Dimethyl fumarate (DMF), a therapeutic agent for relapsing-remitting multiple sclerosis, has cytoprotective and antioxidant effects. Ferroptosis, a pathological cell death process, is recently shown to play a vital part in ischemia-reperfusion injury (IRI). This study aimed to unveil the suppressive role of DMF on ferroptosis in liver IRI. The anti-ferroptosis effect of DMF on hepatic IRI was investigated using a liver IRI mouse model and a hypoxia-reoxygenation injury (HRI) model in alpha mouse liver (AML12) cells. Serum transaminase concentrations reflected liver function. Hematoxylin and eosin staining was used to assess liver damage. Cell viability was evaluated utilizing the CCK-8 assay. Malondialdehyde (MDA), the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, and BODIPY 581/591C11 were measured to estimate the injury caused by lipid peroxidation. Western blotting and real-time polymerase chain reaction (RT-PCR) were performed to explore the underlying molecular mechanisms. We demonstrated the anti-ferroptosis effects of DMF both in vivo and in vitro. DMF treatment ameliorated hepatic IRI. KEGG enrichment analysis and transmission electron microscopy revealed a close relationship between ferroptosis and liver IRI. Furthermore, DMF protected against HRI by inhibiting ferroptosis via activating the nuclear factor E2-related factor 2 (NRF2) pathway. Interestingly, NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of DMF. DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic IRI.

Immune cells, including T and B cells, are key factors in the success of liver transplantation. And the repertoire of T cells and B cells plays an essential function in mechanism of the immune response associated with organ transplantation. An exploration of their expression and distribution in donor organs could contribute to a better understanding of the altered immune microenvironment in grafts. In this study, using single-cell 5’ RNA sequence and single-cell T cell receptor (TCR)/B cell receptor (BCR) repertoire sequence, we profiled immune cells and TCR/BCR repertoire in three pairs of donor livers pre- and post-transplantation. By annotating different immune cell types, we investigated the functional properties of monocytes/Kupffer cells, T cells and B cells in grafts. Bioinformatic characterization of differentially expressed genes (DEGs) between the transcriptomes of these cell subclusters were performed to explore the role of immune cells in inflammatory response or rejection. In addition, we also observed shifts in TCR/BCR repertoire after transplantation. In conclusion, we profiled the immune cell transcriptomics and TCR/BCR immune repertoire of liver grafts during transplantation, which may offer novel strategies for monitoring recipient immune function and treatment of rejection after liver transplantation.

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