In this study, twenty new anthranilic acid hydrazones 6–9 (a–e) were synthesized and their structures were characterized by Fourier‐transform Infrared (FT‐IR), Nuclear Magnetic Resonance (1H‐NMR – 13C‐NMR), and High‐resolution Mass Spectroscopy (HR‐MS). The inhibitory effects of the compounds against COX‐II were evaluated. IC50 values of the compounds were found in the range of >200–0.32 μM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep‐G2) and human healthy embryonic kidney (Hek‐293) cell lines. Doxorubicin (IC50: 8.68±0.16 μM for Hep‐G2, 55.29±0.56 μM for Hek‐293) was used as standard. 8e is the most active compound, with low IC50 against Hep‐G2 (4.80±0.04 μM), high against Hek‐293 (159.30±3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand‐protein interactions between the most potent compounds and COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF‐βII). The docking scores were calculated in the range of −10.609–−6.705 kcal/mol for COX‐II, −8.652–−7.743 kcal/mol for EGFR, and −10.708–−8.596 kcal/mol for TGF‐βII.

SUMMARYObjectives: An increased risk for cardiovascular disease with psoriasis has been reported. Growth Arrest-Specific 6 (GAS6) amplifies pro-inflammatory endothelial cell activation via TAM receptors. However, it also inhibits inflammation by multiple mechanisms including phagocytosis. The objective of this study was to investigate whether plasma GAS6 levels are associated with conventional cardiometabolic (CM) risk factors in patients with psoriasis. Methods: Forty patients diagnosed with psoriasis (22 male, mean age: 43.3 AE 13.8 years) and 40 age-/sex-matched healthy controls (22 male, mean age: 39.3 AE 8.9 years) were included in the study. CM risk factors (hypertension, hyperlipidemia, diabetes mellitus, and cigarette smoking) were identified. GAS6 levels were measured by ELISA. Results: There were no significant differences between the plasma GAS6 levels of patients with psoriasis compared to the control group (6.6 AE 2.0 ng/mL, 7.6 AE 2.8 ng/mL, respectively, P > 0.05). However, GAS6 levels of patients with psoriasis having a smoking history (n = 11) were significantly lower than both patients with psoriasis who had no smoking history (n = 29) and controls (5.5 AE 1.7 ng/mL, 6.9 AE 1.9 ng/mL, 7.6 AE 2.8 ng/mL, respectively, P < 0.05). Similarly, psoriasis patients with at least one CM risk factor showed lower GAS6 levels compared to subjects without any CM risk factor (5.7 AE 1.7 ng/mL, 7.3 AE 2.0 ng/mL, P < 0.01). There was no correlation between the GAS6 level, disease duration or PASI score (r = 0.150, À0.150, and P = 0.310, 0.398, respectively). Conclusions: This pilot study provides the first evidence in humans for an association between low plasma GAS6 levels and conventional risk factors in psoriasis. Further large scale, prospective studies are needed to confirm these results.

The objective of this study was to establish reference intervals for growth arrest-specific 6 (GAS6), a vitamin K-dependent protein, in human adult plasma according to the Guideline of Clinical and Laboratory Standards Institute (CLSI) C28-A3. Blood samples were collected from 308 healthy volunteers aged 18-72 (157 female, 151 male). A non-parametric approach was used to calculate the reference interval. The plasma GAS6 reference interval was determined, with 90% confidence interval: the lower limit (2.5 percentile) was 2.5 (1.9-3.1) μg/L and the upper limit (97.5 percentile) = 18.8 (18.0-22.3) μg/L. Harris-Boyd's test did not suggest partitioning by age or gender: medians for males [7.8 (5.8-10.7) μg/L] and females [9.9 (7.1-13.5) μg/L]. Three age-subgroups were tested: 18-29 years (n = 168); 30-44 years (n = 73); 45-72 years (n = 67). The intra- and inter-assay variations were 12.6% (mean, 5.2 ± 0.7 μg/L) and 14.0% (mean, 9.2 ± 1.3 μg/L), respectively. The mean recovery was 104%. This study reports plasma GAS6 reference intervals established first according to the guideline of CLSI C28-A3.

Objectives: It has been shown that the dysregulation of tyrosine kinase Axl receptor and its ligand growth arrest-specific gene (Gas6) are associated with poor prognosis in various types of tumors but there is not enough study about their importance in bladder cancer (BC). We evaluated the relation of Gas6 gene expression and tyrosine- kinase Axl and Sky (Tyro 3) receptors with tumor stage and grade in patients with BC. Material and Methods: The study group consists of 55 patients whose transurethral resection of bladder (TUR-B) has been performed due to BC and the control group consists of 12 patients with normal bladder mucosa. In tissues mRNAs of Gas6, Axl, and Sky receptors were examined by quantitative (Real-Time) PCR (qPCR). Protein expression was measured by immunohistochemistry. Plasma Gas6 protein levels were compared with control group by ELISA method. Results: Patients with BC were grouped as Ta low (n=17), Ta high (n=5), T1 low (n=9), T1 high (n=8) and T2 (n=16) according to their TUR-B pathologies. The qPCR analysis showed that the expression of Gas6 gene and Axl receptor is higher in the tumor-positive group and the immune-histochemical showed that the bladder samples of the tumor-positive group stained significantly positive. When the patients are grouped according to the TUR-B pathologies, a statistical significant difference was observed among groups in the qPCR analysis ratios of Gas6 gene and Axl receptor by (p < 0.05) but no significance was found for Sky receptor (p > 0.05). When Gas6 protein levels in plasma samples were compared by ELISA method, a statistical significance was determined among groups (p = 0.001). Conclusions: Our findings indicate that mRNAs of Gas6 and Axl receptor are closely related to tumor stage and grade in patients with BC. Further studies are needed for understanding the role of Gas6 and its receptors on the neoplastic transformation in terms of novel biomarkers and potential therapeutic targets.

This pilot study provided, to the best of our knowledge, the first report that GAS6 levels increased significantly after vitamin K1 prophylaxis in preterm newborns but not in term infants. This study may serve as a first step toward more extensive studies in neonates.