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Background: Several studies demonstrated the regulatory effects of vitamin D3 on the immune system. The aim of this study was to investigate the serum levels of IL-12, IL-6, IL-10, IL-17 and IFN-g cytokines in 11-17 year-old female students with 25-hydroxyvitamin D3 (25-(OH) D3) (VitD3) deficiency. Methods: 100 subjects with VitD3 deficiency were selected as the case group and an equal number of individuals with sufficient levels of VitD3 were selected as a control group. The serum levels of IL-10, IL-6, IL-12, IFN-g and IL-17 were measured by ELISA method. Results: The results showed that the serum concentrations of IL-12 (P= 0.005) and IFN-g (P= 0.019) were significantly lower in VitD3-deficient group compared to control group. There were no significant differences in serum levels of IL-6 (P= 0.66), IL-10 (P= 0.647) and IL-17 (P= 0.159) between cases and controls.Conclusion: These results suggest that VitD3deficiency may result in decreased inflammatory cytokines production, which are required for proper immune functions. However, the effects of VitD3 on IL-6 and IL-17A, as the pro-inflammatory and IL-10, as anti-inflammatory cytokines needs more investigations.

Background Altered metabolism is one of the hallmarks of the cancer cells which reciprocally interrelate with epigenetic processes, such as post-translational histone modifications to maintain their desired gene expression profiles. The role of beta-hydroxybutyrate as a ketone body in cancer cell biology and histone modifications are reported. The present study aimed to evaluate the impacts of long-term metabolic reprogramming via glucose restriction and beta-hydroxybutyrate treatment on histone acetylation and butyrylation in MDA-MB231 cells as a model of triple negative stem-like breast cancer. Methods For long-term treatment, cells were set up in three groups receiving DMEM with restricted glucose (250 mg/L), DMEM with restricted glucose but enriched with five millimolar beta-hydroxybutyrate and DMEM with standard glucose (1gL) and investigated for a month. Histone modifications, including H3 acetylation and butyrylation, were investigated by immunoblotting after an acid extraction of the histone proteins. Results and conclusion Neither beta-hydroxybutyrate enrichment nor glucose restriction elicited a significant effect on the butyrylation or acetylation level of histone H3 upon a long-term treatment. Metabolic plasticity of cancer cells, mainly stem-like triple negative breast cancer cells alleviate or neutralize the impact of long-term metabolic reprogramming via restriction of glucose and histone modifications enrichment. These results shed new light upon the mechanism of controversial efficacy of ketogenic diets in clinical trials.

The beneficial impacts of the ketogenic diet and metabolic reprograming were recently reported for ovarian cancer patients. In this study, the effects of glucose restriction with or without beta-hydroxybutyrate (bHB) enrichment were studied in drug-resistant CD133high A2780CP and CD133low SK-OV-3 ovarian cancer cells to scrutinize the impact of experimental ketosis on ATP production, epithelial to mesenchymal transition (EMT), and related signaling pathways including Wnt, Hippo, and Hedgehog. Cells were adapted and maintained for a month with restricted levels of glucose (250 mg/l) with or without the therapeutic concentration of bHB (5 mM). Quantitative PCR, Western blot analysis, flow cytometry, chemiluminescence, and wound healing assay were used in this study. Glucose restriction and bHB enrichment reduced the stemness marker and diminished In Vitro migration in both cell lines. Glucose restriction significantly reduced ATP levels in both cells, but bHB enrichment was partially compensated for the ATP levels solely in SK-OV-3 cells. Glucose restriction mainly inhibited the Wnt pathway in the CD133high A2780CP cells, but the Hedgehog pathway was the main target in CD133low SK-OV-3 cells. In Conclusion, Prior targeted evaluations of key genes' expression would help to predict the distinctive impacts of metabolic fuels and to optimize the efficacy of ketogenic diets.