New insight in the immune mechanisms in hyperuricemia after renal transplantation: a narrative review.

OBJECTIVE: Due to underlying allograft rejection and renal ischemia reperfusion injury (IRI) inducing renal injury, hyperuricemia (HUA) is one of the common complications after renal transplantation and may be a major contributor to reduced renal function. Currently, there are no uniform mechanisms of HUA after renal transplantation. This review aimed to figure out the immune mechanisms of HUA after renal transplantation and the molecular mechanisms of HUA-induced renal injury to provide new insights into renal function protection and prolonged survival time of grafts. MATERIALS AND METHODS: The search terms included 'Hyperuricemia', 'Renal transplantation', 'Urea acid', 'Gout' 'Graft Rejection', 'Graft Survival'. Databases including PubMed, Cochrane Library, Embase, Clinicaltrials.gov and China National Knowledge Infrastructure (CNKI) were searched for studies including mechanisms of hyperuricemia after renal transplantation from the beginning of databases to March 2022. RESULTS: Our study reviews the immune mechanisms of HUA after renal transplantation. HUA induces renal injury mainly by renal inflammation, oxidative stress, and endothelial dysfunction. IRI contributes to increased inflammation in renal grafts, mediates the recruitment of various inflammatory cell types. CONCLUSIONS: Due to underlying allograft rejection and IRI, renal transplant recipients are especially prone to HUA. HUA further reduces renal function and even graft loss. Treg targeting could be a novel therapeutic approach in renal transplantation.

Cuprous oxide nanoparticles inhibit the growth and metastasis of melanoma by targeting mitochondria.

Metal and its oxide nanoparticles show ideal pharmacological activity, especially in anti-tumor therapy. Our previous study demonstrated that cuprous oxide nanoparticles (CONPs) selectively induce apoptosis of tumor cells in vitro. To explore the anti-tumor properties of CONPs in vivo, we used the particles to treat mouse subcutaneous melanoma and metastatic lung tumors, based on B16-F10 mouse melanoma cells, by intratumoral and systemic injections, respectively. The results showed that CONPs significantly reduced the growth of melanoma, inhibited the metastasis of B16-F10 cells and increased the survival rate of tumor-bearing mice. Importantly, the results also indicated that CONPs were rapidly cleared from the organs and that these particles exhibited little systemic toxicity. Furthermore, we observed that CONPs targeted the mitochondria, which resulted in the release of cytochrome C from the mitochondria and the activation of caspase-3 and caspase-9 after the CONPs entered the cells. In conclusion, CONPs can induce the apoptosis of cancer cells through a mitochondrion-mediated apoptosis pathway, which raises the possibility that CONPs could be used to cure melanoma and other cancers.

[Detection of Cre recombinase activity in Mx-Cre transgenic mice induced by INF in vitro].

The Cre recombinase and its activity in C57-TgN(Mx-Cre) transgenic mice is studied by polymerase chain reaction (PCR), Western blot, immunohistochemistry, immunogold electron microscopy and Southern blot. C57-TgN(Mx-Cre) transgenic mice harbouring cre gene in genomic DNA is demonstrated by PCR, and these mice which are induced by INF-alpha 1b could express Cre recombinase, which is confirmed by Western blot. With immunohistochemistry, we find that the Cre recombinase expresses in hepatocyte cytoplasm and nuclear of C57-TgN(Mx-Cre) transgenic mice. Cre recombinase expressed in hepatocyte cytoplasm and nuclear is further confirmed by immunogold electon microscopy. And it is supported that the Cre recombinase which is created from C57-TgN(Mx-Cre) transgenic mice induced by INF-alpha 1b can direct DNA recombination reaction in vitro. All evidence leads us supporting the view that the Cre recombinase expressed in C57-TgN(Mx-Cre) transgenic mice has activity. Thus we find a method to detect the activity of Cre recombinase in vitro.

[Generation of Mx-cre transgenic mice].

To generate the transgenic mice expressing cyclization recombination enzyme, the recombinant gene, in which the coding region of cre gene is derived by the promoter of mouse Mx gene, was microinjected into pronuclei of fertilized mouse eggs. Founders of transgenic mice harbouring the recombinant gene were screened by polymerase chain reaction (PCR) at genomic DNA level and confirmed by Southern blot. One line of Mx-cre transgenic mice was obtained. Then, the Mx-cre transgenic mouse line was cultured and propagated.