis (MS) and progresses over time. The introduction of disease modifying therapies (DMTs) has changed the prognosis for MS patients, offering a potential opportunity for improvement in the cognitive arena as well. MATERIAL AND METHODS: 41 patients with relapsing-remitting multiple sclerosis (MS) were recruited to the study. Thirty patients were available for final follow-up and were included in the analysis. Baseline (BL) brain MRI including volumetry and neuropsychological tests were performed. Blood samples were collected at BL and follow-up (FU) and were tested for: vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM1), soluble platelet-endothelial CAM-1 (sPECAM1), and soluble intercellular CAM-1 (sICAM-1). Patients were invited for a final neuropsychological follow-up after a median of 6 years. Disease activity (relapses, EDSS increase, new/active brain lesions on MRI) was analysed between BL and FU. RESULTS: The study group deteriorated in the Rey-Osterrieth Complex Figure (ROCF) test (p = 0.001), but improved significantly in three other tests, i.e. semantic fluency test (p = 0.013), California Verbal Learning Test (CVLT, p = 0.016), and Word Comprehension Test (WCT, p < 0.001). EDSS increase correlated negatively with semantic fluency and WCT scores (r = -0.579, p = 0.001 and r = -0.391, p = 0.033, respectively). Improvements in semantic fluency test and WCT correlated positively with baseline deep grey matter, grey matter, and cortical volumes (p < 0.05, r > 0). Higher EDSS on FU correlated significantly negatively with baseline left and right pallidum, right caudate, right putamen, right accumbens, and cortical volume (p < 0.05, r < 0). No significant relationship was found between the number of relapses and EDSS on FU or neuropsychological deteriorations. Improvements in WCT and CVLT correlated positively with baseline sPECAM1 and sVCAM1 results, respectively (r > 0, p < 0.05). Deterioration in ROCF test correlated significantly with higher levels of baseline VEGF and sVCAM1 (p < 0.05). CONCLUSIONS: Brain volume is an important predictor of future EDSS and cognitive functions outcome. MS patients have a potential for improving in neuropsychological tests over time. It remains to be established whether this is related to successful disease modification with immunotherapy. Baseline volumetric measures are stronger predictors of cognitive performance than relapse activity, which yet again highlights the importance of atrophy in MS prognosis.

Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis.

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.

Vascular endothelial growth factors and risk of cardio-renal events: Results from the CREDENCE trial.

BACKGROUND: Circulating concentrations of vascular endothelial growth factor (VEGF) family members may be abnormally elevated in type 2 diabetes (T2D). The roles of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFLT-1), and VEGF-A in cardio-renal complications of T2D are not established. METHOD: The 2602 individuals with diabetic kidney disease (DKD) from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial were randomized to receive canagliflozin or placebo and followed for incident cardio-renal outcomes. PlGF, sFLT-1, and VEGF-A were measured at baseline, year 1, and year 3. Primary outcome was a composite of end-stage kidney disease, doubling of the serum creatinine, or renal/cardiovascular death. Cox proportional hazard regression was used to investigate the association between biomarkers with adverse clinical events. RESULTS: At baseline, individuals with higher PlGF levels had more prevalent cardiovascular disease compared to those with lower values. Treatment with canagliflozin did not meaningfully change PlGF, sFLT-1, and VEGF-A concentrations at years 1 and 3. In a multivariable model, 1 unit increases in baseline log PlGF (hazard ratio [HR]: 1.76, 95% confidence interval [CI]: 1.23, 2.54, P-value = .002), sFLT-1 (HR: 3.34, [95% CI: 1.71, 6.52], P-value < .001), and PlGF/sFLT-1 ratio (HR: 4.83, [95% CI: 0.86, 27.01], P-value = .07) were associated with primary composite outcome, while 1 unit increase in log VEGF-A did not increase the risk of primary outcome (HR: 0.96 [95% CI: 0.81, 1.07]). Change by 1 year of each biomarker was also assessed: HR (95% CI) of primary composite outcome was 2.45 (1.70, 3.54) for 1 unit increase in 1-year concentration of log PlGF, 4.19 (2.18, 8.03) for 1 unit increase in 1-year concentration of log sFLT-1, and 21.08 (3.79, 117.4) for 1 unit increase in 1-year concentration of log PlGF/sFLT-1. Increase in 1-year concentrations of log VEGF-A was not associated with primary composite outcome (HR: 1.08, [95% CI: 0.93, 1.24], P-value = .30). CONCLUSIONS: People with T2D and DKD with elevated levels of PlGF, sFLT-1, and PlGF/sFLT-1 ratio were at a higher risk for cardiorenal events. Canagliflozin did not meaningfully decrease concentrations of PlGF, sFLT-1, and VEGF-A. CLINICAL TRIAL: CREDENCE, https://clinicaltrials.gov/ct2/show/NCT02065791.

Relationship between Changes of Serum Vascular Endothelial Growth Factor and Folate Receptor-α Levels and Clinical Efficacy of Toripalimab in Patients with Bladder Cancer

Objective: This study aims to explore the changes of serum vascular endothelial growth factor (VEGF) and folate receptor-α (FR-α) levels in patients with bladder cancer before and after treatment with toripalimab and to analyse the relationship between the changes of VEFG and FR-α and the clinical efficacy of patients. Methods: A total of 176 patients with bladder cancer admitted to our hospital from January 2020 to January 2022 were selected as the research subjects. All patients were treated with toripalimab. The clinical efficacy and changes of serum VEGF and FR-α levels before and after treatment were observed. Logistic regression was used to analyse the relationship between serum VEGF and FR-α levels and the therapeutic effect of toripalimab, and receiver operating characteristic curve was used to evaluate the predictive value of serum VEGF and FR-α on the efficacy. Results: The objective response rate and disease control rate after treatment were 31.82% and 70.45%, respectively. The serum VEGF and FR-α levels in patients after treatment were significantly lower than those before treatment (p < 0.001). The patients were divided into an effective group (n = 124) and an ineffective group (n = 52) according to clinical efficacy. The serum VEGF and FR-α levels of patients in the effective group were significantly lower than those of the ineffective group (p < 0.001). Logistic regression analysis showed that the elevated levels of serum VEGF (odds ratio = 1.226) and FR-α (odds ratio = 1.384) were the risk factors affecting the therapeutic effect of toripalimab (p < 0.05). The area under curve of the combined prediction of VEGF and FR-α was 0.920, the Youden index was 0.722, the sensitivity was 89.52%, the specificity was 82.69%, and the predictive value was higher than the single detection of VEGF or FR-α (p = 0.001, p < 0.001)(AU)

Comparison of VEGF-A levels in women with threatened abortion, early pregnancy loss and uncomplicated healthy pregnancies.

INTRODUCTION: To estimate the possible role of VEGF-A in predicting poor early pregnancy outcomes including threatened abortion and early pregnancy loss. METHODS: We conducted a prospective case-control study with three groups of pregnant women diagnosed with threatened abortion, early pregnancy loss, and uncomplicated healthy pregnancies between 01 March 2023 and 15 March 2023. Maternal serum VEGF-A concentration was measured using the Sandwich-ELISA method in accordance to the commercial kit's instructions. There were 30 patients in each 3 group and the gestational age of the patients was between 6 and 14 weeks. The Kruskal-Wallis test was performed for comparing the median values between the groups. Mann-Whitney U test was conducted for pairwise comparisons. RESULTS: VEGF-A levels were compared between 3 groups and a statistically significant difference was found (p = 0.007). There was a moderately significant correlation between VEGF-A levels and poor early pregnancy outcomes. For poor early pregnancy outcomes, the area under the curve (AUC) was 0.75 (95% CI: 0.64-0.85). The best balance of sensitivity/specificity in ROC curves was 0.60 (63.3% sensitivity, 74.3% specificity). DISCUSSION: In conclusion, this study pointed out the increased VEGF concentrations in pregnant women with threatened miscarriage and early pregnancy loss. VEGF-A may be a potential biomarker for the indication of poor early pregnancy outcomes.

Serum vascular endothelial growth factor affects tissue fluid accumulation and is associated with deteriorating tissue perfusion and oxygenation in severe sepsis: a prospective observational study.

BACKGROUND: Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels. MATERIAL AND METHODS: New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed. RESULTS: Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50-3092.00] mL/day vs. 1069.00 [722.00-1486.75] mL/day, p < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = - 0.246 and - 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038). CONCLUSIONS: In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.

Changes in Serum Concentrations of Vascular Endothelial Growth Factors-A and B after Intravitreal Injection of Ranibizumab and Conbercept for Retinopathy of Prematurity.

INTRODUCTION: The aim of this study was to compare the changes in serum concentrations of vascular endothelial growth factor (VEGF)-A and B after intravitreal injection of ranibizumab (IVR) or conbercept (IVC) for retinopathy of prematurity (ROP). METHODS: In this prospective study, infants with type 1 ROP in both eyes were recruited in our hospital from September 2021 to February 2022, randomly assigned to the ranibizumab and conbercept groups and administered IVR or IVC (0.25 mg/0.025 mL). Blood samples were collected before the operation and 1 and 4 weeks after the operation to measure the concentrations of serum VEGF-A and B. RESULTS: A total of 20 ROP infants were randomly assigned to the ranibizumab (n = 10) and conbercept groups (n = 10). In the ranibizumab group, the serum VEGF-A concentrations before operation and 1 and 4 weeks after the operation were 73.55 ± 40.78, 11.47 ± 7.00, and 75.36 ± 30.87 pg/mL, respectively (p < 0.01). Least Significant Difference (LSD) pairwise comparison did not show any significant difference in the groups between 4 weeks postoperatively and preoperatively (p > 0.05). In the conbercept group, the serum VEGF-A concentrations before operation and 1 and 4 weeks after the operation were 86.69 ± 55.06, 14.68 ± 10.11, and 43.55 ± 57.92 pg/mL, respectively (p < 0.01). LSD comparison showed significant differences between 1 week and 4 weeks postoperatively and preoperatively (p < 0.05), but no significant differences were observed between 1 and 4 weeks postoperatively (p > 0.05). Regarding serum VEGF-B concentrations before the operation and 1 and 4 weeks after the operation, no significant differences were detected in the ranibizumab group (p > 0.05), but significant differences were observed in the conbercept group (7.26 ± 2.34, 3.09 ± 2.41, and 4.55 ± 3.37 ng/mL, respectively; p < 0.01). LSD showed significant differences between 1 or 4 weeks postoperatively and preoperatively (p < 0.05), but no significant difference was detected between 1 and 4 weeks postoperatively (p > 0.05). CONCLUSIONS: Serum VEGF-A levels in infants with ROP were suppressed after IVR or IVC but returned to preoperative levels at 4 weeks after IVR and remained lower than the preoperative levels at 4 weeks after IVC. Serum VEGF-B was not affected by IVR but was suppressed by IVC for 4 weeks.

Circulating levels of vascular endothelial growth factor in patients with Alzheimer's disease: A case-control study.

BACKGROUND: Vascular endothelial growth factor (VEGF) and platelets seem to reflect the Alzheimer's disease (AD) associated either with vascular impairment or disease. This study aimed to compare the circulating levels of VEGF and platelets between AD patients and healthy older adults. METHODS: Seventy-two older adults, divided in 40 older adults (Clinical Dementia Rating Scale - CDR = 0); and 32 Alzheimer's disease patients (clinically diagnosed - CRD = 1) participated in the present study. The groups were paired by sex, age, comorbidities and educational level. The primary outcomes included circulating plasma VEGF and platelet levels obtained by blood collection. RESULTS: The VEGF levels were significantly different between the groups (p = 0.03), with having a large effect size ( η2 =18.15), in which the AD patients presented lower levels compared to healthy older adults. For platelets, the comparison showed a tendency to difference (p = 0.06), with a large effect size (η2 =12.95) between the groups. CONCLUSION: The VEGF levels and the platelet numbers were reduced in AD patients, suggesting that angiogenic factors could be modified due to AD.

Vascular Endothelial Growth Factor and Its Soluble Receptor in Systemic Lupus Erythematosus Patients.

Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Its soluble receptor (sVEGFR) is a potent VEGF antagonist. Systemic lupus erythematosus (SLE) is an autoimmune disease with a diverse array of clinical manifestations that affect virtually any organ. We aimed to analyze the relationship of VEGF and sVEGFR with SLE disease-related features including disease activity, damage, and severity. Serum levels of VEGF165 isoform and sVEGFR (receptor 1) were assessed in 284 well-characterized patients with SLE. Linear regression analysis was performed to analyze the relationship of disease characteristics with both VEGF and sVEGFR. Patients with a disease damage index (SLICC score) equal to or greater than 1 had significantly elevated serum levels of VEGF and sVEGFR. Regarding disease-specific features, musculoskeletal manifestations were the disease feature most commonly associated with the upregulation of both VEGF and sVEGFR. SLE disease damage is associated with higher levels of VEGF and sVEGFR.

MMP-9/BDNF ratio predicts more severe COVID-19 outcomes.

COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. Due to the endothelial, systemic course of the disease, VEGF A participates actively in COVID-19 development, while neurotrophic and metabolic effects of BDNF recommends for the prediction of complications in COVID-19 patients. Searching for a marker that would improve and simplify the ranking in COVID-19, the study intended to evaluate the relationship of MMP-9 with VEGF A, BDNF, and MMP-8 with the COVID-19 severity. Upon admission to the hospital and before the therapy administration, 77 patients were classified into a mild, moderate, severe, or critical group. Due to the inflammatory stage in COVID-19, a comparison between groups showed related differences in leukocytes, neutrophils, lymphocytes, and platelets counts as anticipated. Only in seriously ill patients, there is a significant increase in the serum concentration of MMP-9, MMP-8, and VEGF A, while BDNF values did not show significant variations between groups. However, all those parameters positively correlated with each other. The ratio of MMP-9/BDNF markedly decreased in the severe and critically patients compared to the mild group. Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease.

The Effect of Hypoxia Inducible Factor -1 Alpha and Vascular Endothelial Growth Factor Level in Type 2 Diabetes Microvascular Complications and Development.

Background: Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxia. Objective: The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020. Methods: This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005. Results: The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005). Conclusion: HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.

Serum vascular endothelial growth factor as a marker for tubal pregnancy.

OBJECTIVE: The objective of this study was to evaluate whether a single measurement of vascular endothelial growth factor could distinguish between intrauterine pregnancy and ectopic pregnancy and to correlate the levels of vascular endothelial growth factor with serum levels of progesterone andß-human chorionic gonadotropin in each subgroup. METHODS: Ninety patients with a positive human chorionic gonadotropin test and either abdominal pain or vaginal bleeding were selected; pregnancies were singletons, spontaneously conceived, 42-56 days of gestational age. All patients had a transvaginal ultrasound examination and were divided into three subgroups: abnormal intrauterine pregnancy, tubal pregnancy, and normal intrauterine pregnancy. Tubal pregnancies were surgically treated and histologically confirmed. Blood samples were collected for the determination of ß-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor and their concentrations were compared in each subgroup. Receiver operating characteristic curve was calculated by comparing the subgroup of tubal pregnancy to the other groups. A Fisher discriminant function analysis was performed. The level of significance was 5%. RESULTS: One-way analysis of variance revealed a significant correlation between the different subgroups and ß-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor serum levels (p<0.001). Vascular endothelial growth factor concentration was significantly higher for patients with tubal pregnancy than for other subgroups (p<0.05). ß-Human chorionic gonadotropin and progesterone levels were higher in the subgroup with normal intrauterine pregnancies compared with the subgroups with tubal and abnormal intrauterine pregnancies (p<0.05). Serum vascular endothelial growth factor level >188.7 ng/mL predicted tubal pregnancy with 96.7% sensitivity, 95.0% specificity, 90.6% positive predictive value, and 98.3% negative predictive value. CONCLUSIONS: Serum vascular endothelial growth factor could be a marker in discriminating intrauterine pregnancy from tubal pregnancy; its levels are increased in women with ectopic pregnancy compared with women with normal and abnormal intrauterine pregnancies.