Immunomodulation of cuproptosis and ferroptosis in liver cancer.

According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment of liver cancer is imminent. For early liver cancer, resection surgery is currently the most effective treatment. However, resection does not treat the disease in advanced patients, so finding a method with a better prognosis is necessary. In recent years, ferroptosis and cuproptosis have been gradually defined, and related studies have proved that they show excellent results in the therapy of liver cancer. Cuproptosis is a new form of cell death, and the use of cuproptosis combined with ferroptosis to inhibit the production of hepatocellular carcinoma cells has good development prospects and is worthy of in-depth discussion by researchers. In this review, we summarize the research progress on cuproptosis combined with ferroptosis in treating liver cancer, analyze the value of cuproptosis and ferroptosis in the immune of liver cancer, and propose potential pathways in oncotherapy with the combination of cuproptosis and ferroptosis, which can provide background knowledge for subsequent related research.

Harmonization of distributed multi-center analysis based on dried blood spot reference materials supporting the screening of neonatal inherited metabolic disorders.

BACKGROUND: The standardization of quantification data is critical for ensuring the reliability and measurement traceability in the screening of neonatal inherited metabolic disorders. However, the availability of national certified reference materials is limited in China. METHODS: In this study, we developed a series of dried blood spot (DBS) reference materials containing 9 amino acids (AA) and 10 acylcarnitines (AC) for neonatal screening. Four levels of the reference materials were measured with tandem mass spectrometry (MS/MS) by seven laboratories using different commercial In Vitro Diagnostic Device (IVD) kits. Then, 100 clinical samples were measured using both derivatization and non-derivatization methods by the same laboratory. RESULTS: We found high homogeneity and stability at all levels of the reference materials, with the coefficient of variation (CV) of the analytes less than 15%. These reference materials can be used to assess the testing capabilities of different laboratories. Our test also revealed that the correction factors (CF) calculated by the reference materials, along with clinical samples, could increase the consistency for different kits. CONCLUSION: The DBS reference materials proposed in this study provide reliability for the harmonization in multi-center analysis for the screening of neonatal inherited metabolic disorders. And applying our correction method for the screening could improve the data consistency of the DBS samples prepared by different methods.

Characteristics of Changes in Inflammatory Cytokines as a Function of Hepatic Ischemia-Reperfusion Injury Stage in Mice.

Liver ischemia-reperfusion injury (IRI) can severely compromise the prognosis of patients receiving liver surgery. While inflammation contributes to the damage resulting from IRI, only a limited number of inflammation biomarkers have been identified as being associated with the different stages of hepatic IRI. As an approach to identify some of these inflammatory cytokines and the molecular mechanisms involved within different stages of hepatic IRI, we used an advanced antibody array assay to detect multiple proteins. With this technology, we observed specific differences in the content of inflammatory cytokines between ischemic and sham controls, as well as a function of the different reperfusion stages in a hepatic IRI mouse model. For example, while liver tissue content of IL-12p40/p70 was significantly increased in the ischemic stage, it was significantly decreased in the reperfusion stage as compared with that of the sham group. For other inflammatory cytokines, no changes were obtained between the ischemic and reperfusion stages with levels of IL-17, Eotaxin-2, Eotaxin, and sTNF RII all being consistently increased, while those of TIMP-1, TIMP-2, BLC, and MCSF consistently decreased as compared with that of the sham group at all reperfusion stages examined. Results from protein function annotation Gene Ontology and the KEGG pathway revealed that inflammatory cytokines are enriched in a network associated with activation of inflammatory response signaling pathways such as TLR, TNF, and IL-17 when comparing responses of the IR versus sham groups. The identification of cytokines along with their roles at specific stages of IRI may reveal important new biological markers for the diagnosis and prognosis of hepatic IRI.