Effect of folic acid supplementation on the change of plasma S-adenosylhomocysteine level in Chinese hypertensive patients: a randomized, double-blind, controlled clinical trial.

The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0 mg/day had no effect on SAH level (ß = 0.47, 95% CI: -0.86-1.79, p = 0.491), while folic acid supplementation of 2.4 mg/day significantly increased SAH level (ß = 1.93, 95% CI: 0.22-3.64, p = 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4 mg/day folic acid had no effect on SAH level (ß = 0.30, 95% CI: -2.74-3.34, p = 0.847), while CT and TT genotype supplemented with 2.4 mg/day folic acid showed a significant increase in SAH level (CT: ß = 2.98, 95% CI: 0.34-5.62, p = 0.027; TT: ß = 3.00, 95% CI: -0.51-6.51, p = 0.095; CT combined with TT: ß = 2.99, 95% CI: 0.90-5.09, p = 0.005). In conclusion, supplementation of 2.4 mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.

[Inhibitory effect of lentiviral-mediated RNA on the expression of Foxp3 protein in melanoma cells].

AIM: To explore the feasibility of RNA interference in the treatment of melanoma by inhibiting the Foxp3 gene expression in mouse B16 melanoma cells using RNA interference (RNAi) in vitro. METHODS: Small interfering RNA (siRNA) was designed according to Foxp3 gene. A short hairpin RNA (shRNA) lentivirus expression vector was constructed and transfected into mouse B16 cells, and RNA interference was induced in vitro. Western blot and real-time RT-PCR were performed to detect the expression of Foxp3 gene. ELISA was applied to detect the changes of TGF-ß(1);, TGF-ß(2);, IL-10 and other cytokines. The B16 cells after interference were co-cultured with CD4(+);CD25(-);T lymphocytes. CCK8 assay was used to monitor the proliferation of CD4(+);CD25(-);T lymphocytes. RESULTS: shRNA could suppress the expression level of Foxp3, down-regulate the inhibitory ability of tumor cells on the proliferation of CD4(+);CD25(-);T lymphocytes, and reduce the secretion of TGF-ß(1);, TGF-ß(2);, IL-10 and other cytokines, in particular the expression of TGF-ß(2);. CONCLUSION: RNA interference can inhibit the expression of target gene Foxp3 in mice melanoma cells and the proliferation of tumor cells. It can also reduce the inhibition on the proliferation of CD4(+);CD25(-);T lymphocytes, and the secretion of inhibitory cytokines.