Altretamine

Ferroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIP_PCPO) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIP_PCPO is found to boost lysosomal Fe²⁺ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIP_PCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 cancer cell lines. Furthermore, a strong synergistic ferroptosis effect is observed between LIP_PCPO and an FDA-approved drug, artesunate, as well as X rays. The formula of LIP_PCPO encapsulating artesunate significantly inhibits tumor growth and metastasis and improves the survival rate of breast cancer-bearing female mice. These findings provide a distinct strategy for inducing ferroptosis and highlight the potential of LIP_PCPO as a vector to synergize the therapeutic effects of conventional ferroptosis inducers.

In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence.

Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults.

We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age.

Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 μg/L] and molybdenum in urine (GM = 46.44 μg/L) showed the highest concentrations, while lead in blood (GM = 21.92 μg/L) and arsenic in urine (GM = 19.80 μg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (β = -0.614, 95% CI: -0.809, -0.418) and positively with AST (β = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption.

This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.