Cross-talk and clinical value of m[superscript 6]A regulatory gene in bladder cancer.

BACKGROUND: RNA modification is a regulation at the post-transcriptional level. RNA methylation modification accounts for more than 60% of all RNA modifications, and m[superscript 6]A(6-methyladenine) is the most common type of RNA methylation modification on mRNA of higher organisms. The modification level of transcription m[superscript 6]A is dynamically regulated by methyltransferase (reader), binding protein (writer) and demethylase (eraser). Furthermore, m[superscript 6]A methylation has been found to have an impact on tumor initiation and progression through various mechanisms. METHODS: 13 genes related m[superscript 6]A from all the gene expressions in The Cancer Genome Atlas (TCGA) were screened. Gene Ontology (GO) and KEGG analysis were applied to explore the functions of genes identified in study. We clustered the related regulators of m[superscript 6]A into three subgroups with "ConsensusClusterPlus". 13 genes were used for univariate Cox analysis to find genes associated with prognosis, and the risk model was constructed based on lasso regression. According to the median risk score of each patient, the patients were divided into high and low risk groups for survival analysis. The ROC curve evaluates the model. Then the risk group and clinical characteristics were analyzed. RESULTS: The three subgroups had different clinical characteristics. Our tumor clusters were related to grade, survival status. Moreover, we observed a significantly longer overall survival (OS) in the cluster 1 than the cluster 2 and cluster 3. Three m[superscript 6]A-related genes related to prognosis were used to construct a prognostic risk model. We found age are independent prognostic marker. What's more, risk score can also be an independent prognostic factor. CONCLUSION: Revealing the regulation and functional mechanism of cross-talk among m[superscript 6]A writers, erasers, and readers, and determine its role in bladder cancer may help in developing novel and efficient strategies for the diagnosis, prognosis and treatment of bladder cancer.

Protective effect of cyclosporine A in the treatment of severe hydronephrosis in a rabbit renal pelvic perfusion model

Background/aim: Cyclosporine A (CsA), a traditional immunosuppressive compound, has been reported to specifically prevent isch-emia reperfusion tissue injury via apoptosis pathway. This study aimed to explore the renoprotective effects of CsA on the kidneys of rabbits undergoing renal pelvic perfusion. Materials and methods: A total of 30 rabbits were randomly assigned into a control group (n = 6) and an experimental group (n = 24). The experimental group underwent a surgical procedure that induced severe hydronephrosis and was then stochastically divided into 4 groups (S1, S1', S2, and S2'), consisting of 6 rabbits each. Groups S1 and S1' were perfused with 20 mmHg of fluid, while groups S2 and S2' were perfused with 60 mmHg of fluid. Administration to groups S1' and S2' was done intravenously, with CsA once a day for 1 week before perfusion. In the control group, after severe hydronephrosis was induced, a sham operation was performed in a second laparoto-my. Acute kidney damage was evaluated using hematoxylin and eosin staining, in addition to analyzing the mitochondrial ultrastructure and mitochondrial membrane potential (MMP). The cytochrome C (CytC) and neutrophil gelatinase-associated lipocalin (NGAL) expression were examined immunohistochemically using Western blotting and reverse transcription-polymerase chain reaction. Results: It was found that the renal histopathological damage was ameliorated, mitochondrial vacuolization was lower, MMP was high-er, and the CytC and NGAL contents were decreased after drug intervention (groups S1' and S2') when compared to the experimental groups (S1 and S2). Furthermore, there was no difference between drug intervention groups S1' and S2'. Conclusion: These results suggest that CsA can attenuate renal damage from severe hydronephrosis induced by renal pelvic perfusion in rabbits. It plays a protective role in the acute kidney injury process, possibly through increased MMP and mitochondrial changes.

[Experimental varicocele affects the ipsilateral testis in rats].

OBJECTIVE: To investigate the impact of experimental varicocele (EV) on the ipsilateral testis in rats. METHODS: EV was induced by partial ligation of the left renal vein in male SD rats, the control rats subjected to sham operation, and the testes of the EV models and controls were extirpated 6, 12, and 18 weeks later. Johnson's score, ultrastructure of seminiferous tubules, intratesticular testosterone concentration (ITC) and germ cell apoptotic index (AI) of each left testis were evaluated. RESULTS: Johnson's scores were (6.92 +/- 0.52), (4.83 +/- 0.41) and (2.95 +/- 0.26), ITCswere (6.32 +/- 0.85), (5.17 +/- 0.76) and (4.11 +/- 0.69) and AIs were (5.32 +/- 1.23), (15.21 +/- 0.97) and (21.13 +/- 1.12) respectively in the 6 w , 12 w and 18 w EV groups, significantly lower than in the corresponding control groups, (9.56 +/- 0.35, 9.63 +/- 0.31, 9.39 +/- 0.46), (9.64 +/- 1.23, 9.38 +/- 0.69, 9.73 +/- 0.49) and (3.21 +/- 1.15, 3.43 +/- 1.21, 3.61 +/- 1. 15) (P < 0.05), the former two showing a gradual decline while the latter a significant elevation with the increasing duration of varicocele. The damage to the ultrastructure of seminiferous tubules was aggravated with the prolonging of varicocele. CONCLUSION: EV can cause a progressive decline of ITC, dyszoospermia and increased AI of germ cells.