Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model.

Introduction: Alzheimer's disease (AD) is the most common form of dementia worldwide. This study investigated the effects of lipopolysaccharide on neurosteroidogenesis and its relationship to growth and differentiation using SH-SY5Y cells. Methods: In this study, we used the MTT assay to assess the impact of LPS on SH-SY5Y cell viability. We also evaluated apoptotic effects using FITC Annexin V staining to detect phosphatidylserine in the cell membrane. To identify gene expression related to human neurogenesis, we utilized the RT2 Profiler TM PCR array human neurogenesis PAHS-404Z. Results: Our study found that LPS had an IC50 level of 0.25 µg/mL on the SH-SY5Y cell line after 48 h. We observed Aß deposition in SH-SY5Y cells treated with LPS, and a decrease in DHT and DHP levels in the cells. Our analysis showed that the total rate of apoptosis varied with LPS dilution: 4.6% at 0.1 µg/mL, 10.5% at 10 µg/mL, and 44.1% at 50 µg/mL. We also observed an increase in the expression of several genes involved in human neurogenesis, including ASCL1, BCL2, BDNF, CDK5R1, CDK5RAP2, CREB1, DRD2, HES1, HEYL, NOTCH1, STAT3, and TGFB1, after treatment with LPS at 10 µg/mL and 50 µg/mL. LPS at 50 µg/mL increased the expression of FLNA and NEUROG2, as well as the other genes mentioned. Conclusion: Our study showed that LPS treatment altered the expression of human neurogenesis genes and decreased DHT and DHP levels in SH-SY5Y cells. These findings suggest that targeting LPS, DHT, and DHP could be potential therapeutic strategies to treat AD or improve its symptoms.

Gene polymorphism of leptin and risk for heart disease, obesity, and high BMI: a systematic review and pooled analysis in adult obese subjects.

OBJECTIVES: Leptin polymorphism (LEP) has been associated with coronary heart disease (CAD), obesity, and high body mass index (BMI). However, we performed a systematic review and meta-analysis to discover the association because previous studies reached different conclusions. METHODS: Review Manager, version 5.3.5, and Stata, version 15.0, were used for statistical analysis. We calculated the effect size of the studies using the OR with the corresponding 95% CI, and two-sided (bilateral) p-values of 0.05 were considered significant. To determine heterogeneity among the selected studies, the Q test and I2 statistics were used. Meta-regression was used to examine the disease (heart disease, obesity, and high BMI) and heterogeneity between these subgroups. RESULTS: Eleven studies with 18,984 subjects were included in this study. The G-2548A (rs12112075), rs7799039, and A19G (rs2167270) polymorphisms of the leptin gene (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Our pooled analysis revealed an association between the G-2548A (rs12112075) polymorphism and heart disease, high BMI, and obesity. This indicates that individuals carrying the AA allele are at an increased risk for heart disease, high BMI, and obesity. People with heart failure and coronary artery disease did not have the rs7799039 polymorphism or its alleles linked to them. CONCLUSIONS: Combined analysis of data from current and published research suggests that the leptin gene polymorphisms G-2548A (rs12112075), rs7799039, and A19G (rs2167270) (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Further research is needed to understand this association.

Calcitriol modulates cholesteryl ester transfer protein (CETP) levels and lipid profile in hypercholesterolemic male rabbits: A pilot study.

Vitamin D3 efficacy against cardiovascular disease prevention has been reported in many experimental studies. We aimed to investigate the effect of the calcitriol or active form of Vitamin D3 (1, 25(OH) 2D3) on serum cholesteryl ester transfer protein (CETP) levels in a rabbit model of atherosclerosis. New Zealand white male rabbits were fed with 1% cholesterol diet and randomly assigned into two groups (n = 6). The case group was administrated with 50000 calcitriol (IU/kg/per wk) and the control group which administrated with calcitriol solvent (sesame oil) for 2 months. Then, after two months the lipid profile, CETP and 25OHD3 levels were measured. The serum concentration of CETP was increased after treatment with calcitriol in case group as compared to the control group (41.75 ± 3.19 vs. 34.5 ± 2.3, ng/ml, P < 0.05). We also observed higher levels of the 25OHD3 in the calcitriol group at the 1st month (16.3 ± 1.64 vs. 12.8 ± 1.33 ng/ml) and the 2nd month (19.5 ± 2.14 vs. 12.5 ± 1.25 ng/ml) as compared with the control group. the significant increase in the level of HDL-C was observed in the case group than the control group (P < 0.01). In addition, serum levels of LDL- Cholesterol (LDL-C), Triglyceride (TG) were reduced after assessment at 1st and 2nd month after administration of calcitriol. Our research indicated the significant anti-atherogenic effects of calcitriol in the rabbit model of atherosclerosis. However, increased in CETP levels by calcitriol may know as an additional way, which interfere with the anti-atherogenic effects of calcitriol.