The exact link between obesity, vitamin D deficiency, and their relation to cellular senescence in the pathogenesis of subclinical atherosclerosis is still under debate. Therefore, the current study aims to verify the possible role of vitamin D deficiency and cellular senescence in the pathogenesis of obesity-related subclinical atherosclerosis. Moreover, it aims to investigate the possible protective role of vitamin D supplementation. Fifty-seven male albino rats were enrolled in the study and classified into four groups: negative (10) and positive control groups (10), an obese model group (24), and a vitamin-D-supplemented obese group (13). Aortic tissue samples and fasting blood samples were collected. The following biochemical investigations were performed: serum cholesterol, triglycerides, HDL-C, LDL-C, ALT, AST, CPK, CK-MB, and hs-cTnt. HOMA-IR was calculated. Moreover, serum SMP-30, 25 (OH)Vitamin D3, and eNOS were determined by the ELISA technique. Aortic gene expression of eNOS, SMP-30, and P53 was estimated by real-time qRT-PCR. Serum 25(OH) D3 and SMP-30 were lower in the obese group. In addition, the obese group showed higher serum lipid profile, HOMA-IR, eNOS, ALT, AST, CPK, CK-MB, and hs-cTnt than the control groups, while decreased levels were found in the vitamin-D-treated obese group. Gene expression of eNOS and SMP-30 were in accordance with their serum levels. A positive correlation was found between vitamin D level and SMP-30. In conclusion, obesity is associated with vitamin D deficiency and enhanced cellular senescence. They could play a role in the pathogenesis of obesity-associated subclinical atherosclerosis and endothelial dysfunction. Vitamin D supplements could play a protective role against such obesity-related comorbidity.

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Background: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. Methods: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. Results: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, α, and β cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. Conclusion: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of α-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a suggested genetic basis. The newly identified human programmed cell death 1 gene could be associated with SLE susceptibility. We aimed to investigate the association between programmed cell death 1 polymorphism (PD1.3G/A (rs11568821) and PD1.5C/T (rs2227981)) with the risk of SLE in the Egyptian female population. This retrospective case–control study included 150 Egyptian females; 70 patients diagnosed to have SLE and 80 age-matched healthy controls. The two single nucleotide polymorphisms of the pdcd1 gene were genotyped by allelic discrimination through TaqMan real-time polymerase chain reaction. The PD1.3GG genotype and G allele as well as the PD1.5CC genotype were significantly more frequent in SLE patients (67.1%; p = 0.023, 82.1%; p = 0.0021, 62.9%; p = 0.0287 respectively). The GC haplotype was the most common haplotype among SLE patients (70.77%) with a reported significant linkage disequilibrium between the two studied polymorphisms ( p = 0.0041). Although most of the studies showed significant association of SLE with the minor alleles, we reported a significant association between the dominant genotypes (PD1.3GG and PD1.5CC) as well as the major G allele with the risk of SLE among Egyptian females.