Table 5.

Mechanisms of micronutrients in survival.

Mechanism of Action	Se	Zn
Generating oxygen free radicals/involved in oxidative stress/antioxidant	–Selenoproteins, thioredoxin reductase, and glutathione peroxidase reduce the number of free radicals [32,33]	–Zn/Cu superoxide dismutase [34,35,36]
Neoplastic growth	–Different proteins containing Se, such as thioredoxin reductase and glutathione peroxidase 1, 2, 3, 4, 6 [37,38,39]	–Induction of signaling pathway WNT/β-catenin suppresses the proliferation of cancer cells [40] –Inhibition of cell migration and invasion [41]
DNA repair	–Increase in tumor-suppressor protein p53 [32,42,43]	–Transcription and replication are regulated by zinc-finger proteins, which modulate the activity of DNA binding, including p53, AP-1, and NFκB [44,45,46,47,48]
Apoptosis and cell signaling	–Induction of apoptosis by p53 serines 20 and 37 [49,50,51,52,53,54]	–Apoptosis induction by pathway NFκB, AP-1, and ERK; dependent on H-Ras activation [41,44,47,55,56,57] –Activation of the signaling pathway WNT/β-catenin induces apoptosis in cells and inhibits cancer growth in osteosarcoma [40]
Maintaining DNA integrity in humans	–Selenomethionine reduces DNA damage [32]	–Prevention of DNA strand breaks [34,35,58,59]
Inflammation suppression	–Selenoenzymes have the ability to lower hydroperoxide compounds within the lipoxygenase and COX pathways, thus inhibiting the synthesis of PGL (proinflammatory ones) and LTR [32,33,60,61,62]	–Anti-inflammatory function of zinc-finger protein 36 (ZFP36) by downregulating pro-inflammatory cytokines, i.e., TNF-α [63] –Increase in production of IL-1β and IL-6, recognition of MCH-1, and suppression of NK cell cytotoxicity in the case of Zn deficiency [35]
Immune response enhancement	–Supplementing with Se (Na2SeO3) amplifies the immunological response by elevating the counts of cytotoxic lymphocytes and NK cells [64]	–Regulatory T cell function suppression by ZFP36L2 [63] –Granulocyte recruitment impairment, phagocytosis, chemotaxis, ROS generation, and epithelial cell–monocyte adhesion are regulated by Zn levels [35] –Deficiency results in decreased T cell immunity [65]
Protein kinase C inactivation	–The specific deactivation of PKC occurs through the interaction of its catalytic domain with selenometabolites, like CH3SeO2H, which is produced from membrane-bound CH3SeH and fatty acid hydroperoxides. This interaction hinders tumor promotion and the proliferation of cells [66]
DNA methylation alteration	–DNA demethylation [67,68]	–Cofactor required for DNA methylation [69,70,71,72]
Angiogenesis inhibition	–Se promotes vascular endothelial cell apoptosis and inhibits angiogenesis through the MAPK pathway [73]
Cell cycle blockage	–Cell cycle blockage caused by CH3SeH precursors [74]	–Cell cycle blockage properties of Zn (II)-phthalocyanine in photodynamic therapy [75] –Inhibition of cell cycle [41]
Telomere length—preserving telomere length leads to a decrease in the occurrence of age-related chronic diseases and cancers	–Antioxidant properties of Se reduce telomere attrition [76]	–Antioxidant properties of Zn preserve telomere length [77]
Regulation of thyroid function	–Se deficiency is associated with hypothyreosis, which is associated with increased survival, especially in older people [78] –Protein that includes a selenocysteine plays a role in the metabolic processes of thyroid hormones [79]	–Zn participates in the biosynthesis of thyroid hormones [80]
Cardiovascular disease	–Reduces levels of oxidized LDL, damage to DNA caused by oxidation, and the generation of deoxyguanosine [81] –Heart failure decreases survival [82]	–Low Zn levels lead to calcification of blood vessels [83] –Ischemia-reperfusion injury [84]