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Several metal-based nanoparticles harboring multivalent elements, such as Cu 2+ /Cu + , Mn 4+/3+ /Mn 2+ , Mo 6+ /Mo 4+ , and Ir 4+ /Ir 3+ , possess strong oxidization, and can directly react with GSH ( via the redox reaction between Cu 2+ and intracellular GSH, and the activation of a Fenton-like reaction by generating Cu + to amplify oxidative stress ( in situ GSH in tumor triggered mCMSNs biodegradation and reduced Cu 2+ into Cu + for enhanced hydroxyl radical production, leading to a powerful inhibition effect on tumors ( 2 , Mn 2 O 3 , and Mn 3 O 4 , possess a similar GSH elimination property to Cu-based nanomaterials, and react with GSH along with the decomposition of MnO x into Mn 2+ for initiation of the Fenton-like reaction ( 2 -based nanoagent with both Fenton metal ion delivery and GSH exhaustion capability (Figure 1E) ( 2+ and GSSG, accompanied by the elimination of intracellular GSH (Figure 1F)

309 , R795R804 (2015)

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Although the present study did not directly measure the activity or expression of these signaling molecules, these pathways were discussed based on previously published mechanistic studies demonstrating bromelains regulatory effects on NF-B, MAPK, MLCK, Nrf2, and Akt/FOXO signaling in various experimental models

Products formulated outside these ranges may contain degraded copper peptides delivering less activity than their concentration suggests

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