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Objective To employ high-throughput next generation sequencing (NGS) for analyzing the expression of lneRNAs and mRNAs in donor samples from pediatric living donor liver transplantation and search differentially expressed lncRNAs and drag metabolic gene for individualized guidance of immunosuppressive agents.Methods Between October 2016 and December 2017,10 liver tissue specimens from living donor liver transplantation children were collected and divided into fast and slow metabolic groups (n =5 each) according to the postoperative profiles of drug metabolism.Samples were assayed for high-throughput NGS.Target analysis was used for functional pathways and screening target genes prediction.Results There were differentially expressed 908 mRNAs and 1228 lncRNAs between slow metabolic and fast metabolic groups (P＜0.05).According to the abundance and difference,22 up-regulated and 18 down-regulated mRNAs,13 up-regulated and 24 down-regulated lncRNAs were selected.In addition to CYP3A5,CYP2C19,CYP1A2 and UGT1A1 might affect the metabolism of tacrolimus.At the same time,NONHSAT108617.2 in differemially expressed lncRNAs might regulate the expression of CYP3A5 gene.Conclusions This study has comprehensively analyzed the expression of lncRNAs in donor liver from pediatric liver transplantation.Some differentially expressed drug metabolism related genes may affect tacrolimus metabolism in vivo and thus the postoperative use of immunosuppressive drugs.
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Objective To investigate the expression levels of DNA methyltransferases 1, 3A and 3B in CD4+ T cells of MRL/lpr mice, and explore their relationship with the expression levels of methylation-sensitive genes (ITGAL, CD70). Methods CD4+ T ceils were isolated from spleens of 16-week-old MRL/lpr and BALB/c control mice by anti-CIM antibody labeled magnetic beads. Transcription levels of DNA methyhransferases 1, 3A and 3B and methylation-sensitive genes(ITGAL, CD70) were measured by real-time mice when compared with BALB/c control mice and the difference was significant (P<0.05), while the expression of DNMTI and DNMT3A showed a tendency of decrease (P>0.05). The mRNA expression of CD70 was significantly higher (P<0.01), but the expression of ITGAL had no significant difference between the two P<0.01 ). Conclusion Decreased expression of DNMT3B may attribute to the elevated expression of methylation-seusitive gene CD70, thus lead to the dysfunction of CD4+ T cell and play an important role in the pathogenesis of SLE.
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Systemic lupus erythematosus (SLE) is an archetypical systemic, autoimmune inflammatory disease , of which the mechanism still not unveiled. Studies on epigenetics in SLE have long been the subject of investigation and as part of epigenetics. DNA methylation has been confirmed to play a role in the pathogenesis of SLE. The high autore-activity of CD4~+ T cell from SLE patients is associated with DNA hypomethylation. DNA hypomethylation is crucial to induce SLE - like autoimmune disease in SLE - non - susceptible mice. The reactivation of inactive X chromosome by hypomethylation may lead to high incidence of SLE in women. Drug - induced SLE is also connected with DNA hypomethylation. To understand the role of DNA methylation in the onset of SLE comprehensively, we review the findings reported in the literatures about DNA methylation and SLE.
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AIM: To study the function of N-copine on cell level by investigating the effect of N-copine antisense on the cultured cortical neuron of mouse embryos. METHODS: Neuronal cultures were prepared from cerebral cortices of 16-day old mouse (BALB/C) embryos. N-copine expression was blocked by using antisense oligonucleotides. The effect of inhibition of N-copine expression on the cultured neuronal viability and development was observed. RESULTS: With oligonucleotides treatment for 72 h, the length of neuronal axon and the area of neurosoma in antisense group were decreased markedly as compared with those in control group. The number of trypan-blue-stained neurons and the LDH activity of the culture media were increased significantly as compared with those in control groups. CONCLUSIONS: Inhibition of N-copine expression affects the development of cortical neuron cultured in vitro, and induces the neuron demaged severely. The results suggest that N-copine is a functional protein in neurons, and it may play an important role in the regeneration of nervous system and preventing neuronal degeneration.