The Alteration human of gut microbiota and metabolites before and after renal transplantation.

BACKGROUND: Recent studies have revealed that gut microbiota play an important part in the regulation of the immune function. With the development of newer detection methods, our cognition of the human gut microbiota continues to evolve with startling speed, but our understanding of the changes in the structure and function of gut microbiota before and after renal transplantation and the practical applications of this knowledge are still in their infancy. METHODS: We prospectively recruited 10 renal transplant recipients and collected serial fecal specimens (N = 30) before the operation, and on the 7th and 30th day after the operation, and characterized their gut microbiota structure through deep sequencing of the 16S rRNA V4-V5 variable region and analyzed the presence of metabolites using LC-MS methods. RESULTS: A decrease in the relative abundance of overall gut microbiota was detected in post-transplantation samples compared to that in pre-transplantation samples. Principal coordinate analysis (PCoA) inhibited a obvious separation between the three groups, and the linear discriminant analysis effect size (LEfSe) method showed that Clostridiales, Clostridia, Ruminococcaceae, Faecalibacterium, and Veillonellaceae were all significantly more abundant in the fecal specimens from the pre-transplantation group while Bacilli, Enterococcaceae, and Enterococcus were significantly more abundant in the fecal specimens from the four weeks post-transplantation group. Anaerostipes and Clostridia-bacterium were detected in the fecal samples from the one week post-transplantation group. Analysis of community composition did not reveal any significant difference between the pre-transplantation group and the post-transplantation group. The metabolic profiling of the volunteers before renal transplantation were distinct from the post-transplantation profiling, which gather together in PCA (Fig. 4A). After renal transplantation, the metabolic profiling of post-transplantation specimens revealed marked diversity and complexity. CONCLUSIONS: Our research indicated remarkable variations in the gut microbiota and metabolites following renal transplantation, and that the gut microbiota and metabolites of patients with uremia were relatively stable and showed reasonable concordance. Distinct microbial compositions and metabolites were observed in patients after transplantation.

High SENP3 Expression Promotes Cell Migration, Invasion, and Proliferation by Modulating DNA Methylation of E-Cadherin in Osteosarcoma.

SENP3, a sentrin/SUMO2/3-specific protease, is recognized as a transcriptional factor that accumulates under cellular oxidative stress and plays a significant role in the removal of SUMO2/3 modification. In our study, we examined a TCGA dataset and found that the transcripts per million (TPM) value of SENP3 is high in sarcoma, including osteosarcoma (OS). We found that SENP3 was highly expressed in OS cancer tissues when compared with osteofibrous dysplasia tissues. The survival data of SENP3 in TCGA showed that the sarcoma patients with higher SENP3 expression levels showed poor prognosis. In vitro, SENP3 knockdown in OS cancer cells inhibited cell proliferation, migration, and invasion and induced apoptosis. In contrast, SENP3 overexpression reversed these effects. Next, we found that SENP3 inhibited the expression of E-cadherin (E-Cad) by increasing methylation of the E-Cad promoter. Finally, E-Cad expression was increased in the OS cell line MG63 following methylation, and the cell proliferation, migration, and invasion capacity were decreased. In summary, SENP3 played a significant role in OS carcinogenesis and may act as a potential biomarker in the diagnosis and treatment of OS.