The Association Between Forkhead Box Class O3A Gene Polymorphism and Psoriasis and Its Relationship with Psoriasis Severity.

Background: Psoriasis vulgaris is a chronic, relapsing, inflammatory disorder marked by an intensified immune response. The role of immunogenetics in psoriasis is still poorly understood; however, experts agree that its expression depends on proinflammatory cytokines.Forkhead box class O3A (FOXO3a), a transcription factor, plays a crucial role in intercellular regulation, oxidative stress, deoxyribonucleic acid (DNA) repair, and cell death. Objective: The objective of this study was to investigate the role of FOXO3a genetic polymorphism as a risk factor for psoriasis vulgaris and assess its possible relationship with disease severity. Methods: A comparative case-control study included 53 patients with psoriasis and 41 matched healthy controls. We measured serum FOXO3a levels and used the PCR-RFLEP technique to detect FOXO3a genetic polymorphism (rs13217795) in both groups. Results: Our results revealed significantly higher serum FOXO3a levels in the psoriasis group compared to the control group (p≤0.001). Serum FOXO3a levels were significantly higher in patients with severe psoriasis than in those with mild-to-moderate disease. FOXO3a genotypes found homozygous mutant genotype (TT) was substantially more frequent in the psoriasis group than in the control group. Furthermore, the T allele was more frequent in the psoriasis group than in the control group. Conclusion: The study indicates that rs13217795 polymorphism of the FOXO3a gene is strongly associated with susceptibility to psoriasis. Also, the serum level of FOXO3a is significantly higher in patients with severe psoriasis, compared to patients with mild-to-moderate psoriasis. This finding could be an area of future targeted therapy.

Discrepancy between the Actions of Glucagon-like Peptide-1 Receptor Ligands in the Protection of the Heart against Ischemia Reperfusion Injury.

Tirzepatide is a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and a promising therapy for type 2 diabetes mellitus (T2DM). GLP-1 is an incretin hormone with therapeutic potential beyond type 2 diabetes mellitus. However, GLP-1 is rapidly degraded by dipeptdyl peptidase-IV (DPP-IV) to GLP-1 (9-36). Exendin-4 (Ex-4) is a DPP-IV-resistant GLP-1 receptor agonist which, when truncated to Ex-4 (9-39), acts as a GLP-1 receptor antagonist. In the present study, hearts isolated from Wistar rats (n = 8 per group) were perfused with a modified Langendorff preparation. Left ventricular (LV) contractility and cardiovascular hemodynamics were evaluated by a data acquisition program and infarct size was evaluated by 2,3,5-Triphenyl-2H-tetrazolium chloride (TTC) staining and cardiac enzyme levels. Hearts were subjected to 30 min regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery followed by 30 min reperfusion. Hearts were treated during reperfusion with either the non-lipidated precursor of tirzepatide (NLT), GLP-1, GLP-1 (9-36), or Ex-4 in the presence or absence of Ex-4 (9-39). Infusion of GLP-1 (9-36) or Ex-4 protected the heart against I/R injury (p > 0.01) by normalizing cardiac hemodynamic and enzyme levels. Neither GLP-1, NLT, nor Ex-4 (9-39) showed any protection. Interestingly, Ex-4 (9-39) blocked Ex-4-mediated protection but not that of GLP-1 (9-36). These data suggest that Ex-4-mediated protection is GLP-1-receptor-dependent but GLP-1 (9-36)-mediated protection is not.