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Background: The new Family-Community-Hospital (FCH) three-level comprehensive management aimed to improve the efficiency and scale of peritoneal dialysis (PD) to meet the increased population of end-stage renal disease (ESRD). Our study focused on the clinical outcomes, quality of life, and costs evaluation of this model in a multi-center and prospective cohort study.Methods: A total of 190 ESRD patients who commenced PD at Shanghai Songjiang District were enrolled. According to different PD management models, patients were divided into the Family-Community-Hospital three-level management model (n = 90) and the conventional all-course central hospital management model (n = 100). The primary outcome was clinical outcomes of PD. The secondary outcomes were health-related quality of life (HRQOL) and medical costs evaluation.Results: Compared to conventional management, community-based FCH management achieved a similar dialysis therapeutic effect, including dropout rate (p = 0.366), peritonitis rate (p = 0.965), patient survival (p = 0.441), and technique survival (p = 0.589). Follow-up data showed that similar levels of the renal and peritoneal functions, serum albumin, cholesterol and triglyceride, PTH, serum calcium, and phosphorus between the two groups (all p > 0.05). HRQOL survey showed that the FCH management model helped to improve the psychological status of PD patients, including social functioning (p = 0.006), role-emotional (p = 0.032), and mental health (p = 0.036). FCH management also reduced the hospitalization (p = 0.009) and outpatient visits (p = 0.001) and saved annual hospitalization costs (p = 0.005), outpatient costs (p = 0.026), and transport costs (p = 0.006).Conclusions: Compared with conventional management, community-based FCH management achieved similar outcomes, improved psychological health, reduced medical budgets, and thus had a good social prospect.
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Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Peritonitis/etiología , Calidad de Vida , Anciano , China , Femenino , Hospitalización/economía , Humanos , Fallo Renal Crónico/economía , Fallo Renal Crónico/psicología , Masculino , Salud Mental , Persona de Mediana Edad , Diálisis Peritoneal/economía , Peritonitis/epidemiología , Estudios ProspectivosRESUMEN
Hyperuricemia has been identified as an independent risk factor for chronic kidney disease (CKD) and is associated with the progression of kidney diseases. It remains unknown whether enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, can regulate metabolism of serum uric acid and progression of renal injury induced by hyperuricemia. In this study, we demonstrated that blockade of EZH2 with 3-DZNeP, a selective EZH2 inhibitor, or silencing of EZH2 with siRNA inhibited uric acid-induced renal fibroblast activation and phosphorylation of Smad3, epidermal growth factor receptor (EGFR), and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured renal fibroblasts. Inhibition of EZH2 also suppressed proliferation of renal fibroblasts and epithelial-mesenchymal transition of tubular cells. In a mouse model of renal injury induced by hyperuricemia, EZH2 and trimethylation of histone H3 at lysine27 expression levels were enhanced, which was coincident with renal damage and increased expression of lipocalin-2 and cleaved caspase-3. Inhibition of EZH2 with 3-DZNeP blocked all these responses. Furthermore, 3-DZNeP treatment decreased the level of serum uric acid and xanthine oxidase activity, alleviated renal interstitial fibrosis, inhibited activation of transforming growth factor-ß/Smad3, EGFR/ERK1/2, and nuclear factor-κB signaling pathways, as well as reduced expression of multiple chemokines/cytokines. Collectively, EZH2 inhibition can reduce the level of serum uric acid and alleviate renal injury and fibrosis through a mechanism associated with inhibition of multiple signaling pathways. Targeting EZH2 may be a novel strategy for the treatment of hyperuricemia-induced CKD.
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Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Fibroblastos/metabolismo , Hiperuricemia/metabolismo , Enfermedades Renales/metabolismo , Animales , Metilación de ADN/efectos de los fármacos , Proteína Potenciadora del Homólogo Zeste 2/antagonistas & inhibidores , Proteína Potenciadora del Homólogo Zeste 2/genética , Fibroblastos/efectos de los fármacos , Fibrosis/genética , Fibrosis/metabolismo , Histonas/metabolismo , Hiperuricemia/genética , Enfermedades Renales/genética , Ratones , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , ARN Interferente Pequeño , Transducción de Señal/efectos de los fármacos , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Ácido Úrico/farmacología , Xantina Oxidasa/metabolismoRESUMEN
Prostate cancer is one of the most common malignancies in men worldwide. Altered expression of ARHGAP10, a member of the Rho GTPase activating protein (RhoGAP) family, has been found in several human cancers. However, its clinical significance in prostate cancer remains unknown. In the current study, we found that mRNA levels of ARHGAP10 were significantly higher in prostate cancer tissues than in the non-cancerous controls. Gene set enrichment analysis (GSEA) revealed that ARHGAP10 expression was negatively correlated with the Wnt signaling pathway. Immunohistochemical staining results showed that 62.2% (56/90) and 65.5% (59/90) of prostate cancer tissues displayed low expression of ARHGAP10 and high expression of ß-catenin, respectively. ARHGAP10 protein expression was significantly correlated with histologic grade (P < 0.0001), tumor stage (P = 0.0298), preoperative prostate specific antigen level (P = 0.0261), vital status (P = 0.0017) and ß-catenin expression (P < 0.0001). Kaplan-Meier survival analysis indicated that patients with low levels of ARHGAP10 and high levels of ß-catenin had poor overall survival. Multivariate analyses revealed that ARHGAP10 and ß-catenin expression was independent prognostic factor for prostate cancer. In summary, the current study suggests that ARHGAP10 in association with ß-catenin may play a role in the development of prostate cancer and serve as a prognostic factor for this disease.
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The regulation of microRNA-192 (miR-192) is impaired in many cancers. Here, we investigated the role of miR-192 in the proliferation, cell cycle progression, and apoptosis of bladder cancer cells. Human bladder cancer cells were transfected with human miR-192 precursor or non-specific control miRNA. The effect of miR-192 on cell proliferation was assessed by a MTT assay. The effects of miR-192 on cell cycle regulation and apoptosis were evaluated by flow cytometry. Western blot was used to analyze the protein levels of cyclin D1, p21, p27, Bcl-2, Bax, and Mcl-1. We found that overexpression of miR-192 significantly decreased the proliferation of bladder cancer cells by 22 and 54 % at 48 and 72 h, respectively. MiR-192-overexpressing cells exhibited a significant increase in G0/G1 phase and a significant decrease in S phase compared to the control miRNA-transfected cells. Moreover, overexpression of miR-192 significantly induced apoptotic death in bladder cancer cells, increased the levels of p21, p27, and Bax, and decreased the levels of cyclin D1, Bcl-2, and Mcl-1. Taken together, these data suggest that miR-192 may be a suppressor for bladder cancer cells by cell cycle regulation.
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Apoptosis/genética , Proliferación Celular/genética , MicroARNs/biosíntesis , Neoplasias de la Vejiga Urinaria/genética , Ciclo Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Prostate cancer (PCa) is a biologically heterogeneous disease with considerable variation in clinical aggressiveness. In this study, bioinformatics was used to detect the patterns of gene expression alterations of PCa patients. METHODS: The gene expression profile GSE21034 and GSE21036 were downloaded from Gene Expression Omnibus (GEO) database. Significantly changed mRNA transcripts and microRNAs were identified between subtypes with favorable (cluster 2) and unfavorable (cluster 5) prognosis by two-side unequal variances t test. MicroRNAs and their potential target genes were identified by TargetScan and miRTarBase, respectively. Besides, the overlapped genes between the target genes of microRNAs and mRNA transcripts were assessed by Fisher' exact test (one side). The functional annotation was performed by DAVID, followed by construction of protein-protein interaction (PPI) network. RESULTS: Compared to cluster 2, 1556 up-regulated and 1288 down-regulated transcripts were identified in cluster 5. Total 28 microRNAs were up-regulated and 30 microRNAs were down-regulated in cluster 5. Besides, 12 microRNAs target transcripts were significantly overlapped with down-regulated transcripts in cluster 5 with none of them was found overlapped with up-regulated transcripts. Functional annotation showed that cell cycle was the most significant function. In the PPI network, BRCA1, CDK1, TK1 and TRAF2 were hub protein of signature genes in cluster 5, and TGFBR1, SMAD2 and SMAD4 were hub proteins of signature gnens in cluster 2. CONCLUSIONS: Our findings raise the possibility that genes related with cell cycle and dysregulated miRNA at diagnosis might have clinical utility in distinguishing low- from high-risk PCa patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_156.
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The goal of this study was to identify cancer-associated differentially expressed genes (DEGs), analyze their biological functions and investigate the mechanism(s) of cancer occurrence and development, which may provide a theoretical foundation for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes 165 BCa and 68 control samples. Ttests were used to identify DEGs. To further study the biological functions of the identified DEGs, we performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we built a network of potentially interacting pathways to study the synergistic relationships among DEGs. A total of 12,105 genes were identified as DEGs, of which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT) proteins, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and interleukin (IL)-10 were revealed to participate in the significantly enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis revealed 7 significantly upregulated and 47 significantly downregulated pathways enriched among the DEGs. We found a crosstalk interaction among a total of 44 pathways in the network of BCa-affected pathways. In conclusion, our results show that BCa involves dysfunctions in multiple systems. Our study is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.