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Although the previous studies indicated the therapeutic effects of migraine supplementation, more RCT studies are required to define the best dose and duration of omega-3 supplementation for migraine patients

1 Introduction Methotrexate (MTX) is a dihydrofolate reductase inhibitor and chemotherapeutic agent with proven efficiency against cancers and rheumatoid arthritis ( Oxidative stress, which results from the excess production of reactive oxygen species (ROS), has a fundamental role in the MTX-associated toxicities pathogenesis ( The endoplasmic reticulum (ER) is a fundamental cellular organelle responsible for the newly synthesized proteins folding into their final 3-dimentional structures, post-translational modification, transportation, and quality control ( Apoptosis is essential in cellular homeostasis maintenance and is activated during adverse conditions (Figure 1)

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Acknowledgments We would like to acknowledge the children and parents who participated in this clinical trial

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All details are summarized in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart ( in Figure 2