Ya Xiao

CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model

CD4(+)CD25(+) regulatory T cells (Tregs) are negative regulators of the immune system that induce and maintain immune tolerance. Exosomes are natural products released from many sources and play a role in antigen presentation, immunoregulation, and signal transduction. In order to determine whether exosomes can be released from Tregs and participate in transplantation tolerance, we isolated and purified Tregs-derived exosomes and established a rat model of kidney transplantation. We then transferred the autologous exosomes into recipients to observe the effect of transplantation tolerance in vivo and in vitro. From in vivo study, serum analysis and histology showed that the function of exosomes can postpone allograft rejection and prolong the survival time of transplanted kidney. From in vitro study, exosomes possessed the capacity to suppress T cells proliferation. Taken together, these results suggest that the Tregs-derived exosomes have a suppressive role on acute rejection and inhibit T cells proliferation, especially exosomes derived from donor-type Tregs, which imply that the Tregs-derived exosomes are one of far-end regulation mechanisms of Tregs. Thus, exosomes released from Tregs could be considered as a possible immunosuppressive reagent for the treatment of transplant rejection.

Screening Biomarkers of Prostate Cancer by Integrating microRNA and mRNA Microarrays

OBJECTIVE In this study, we screened microRNA (miRNA) target genes of prostate cancer by integrating miRNA and mRNA expression profiles after target prediction and performed function enrichment analysis for selected candidate genes. METHODS The miRNA expression profile (GSE36802) and mRNA expression profile (GSE36801) were downloaded from the Gene Expression Omnibus database. We processed data and identified the differentially expressed miRNAs and mRNAs with R packages. Verified targets of miRNAs were identified through miRecods and miRTarBase. Then, software of Search Tool for the Retrieval of Interacting Genes was used to construct the interaction network of target genes. Finally, we performed function enrichment analysis for genes in the interaction network with the Functional Classification Tool. RESULTS A total of 22 upregulated and 8 downregulated miRNAs were detected in this study, of which, hsa-mir-31 was the most overexpressed miRNA in prostate cancer. Both ITGA5 and RDX, two target genes of hsa-mir-31, were found to be differentially expressed from mRNA profiles by overexpressing hsa-mir-31. The cell adhesion molecule was found to be the most significant pathway enriched by ITGA5 and RDX. CONCLUSION Overexpression of hsa-mir-31 can be a significant marker to distinguish cancer tissues from benign tissues. The targets such as ITGA5 and RDX regulated by hsa-mir-31 are candidate genes of prostate cancer, which provide new treatment strategies for its gene therapy.

Modified Urethral Pull-Through Operation for Posterior Urethral Stricture and Long-Term Outcome

PURPOSE We present our experience, technique and long-term results of the modified urethral pull-through operation for posttraumatic posterior urethral stricture. MATERIALS AND METHODS A total of 113 patients with posttraumatic posterior urethral stricture resulting from pelvic fracture injury underwent the modified urethral pull-through operation at our department from August 1999 to March 2007. Patient age was 17 to 69 years (mean 35.2). Stricture length was 1.5 to 4.7 cm (mean 2.6). Of the patients 52 (46.0%) had undergone at least 1 previous failed management for stricture, including urethroplasty in 29 (25.7%). Followup included symptomatic and urinary flow rate evaluation, which was performed 6 and 12 months after the modified urethral pull-through operation in all patients and thereafter when needed, and urethrography and/or urethroscopy in patients with voiding symptoms. Clinical outcomes were considered a success when no postoperative procedure was needed. RESULTS Patients were followed for 12 to 86 months (mean 48.5). During that period 109 patients were symptom-free and required no further procedures. The maximal flow rate in each case was greater than 15 ml per second. Recurrent stricture developed in 4 patients. All treatment failures occurred within the first 8 months postoperatively. Failed repairs were successfully managed endoscopically in 1 patient by urethral dilation in 1 and by repeating the pull-through operation in the remaining 2 for a primary success rate of 96.5% and a final success rate of 100%. All patients were continent. Erectile dysfunction was noted postoperatively in 5 patients (3.7%). There was no chordee, penile shortening or urethral diverticula. CONCLUSIONS The modified urethral pull-through operation is effective for the surgical treatment of posttraumatic posterior urethral stricture. It has a high success rate with durable long-term results. Complications are few. The procedure is simple, less demanding and especially suitable in patients who had previously undergone failed surgical treatments.

Prolonged survival time of allografts by the oral administration of RDP58 linked to the cholera toxin B subunit.

Oral administration, which has been identified as a tool for boosting physiological immunoregulatory mechanisms in an antigen-specific manner, is a more convenient way than classical parenteral injection methods. RDP58 is derived from specific regions of class-I MHC molecules and is known to have immunomodulatory effects after intraperitoneal injection or intravenous administration. To determine whether the oral administration of RDP58 conjugated to the cholera toxin B subunit (CTB) can better induce peripheral tolerance than the use of traditional methods, we used various feeding regimens and methods of administration using equivalent doses of antigen during rat kidney transplantation. The results showed that RDP58-GC/CTB treatment increased the activity of Haem oxygenase-1 (HO-1) in vivo and significantly improved the survival and histopathology of allograft kidney tissue relative to the oral administration of RDP58 alone. These results suggest that the administration of RDP58 linked to CTB outweighs the benefits of oral administration of RDP58 alone for prolonging the survival time of kidney transplantation. This study supports the potential therapeutic use of oral administration of RDP58 linked to CTB as a platform molecule in the treatment of allograft rejection.

Uridine diphosphate-glucuronosyltransferase 2B15 D85Y gene polymorphism is associated with lower prostate cancer risk: a systematic review and meta-analysis

UGT2B15 (uridine diphosphate-glucuronosyltransferase 2B15) catalyzes the conversion of lipophilic C19 steroid androgens such as dihydrotestosterone (DHT) into water-soluble metabolites that can be excreted. Studies of the association between the UGT2B15 gene D85Y polymorphism and prostate cancer have yielded contradictory results. We therefore systematically searched in the PubMed, EMBASE, Science Direct/Elsevier, CNKI, and Cochrane Library databases, and identified six relevant studies with which to perform a meta-analysis of the relation between UGT2B15 D85Y polymorphism and prostate cancer risk. Our meta-analysis revealed a significant association between UGT2B15 D85Y gene polymorphism and prostate cancer in all genetic models (P<0.05). The combined odds ratios and 95% confidence intervals were as follows: additive model, 0.53 and 0.32-0.88; dominant model, 0.51 and 0.33-0.79; recessive model, 0.76 and 0.60-0.96; co-dominant model, 0.55 and 0.35-0.86; and allele model, 0.70 and 0.55-0.89. These results are consistent with the idea that the UGT2B15 D85Y enzyme variant reduces the risk of prostate cancer by efficiently metabolizing dihydrotestosterone (DHT), which is associated with prostate cancer progression.UGT2B15 (uridine diphosphate-glucuronosyltransferase 2B15) catalyzes the conversion of lipophilic C19 steroid androgens such as dihydrotestosterone (DHT) into water-soluble metabolites that can be excreted. Studies of the association between the UGT2B15 gene D85Y polymorphism and prostate cancer have yielded contradictory results. We therefore systematically searched in the PubMed, EMBASE, Science Direct/Elsevier, CNKI, and Cochrane Library databases, and identified six relevant studies with which to perform a meta-analysis of the relation between UGT2B15 D85Y polymorphism and prostate cancer risk. Our meta-analysis revealed a significant association between UGT2B15 D85Y gene polymorphism and prostate cancer in all genetic models (P<0.05). The combined odds ratios and 95% confidence intervals were as follows: additive model, 0.53 and 0.32-0.88; dominant model, 0.51 and 0.33-0.79; recessive model, 0.76 and 0.60-0.96; co-dominant model, 0.55 and 0.35-0.86; and allele model, 0.70 and 0.55-0.89. These results are consistent with the idea that the UGT2B15 D85Y enzyme variant reduces the risk of prostate cancer by efficiently metabolizing dihydrotestosterone (DHT), which is associated with prostate cancer progression.