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Computational Analysis and Experimental Data Exploring the Role of Hesperetin in Ameliorating ADHD and SIRT1/Nrf2/Keap1/OH-1 Signaling

Authors: Hatem I. Mokhtar,Noha M. Abd El-Fadeal,Rehab M. El-Sayed,Ann Hegazy,Mohamed K. El-Kherbetawy,Ahmed G. Hamad,Mohamed H. ElSayed,Sawsan A. Zaitone
Journal: International Journal of Molecular Sciences
Publisher: MDPI AG
Publish date: 2024-8-27
ISSN: 1422-0067 DOI: 10.3390/ijms25179284
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Without a Hesperetin-only control group, how can you definitively rule out that the observed restoration of SIRT1/Nrf2 pathway components is not due to Hesperetin independently elevating these pathways in a normal physiological state? Could the effects seen in the ADHD/HSP groups be a combination of blocking MSGL’s effects and an inherent, baseline-upgrading action of Hesperetin?

Consequently, wouldn’t it be more accurate to conclude that Hesperetin “prevented the MSGL-induced downregulation” of the SIRT1/Nrf2 pathway, rather than claiming it caused “upregulation”? The current language implies an enhancing effect that the experimental design cannot verify.

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