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1.
Med Sci Monit ; 26: e919185, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32024811

RESUMO

BACKGROUND The present study was conducted to explore the influence of remote ischemic preconditioning (RIPC) on the adjustment of renal fibrosis after ischemia-reperfusion injury (IRI). MATERIAL AND METHODS Male Sprague-Dawley rats were randomly assigned to 3 groups following right-side nephrectomy: the Sham group (without renal artery clamping), the IRI group (45 min left renal artery clamping), and the RIPC group (rats were treated daily with 3 cycles of 5 min of limb ischemia and 5 min of reperfusion on 3 consecutive days before left renal artery occlusion). After 3 months of reperfusion, the renal function and the extent of tubular injury and renal fibrosis were assessed. The expressions of transforming growth factor beta1 (TGF-ß1), p-Smad2, Smad2, p-Smad3, and Smad3 were also evaluated. RESULTS There was no significant difference in renal function and tubular damage among the 3 groups after 45 min of kidney ischemia followed by 3 months of reperfusion. However, an obvious increase of extracellular matrix components and alpha-SMA could be observed in the kidney tissues of the IRI group, and the changes were significantly ameliorated in rats treated with enhanced RIPC. Compared with the IRI group, the expression of TGF-ß1 and the level of p-Smad2 and p-Smad3 were decreased after the intervention of enhanced RIPC. CONCLUSIONS Enhanced RIPC ameliorated renal fibrosis after IRI in rats, which appears to be associated with inhibition of the TGF-ß1/p-Smad2/3 signalling pathway.

2.
Tissue Eng Part A ; 26(1-2): 78-92, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31238789

RESUMO

Tissue engineering technology provides an alternative for bladder reconstruction, which remains confronted with challenges, such as insufficient vascularization in regenerated bladder tissue. Short-term hypoxic preconditioning has been reported to be an effective method to enhance the angiogenic effect of stem cells. This study evaluated the effect and mechanism of hypoxia-preconditioned adipose-derived endothelial progenitor cells (hp-ADEPCs) on the vascularization and smooth muscle regeneration of tissue-engineered bladders. Rats were randomly divided into the following four groups: hp-ADEPC, ADEPC, bladder acellular matrix (BAM), and cystotomy groups. A partial cystectomy was performed to remove 50% of the bladder, which was augmented with hp-ADEPC-BAM, ADEPC-BAM, or BAM. Histological and functional assessments of the engineered neobladder were performed at 1 and 3 months after surgery, while the mechanism of hp-ADEPCs on vascularization was also investigated. Immunohistochemical analysis revealed that hp-ADEPC-BAM significantly promoted urothelium, blood vessel, smooth muscle, and nerve cell regeneration. Animals in the hp-ADEPC-BAM group exhibited higher bladder compliance and a relatively normal micturition pattern compared with the ADEPC-BAM and BAM groups. In addition, compared with ADEPCs, hp-ADEPCs promoted ERK phosphorylation activation and hypoxia-inducible factor-1α expression, thereby secreting more vascular endothelial growth factor and basic fibroblast growth factor and significantly enhancing the migration and angiogenesis abilities of rat endothelial cells. This is the first study to demonstrate that a combination of ADEPCs and BAM with short-term hypoxic preconditioning enhances angiogenesis and promotes the functional recovery of tissue-engineered bladders. Impact Statement Insufficient vascularization in regenerated bladder tissue remains a challenge for bladder tissue engineering. We successfully isolated adipose-derived endothelial progenitor cells (ADEPCs) with high proliferative potential and angiogenic properties. Hypoxic preconditioning was confirmed to effectively enhance stem cell activity. In this study, a porcine bladder acellular matrix (BAM) was established, and hypoxia-preconditioned autologous ADEPCs were simultaneously introduced for bladder reconstruction in a rat model, followed by an assessment of their feasibility and potential for bladder vascularization. For the first time, we demonstrated that hypoxic preconditioning of ADEPCs improves angiogenesis and the functional recovery of tissue-engineered bladders.

3.
J Tissue Eng ; 10: 2041731419891256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827758

RESUMO

The formation of an effective vascular network can promote peripheral angiogenesis, ensuring an effective supply of blood, oxygen, and nutrients to an engineered bladder, which is important for bladder tissue engineering. Stromal vascular fraction cells (SVFs) promote vascularization and improve the function of injured tissues. In this study, adipose tissue-derived SVFs were introduced as an angiogenic cell source and seeded into the bladder acellular matrix (BAM) to generate a SVF-BAM complex for bladder reconstruction. The morphological regeneration and functional restoration of the engineered bladder were evaluated. In addition, we also explored the role of the Wnt5a/sFlt-1 noncanonical Wnt signaling pathway in regulating the angiogenesis of SVFs, and in maintaining the rational capability of SVFs to differentiate into vasculature in regenerated tissues. Histological assessment indicated that the SVF-BAM complex was more effective in promoting smooth muscle, vascular, and nerve regeneration than BAM alone and subsequently led to the restoration of bladder volume and bladder compliance. Moreover, exogenous Wnt5a was able to enhance angiogenesis by increasing the activity of MMP2, MMP9, and VEGFR2. Simultaneously, the expression of sFlt-1 was also increased, which enhanced the stability of the SVFs angiogenic capability. SVFs may be a potential cell source for tissue-engineered bladders. The Wnt5a/sFlt-1 pathway is involved in the regulation of autologous vascular formation by SVFs. The rational regulation of this pathway can promote neo-microvascularization in tissue-engineered bladders.

4.
Life Sci ; : 117176, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31843532

RESUMO

Circular RNAs (circRNAs) are a new type of endogenous noncoding RNAs with closed circular structure. Emerging evidence indicates that circRNAs play crucial roles in many biological processes by regulating linear RNA transcription, downstream gene expression and protein production. Meanwhile, recent studies have suggested that circRNAs have the potential to be oncogenic or anti-oncogenic and play vital regulatory roles in the initiation and progression of tumors. Circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH), a novel circular RNA originated from several exons of ITCH and located on chromosome 20q11.22, was proved to be declined in many malignant tumors, such as melanoma and ovarian cancer, resulting in tumor occurrence and progression. This review summarizes the biogenesis, characteristics, and functions of circRNAs, as well as recent progression regarding the biological functions and potential molecular mechanisms of circ-ITCH, and future challenges in cancer research.

5.
Aging (Albany NY) ; 11(21): 9295-9309, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31692452

RESUMO

The present study was performed to determine the protective effect of Zinc on the rat testicular ischemia-reperfusion (I/R) injury and its mechanism. In vivo, the pathological changes and the apoptosis index were significantly relieved in the rats with Low-dose Zinc pretreatment, compared to the I/R group. After Low-dose Zinc treatment, the levels of tissue Malondialdehyde (MDA) were significantly decreased, while tissue antioxidant indices were significantly increased. Meanwhile, the level of NF-κB was significantly lower compared to I/R group, while the levels of Nrf2-dependent antioxidant enzymes were significantly higher in Low-dose Zinc+I/R group. In vitro, Low-dose Zinc markedly increased Leydig cell (TM3) cell viability, and relieved testicular oxidative damage via down-regulating ROS. A total of 22 differently expressed microRNAs were screened out using microRNA microarray in rat testicular tissue caused by I/R injury, especially showing that miR-101-3p was selected as the target miRNA. Furthermore, the levels of Nrf2 and NF-κB were apparently increased/decreased in TM3 cells treated with Hypoxic/Reoxygenation (H/R) after miR-101-3p mimics/inhibitor. In addition, H/R-induced testicular oxidative damage was recovered in TM3 administrated with miR-101-3p inhibitor and si-Nrf2. Therefore, this study provided a novel insight for investigating protective effect of Zinc on testicular I/R injury by promoting antioxidation via miR-101-3p/Nrf2.

6.
Stem Cells Transl Med ; 8(4): 383-391, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30569668

RESUMO

Torsion-detorsion (T/D)-induced testicular injury may lead to male subfertility and even infertility. Stem cell therapy provides an alternative to attenuate testicular injury and promote spermatogenesis. Adipose-derived stromal vascular fraction (SVF) can be acquired conveniently without in vitro expansion, which may avoid the potential risks of microbial contamination, xenogenic nutritional sources, etc., during cell culture. In this study, we investigate the protective effects of autologous uncultured SVF on testicular injury and spermatogenesis in a rat model of T/D. Animals were randomly divided into sham, T/D+ phosphate-buffered saline, and T/D + SVF groups (18 rats in each group). SVF was isolated, labeled with lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine, and transplanted into T/D testis by local injection. At 3, 7, 14, and 28 days F surgery, testicular tissue and serum samples were harvested for histopathological, immunohistochemical, Western blot, and enzyme-linked immunosorbent assays. Histopathological findings demonstrated severe injury in the testis with decreased Johnsen's score led by T/D, while uncultured SVF reduced testicular injury and elevated the decreased score. Injected SVF cells were mainly integrated into interstitial region and seminiferous tubules, enhanced the secretion of basic fibroblast growth factor and stem cell factor in the testis, contributed to the declining level of malondialdehyde and restoration of hormonal homeostasis, and then reduced the injury of Leydig cells and germ cells, as well as promoting spermatogenesis. Our findings demonstrated that autologous uncultured SVF could protect the testis from testicular ischemia-reperfusion injury and promote spermatogenesis, which provide significant clinical implications for the prevention of infertility induced by testicular T/D. Stem Cells Translational Medicine 2019;8:383-391.

7.
Int Braz J Urol ; 452019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31961625

RESUMO

BACKGROUND: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. MATERIALS AND METHODS: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR-), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. RESULTS: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR-, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. CONCLUSIONS: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.

8.
Onco Targets Ther ; 10: 5551-5559, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200870

RESUMO

Bladder cancer (BC) is a common urinary system tumor with high aggressiveness, and it results in relatively high mortality due to a lack of precise and suitable biomarkers. In this study, we applied the weighted gene coexpression network analysis method to miRNA expression data from BC patients, and screened for network modules associated with BC progression. Hub miRNAs were selected, followed by functional enrichment analyses of their target genes for the most closely related module. These hub miRNAs were found to be involved in several functional pathways including pathway in cancer, regulation of actin cytoskeleton, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, proteoglycans in cancer, focal adhesion and p53 signaling pathway via regulating target genes. Finally, their prognostic significance was tested using analyses of overall survival. A few novel prognostic miRNAs were identified based on expression profiles and related survival data. In conclusion, several miRNAs that were critical in BC initiation and progression have been identified in this study. These miRNAs, which may contribute to a comprehensive understanding of the pathogenesis of BC, could serve as potential biomarkers for BC prognosis or as new therapeutic targets.

9.
Cell Physiol Biochem ; 44(3): 1213-1223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29179219

RESUMO

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim , RNA Longo não Codificante/sangue , Doença Aguda , Área Sob a Curva , Biomarcadores/sangue , Estudos de Coortes , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Curva ROC , Transcriptoma , Transplante Homólogo
10.
Oncotarget ; 8(45): 79323-79336, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108311

RESUMO

Objective: We conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon. Methods: Pubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively. Results: A total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months. Conclusion: RIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.

11.
J Cancer ; 8(13): 2643-2652, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900502

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

12.
Yi Chuan ; 39(3): 177-188, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28420614

RESUMO

The emergence of genome editing tools, such as the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has enabled researchers to achieve somatic and germline genomic manipulations in cell lines and model organisms. Within a couple of years, genome editing is now being rapidly developed for multiple applications and widely used in biomedical researches, including creation of disease models with desired genetic mutations, screening in a high-throughput manner for drug resistance genes, and making appropriate editions to genes in vivo for disease treatment. All these applications have been facilitating the development of precision medicine research. In this review, we describe the use of genome editing technologies for a variety of research and translational applications in the precision medicine field. We also highlight some of the existing limitations or challenges as well as future directions.


Assuntos
Edição de Genes , Medicina de Precisão/métodos , Animais , Pesquisa Biomédica , Sistemas CRISPR-Cas/genética , Humanos
13.
Sci Rep ; 7: 44058, 2017 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-28276451

RESUMO

Stem cells therapy has been suggested as a promising option for the treatment of acute kidney injury (AKI). This study was performed to compare the abilities of xenogenic transplantation of human adipose stromal vascular fraction (SVF) and adipose-derived mesenchymal stem cells (AdMSCs) to facilitate the recovery of renal function and structure in a rat model of ischemia/reperfusion (IR) induced AKI. SVF or AdMSCs were transplanted to the injured kidney through intra-parenchymal injection. Significantly improved renal function and reduced tubular injury were observed in SVF and AdMSCs groups. Administration of SVF or AdMSCs contributed to significantly improved cell proliferation and markedly reduced cell apoptosis in parallel with reduced microvascular rarefaction in injured kidney. IR injury resulted in higher levels of inflammatory cytokines, whereas xenogenic transplantation of SVF or AdMSCs reduced but not induced inflammatory cytokines expression. Additionally, in vitro study showed that administration of SVF or AdMSCs could also significantly promote the proliferation and survival of renal tubular epithelial cells underwent hypoxia/reoxygenation injury through secreting various growth factors. However, cell proliferation was significantly promoted in SVF group than in AdMSCs group. In conclusion, our study demonstrated that administration of SVF or AdMSCs was equally effective in attenuating acute renal IR injury.


Assuntos
Tecido Adiposo/metabolismo , Nefropatias/terapia , Rim/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão/terapia , Tecido Adiposo/patologia , Adulto , Animais , Feminino , Xenoenxertos , Humanos , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
14.
RNA ; 23(1): 1-5, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27742910

RESUMO

Multiplex genome engineering in vivo with CRISPR/Cas9 shows great promise as a potential therapeutic approach. The ability to incorporate multiple single guide RNA (sgRNA) cassettes together with Cas9 gene expression in one AAV vector could greatly enhance the efficiency. In a recent Method article, Mefferd and coworkers indicated that small tRNA promoters could be used to drive sgRNA expression to facilitate the construction of a more effective AAV vector. In contrast, we found that when targeting endogenous genomic loci, CRISPR/Cas9 with tRNA promoter-driven sgRNA expression showed much reduced genome editing activity, compared with significant cleavage with U6 promoter-driven sgRNA expression. Though the underlying mechanisms are still under investigation, our study suggests that the CRISPR/Cas9 system with tRNA promoter-driven sgRNA expression needs to be reevaluated before it can be used for therapeutic genome editing.


Assuntos
Exorribonucleases/genética , Edição de Genes/métodos , Regiões Promotoras Genéticas , RNA Guia/genética , RNA de Transferência/genética , Sistemas CRISPR-Cas , Expressão Gênica
15.
Stem Cells Transl Med ; 5(9): 1277-88, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27365485

RESUMO

UNLABELLED: : Ischemia/reperfusion (IR)-induced acute kidney injury (AKI) is a common clinical syndrome. Stem/progenitor cell therapy is a promising option to foster the intrinsic capacity for kidney regeneration. However, there are still several challenges to be resolved, including the potential risks during cell culture, low retention rate after transplantation, and unclear effect on the progression of chronic kidney disease (CKD). Recently, nonexpanded adipose stromal vascular fraction (SVF) has been regarded as an attractive cell source for cell-based therapy. Preconditioning with ischemia has been suggested as a useful method to promote the retention and survival of transplanted cells in vivo. In this study, freshly isolated autologous SVF was transplanted to the kidney of rats before ischemia, and then an IR-induced AKI model was established. Postischemic administration of SVF to the kidney was performed after renal IR injury was induced. A higher cell retention rate was detected in the preischemic group. Preischemic administration of SVF showed stronger functional and morphologic protection from renal IR injury than postischemic administration, through enhancing tubular cell proliferation and reducing apoptosis. Progression of kidney fibrosis was also significantly delayed by preischemic administration of SVF, which exhibited stronger inhibition of transforming growth factor-ß1-induced epithelia-mesenchymal transition and microvascular rarefaction. In addition, in vitro study showed that prehypoxic administration of SVF could significantly promote the proliferation, migration, and survival of hypoxic renal tubular epithelial cells. In conclusion, our study demonstrated that preischemic administration of nonexpanded adipose SVF protected the kidney from both acute IR injury and long-term risk of developing CKD. SIGNIFICANCE: Renal ischemia/reperfusion (IR) injury is a common clinical syndrome. Cell-based therapy provides a promising option to promote renal repair after IR injury. However, several challenges still remain because of the potential risks during cell culture, low retention rate after transplantation, and unclear effect on the progression of chronic kidney disease. Stromal vascular fraction (SVF) is considered as an attractive cell source. This study demonstrated that preischemic administration of uncultured SVF could increase cell retention and then improve renal function and structure at both early and long-term stage after IR, which may provide a novel therapeutic approach for IR injury.


Assuntos
Tecido Adiposo/irrigação sanguínea , Movimento Celular , Proliferação de Células , Nefropatias , Túbulos Renais/metabolismo , Traumatismo por Reperfusão , Animais , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/prevenção & controle , Túbulos Renais/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Células Estromais/metabolismo , Células Estromais/patologia , Células Estromais/transplante
16.
Tumour Biol ; 36(10): 8159-66, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25990459

RESUMO

Bladder cancer ranks the second most common genitourinary tract cancer, and muscle-invasive bladder cancer (MIBC) accounts for approximately 25 % of all bladder cancer cases with high mortality. In the current study, with a total of 202 treatment-naïve primary MIBC patients identified from The Cancer Genome Atlas dataset, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in MIBC, with the aim to investigate the relationship of miRNA expression with the progression and prognosis of MIBC, and generate a miRNA signature of prognostic capabilities. In the progression-related miRNA profiles, a total of 47, 16, 3, and 84 miRNAs were selected for pathologic T, N, M, and histologic grade, respectively. Of the eight most important progression-related miRNAs, four (let-7c, mir-125b-1, mir-193a, and mir-99a) were significantly associated with survival of patients with MIBC. Finally, a four-miRNA signature was generated and proven as a promising prognostic parameter. In summary, this study identified the specific miRNAs associated with the progression and aggressiveness of MIBC and a four-miRNA signature as a promising prognostic parameter of MIBC.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Musculares/genética , Neoplasias Musculares/mortalidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Carcinoma Papilar/genética , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
17.
Int J Clin Exp Pathol ; 8(2): 1128-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25972999

RESUMO

BACKGROUND: Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO). METHODS: Male Sprague-Dawley rats were randomly divided into five groups after right-side nephrectomy: Sham group (surgery without vascular clamping); IRI group (the left renal artery was clamped for 45 min); IPC group (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L-arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC). The renal and systemic hemodynamic parameters, renal function and morphology, as well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the indicated time points after reperfusion. RESULTS: IPC rats exhibited significant improvements in renal function, morphology, and renal artery blood flow (RABF), without obvious influence on the systemic hemodynamics and renal vein blood flow. Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully abolished by the administration of L-NAME. CONCLUSIONS: The results suggest that IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated NO production, thereby alleviating the renal dysfunction and histological damage caused by IRI.


Assuntos
Precondicionamento Isquêmico/métodos , Rim/irrigação sanguínea , Traumatismo por Reperfusão/fisiopatologia , Animais , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
18.
Sci Rep ; 5: 10328, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-25981392

RESUMO

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of kidney cancers. In the present study, we identified 58 treatment-naïve primary chRCC patients from The Cancer Genome Atlas dataset and analyzed the genome-wide microRNA (miRNA) expression profiles, with the aim to assess the relationship of miRNA expression with the progression and prognosis of chRCC. Overall, a total of 105 miRNAs were found to be differentially expressed between tumor and the adjacent normal tissues from 22 chRCC patients. In the unpaired condition (58 chRCC vs. 22 normal tissues), 77 (96.3%) samples were distinguished correctly by the signatures. In the progression-related profiles, 27 miRNAs were selected for pathologic T and 9 for lymph node involvement. In the survival analyses, the expression levels of mir-191, mir-19a, mir-210, and mir-425 were significantly associated with both recurrence-free survival (RFS) and overall survival, while mir-210 was proven as an independent prognostic factor in terms of RFS. In summary, miRNAs are expressed differentially in chRCC, and unique expression of miRNAs is associated with the progression and prognosis of chRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/genética , Transcriptoma , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Análise por Conglomerados , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
19.
Medicine (Baltimore) ; 94(16): e767, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25906110

RESUMO

Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC.A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan-Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda).In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways.Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/biossíntese , Fatores Etários , Idoso , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores Sexuais
20.
J Cancer Res Clin Oncol ; 141(7): 1291-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25633718

RESUMO

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers in adults, and microRNAs (miRNAs) differentially expressed in ccRCC tumors have been identified and proposed to predict prognosis. In the present study, we comprehensively analyzed the genome-wide miRNA expression profiles in ccRCC, with the aim to generate a tumor-specific miRNA signature of prognostic values. METHODS: The miRNA profiles in tumor and the adjacent normal tissue were analyzed, and the association of the differentially expressed miRNAs with patient survival was examined with univariate Cox regression analysis. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate, and multivariate Cox regression analyses. RESULTS: A total of 147 miRNAs were found differentially expressed between tumor and matched non-tumor tissues from 58 ccRCC patients. The prognostic values of these differentially expressed miRNAs were subsequently analyzed in the 411 ccRCC patients, and 22 miRNAs were found significantly correlated with patient survival. Finally, a tumor-specific miRNA signature of 22 miRNAs was generated and validated as an independent prognostic parameter. CONCLUSIONS: A tumor-specific miRNA signature consisting of 22 miRNAs was identified and validated as an independent prognostic factor, which could serve as a novel biomarker for ccRCC prognostication and help in predicting treatment outcome.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , MicroRNAs/genética , Transcriptoma , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/diagnóstico , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Especificidade de Órgãos/genética , Prognóstico , Análise de Sobrevida
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