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The red blood cells (RBCs) are essential to transport oxygen (O 2 ) and nutrients throughout the human body. Changes in the structure or functioning of the erythrocytes can lead to several deficiencies, such as hemolytic anemias, in which an increase in reactive oxidative species generation is involved in the pathophysiological process, playing a significant role in the severity of several clinical manifestations. There are important lines of defense against the damage caused by oxidizing molecules. Among the antioxidant molecules, the enzyme peroxiredoxin (Prx) has the higher decomposition power of hydrogen peroxide, especially in RBCs, standing out because of its abundance. This review aimed to present the recent findings that broke some paradigms regarding the three isoforms of Prxs found in RBC (Prx1, Prx2, and Prx6), showing that in addition to their antioxidant activity, these enzymes may have supplementary roles in transducing peroxide signals, as molecular chaperones, protecting from membrane damage, and maintenance of iron homeostasis, thus contributing to the overall survival of human RBCs, roles that seen to be disrupted in hemolytic anemia conditions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oxidative stress is a major cause of morbidity and mortality in human health and disease. In this review, we focus on the Forkhead Box (Fox) subclass O3 (FoxO3), an extensively studied transcription factor that plays a pleiotropic role in a wide range of physiological and pathological processes by regulating multiple gene regulatory networks involved in the modulation of numerous aspects of cellular metabolism, including fuel metabolism, cell death, and stress resistance. This review will also focus on regulatory mechanisms of FoxO3 expression and activity, such as crucial post-translational modifications and non-coding RNAs. Moreover, this work discusses and evidences some pathways to how this transcription factor and reactive oxygen species regulate each other, which may lead to the pathogenesis of various types of diseases. Therefore, in addition to being a promising therapeutic target, the FoxO3-regulated signaling pathways can also be used as reliable diagnostic and prognostic biomarkers and indicators for drug responsiveness., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)