Background: With environmental and lifestyle changes, recent epidemiological studies have shown that the prevalence of Ulcerative Colitis (UC) is on the rise, while treatment options are limited. There is an urgent need to explore the underlying mechanisms of vitamin D (VD) as an effective treatment. Methods: Dextran sulfate sodium-induced mice and lipopolysaccharide-induced HCT116 cells were used to establish the classic UC models in vivo and in vitro, respectively. Typical symbols of inflammation (IL-6, COX-2), oxidative stress (MDA, MPO, GSH), and ferroptosis (ACSL4, GPX4, SLC7A11, and Iron) were analyzed by Western blot, Immunohistochemistry, RT-PCR, and relative assay kits. The inflammation factors and oxidative stress injury of cells transfected with ACSL4^+/+ plasmids were tested by Western blot, MDA, and MPO methods. Results: Vitamin D attenuated the levels of COX-2, IL-6, Iron, MDA, and MPO and improved SOD1 and GSH contents in DSS + VD and LPS + VD groups, compared with model groups. Ferrostatin-1 (Fer-1) could relieve the levels of COX-2, IL-6, Iron, MDA, and MPO while increasing the contents of SOD1 and GSH in DSS + Fer-1 and LPS + Fer-1 compared to model groups. VD downregulated the expression of ACSL4 and upregulated GPX4 in tissues and cells. After transfected with ACSL4^+/+ plasmids, we found VD’s role of downregulating inflammation and oxidative stress was relieved. Conclusions: Vitamin D can relieve UC by inhibiting ferroptosis both in mice and in cells through the negative regulation of ACSL4, providing new insight into the therapeutic function of VD on UC.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular and cerebrovascular diseases where the plasma homocysteine (Hcy) concentration exceeds 15 µmol/L. HHcy is affected by vitamins B12, B6, and folic acid (fol); however, its relationship with other nutrients is not fully understood. We investigated the nutritional and genetic factors associated with HHcy and the possible dose–response relationships or threshold effects in patients in Northeast China. Genetic polymorphisms and micronutrients were tested with polymerase chain reaction and mass spectrometry, respectively. This trial was registered under trial number ChiCTR1900025136. The HHcy group had significantly more males and higher body mass index (BMI), methylenetetrahydrofolate reductase (MTHFR 677TT) polymorphism proportion, and uric acid, Zn, Fe, P, and vitamin A levels than the control group. After adjusting for age, sex, BMI, vitamin B12, fol, and MTHFR C677T, the lowest Zn quartile reduced the odds ratio of HHcy compared with the highest Zn quartile. The dose–response curves for the association between plasma Zn and HHcy were S-shaped. High plasma Zn concentrations were significantly correlated with high HHcy odds ratios, and the curve leveled off or slightly decreased. Most importantly, HHcy risk decreased with decreasing plasma Zn concentration; the threshold was 83.89 µmol/L. Conclusively, individuals residing in Northeast China, especially those with the MTHFR 677TT polymorphism, must pay attention to their plasma Zn and Hcy levels.