NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)

Cytotoxicity was synergistic; however, apoptotic and stress indicators may be antagonistic. In clinical circumstances, caffeine may be an adjuvant in breast cancer treatment, however mechanistic and in vivo investigations are needed.

In 3D spheroids, both agents disrupted tumor architecture and reduced viability, alone or in combination with carboplatin. Our findings highlight that platinum resistance in HGSOC can be tackled by repurposing MEF and MPA that act also as AKR1C inhibitors.

However, chrysin significantly reversed the effects of MTX on these parameters. In conclusion, chrysin exhibits neuroprotective effects against MTX-induced neurogenesis impairment by upregulating antioxidant enzyme activity, reducing oxidative stress, and improving protein expression related to neurogenesis.

PCE downregulated the expression of caspase-3 and nuclear factor kappa B (NF-κB) and B-cell lymphoma 2 (Bcl-2) associated X-protein (Bax) and toll like receptor 4 (TLR-4) but it increased the expression of Bcl-2 and nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). The research showed that PCE treatment resulted in decreased blood sugar levels and better liver enzyme and lipid profile results and decreased lipid peroxidation and enhanced antioxidant enzyme activities and reduced oxidative stress in DM rats according to biochemical and histopathological results.

β-Estradiol mitigates oxidative stress, induces apoptosis, and suppresses pro-survival, metastatic, and chemoresistant pathways-contrasting testosterone's minimal effects. These findings align with HCC's male predominance and highlight the hormone-modulated strategies' potential for future therapeutic exploration.

LINC00092 exerts tumor-suppressive effects in ESCC cells by inhibiting cancer progression through the LINC00092/MAZ/NFE2L2 axis and promoting ferroptosis. Therefore, LINC00092 may serve as a potential therapeutic target for ESCC.

CRC patients showed a systemic and peritumoral oxidative imbalance, along with elevated superoxide production in the PAT. The oxidative modifications worsened with the progression of CRC stage and were associated with the downregulation of the Nrf2/HO-1 antioxidant cascade in peritumoral adipose tissue.

The combined lemon-guava leaf extract alleviates fructose-induced cardiac stress, demonstrating potential as a plant-based therapeutic agent for metabolic and cardiovascular protection.

Additionally, molecular docking is used to predict direct binding between CaA and the PI3K p110α subunit (PIK3CA). Together, these procedures provide a reproducible framework to examine ferroptosis mechanisms and the therapeutic efficacy of natural compounds in glioma research.

SIGNIFICANCE STATEMENT: Amt-1 exhibits a dual mechanism of action, including direct antiviral effects through residual M2 affinity and host-directed anti-inflammatory activity mediated by the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and nuclear factor kappa-B pathways. This balanced immunomodulatory and antiviral profile presents a distinct approach in adamantane-based drug development.

The combination of brusatol with RAS-selective lethal 3 (RSL3) significantly enhanced ferroptosis in NPC cells, accompanied by increased levels of cellular reactive oxygen species (ROS) and lipid peroxidation. These effects were further confirmed in NPC xenograft mouse models, as demonstrated by reduced tumor volumes, decreased Ki-67 and Nrf2 staining, and increased expression of cyclooxygenase-2 (COX2). In conclusion, brusatol promotes ferroptotic cell death in NPC cells by inducing Nrf2 degradation and enhancing lipid peroxidation, suggesting its promising therapeutic potential for the treatment of NPC.

Furthermore, HMGB1 overexpression promoted the polarization of microglia to both the M1 and M2 types (P < 0.01) and upregulated the mRNA levels of pro-inflammatory (IL-1β and TNF-α) and anti-inflammatory (IL-10 and Arg-1) cytokines (P < 0.01), whereas 5-HT7R knockout attenuated microglial M1-type polarization and reduced the mRNA levels of the aforementioned pro-inflammatory cytokine (P < 0.01) while promoting microglial M2-type polarization and increasing the mRNA levels of the aforementioned anti-inflammatory cytokines (P < 0.01). HMGB1 activates 5-HT7R and downregulates the cAMP/PKA/AKT/Nrf2/GPX4 signaling pathways, thereby mediating M2 microglial ferroptosis and neuroinflammation, ultimately promoting depressive-like behaviors in mice.