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1.
Urology ; 130: 191-195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029670

RESUMO

OBJECTIVE: To introduce our hybrid technique using an endo-Satinsky clamp and in situ cold perfusion for right-sided retroperitoneoscopic donor nephrectomy (RDN) and to investigate efficacy and safety compared with those standard right-sided RDN. METHODS: This retrospective study included 16 transplant donors who underwent right-sided RDN from January 2016 to January 2018. Donors received either hybrid RDN (n = 6) or standard RDN (n = 10). Perioperative outcomes, including operative time, estimated blood loss, warm ischemic time, hospital stay, length of renal vein obtained as well as postoperative renal function of their recipients were collected and compared between the hybrid RDN and standard RDN groups. RESULTS: Procedures were performed successfully in all 16 donors. The hybrid RDN group required longer operation times (135 vs 115 minutes), demonstrated increased blood loss (175 vs 140 mL), but shorter warm ischemic times (1.5 vs 5.5 minutes) and resulted in longer length of the procured renal vein (2.8 vs 1.7 cm) as compared with the standard RDN group. No difference in perioperative complication rates was witnessed between the 2 groups. Also, there were no significant differences in serum creatinine levels and glomerular filtration rates of recipients between the 2 groups at both postoperative day 3 and 1 month. CONCLUSION: The hybrid RDN potentially extends the length of the right donor renal vein. The perioperative outcomes of hybrid RDN were comparable with those of the standard RDN. This hybrid technique can be a technically safe and feasible option for right kidney donation.


Assuntos
Laparoscopia/métodos , Nefrectomia/métodos , Coleta de Tecidos e Órgãos/instrumentação , Coleta de Tecidos e Órgãos/métodos , Adulto , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão/métodos , Veias Renais/cirurgia , Espaço Retroperitoneal , Estudos Retrospectivos , Instrumentos Cirúrgicos
2.
World J Urol ; 37(7): 1441-1447, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30361956

RESUMO

PURPOSE: To compare the perioperative and long-term outcomes of retroperitoneal laparoscopic pyelolithotomy (RLP) and percutaneous nephrolithotomy (PCNL) for the treatment of staghorn calculi. METHODS: From May 2011 to March 2017, eligible patients with staghorn calculi were randomly assigned to two groups: RLP and PCNL. Patients underwent the operations prospectively. Subsequently, a follow-up protocol was performed. Perioperative data related to the efficacy, safety and long-term outcomes (stone recurrence and functional changes in the affected kidney) were comparatively analyzed between the two groups. RESULTS: Overall, 105 patients underwent surgical treatment, including 51 in the RLP group and 54 in the PCNL group. There was no difference in demographics or stone characteristics between the two groups. The single-session stone-free rate (SFR) was higher (88.2% vs. 64.8%), the mean hemoglobin drop was lower (0.4 ± 0.3 vs. 1.7 ± 0.9 g/dL), the rate of postoperative fever was lower (5.9% vs. 20.4%), but operative time was longer (135.7 ± 35.5 vs. 101.9 ± 41.2 min) and the total cost was more expensive (5546 ± 772 vs. 3861 ± 402 USD)in the RLP group than in the PCNL group (all p < 0.05). The mean increase in the split function (8.3 ± 3.1 vs. 4.2 ± 2.4 mL/min) and the rate of improvement of the affected kidney (56.3% vs. 35.3%) were significantly higher in the RLP group than in the PCNL group at 1 year after surgery (both p < 0.05). However, the rate of stone recurrence was similar between the groups at a mean follow-up of 47.3 ± 18.6 months. CONCLUSIONS: PCNL remains the first-line treatment for most cases of staghorn calculi. Nevertheless, in some selected cases with the extrarenal and dilated pelvis, RLP can be considered as an alternative management of staghorn calculi, which was associated with a high single-session SFR, low rates of complications, and better functional preservation of the affected kidney.


Assuntos
Pelve Renal/cirurgia , Laparoscopia/métodos , Nefrolitotomia Percutânea/métodos , Cálculos Coraliformes/cirurgia , Adulto , Idoso , Feminino , Humanos , Cálculos Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrotomia/métodos , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Espaço Retroperitoneal/cirurgia , Resultado do Tratamento
3.
J Cell Biochem ; 120(6): 9147-9158, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30582204

RESUMO

Interstitial cystitis (IC) is a heterogeneous syndrome with unknown etiology, and microRNAs (miRs) were found to be involved in IC. In our study, we aim to explore the role of miR-132 in the inflammatory response and detrusor fibrosis in IC through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway in rat models. A rat model of IC was established and treated with the miR-132 mimic, miR-132 inhibitor, and/or JAK-STAT signaling pathway inhibitor AG490. Enzyme-linked immunosorbent assay was applied to measure the expression of interleukin (IL)-6, IL-10, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1). The urodynamic test was performed to assess urodynamic parameters, and reverse transcription quantitative polymerase chain reaction and Western blot analysis for the expression of miR-132, STAT4, suppressors of cytokine signaling 3 (SOCS3), JAK2, vascular endothelial growth factor (VEGF), IFN-γ, and TNF-α. IC rats treated with miR-132 inhibitor and AG490 had decreased collagen fiber, inflammatory cell infiltration, and mast cells, lower expression of IL-6, IL-10, IFN-γ, TNF-α, ICAM-1, collagens I and III, and alleviated urodynamic parameters and decreased expression of STAT4, VEGF, JAK2, IFN-γ, TNF-α, and increased expression of SOCS3. Taken together, our data indicate that downregulation of miR-132 alleviates inflammatory response and detrusor fibrosis in IC via the inhibition of the JAK-STAT signaling pathway.

4.
Am J Transl Res ; 10(3): 806-815, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29636870

RESUMO

To investigate whether the reverse mode of sodium/calcium exchanger subtype 1 (NCX1) plays an important role in the excitability of detrusor cells in rats with partial bladder outflow obstruction (PBOO), PBOO was maintained for 6 weeks in forty female Wistar rats. Thirty of the animals exhibited non-voiding bladder contraction and comprised the DO group. An additional thirty sham-operated female Wistar rats were used as the control group. The expression levels of NCX1 were compared between the two groups by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting (WB), and double-label immunofluorescence. The contractions of detrusor strips in NCX reverse mode were measured in both groups using isometric tension. The role of NCX in the regulation of the intracellular Ca2+ concentration ([Ca2+]i) of smooth muscle cells was observed in reverse mode using confocal microscopy, and the current was evaluated in the presence of the antagonist KB-R7943 (5 µM and 10 µM) using the whole-cell patch-clamp technique. The expression of NCX1 was significantly higher in the DO group than in the control group, as assessed by qRT-PCR, WB analysis and immunofluorescence. The volume and rate of Ca2+ ion flux through the NCX, as well as the NCX currents, were higher in the DO group than in the control group in both modes. Increased NCX1 levels may contribute to the establishment of DO after PBOO by elevating [Ca2+]i in reverse mode under depolarization, potentially inducing cell excitability.

5.
Oncotarget ; 8(32): 52837-52845, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28881775

RESUMO

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.

6.
J Invest Dermatol ; 137(12): 2513-2522, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28733202

RESUMO

Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδ T cells and their subsets-Vγ5 (epidermis), Vγ1, and Vγ4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T-cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1ß and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αß T-cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A.


Assuntos
Rejeição de Enxerto/imunologia , Interleucina-17/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Transplante de Pele , Animais , Quimiocina CCL20/metabolismo , Quimiocinas/metabolismo , Feminino , Interleucina-23/metabolismo , Ligantes , Linfonodos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores CCR6/metabolismo , Pele/imunologia , Pele/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
7.
Sci Rep ; 7(1): 6028, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28729536

RESUMO

Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regulate DETC homeostasis in diabetes. Here, we show that the reduction of DETCs in the epidermis of diabetic mice is caused by altered homeostasis mediated by a reduction in IL-15 levels. Both impaired mTOR activation and reduction of IL-15 in the epidermis play important roles in DETC homeostasis. Moreover, IGF-1 drives keratinocytes to produce IL-15. The activation of IL-15 is dependent on mTOR, and conversely, mTOR regulates IGF-1 production in DETC, in a classic feedback regulatory loop. Our data suggest that in the setting of diabetes, reduced IGF-1, impaired mTOR pathway activation and reduced IL-15 in the epidermis function coordinately to promote altered DETC homeostasis and delayed skin wound closure.


Assuntos
Células Epidérmicas/metabolismo , Homeostase , Interleucina-15/biossíntese , Subpopulações de Linfócitos T/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Biomarcadores , Diabetes Mellitus Experimental , Células Epidérmicas/imunologia , Imunofenotipagem , Fator de Crescimento Insulin-Like I/metabolismo , Queratinócitos/metabolismo , Camundongos , Modelos Biológicos , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Cicatrização
8.
Am J Transl Res ; 9(3): 1193-1202, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28386345

RESUMO

OBJECTIVE: This study aimed to explore the role of the transforming growth factor-ß/mitogen activated protein kinase (TGF-ß/MAPK) signaling pathway in the effects of bone marrow mesenchymal stem cells (BMSCs) on urinary control and interstitial cystitis in a rat model of urinary bladder transplantation. METHODS: A urinary bladder transplantation model was established using Sprague-Dawley rats. Rats were assigned to normal (blank control), negative control (phosphate-buffered saline injection), BMSCs (BMSC injection), sp600125 (MAPK inhibitor injection), or protamine sulfate (protamine sulfate injection) groups. Immunohistochemistry, urodynamic testing, hematoxylin-eosin staining, Western blotting, enzyme-linked immunosorbent assay, and MTT assay were used to assess BMSC growth, the kinetics of bladder urinary excretion, pathological changes in bladder tissue, bladder tissue ultrastructure, the expression of TGF-ß/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and the effects of antiproliferative factor on cell proliferation. RESULTS: Compared with normal, negative control, BMSCs, and sp600125 groups, rats in the PS group exhibited decreased discharge volume, maximal micturition volume, contraction interval, and bladder capacity but increased residual urine volume, bladder pressure, bladder peak pressure, expression of TGF-ß/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and growth inhibition rate. Levels of inflammatory cytokines and the growth inhibition rate were positively correlated with the expression of TGF-ß/MAPK signaling pathway-related proteins. CONCLUSIONS: Our findings demonstrate that the TGF-ß/MAPK signaling pathway mediates the beneficial effects of BMSCs on urinary control and interstitial cystitis.

9.
Patient Prefer Adherence ; 10: 2519-2529, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28008237

RESUMO

Effective doctor-patient communication is essential for establishing a successful doctor-patient relationship and implementing high-quality health care. In this study, a novel urinary system-simulating physical model was designed and fabricated, and its content validity for improving doctor-patient communication was examined by conducting a randomized controlled trial in which this system was compared with photographs. A total of 240 inpatients were randomly selected and assigned to six doctors for treatment. After primary diagnosis and treatment had been determined, these patients were randomly divided into the experimental group and the control group. Patients in the experimental group participated in model-based doctor-patient communication, whereas control group patients received picture-based communication. Within 30 min after this communication, a Demographic Information Survey Scale and a Medical Interview Satisfaction Scale (MISS) were distributed to investigate patients' demographic characteristics and their assessments of total satisfaction, distress relief, communication comfort, rapport, and compliance intent. The study results demonstrated that the individual groups were comparable with respect to demographic variables but that relative to patients in the picture-based communication group, patients in the model-based communication group had significantly higher total satisfaction scores and higher ratings for distress relief, communication comfort, rapport, and compliance intent. These results indicate that the physical model is more effective than the pictures at improving doctor-patient communication and patient outcomes. The application of the physical model in doctor-patient communication is helpful and valuable and therefore merits widespread clinical popularization.

10.
BMC Med Educ ; 15: 93, 2015 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-26032174

RESUMO

BACKGROUND: Simulators have been widely used to train operational skills in urology, how to improve its effectiveness deserves further investigation. In this paper, we evaluated training using a novel transparent anatomic simulator, an opaque model or no simulator training, with regard to post-training ureteroscopy and cystoscopy proficiency. METHODS: Anatomically correct transparent and non-transparent endourological simulators were fabricated. Ten experienced urologists provided a preliminary evaluation of the models as teaching tools. 36 first-year medical students underwent identical theoretical training and a 50-point examination of theoretical knowledge. The students were randomly assigned to receive training with the transparent simulator (Group 1), the non-transparent simulator (Group 2) or detailed verbal instruction only (Group 3). 12 days after the training session, the trainees' skills at ureteral stent insertion and removal were evaluated using the Uro-Scopic Trainer and rated on an Objective Structured Assessment of Technical Skills (OSATS) scale. RESULTS: The new simulators were successfully fabricated in accordance with the design parameters. Of the ten urologists invited to evaluate the devices, 100% rated the devices as anatomically accurate, 90% thought both models were easy to use and 80% thought they were good ureteroscopy and cystoscopy training tools. The scores on the theoretical knowledge test were comparable among the training groups, and all students were able to perform ureteral stent insertion and removal. The mean OSATS scores of groups 1, 2 and 3 were 21.83 ± 3.64, 18.50 ± 4.03 and 15.58 ± 2.23 points, respectively, (p = 0.001). CONCLUSIONS: Simulator training allowed students to achieve higher ureteroscopic and cystoscopic proficiency, and transparent simulators were more effective than non-transparent simulators.


Assuntos
Competência Clínica , Simulação por Computador , Cistoscopia/educação , Educação de Graduação em Medicina , Ureteroscopia/educação , Adulto , Educação Médica Continuada , Avaliação Educacional , Desenho de Equipamento , Feminino , Humanos , Internato e Residência , Masculino , Pessoa de Meia-Idade , Urologia/educação
11.
Urol Int ; 95(1): 38-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25720440

RESUMO

OBJECTIVE: This randomized controlled study compared a novel transparent urinary tract simulator with the traditional opaque urinary tract simulator as an aid for efficiently teaching urological surgical procedures. METHODS: Senior medical students were tested on their understanding of urological theory before and after lectures concerning urinary system disease. The students received operative training using the transparent urinary tract simulator (experimental group, n = 80) or the J3311 opaque plastic urinary tract simulator (control, n = 80), specifically in catheterization and retrograde double-J stent implantation. The operative training was followed by a skills test and student satisfaction survey. RESULTS: The test scores for theory were similar between the two groups, before and after training. Students in the experimental group performed significantly better than those in the control group on the procedural skills test, and also had significantly better self-directed learning skills, analytical skills, and greater motivation to learn. CONCLUSION: During the initial step of training, the novel transparent urinary tract simulator significantly improved the efficiency of teaching urological procedural skills compared with the traditional opaque device.


Assuntos
Educação de Graduação em Medicina/métodos , Procedimentos Cirúrgicos Urológicos , Urologia/educação , Adulto , Cateterismo , Competência Clínica , Simulação por Computador , Feminino , Humanos , Masculino , Stents , Estudantes de Medicina , Inquéritos e Questionários , Sistema Urinário/cirurgia , Adulto Jovem
12.
Urology ; 84(4): 960-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25151437

RESUMO

OBJECTIVE: To develop a simple minimally invasive method for ureteral stent removal that does not require cystoscopy or fluoroscopic guidance. MATERIALS AND METHODS: We developed a novel ureteral stent comprising the main body of a stent and an iron oxide-coated net that was woven of processed polyester sutures. The ureteral stent was retrieved by a magnetic retrieval catheter with small hooks on the neck surface. Detailed analysis of the necessary mechanical and magnetic properties was performed, and we conducted retrieval tests of the ureteral stent from a specially designed urinary system model. RESULTS: The breaking strength and Young modulus of the processed polyester sutures were 10.12 ± 0.30 N and 9143 ± 7 N/tex, respectively. Thermogravimetric tests showed that the iron (III) oxide powders on the processed sutures accounted for 23% of the total weight. The magnetization value of the magnetic retrieval catheter was 578 emu/g. The dissolution times of polyvinyl alcohol wrapped the net in saline or urine were 24.2 ± 2.0 and 23.6 ± 3.1 hours, respectively. All stents in both the experimental and the control groups were successfully removed from the specially designed urinary model. However, the retrieval time in the experimental group was significantly shorter than that in the control group (38.6 ± 12.6 vs 59 ± 15.7 seconds; P <.05). CONCLUSION: Ureteral stent removal using a magnetic retrieval catheter with small capture devices is considered feasible. This technique is easy to learn and should be considered as suitable for use on an outpatient basis.


Assuntos
Remoção de Dispositivo/instrumentação , Remoção de Dispositivo/métodos , Stents , Ureter/cirurgia , Cateteres , Desenho de Equipamento , Humanos , Imãs , Desenho de Prótese
13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 31(2): 293-7, 313, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25039130

RESUMO

This article describes a novel Multifunctional and Transparent Urinary System Model (MTUSM), which can be applied to anatomy teaching, operational training of clinical skills as well as simulated experiments in vitro. This model covers kidneys, ureters, bladder, prostate, male and female urethra, bracket and pedestal, etc. Based on human anatomy structure and parameters, MTUSM consists of two transparent layers i. e. transparent organic glass external layer, which constraints the internal layer and maintains shape of the model, and transparent silica gel internal layer, which possesses perfect elasticity and deformability. It is obvious that this model is preferable in simulating the structure of human urinary system by applying hierarchical fabrication. Meanwhile, the transparent design, which makes the inner structure, internal operations and experiments visual, facilitates teaching instruction and understanding. With the advantages of simple making, high-findelity, unique structure and multiple functions, this model will have a broad application prospect and great practical value.


Assuntos
Modelos Anatômicos , Modelos Biológicos , Sistema Urogenital/anatomia & histologia , Feminino , Humanos , Rim , Masculino , Próstata , Ureter , Uretra , Bexiga Urinária
14.
PLoS One ; 9(5): e96671, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24801713

RESUMO

Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.


Assuntos
Receptor beta de Fator de Crescimento Derivado de Plaquetas/urina , Neoplasias da Bexiga Urinária/diagnóstico , Fatores Etários , Idoso , Área Sob a Curva , Biomarcadores/urina , Biologia Computacional , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Mapas de Interação de Proteínas , Curva ROC , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
15.
Cell Immunol ; 285(1-2): 62-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24095986

RESUMO

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.


Assuntos
Exossomos/imunologia , Sobrevivência de Enxerto/imunologia , Transplante de Rim , Linfócitos T Reguladores/imunologia , Tolerância ao Transplante/imunologia , Animais , Antígenos CD4/metabolismo , Proliferação de Células , Rejeição de Enxerto/prevenção & controle , Imunossupressores/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Rim/imunologia , Masculino , Ratos , Ratos Endogâmicos Lew , Transplante Homólogo
16.
Genet Test Mol Biomarkers ; 17(11): 807-13, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23984644

RESUMO

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.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , RNA Mensageiro/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Programas de Rastreamento/métodos , MicroRNAs/isolamento & purificação , Análise em Microsséries , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Integração de Sistemas
17.
J Exp Clin Cancer Res ; 32(1): 21, 2013 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-23594563

RESUMO

BACKGROUND: Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC). METHODS: MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays. RESULTS: MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells. CONCLUSIONS: MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/biossíntese , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Processos de Crescimento Celular/genética , Progressão da Doença , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real
18.
Transpl Immunol ; 27(2-3): 122-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22709942

RESUMO

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.


Assuntos
Toxina da Cólera/administração & dosagem , Rejeição de Enxerto/tratamento farmacológico , Transplante de Rim , Peptídeos/administração & dosagem , Administração Oral , Animais , Células Cultivadas , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Masculino , Tolerância Periférica , Ratos , Ratos Endogâmicos BN
19.
Proteomics ; 12(7): 1059-72, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22522811

RESUMO

Just as biomarkers specific for diseases, biomarkers indicative of healthy conditions are valuable for the early diagnosis, monitoring, and prognosis of diseases. Our study focused on discovering via proteomics a stable panel of urinary proteins in the human healthy population. Urine samples were collected three times during 4 months from 100 male and 100 female healthy donors and analyzed through four different fractionation techniques (i.e. in-gel, 2D-LC, OFFGEL, and mRP) coupled with HPLC-Chip-MS/MS. Thus, 1641 urinary proteins were identified with a high confidence, among which 70 exhibiting an intergender/day variation <0.25 were selected and matched with the previously published five largest urinary proteomes to get 56 candidate proteins. Next, a panel comprising 18 intact urinary proteins was constructed by comparing the urinary proteomes via SDS-PAGE and 2DE. Finally, such 18 urinary proteins were validated via enzyme-linked immunosorbent assay in eight healthy individuals. Most of these proteins had been related to multiple rather than to single diseases. Therefore, we surmise that this protein set could be used as a biomarker to assess the human health status. Further determinations of the normal fluctuations of the single urinary proteins in this series using samples from large numbers of healthy individuals are required prior to any application in clinical settings.


Assuntos
Proteinúria/urina , Proteoma/análise , Adolescente , Análise de Variância , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Espectrometria de Massas , Proteômica/métodos , Reprodutibilidade dos Testes , Adulto Jovem
20.
Zhonghua Wai Ke Za Zhi ; 50(2): 135-8, 2012 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-22490352

RESUMO

OBJECTIVE: To determine the effects of modified pull-through operation (Badenoch operation) on the treatment of posterior urethral stricture. METHODS: From September 2001 to December 2010 traditional pull-through operation was Modified for two times in our center. A total of 129 patients with posttraumatic posterior urethral stricture resulting from pelvic fracture injury underwent the modified urethral pull-through operation. Stricture length was 1.5 to 5.3 cm (mean 2.9 cm). Of the patients 43 had undergone at least 1 previous failed management for stricture. In phase 1 (from September 2001 to January 2008), the improving items include: (1) The distal urethral end was stitched and tied to the catheter. (2) As catheter was inserted into bladder and 20 ml water was injected into catheter balloon, the distal urethral end was fixed in the proximal urethra and an overlaying of 1.5 cm was formed between the two ends. (3) Three weeks later, it was tried to insert the catheter to bladder. After the urethral stump necrosis and the catheter separating from the urethra, the catheter was removed. In phase 2 (from February 2008 to December 2010), based on the above, irrigating catheter was used. After the surgery, urethra was irrigated with 0.02% furacillin solution through the catheter 3 times a day. All patients were followed up for at least 6 months. If patients had no conscious dysuria and maximum urinary flow rate (Qmax) > 15 ml/s, the treatment was considered successful. All complications were recorded. RESULTS: In phase 1, the 96 patients (101 times) underwent the procedure. The treatment was successful in 88 patients (success rate 92%). Within 1 to 13 days after removal of the catheter, urethral stricture was recurred in 8 patients. They had to undergo cystostomy once more for 3 to 11 months before reoperation (the 3 patients' reoperation was in phase 2). The 8 cases were treated successfully. In phase 2, 33 patients (total 36 times) underwent the procedure. One patient was failed (success rate 97%). The actual follow-up time is 7 to 93 months (An average of 37.6 months). Qmax is (22 ± 5) ml/s. No complications such as urinary incontinence, erectile pain, urinary shortening happened. 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.


Assuntos
Uretra/cirurgia , Estreitamento Uretral/cirurgia , Adulto , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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