An effective steady-state redox balance is maintained in cancer cells, allowing for protection against oxidative stress and thereby enhancing cell proliferation and tumor growth. Disruption of this redox balance would increase the cellular content of reactive oxygen species (ROS) and potentiate oxidative stress-induced cell death in tumor cells, thus representing an effective strategy for cancer treatment. Glutathione (GSH) is a major reducing agent, and its cellular levels are determined at least partly by the availability of cysteine via xCT (SLC7A11)-mediated entry of cystine into cells. We developed a nanoplatform using ZnO nanoparticles (NPs) as a carrier, loaded with salicylazosulfapyridine (SASP), and stabilized with DSPE-PEG, to form ultra-small NPs (SASP/ZnO NPs). The goal of this NP strategy is to disrupt the redox balance in cells by two mechanisms: increased generation of ROS and decreased synthesis of GSH. Such an approach would be effective in killing tumor cells. As expected, the SASP/ZnO NPs enhanced ROS production because of ZnO and impaired GSH synthesis because of SASP-induced inhibition of xCT (SLC7A11) transport function. As a consequence, treatment of tumor cells with SASP/ZnO NPs in vitro and in vivo resulted in a synergistic disruptive effect on redox balance in tumor cells and induced cell death and decreased tumor growth. This ambidextrous approach has potential in cancer therapy by combining two complementary pathways to disrupt the redox balance in tumor cells.

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Type 2 diabetes has been linked to cognitive impairment, but its potential metabolic mechanism is still unclear. The present study aimed to explore neuron-astrocyte metabolic cooperation in the brain of diabetic (db/db, BKS.Cg-m þ/þ Leprdb/J) mice with cognitive decline using 13 C]-lactate resulted in increased 13 C-enrichments in neurotransmitters in db/db mice with cognitive decline. This may indicate that the disturbance of neurotransmitter metabolism occurred during the development of cognitive decline. In addition, a reduction in 13 C-labeling of lactate and an increase in gluconeogenesis were found from both labeled infusions in db/db mice with cognitive decline. Therefore, our results suggest that the development of cognitive decline in type 2 diabetes may be implicated to an unbalanced metabolism in neuron-astrocyte cooperation and an enhancement of gluconeogenesis.

Alzheimer’s disease (AD) is regarded as a metabolic disorder, and more attention has been paid to brain metabolism. However, AD may also affect metabolism in the peripheral organs beyond the brain. In this study, therefore, we investigated metabolic changes in the liver, kidney, and heart of amyloid precursor protein/presenilin 1 (APP/PS1) mice at 1, 5, and 10 months of age by using 1H NMR-based metabolomics and chemometrics. Metabolomic results reveal that the liver was the earliest affected organ in APP/PS1 mice during amyloid pathology progression, followed by the kidney and heart. Moreover, a hypometabolic state was found in the liver of APP/PS1 mice at 5 months of age, and the disturbed metabolites were mainly involved in energy metabolism, amino acid metabolism, nucleic acid metabolism, as well as ketone and fatty acid metabolism. In conclusion, our results suggest that AD is a systemic metabolic dysfunction, and hepatic metabolic abnormality may reflect amyloid pathology progression.

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