ABSTRACT Free radicals, molecules with unpaired electrons, are double‐edged swords. While they may cause damages to cells and threaten human health, they play essential roles in cellular signaling toward mitochondrial and immune homeostasis. Overproduction or insufficient supply of free radicals can both lead to health concerns and disease syndromes by causing oxidative or reductive stress to cells. Current redox therapies frequently fail clinically due to imprecise dosing and targeting, causing therapeutic futility or paradoxical harm by disrupting redox homeostasis, necessitating integrated frameworks linking redox biology to precision interventions alongside therapeutic innovation. This review explores free radicals’ generation sources, characterizes mitochondrial oxidative phosphorylation and pathological hyperglycemia as pivotal endogenous sources, and proposes oxygen and transition metals as fundamental regulators. This paper synthesizes multidimensional molecular mechanisms and pathologies arising from redox dysregulation and establishes reductive stress as a critical pathogenesis driver alongside oxidative stress. This review discusses free radical approaches and proposes cold atmospheric plasma as a transformative redox‐modulating technology capable of bridging therapeutic dichotomies through calibrated interventions. By integrating mechanistic insights with innovative methodologies, this work underscores the imperative to innovatively harness the dual nature of free radicals for precision health and disease management.
Dai et al. (Sun,) studied this question.