Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

Ferroptosis is a newfound mode of regulated cell death that may have potential to associate with prognostic or diagnostic factors in glioma. In this research, 5 genes related to glioma were screened through the FerrDb database, and we analyzed the combination between genes and glioma of survival and prognosis via TCGA, GEPIA, TIMER, and other databases. Survival curve and prognostic analysis showed that the overexpression of NFE2L2 and NOX4, respectively, has a remarkable link with a worse prognosis in glioma. Then, the association between the expression of the two genes and tumor-infiltrating immune cells level was explored based on the GSCA, and the immunity of NFE2L2 and NOX4 based on the TISIDB database was also investigated. In glioma, especially GBM, there is a strong association between gene expression and immune infiltration, even in macrophages, nTreg, and Th2 cells, which play immunosuppressive functions in TME. In conclusion, these results indicate that NFE2L2 and NOX4 could be risk prognosis biomarkers in glioma, and they bound up with immune infiltration and tumor immunity in tumorigenesis.

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.

The relationship between dietary vitamin B6 and stroke risk is controversial; thus, we analyzed their correlation using data from the National Health and Nutrition Examination Survey (NHANES). Data from 2005 to 2018 were collected from the NHANES database. Two 24-h dietary recalls and a standard questionnaire were used to evaluate vitamin B6 intake and stroke prevalence. We used logistic regression models to estimate the association between dietary vitamin B6 intake and stroke risk and investigated the nonlinear relationship between them using a restricted cubic spline (RCS). Sensitivity analysis was conducted using propensity score matching (PSM). Among 24,214 participants, 921 were patients diagnosed with stroke, while 23,293 were without stroke. The multivariate logistic regression model revealed that individuals in the highest quartile of vitamin B6 consumption had a significantly lower stroke risk than those in the lowest quartile under the fully adjusted model (OR: 0.48, 95 % CI: 0.35–0.66, P < 0.001). Subgroup analyses showed that dietary intake of vitamin B6 was a significant protective factor against stroke risk in different populations, with the most pronounced effect in the population engaging in moderate-intensity physical activity (OR: 0.34, 95%CI: 0.20–0.57). The RCS models revealed a non-linear L-shaped relationship (P for nonlinearity = 0.006) between stroke and dietary intake of vitamin B6. Our study shows that an increased intake of vitamin B6 could be an effective strategy in reducing the risk of stroke.

Backgrounds: Growing evidence has indicated that the nutritional quality of dietary intake and alterations in blood metabolites were related to human brain activity. This study aims to investigate the causal relationship between dietary component intake, blood metabolites, and delirium risks.Methods: We performed Mendelian randomization (MR) analysis using genetic variants as instrumental variables for dietary component intake, blood metabolites, and delirium. Inverse variance weighting, maximum likelihood, weighted median, weighted mode, and MR-Egger methods were used for statistical analyses.Results: We found that genetic prediction of salt added to food (odds ratio [OR] 1.715, 95% confidence interval [CI] 1.239–2.374, p = 0.001) significantly increased the risks of delirium, while low-fat polyunsaturated margarine used in cooking (OR 0.044, 95%CI 0.004–0.432, p = 0.007), cheese intake (OR 0.691, 95%CI 0.500–0.955, p = 0.025) and coffee intake (OR 0.595, 95%CI 0.370–0.956, p = 0.032) was suggestively associated with decreased risks of delirium. Moreover, increased blood 1-stearoylglycerol levels (OR 0.187, 95%CI 0.080–0.435, p = 9.97E-05) significantly contributed to reducing the risks of delirium. 3-methoxytyrosine (OR 0.359, 95%CI 0.154–0.841, p = 0.018) also has the potential to decrease the risk of delirium.Conclusion: Our study highlights the potential causal effect relationships of dietary component intake and blood metabolites on the risk of delirium, which potentially provides novel insights into targeted dietary prevention strategies or biomarkers for delirium.