Numerous studies have reported vascular endothelial growth factor A (VEGF-A) has a significant impact on the pathophysiology of COVID-19. The objective of this systematic review and meta-analysis is to determine the prognostic value of increased levels of VEGF-A in individuals with COVID-19. A systematic literature search was conducted across multiple electronic databases, including PubMed, Web of Science, Cochrane Library, Scopus, EMBASE, and Google Scholar, up to January 2024. Studies examining the levels of VEGF-A in the serum or plasma of COVID-19 patients were incorporated, with specific attention given to contrasting severe/critical cases against moderate cases. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model to determine overall effect sizes. Meta-regressions and subgroup analyses were performed to explore potential sources of heterogeneity. The meta-analysis synthesized data from 11 studies involving a total of 1119 COVID-19 patients. Elevated levels of VEGF-A were significantly associated with disease severity, with a pooled SMD of 0.525 (95% CI 0.239–0.058; P = 0.028). Research has indicated that the nature of the relationship differs among various age groups, and there were minor discrepancies in the techniques employed to obtain VEGF-A measurements. Furthermore, meta-regression analysis indicated a potential correlation between VEGF-A levels and assay technique and body mass index (BMI). This meta-analysis provides compelling evidence for the prognostic potency of VEGF-A in COVID-19. Understanding the intricate interplay between VEGF-A and COVID-19 pathophysiology holds promise for the development of targeted therapeutic strategies and prognostic indicators in the management of COVID-19.

Background: Syringic acid (SA) is a natural phenolic compound with antioxidant and anti-inflammatory properties. Due to limited studies on the analgesic effect of SA, we decided to comprehensively investigate this effect. Thus, the analgesic activity of SA was assessed for the first time using the formalin and writhing models, in addition to the hot plate (HP) test, involving its action on opioid, GABAergic, nitric oxide (NO)/cGMP, and ATP-sensitive K⁺ channel pathways. Furthermore, we examined exploratory and locomotor behaviors post SA administration. Methods: A total of 231 mice were randomly assigned to groups of 7. SA was administered at doses of 25, 50, and 100 mg/kg. To investigate the possible pathways, naloxone, flumazenil, L-NAME/methylene blue, and glibenclamide were administered before SA injection. Behavioral tests were performed using the open-field (OF) apparatus. Statistical analysis was performed using one-way (or two-way) analysis of variance (ANOVA) with Tukey, least significant difference (LSD), and Bonferroni post hoc tests. All the results were evaluated under blind conditions. Results: SA showed significant analgesic effects in the acute (P < 0.050) and chronic (P < 0.001) phases of formalin (P < 0.050) and writhing tests (P < 0.001) but not in the HP test. Furthermore, SA decreased exploratory behavior. Opioid receptor blockade reduced the number of writhes (P < 0.050). Moreover, using L-NAME increased the pain reaction time in the HP test (P < 0.010). Conclusion: SA exhibited analgesic effects in the formalin and writhing models, but not in the HP test Blocking opioid receptors in the writhing test reduced the analgesic effect of SA. Exploratory behavior increased when flumazenil, naloxone, and L-NAME were injected before SA administration.

Aim: Islets of Langerhans are more sensitive to oxidative damage because of their low antioxidant capacity. In diabetes, methylglyoxal (MG) accumulates in the pancreas. The present study examined the effect of crocin on oxidative stress induced by MG in isolated Langerhans islets from male mice. Material and Methods: Twenty-four male mice weighing 20 to 25 g were prepared. The isolated Langerhans islets were transferred to the culture medium. Oxidative stress was induced through MG administration for 30 min, and then 10, 20, 30, and 40 μM of crocin was used for 2 h. Samples were divided into seven groups with 2.8, 5.6, and 16.7 mM glucose concentrations: control, MG 300 μM, MG+glibenclamide 10 μM, and MG+crocin in four doses of 10, 20, 30, and 40 μM. At the end, the islet’s insulin, antioxidant levels, and lipid peroxidation were assessed by ELISA and calorimetry methods. Results: Increased levels of malondialdehyde (MDA) in MG groups significantly decreased in 2.8 (p=0.008), 5.6 (p=0.004), and 16.7 (p˂0.001) mM glucose concentrations, with administration of 30 and 40 μM crocin. Total antioxidant capacity (TAC) was reduced in MG groups (p˂0.001) and significantly restored in all crocin-treated groups in 2.8, 5.6, and 16.7 mM glucose concentrations. Also, a significant decrease in insulin secretion and content was observed in MG groups of all three glucose concentrations (p˂0.001). Crocin at high doses improved these alterations. Conclusion: MG caused oxidative damage and reduced insulin secretion in isolated islets. Crocin improved the antioxidant defense system, diminished MDA, and increased insulin secretion.