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Background: Bladder cancer (BCa), among the world’s most common malignant tumors in the urinary system, has a high morbidity and mortality. Though cuproptosis is a new type of cell death mediated by lipoylated tricarboxylic acid (TCA) cycle proteins, the role of cuproptosis-related long noncoding RNAs (crlncRNAs) in bladder tumors awaits further elucidation. In this paper, we tried to explore how important crlncRNAs are for BCa.Methods: The crlncRNAs were first obtained through Pearson correlation analysis of the RNA-seq data and corresponding clinical data downloaded from The Cancer Genome Atlas (TCGA). Then, three lncRNAs were acquired by Cox regression and Lasso regression to build a prognostic model of crlncRNAs for verification. In the meantime, clinicopathological correlation analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, principal component analysis (PCA), immunoassay, and half-maximal inhibitory concentration prediction (IC50) were carried out. Then, an entire tumor was classified into two clusters by crlncRNA expression to further discuss the differences in prognosis, immune status and drug susceptibility among different subgroups.Results: We obtained a total of 152 crlncRNAs and built a risk model for screened crlncRNAs. We validated the model and found that calibration charts feature a high consistency in verifying nomogram prediction. Receiver operating characteristic (ROC) curve and univariate and multivariate Cox regression suggested that this model can be applied as an independent prognostic factor of bladder cancer due to its high accuracy. According to KEGG analysis, high-risk groups were enriched in cancer and immune-related pathways. During tumor immunoassay, noticeable differences were observed in both immune infiltration and checkpoints between high- and low-risk patients. Of the two subgroups divided among patients by consensus clustering, cluster 2 had a better prognosis, whereas cluster 1 had higher immunoreactivity scores, more immune cell infiltrations and immune checkpoint expressions, and different sensitivities to drugs.Conclusion: The research findings demonstrate that crlncRNAs can be used to predict the prognosis and immune microenvironment of patients suffering from BCa, and differentiate between BCa subgroups to improve the individual therapy of BCa.

Hyperbranched polyglycerol (HPG) is a biocompatible polyether polymer that is a potential colloid component in a preservation solution for suppressing interstitial edema during cold storage of a donor organ. This study evaluated the outcomes of kidney transplants after cold perfusion and storage with a HPG‐based preservation solution (HPGS) in a pig model of kidney autotransplantation. The left kidneys of farm pigs (weighing 35–45 kg) were perfused with and stored in either cold HPGS or standard UW solution (UWS), followed by transplantation to the right side after right nephrectomy. The survival and function of transplants were determined by the urine output, and serum creatinine (SCr) and blood urea nitrogen (BUN) of recipients. Transplant injury was examined by histological analysis. Here, we showed that there was no significant difference between HPGS and UWS in the prevention of tissue edema, but HPGS was more effective than UWS for initial blood washout of kidney perfusion and for the prevention of cold ischemia injury during cold storage. After autotransplantation, the kidneys preserved with HPGS (HPG group) had better functional recovery than those with UWS (UW group), indicated by significantly more urine output and lower levels of SCr and BUN. The survived grafts in HPG group had less tissue damage than those in UW group. In conclusion, as compared to the UWS the HPGS has less negative impact on kidney cold ischemia during cold storage, resulting in improving immediate functional recovery after transplantation, suggesting that HPG is a promising colloid for donor kidney preservation.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding with a greater affinity. Co-expression specific antigens and extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for its enhancement on G250/MN/CA IX (G250)-specific immune responses and its anti-tumor effects in renal carcinoma mice model. Consequently, we constructed a DNA vaccine containing the G250 and the CTLA-4 gene. Vaccination with the co-expression DNA not only induced much higher level of anti-CTLA4 and anti-G250 antibody, but also increased G250-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with G250-expressing tumors were generated. After injection into the tumor-bearing mouse model, the plasmid carrying the co-expression gene of CTLA4 and G250 showed stronger inhibition of tumor growth than the plasmid expressing CTLA4 or G250 alone. These observations emphasize the potential of the CTLA4 and G250 co-expression DNA vaccine, which could represent a promising approach for tumor immunotherapy.

Background Efficient and effective perfusion during organ procurement is required for the best prevention of donor organ injury preceding transplantation. However, current organ preservation solutions, including hydroxyethyl starch (HES)–based University of Wisconsin (UW) solution, do not always yield the best outcomes. Our previous study demonstrated that replacing HES with hyperbranched polyglycerol (HPG) reduced donor heart injury during cold storage. The current research was designed to examine the advantages of HPG-based solution for cold kidney perfusion. Methods Perfusion efficiency of HPG versus UW solution was tested using mouse kidneys at 4°C. The blood washout was evaluated by using a semiquantitative scoring system and tissue damage by histologic analysis. The interaction of HPG or UW solution with human red blood cells (RBCs) was examined by measuring RBC sedimentation and aggregation. Results The lower viscosity of HPG solution was correlated with faster and more efficient perfusion through donor kidneys as compared with UW. HPG solution was also more effective than UW in removing RBCs from the kidney and was associated with less tissue damage to donor kidneys. In vitro UW solution caused significant RBC sedimentation and hyperaggregation, whereas HPG showed minimal impact on RBC sedimentation and prevented RBC aggregation. Conclusions This experimental study demonstrated that compared with UW, HPG solution was more efficient and effective in the removal of the blood from donor kidneys and offered better protection from donor tissue damage, suggesting that the HPG solution is a promising candidate to supplant standard UW solution for donor kidney perfusion in transplantation.

To investigate whether ESM-1 expression change reflects the impairment of endothelial cells and rejection after kidney transplantation, ESM-1 expression was detected under various immune states in this study.Kidney transplantations were performed from BN to LEW rats. Syngenic LEW-LEW grafts were used as controls. The LEW recipient rats were divided into acute rejection (AR) group, ciclosporin A (CsA) group and control group. In each group, 10 rats were sacrificed at 1, 5, and 7d after operation, respectively, and blood and kidney samples were collected. In the rat model of kidney transplantation, ESM-1 mRNA and ESM-1 protein expression were detected in various immune states to verify if ESM-1 can reflect endothelial cell impairment sensitively.ESM-1 mRNA (1d vs. 3d, P0.01;3d vs. 7d, P=0.018) and ESM-1 protein expression was upregulated significantly in the AR group (P0.01, 5 and 7d), when compared to CsA group and control group. In CsA group, the cell apoptosis rate decreased when compared to AR group (P0.01). Pathological impairment was more serious in AR group than in CsA group (P0.01).Peripheral blood ESM-1 mRNA and ESM-1 protein expression in kidney grafts can reflect the severity of endothelial cell impairment. Thus, ESM-1 may be used as a new indicator for AR prediction and diagnosis. Nevertheless, further investigation is required to test if it meets the criteria for clinical utility.

Clinicopathologic factors and SPAG5 protein expression in 180 PCa patients. (DOC 68Â kb)

Clinicopathologic factors and SPAG5 protein expression in 180 PCa patients. (DOC 68Â kb)

Prognostic value of SPAG5 protein expression for the biochemical recurrence free survival in univariate and multivariate analyses by Cox regression. (DOC 34Â kb)

Prognostic value of SPAG5 protein expression for the overall survival in univariate and multivariate analyses by Cox regression. (DOC 34Â kb)

Prognostic value of SPAG5 protein expression for the overall survival in univariate and multivariate analyses by Cox regression. (DOC 34Â kb)

Prognostic value of SPAG5 protein expression for the biochemical recurrence free survival in univariate and multivariate analyses by Cox regression. (DOC 34Â kb)

Background Bladder transitional cell carcinoma greatly threatens human health all over the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows a strong apoptosis-inducing effect on a variety of cancer cells including bladder cancer. However, adenovirus-mediated TRAIL expression still showed cytotoxicity to normal cells mainly due to lack of tumor specificity. Methods To solve the problem, we applied miRNA response elements (MREs) of miR-1, miR-133 and miR-218 to confer TRAIL expression with specificity to bladder cancer cells. Results Expression of miR-1, miR-133 and miR-218 was greatly decreased in bladder cancer than normal bladder tissue. Luciferase assay showed that application of the 3 MREs was able to restrain exogenous gene expression to within bladder cancer cells. Subsequently, we constructed a recombinant adenovirus with TRAIL expression regulated by MREs of miR-1, miR-133 and miR-218, namely Ad-TRAIL-MRE-1-133-218. qPCR, immunoblotting and ELISA assays demonstrated that Ad-TRAIL-MRE-1-133-218 expressed in bladder cancer cells, rather than normal bladder cells. The differential TRAIL expression also led to selective apoptosis-inducing and growth-inhibiting effect of Ad-TRAIL-MRE-1-133-218 on bladder cancers. Finally, bladder cancer xenograft in mouse models further confirmed that Ad-TRAIL-MRE-1-133-218 effectively suppressed the growth of bladder cancers. Conclusions Collectively, we demonstrated that MREs-based TRAIL delivery into bladder cancer cells was feasible and efficient for cancer gene therapy.

Background Cytokines have been implicated in the acute rejection of solid organ transplantation. Many studies have investigated the association between recipient or donor IL-4 polymorphism and acute rejection, with different studies reporting inconclusive results. Methods We searched PUBMED and EMBASE until June 2012 to identify eligible studies investigating the association between IL-4 polymorphism with acute rejection after solid organ transplantation. Statistical analysis was performed using STATA10.0. Results A total of 12 studies were included. Pooled ORs suggested 1) no significant association was detected between recipient or donor IL-4 − 590C/T polymorphism and acute rejection of solid allograft; 2) no significant association was detected between recipient IL-4 − 33C/T polymorphism and acute rejection of solid allograft; 3) when stratified by transplantation type, IL-4 − 590C/T polymorphism was associated with acute rejection of liver transplantation (T/T + C/T vs. C/C: OR = 0.36, 95%CI = 0.14–0.90); 4) significantly decreased risk of acute rejection was detected in recipient IL-4 − 590*T-negative/donor T-positive genotype pairs than all other recipient–donor IL-4 − 590T/C pairs (OR = 0.14, 95%CI = 0.03–0.66). Conclusions Our meta-analysis suggested that recipient IL-4 − 590C/T polymorphism was associated with acute rejection of liver transplantation, but nor renal or heart transplantation. It was also suggested that combined recipient IL-4 − 590*T-negative/donor T-positive genotype may suffer decreased risk of acute rejection of solid allograft. Further well-designed studies with larger sample size were required to verify our findings, with focus on the association of IL-4 polymorphism with acute rejection in patients with liver transplantation and studies investigating combined recipient–donor genotype.