Search

Objective: To investigate the relationship between anthropometric, biochemical, and hematologic parameters and serum leptin and homocysteine (Hcy) levels. Also, to determine the effect of leptin and Hcy on expression of genes associated with cardiovascular disease susceptibility (APOA1, LRP1, COX-1, and COX-2) in mononuclear cells of healthy pregnant women., Methods: Between August 2018 and January 2020, a cross-sectional study was conducted on 161 healthy pregnant women in Tabasco, southeastern Mexico. The study population was classified by trimester, according to gestational pregnancy. Anthropometric, biochemical (leptin and homocysteine), and hematologic data were obtained under fasting conditions. APOA1, LRP1, COX-1, and COX-2 expression in mononuclear cells was evaluated using RT-qPCR., Results: Red cell indices (hemoglobin, hematocrit, and erythrocytes) were negatively and positively correlated with leptin and Hcy levels, respectively, in the first- and second-trimester groups. Increased leptin levels and low red cell indices were significantly associated with BMI <25.0 in the second-trimester group; however, no significant differences were observed in Hcy levels. Increased leptin and Hcy levels were significantly associated with high lipid indicators in the first- and third-trimester groups, respectively. High APOA1 and COX-2 expression was significantly associated with reduced leptin and increased Hcy levels in the second- and third-trimester groups., Conclusion: Increased leptin and Hcy levels during pregnancy, mainly associated with modifications in erythrocytes and lipid indices, may lead to early modification of genes related to lipid metabolism (APOA1) and proinflammatory response (COX-2) and, thereby, increase cardiovascular disease risk., (© 2023 International Federation of Gynecology and Obstetrics.)

Increased homocysteine (Hcy) levels have been associated with a higher risk of cardiovascular and neurodegenerative diseases. Passive DNA demethylation has been suggested as one of the mechanisms implicated in the development of these conditions, and most studies have investigated this relationship in older adult populations. Therefore, this study aimed to evaluate the relationship between corporal composition and biochemical and haematological indicators with plasma homocysteine levels and genome-wide methylation (Alu, LINE-1, and SAT2) in a population of healthy young adults (median age, 18 years). We showed that the prevalence of hyperhomocysteinemia was significantly higher in men (18.5%) than in women (6.6%) ( P = 0.034). Increased Hcy level was substantially associated with higher levels of body mass index and visceral fat in females, whereas in males, it was significantly associated with reduced red cell distribution width and high-density lipoprotein (HDL) cholesterol (HDL-C) levels and increased low-density lipoprotein/HDL ratio. Hypomethylation of Alu was significantly associated with reduced levels of HDL-C (<40.0 mg dL -1 ), whereas hypomethylation of LINE-1 and SAT2 was significantly associated with higher levels of skeletal muscle (<39.3%) in males. These results highlight the participation of hormonal factors in regulating Hcy metabolism, primarily in the female population, whereas changes in DNA methylation observed in males might be associated with the consumption of a protein diet with high levels of methionine, independent of increased Hcy levels.

Previous studies have proposed that the human papillomavirus (HPV) E6 oncoproteins modify the transcriptional activity of eIF4E through mechanisms dependent on p53 degradation. However, the effect of these oncoproteins on pathways regulating the activity of the eIF4E protein remains poorly understood. Hence, we investigated the mechanisms whereby E6 proteins regulate the activity of the eIF4E protein and its effect on target genes. Overexpression of E6 constructs (HPV-6, HPV-16, HPV-18, and HPV52) showed that E6 oncoproteins increased phosphorylation of the eIF4E protein (Serine-209). This result was mainly mediated by phosphorylation of the 4EBP1 protein via the PI3K/AKT pathway. Additionally, the pharmacological inhibition of eIF4E phosphorylation in cervical cancer cell lines substantially reduced the protein levels of CCND1 and ODC1, indicating that E6 of the high-risk genotypes may modify protein synthesis of the eIF4E target genes by increasing the activity of the AKT and ERK pathways., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)