Selenium (Se) is important and plays significant roles in many biological processes or physiological activities. Prolonged selenium deficiency has been conclusively linked to an elevated risk of various diseases, including but not limited to cancer, cardiovascular disease, inflammatory bowel disease, Keshan disease, and acquired immunodeficiency syndrome. The intricate relationship between selenium status and health outcomes is believed to be characterized by a non-linear U-shaped dose-response curve. This review delves into the significance of maintaining optimal selenium levels and the detrimental effects that can arise from selenium deficiency. Of particular interest is the important role that selenium plays in both prevention and treatment of cancer. Finally, this review also explores the diverse classes of selenium entities, encompassing selenoproteins, selenium compounds and selenium nanoparticles, while examining the mechanisms and molecular targets of their anticancer efficacy.

The reduction of the cerebral glucose metabolism is closely related to the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in Alzheimer’s disease (AD); however, its underlying mechanism remains unclear. In this paper, ¹⁸F-flurodeoxyglucose positron emission tomography was used to trace cerebral glucose metabolism in vivo, along with Western blotting and immunofluorescence assays to examine the expression and distribution of associated proteins. Glucose and insulin tolerance tests were carried out to detect insulin resistance, and the Morris water maze was used to test the spatial learning and memory ability of the mice. The results show increased NLRP3 inflammasome activation, elevated insulin resistance, and decreased glucose metabolism in 3×Tg-AD mice. Inhibiting NLRP3 inflammasome activation using CY-09, a specific inhibitor for NLRP3, may restore cerebral glucose metabolism by increasing the expression and distribution of glucose transporters and enzymes and attenuating insulin resistance in AD mice. Moreover, CY-09 helps to improve AD pathology and relieve cognitive impairment in these mice. Although CY-09 has no significant effect on ferroptosis, it can effectively reduce fatty acid synthesis and lipid peroxidation. These findings provide new evidence for NLRP3 inflammasome as a therapeutic target for AD, suggesting that CY-09 may be a potential drug for the treatment of this disease.

Neuroinflammation plays a pivotal role in the pathophysiology of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. During brain neuroinflammation, activated microglial cells resulting from amyloid-beta (Aβ) overload trigger toxic proinflammatory responses. Bis(ethylmaltolato)oxidovanadium (BEOV) (IV), an important vanadium compound, has been reported to have anti-diabetic, anti-cancer, and neuroprotective effects, but its anti-inflammatory property has rarely been investigated. In the present study, the inhibitory effects of BEOV on neuroinflammation were revealed in both Aβ-stimulated BV2 microglial cell line and APPswe/PS1E9 transgenic mouse brain. BEOV administration significantly decreased the levels of tumor necrosis factor-α, interleukin-6, interleukin-1β, inducible nitric oxide synthase, and cyclooxygenase-2 both in the hippocampus of APPswe/PS1E9 mice and in the Aβ-stimulated BV2 microglia. Furthermore, BEOV suppressed the Aβ-induced activation of nuclear factor-κB (NF-κB) signaling and upregulated the protein expression level of peroxisome proliferator-activated receptor gamma (PPARγ) in a dose-dependent manner. PPARγ inhibitor GW9662 could eliminate the effect of BEOV on Aβ-induced NF-κB activation and proinflammatory mediator production. Taken altogether, these findings suggested that BEOV ameliorates Aβ-stimulated neuroinflammation by inhibiting NF-κB signaling pathway through a PPARγ-dependent mechanism.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by decreased glucose metabolism and increased neuroinflammation. Hexokinase (HK) is the key enzyme of glucose metabolism and is associated with mitochondria to exert its function. Recent studies have demonstrated that the dissociation of HK from mitochondria is enough to activate the NOD-like receptor protein 3 (NLRP3) inflammasome and leads to the release of interleukin-1β (IL-1β). However, the effect of increased IL-1β on the expression of HK is still unclear in AD. In this paper, we used positron emission tomography (PET), Western blotting and immunofluorescence to study the glucose metabolism, and the expression and distribution of HK in AD. Furthermore, we used lipopolysaccharide (LPS), nigericin (Nig), CY-09 and lonidamine (LND) to treat N2a and N2a-sw cells to investigate the link between IL-1β and HK in AD. The results show decreased expression of HK and the dissociation of HK from mitochondria in AD. Furthermore, a reduction of the expression of IL-1β could increase the expression of HK in AD. These results suggest that inhibiting inflammation may help to restore glucose metabolism in AD.

As a functional beverage, selenium (Se)-enriched green tea (Se-GT) has gained increasing popularity for its superior properties in promoting health. In this study, we compared the brewing characteristics, in vitro digestion profiles, and protective effects on neurotoxicity induced through the amyloid-beta (Aβ) peptide of two typical Se-GTs (Enshi Yulu (ESYL) and Ziyang Maojian (ZYMJ), representing the typical low-Se green tea and high-Se green tea, respectively). ESYL and ZYMJ showed similar chemical component leaching properties with the different brewing methods, and the optimized brewing conditions were 5 min, 90 °C, 50 mL/g, and first brewing. The antioxidant activities of the tea infusions had the strongest positive correlation with the tea polyphenols among all of the leaching substances. The tea infusions of ESYL and ZYMJ showed similar digestive behaviors, and the tea polyphenols in the tea infusions were almost totally degraded or transferred after 150 min of dynamic digestion. Studies conducted in a cell model of Alzheimer’s disease (AD) showed that the extract from the high-Se green tea was more effective for neuroprotection compared with the low-Se green tea. Overall, our results revealed the best brewing conditions and digestion behaviors of Se-GT and the great potential of Se-GT or Se-enriched green extract (Se-GTE) to be used as promising AD-preventive beverages or food ingredients.

Alzheimer’s disease (AD) is an intractable neurodegenerative disease that leads to dementia, primarily in elderly people. The neurotoxicity of amyloid-beta (Aβ) and tau protein has been demonstrated over the last two decades. In line with these findings, several etiological hypotheses of AD have been proposed, including the amyloid cascade hypothesis, the oxidative stress hypothesis, the inflammatory hypothesis, the cholinergic hypothesis, et al. In the meantime, great efforts had been made in developing effective drugs for AD. However, the clinical efficacy of the drugs that were approved by the US Food and Drug Association (FDA) to date were determined only mild/moderate. We recently adopted a vanadium compound bis(ethylmaltolato)-oxidovanadium (IV) (BEOV), which was originally used for curing diabetes mellitus (DM), to treat AD in a mouse model. It was shown that BEOV effectively reduced the Aβ level, ameliorated the inflammation in brains of the AD mice, and improved the spatial learning and memory activities of the AD mice. These finding encouraged us to further examine the mechanisms underlying the therapeutic effects of BEOV in AD. In this review, we summarized the achievement of vanadium compounds in medical studies and investigated the prospect of BEOV in AD and DM treatment.