Furthermore, CDDO-Me did not compromise the antitumor efficacy of DOX/LAP in breast cancer cells. CDDO-Me protects against DOX/LAP-induced cardiotoxicity by stabilizing GPX4 and inhibiting ferroptosis, offering a promising therapeutic strategy that preserves cardiac function without interfering with chemotherapy.

Notably, 8 exhibited significant antitumor efficacy comparable to CDDO-Me (bardoxolone methyl), which had entered clinical trials. Taken together, 8 represents a promising candidate for the treatment of cancer and merits further study.

JXZDF alleviated tic-like behaviors in a TD rat model by restoring striatal excitatory-inhibitory neurotransmitter balance and inhibiting microglial-mediated neuroinflammation. Its therapeutic effect was at least partially mediated by suppression of IKK/NF-κB. These findings provide a pharmacological basis for the clinical application of JXZDF in TD treatment.

As a proof-of-concept, we develop a nanoplatform for ferroptosis named MICLM, which is obtained by encapsulating chlorin e6 (Ce6, a photosensitizer) and IMD-0354 (an SLC1A5 inhibitor) into metal-organic framework (NH2-MIL-101(Fe)), followed by surface coating for tumor-targeting. Additionally, Gln metabolism inhibition attenuates immunosuppressive M2 macrophage polarization, ultimately boosting antitumor immunity. Thus, MICLM effectively induces ferroptosis and remodels the tumor immune microenvironment via amino acid metabolic intervention, offering a promising strategy for ferroptosis-based therapy.

In contrast, NRF2 activators, such as bardoxolone methyl (CDDO-Me), sulforaphane, and dimethyl fumarate, exhibit chemopreventive effects by enhancing detoxification and mitigating oxidative DNA damage during early tumorigenesis...Therefore, understanding the temporal and contextual effects of NRF2 signaling is crucial for therapeutic design. The aim of this review is to examine how pharmacological modulation of NRF2 influences the invasive and metastatic dimensions of tumor progression, in addition to discussing its potential integration into TNM-based prognostic and treatment frameworks.

Similarly, subcutaneous KEAP1 KO tumors were larger and more immune-suppressed compared to WT tumors. Both CDDO-Me and omaveloxolone reduced the tumor burden and improved immune cell phenotypes within the TIME independent of KEAP1 mutational status.

RNA-seq analysis was also utilised to highlight the molecular mechanisms underpinning the effects DOX in AC16 cells and the CDDO-mediated mitigation of cardiotoxicity. This study provides novel insight into NRF2 dynamics in the widely utilised AC16 cells whilst further elucidating the molecular mechanisms contributing to DOX cardiotoxicity and potential NRF2-orchestrated defence.

Four immune metabolism-associated diagnostic genes were identified, including TRAF3IP2, RIPK1, KEAP1, and DPP4 for OMAS.

Furthermore, CHL reduced p-p65 expression by 5-fold, indicating its effective inhibition of NF-κB transcriptional activity and thereby alleviating inflammatory responses. Therefore, the LAP-activable co-prodrug CHL holds promising potential as a candidate for the synergistic treatment of liver injury.

Cisplatin treatment significantly decreased tumor burden compared to vehicle-treated mice (p < 0.05 after two cisplatin doses) - a response that was not altered by BARD co-treatment. Overall, the results of this study demonstrate that BARD has the potential to improve survival and reduce clinical measures of kidney injury in tumor-bearing mice treated with cisplatin, suggesting it could be used as a nephroprotectant to mitigate cisplatin-induced AKI.

CDDO-Me induces CC cell lines apoptosis and ferroptosis through the PI3K/Nrf2 signaling pathway, for exerting anti-proliferation effects.

Additionally, the levels of protein expression of Nrf2 and NQO1 were reversed by two activators of Nrf2, bardoxolone (CDDO) and sulforaphane (SFN). In summary, we provide evidence that HT may induce ferroptosis in colorectal cancer cells. Mechanistically, HT induces ferroptosis via the Nrf2 signaling pathway.