Yuning Lin

Polyamines are essential metabolites whose biological effects depend on the balance among putrescine, spermidine, and spermine. Spermine synthase (SMS) catalyzes the terminal step of mammalian spermine biosynthesis, simultaneously consuming spermidine and producing spermine. We use this reaction as the organizing framework of the review: SMS changes redox biology indirectly by redistributing spermidine and spermine and by altering the substrate available for oxidative catabolism. In Snyder–Robinson syndrome (SRS), severe SMS deficiency causes spermine depletion, spermidine accumulation, oxidative and organelle stress, and multisystem disease. In cancer, SMS-dependent remodeling can support or restrain tumor growth according to the resulting polyamine profile and downstream metabolic context. Intact spermine can scavenge reactive species and chelate Fe²⁺, whereas SMOX- and SSAT–PAOX-mediated oxidation generates H₂O₂ and reactive aldehydes; these opposing routes help explain divergent effects on lipid peroxidation and ferroptosis. This review focuses on evidence that directly connects SMS perturbation or altered spermidine/spermine balance with redox-relevant outcomes in SRS and cancer, distinguishes causal studies from metabolite-level associations, and defines the present limits of therapeutic translation. Together, these findings identify the SMS–polyamine axis as a regulator of the balance between antioxidant protection and oxidase-driven oxidative stress.

Compared with classical Fc N-glycosylation, Fab N-glycosylation displays site heterogeneity and structural diversity. It contributes to immune regulation by modulating antibody stability, half-life, and antigen-binding activity, as well as by mediating blocking antibody effects. This review highlights the expression patterns and potential mechanisms of Fab N-glycosylated IgG in autoimmune diseases, pregnancy-induced immune tolerance, and tumor immune evasion, and discusses its structural and functional similarities to IgG4. Although Fab N-glycosylation plays an important role in both physiological and pathological conditions, the complexity of its glycan structures and variability in glycosylation sites hinder a precise understanding of its functional impacts. Clarifying these aspects is expected to emerge as a major focus in glycomics and antibody engineering research.