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Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 µM H2O2 for 8 h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.
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Hipogonadismo , MicroARNs , ARN Largo no Codificante , Animales , Humanos , Masculino , Ratones , Apoptosis , Proliferación Celular/genética , Peróxido de Hidrógeno , Hipogonadismo/genética , Hibridación Fluorescente in Situ , Células Intersticiales del Testículo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Endógeno Competitivo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño/metabolismo , Sirtuina 1/genética , Testosterona/farmacologíaRESUMEN
BACKGROUND AIMS: Cell failure and angiogenesis are the key to bladder wall regeneration. Three-dimensional (3D) culture using porous gelatin microspheres (GMs) as a vehicle promotes stem cell proliferation and improves the paracrine capacity of cells. This study aimed to evaluate the therapeutic potential of GMs constructed from adipose-derived mesenchymal stromal cells (ADSCs) (ADSC-GMs) combined with bladder acellular matrix (BAM) in tissue-engineered bladders. METHODS: Isolation of ADSCs, flow cytometry, scanning electron microscopy and cell counting kit-8, ß-galactosidase and enzyme-linked immunosorbent assays were performed in vitro to compare two-dimensional (2D) and 3D cultures. In the in vivo study, male Sprague-Dawley rats were randomly divided into three groups: the BAM replacement alone (BAM) group, ADSCs grown on BAM in replacement (ADSC) group and ADSC-GMs combined with BAM followed by replacement (ADSC-GM) group. Bladder function assessed by urodynamics after 12 weeks of bladder replacement, and the rats were sacrificed at 4 and 12 weeks for further experiments. RESULTS: The in vitro results showed that GM culture promoted ADSC proliferation, inhibited apoptosis and delayed senescence compared with those in the 2D culture. In addition, ADSC-GMs increased the secretion of the angiogenic factors vascular endothelial growth factor, platelet-derived growth factor-BB, and basal fibroblast growth factor. In vivo experiments revealed that ADSC-GMs adhered to the BAM for longer than ADSCs. Moreover, ADSC-GMs significantly promoted the regeneration of bladder vessels and smooth muscle, thereby facilitating the recovery of bladder function. The expression of phosphorylated protein kinase B (AKT) and phosphorylated endothelial nitric oxide synthase (eNOS) was significantly greater in the ADSC-GMs group compared with the BAM and ADSCs groups. CONCLUSIONS: ADSC-GMs increased retention of ADSCs on the BAM, thereby promoting the regeneration and functional recovery of the bladder tissue. ADSC-GMs promoted angiogenesis by activating the AKT/eNOS pathway.
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Células Madre Mesenquimatosas , Vejiga Urinaria , Ratas , Masculino , Animales , Vejiga Urinaria/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Gelatina/metabolismo , Tejido Adiposo , Ratas Sprague-Dawley , Microesferas , Óxido Nítrico Sintasa de Tipo III/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Porosidad , Transducción de SeñalRESUMEN
PURPOSE: To develop and validate a nomogram for preoperative predicting the pathological upgrading of prostate cancer (PCa). METHODS: The prediction model was developed in a primary cohort that consisted of 208 PCa patients. All patients included in the study possessed both biopsy pathology specimens and radical prostatectomy pathology specimens, and completed the (68 Ga-prostate-specific membrane antigen [PSMA]) positron emission tomography/computed tomography (PET/CT) detection. The R function "createDataPartition" was used in a 7:3 ratio to randomly divide the patients into training and validation cohorts. In the training cohort, the independent predictors of pathological upgrading of PCa were determined by univariate analysis, univariate regression analysis and multivariate regression analysis. Based on these independent predictors, a nomogram was developed, and its performance was evaluated by receiver operating characteristic (ROC) curve, area under the curve (AUC) and calibration curve of training cohort and validation cohort. RESULTS: The nomogram incorporated five independent predictors including prostate volume (PV), SUVmax of the 68 Ga-PSMA PET/CT examination on prostate lesions (SUVmax ), body mass index (BMI); percentage of cancer positive biopsy cores (PPC) and biopsy International Society of Urological Pathology (ISUP) grade. The nomogram showed good diagnostic accuracy for the pathological upgrading of both the training cohort and the validation cohort (AUC = 0.818 and 0.806, respectively). The calibration curves for the two cohorts both showed optimal agreement between nomogram prediction and actual observation. CONCLUSIONS: We developed and validated a nomogram to accurately predict the risk of pathological upgrading after radical PCa surgery, which can provide accurate basis for therapeutic schedule and prognostic data of PCa patients.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Radioisótopos de Galio , Humanos , Masculino , Nomogramas , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Próstata/patología , Prostatectomía/métodos , Neoplasias de la Próstata/patologíaRESUMEN
BACKGROUND: Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. METHODS: Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. RESULTS: The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-ß) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-ß and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. CONCLUSION: Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract.
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Carcinoma de Células Renales , Exosomas , Neoplasias Renales , MicroARNs , ARN Largo no Codificante , Animales , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Exosomas/metabolismo , Humanos , Interleucina-10/metabolismo , Neoplasias Renales/metabolismo , Activación de Macrófagos/genética , Macrófagos/metabolismo , Ratones , MicroARNs/genética , FN-kappa B/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factores de Crecimiento Transformadores/metabolismoRESUMEN
OBJECTIVE: Stem cell therapy represents a new approach to induce immune tolerance in solid organ transplantation. However, the time-consuming process of stem cell expending limits the range of stem cell treatment. Uncultured adipose stromal vascular fraction is considered an attractive cell source for cell-based therapy. This study aimed to evaluate the effect of stromal vascular fraction on the immune system in donation after circulatory death rat renal transplantation. METHODS: Stromal vascular fraction cells and splenocytes were co-cultured to evaluate the effect of stromal vascular fraction on splenocyte proliferation and viability. Sprague-Dawley rats were used as donors. and Wistar rats as recipients to establish a donation after a circulatory death rat renal transplantation model. Warm ischemia time was 5 min. Stromal vascular fraction was administered in the rat model following the intra-arterial route. The spleens and grafts of recipients were harvested on days 1, 3 and 7 post-transplantation for assessing acute rejection, infiltration of inflammatory cells, indoleamine 2, 3-dioxygenase expression and T-cell frequency in the spleen. RESULTS: Stromal vascular fraction could inhibit proliferation and induce apoptosis of splenocytes in vitro (P < 0.05). The administration of stromal vascular fraction could significantly reduce acute rejection and infiltration of CD8+ T cells and mononuclear macrophages in grafts, and increase indoleamine 2, 3-dioxygenase expression (P < 0.05). The frequency of CD8+ T cells decreased, and the frequency of CD25+ Foxp3+ regulatory T cells increased in the spleen of the acute rejection + stromal vascular fraction group on day 7 post-transplantation (P < 0.05). CONCLUSION: Administration of the adipose stromal vascular fraction could attenuate acute rejection in donation after circulatory death renal transplantation by increasing the ratio of regulatory T cells and enhancing indoleamine 2, 3-dioxygenase expression.
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Trasplante de Riñón , Animales , Linfocitos T CD8-positivos , Rechazo de Injerto/prevención & control , Trasplante de Riñón/efectos adversos , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Fracción Vascular EstromalRESUMEN
OBJECTIVE: To discuss the clinical diagnosis and treatment of extragonadal germ cell tumor. METHODS: We analyzed the clinical data on a case of extragonadal germ cell tumor diagnosed and treated in the General Hospital of Eastern Theater Command and reviewed the relevant literature. RESULTS: The patient was initially diagnosed with retroperitoneal tumor and treated by resection of the tumor together with the left kidney due to the large volume of the tumor, which was complicated by pancreatic injury. Postoperative pathology showed it to be extragonadal germ cell malignancy. Postoperative examination revealed space-occupying lesion in the left testis, with serum alpha fetoprotein (AFP), human chorionicgonadotropin (hCG) and lactate dehydrogenase (LDH) negative, followed by stage-two resection of the left testis, which was pathologically shown with testicular seminoma. The patient received 7 courses of cisplatin, etoposide bleomycin (PEB) regimen and was followed up for 8 years, which found no recurrence or metastasis, and the patient fathered no child during the postoperative follow-up. CONCLUSION: For patients with a history of cryptorchidism and tumors located in the central axis, special attention should be paid to physical examination of the testes, testicular ultrasonography, and determination of AFP and other indicators to identify gonadal tumor metastasis. And if so, radiotherapy and chemotherapy can be considered first to reduce surgical complications and achieve accurate management.
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Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , alfa-Fetoproteínas/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/terapia , Etopósido/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Bleomicina/uso terapéuticoRESUMEN
Circular RNAs (circRNAs) are a novel group of endogenous RNAs with a circular structure. Growing evidence indicates that circRNAs are involved in a variety of human diseases including malignancies. CircRNA ZNF609 (circ-ZNF609), derived from the ZNF609 gene sequence, has been demonstrated to be involved in the development and progression of many diseases. circ-ZNF609 is thought to be a viable diagnostic and prognostic biomarker for several diseases and might be a new therapeutic target, but further research is needed to accelerate clinical application. Here, we review the biogenesis and function of circRNAs and the functional roles and molecular mechanism related to circ-ZNF609 in neoplasms and other diseases.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Neoplasias/etiología , ARN Circular , Dedos de Zinc/genética , Animales , Susceptibilidad a Enfermedades , Humanos , Neoplasias/diagnóstico , Neoplasias/metabolismo , Especificidad de Órganos/genética , Unión Proteica , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
PURPOSE: To evaluate the oncologic efficacy and feasibility of nephron-sparing surgery (NSS) in adult Xp11.2 translocation renal cell carcinoma (RCC). PATIENTS AND METHODS: Seventy patients with Xp11.2 translocation RCC and 273 with conventional RCC from five institutions in Nanjing were retrospectively studied. All patients were older than 18 years and were categorized into clinical T1 (cT1) stage using preoperative imaging. Using the preoperative imaging and electronic medical records, anatomical and pathological features were collected and analyzed. RESULTS: Among patients with Xp11.2 translocation RCC, 18/36 (50.0%) with cT1a and 12/34 (35.3%) with cT1b tumors underwent NSS. The respective proportions in the conventional RCC group were 121/145 (83.4%) and 93/128 (72.7%). Among cT1a tumors, the Xp11.2 translocation RCCs tended to be adjacent to the collecting system, sinus, and axial renal midline compared with conventional RCCs. Patients with Xp11.2 translocation RCCs who underwent NSS had comparable progression-free survival (PFS) and overall survival to radical nephrectomy (RN) patients (P > 0.05). Among cT1b tumors, surgical margin positivity and pelvicalyceal, vascular, and region lymphatic involvement were more likely to occur in the Xp11.2 translocation RCCs (P < 0.05). Patients with Xp11.2 translocation RCC who underwent RN had a more favorable PFS than those who underwent NSS (P = 0.048). However, multivariate analysis of PFS did not identify surgical method as a risk factor (P = 0.089). CONCLUSIONS: Among adults with Xp11.2 translocation RCC, NSS can be an alternative for patients with cT1a tumor but should be performed with more deliberation in patients with cT1b tumors.
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Carcinoma de Células Renales , Neoplasias Renales , Adulto , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/cirugía , China , Femenino , Humanos , Neoplasias Renales/genética , Neoplasias Renales/cirugía , Masculino , Nefrectomía , Nefronas/cirugía , Estudios RetrospectivosRESUMEN
Low-energy shock wave (LESW) has been recognized as a promising non-invasive intervention to prevent the organs or tissues against ischaemia reperfusion injury (IRI), whereas its effect on kidney injury is rarely explored. To investigate the protective role of pretreatment with LESW on renal IRI in rats, animals were randomly divided into Sham, LESW, IRI and LESW + IRI groups. At 4, 12, 24 hours and 3 and 7 days after reperfusion, serum samples and renal tissues were harvested for performing the analysis of renal function, histopathology, immunohistochemistry, flow cytometry and Western blot, as well as enzyme-linked immunosorbent assay. Moreover, circulating endothelial progenitor cells (EPCs) were isolated, labelled with fluorescent dye and injected by tail vein. The fluorescent signals of EPCs were detected using fluorescence microscope and in vivo imaging system to track the distribution of injected circulating EPCs. Results showed that pretreatment with LESW could significantly reduce kidney injury biomarkers, tubular damage, and cell apoptosis, and promote cell proliferation and vascularization in IRI kidneys. The renoprotective role of LESW pretreatment would be attributed to the remarkably increased EPCs in the treated kidneys, part of which were recruited from circulation through SDF-1/CXCR7 pathway. In conclusion, pretreatment with LESW could increase the recruitment of circulating EPCs to attenuate and repair renal IRI.
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Células Progenitoras Endoteliales/fisiología , Tratamiento con Ondas de Choque Extracorpóreas , Riñón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Apoptosis , Movimiento Celular , Quimiocina CXCL12/biosíntesis , Quimiocina CXCL12/genética , Quimiocina CXCL12/fisiología , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Colorantes Fluorescentes/farmacocinética , Etiquetado Corte-Fin in Situ , Riñón/patología , Riñón/fisiología , Masculino , Microscopía Fluorescente , Microvasos/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores CXCR/antagonistas & inhibidores , Receptores CXCR/biosíntesis , Receptores CXCR/genética , Receptores CXCR/fisiología , Regeneración , Daño por Reperfusión/sangre , Daño por Reperfusión/patología , Transducción de Señal , Factores de TiempoRESUMEN
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.
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Precondicionamiento Isquémico , Riñón/irrigación sanguínea , Riñón/patología , Daño por Reperfusión/complicaciones , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Actinas/metabolismo , Animales , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Fibronectinas/metabolismo , Fibrosis , Riñón/fisiopatología , Masculino , Fosforilación , Ratas Sprague-Dawley , Daño por Reperfusión/fisiopatología , Proteínas Smad/metabolismoRESUMEN
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.
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Neoplasias de la Próstata , Antígenos de Neoplasias , Biomarcadores de Tumor , Humanos , Masculino , Oportunidad Relativa , Neoplasias de la Próstata/diagnóstico , Curva ROC , Sensibilidad y EspecificidadRESUMEN
microRNAs have been recognized to regulate a wide range of biology of renal cell carcinoma (RCC). Although miR-505 has been reported to play as a suppressor in several human tumors, the physiological function of miR-505 in RCC still remain unknown. Therefore, the role of miR-505 and relevant regulatory mechanisms were investigated in RCC in this study. Quantitative real-time polymerase chain reaction was conducted to detect the expression of miR-505 and high mobility group box 1 (HMGB1) in both RCC tissues and cell lines. Immunohistochemical staining was used to assess the correlation between HMGB1 expression and PCNA expression in RCC tissues. Subsequently, the effects of miR-505 on proliferation were determined in vitro using cell counting kit-8 proliferation assays and 5-ethynyl-2'-deoxyuridine incorporation. The molecular mechanism underlying the relevance between miR-505 and HMGB1 was confirmed by luciferase assay. Xenograft tumor formation was used to reflect the proliferative capacity of miR-505 in vivo experiments. Overall, a relatively lower miR-505 and higher HMGB1 expression in RCC specimens and cell lines were found. HMGB1 was verified as a direct target of miR-505 by luciferase assay. In vitro, overexpression of miR-505 negatively regulates HMGB1 to suppress the proliferation in Caki-1; meanwhile, knock-down of miR-505 negatively regulates HMGB1 to promote the proliferation in 769P. In addition, in vivo overexpression of miR-505 could inhibit tumor cell proliferation in RCC by xenograft tumor formation. Therefore, miR-505, as a tumor suppressor, negatively regulated HMGB1 to suppress the proliferation in RCC, and might serve as a novel therapeutic target for RCC clinical treatment.
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MicroRNAs (miRNAs), a group of small noncoding RNAs, are widely involved in the regulation of gene expression via binding to complementary sequences at 3'-untranslated regions (3'-UTRs) of target messenger RNAs. Recently, downregulation of miR-133b has been detected in various human malignancies. Here, the potential biological role of miR-133b in bladder cancer (BC) was investigated. In this study, we found the expression of miR-133b was markedly downregulated in BC tissues and cell lines (5637 and T24), and was correlated with poor overall survival. Notably, transgelin 2 (TAGLN2) was found to be widely upregulated in BC, and overexpression of TAGLN2 also significantly increased risks of advanced TMN stage. We further identified that upregulation of miR-133b inhibited glucose uptake, invasion, angiogenesis, colony formation and enhances gemcitabine chemosensitivity in BC cell lines by targeting TAGLN2. Additionally, we showed that miR-133b promoted the proliferation of BC cells, at least partially through a TAGLN2-mediated cell cycle pathway. Our results suggest a novel miR-133b/TAGLN2/cell cycle pathway axis controlling BC progression; a molecular mechanism which may offer a potential therapeutic target.
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Puntos de Control del Ciclo Celular/genética , MicroARNs/genética , Proteínas de Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Neovascularización Patológica/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/prevención & control , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Humanos , Ratones , Ratones Desnudos , MicroARNs/biosíntesis , Invasividad Neoplásica/genética , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
The Longfeng Wetland of Daqing City in China was taken as the research object to determine a reasonable sewage reduction scheme and resolve the pollution of urban wetland ecosystems. First, the main pollutants, including dichromate oxidizability (CODCr), ammonia nitrogen (NH3-N), total phosphorus (TP), and petroleum, were selected as indices. A two-dimensional hydrodynamic and water quality coupling model was established using MIKE 21. An optimal regulation method to improve the water quality of the wetland was then proposed following the numerical simulation method, and a multi-objective optimization model is established. The model establishes two objective functions based on wetland pollutant and water quality requirements. The model's constraints include hydrodynamic conditions and water quality conditions, and it considers the control point of the sewage concentration, sewage outfall processing capacity, depth of treatment, and changes in the water cycle. The wolf pack algorithm is introduced to resolve the multi-objective problem of sewage outfall optimization, and an optimal sewage scheme is obtained. According to the results of the scheme, some measures are proposed to manage the pollutants in urban wetland waters.
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Algoritmos , Monitoreo del Ambiente , Aguas del Alcantarillado , Humedales , Amoníaco , China , Ciudades , Ecosistema , Nitrógeno/análisis , Fósforo/análisis , Calidad del AguaRESUMEN
Benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) is a common disease with frequent occurrence in elderly men, and its incidence shows a significant positive correlation with age. Evidence has confirmed that BPH/LUTS is closely related to erectile dysfunction (ED) and significantly affects the quality of life of elderly males. Phosphodiesterase 5 inhibitors (PDE5i) can improve both ED and BPH/LUTS of the patients and PDE5 is expected to be a new therapeutic target for BPH/LUTS with ED. This review explores the structure and function of PDE5 and the action mechanisms of PDE5i so as to provide a more effective strategy for the clinical treatment of BPH/LUTS with ED.
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Disfunción Eréctil/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Anciano , Quimioterapia Combinada , Disfunción Eréctil/complicaciones , Humanos , Síntomas del Sistema Urinario Inferior/complicaciones , Masculino , Hiperplasia Prostática/complicaciones , Calidad de VidaRESUMEN
OBJECTIVE: To investigate the success rate and safety of percutaneous vasoseminal vesiculography with the disposable vasographic interventional therapy kit (VITK). METHODS: This study included ninety-six 19ï¼65 (mean 43) years old male patients with infertility, hematospermia, seminal vesicle cyst, ejaculatory duct cyst, ejaculatory dysfunction, or vas deferens injury, with disease courses varying from 1 month to 7 years. With an open, multi-centered, single-group, self-controlled design and using the disposable VITK, we treated the patients by percutaneous vasoseminal vesiculography via injection of contrast medium into the vas deferens cavity under local anesthesia. RESULTS: Percutaneous vasoseminal vesiculography was successfully performed in 92 (97.87%) of the patients, which revealed abnormal seminal ducts in 51 cases (54.3%). Among the 28 infertile patients, 3 were found with bilateral and 5 with unilateral vas deferens obstruction. Vesiculitis was detected in 36 (81.8%) of the 44 hematospermia patients and bilateral vas deferens abnormality in 5 (38.5%) of the 13 patients with ejaculatory dysfunction. Transectional damage was observed in 2 patients with vas deferens injury induced by bilateral inguinal hernia repair. Three cases of seminal vesicle cyst and 4 cases of ejaculatory cyst were definitely diagnosed by vasoseminal vesiculography. CONCLUSIONS: The disposable vasographic interventional therapy kit, with the advantages of simple operation and high safety, deserves a wide clinical application in vasoseminal vesiculography.
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Quistes/diagnóstico por imagen , Enfermedades de los Genitales Masculinos/diagnóstico por imagen , Infertilidad Masculina/diagnóstico por imagen , Vesículas Seminales/diagnóstico por imagen , Conducto Deferente/diagnóstico por imagen , Adulto , Anciano , Medios de Contraste/administración & dosificación , Conductos Eyaculadores/diagnóstico por imagen , Hematospermia/diagnóstico por imagen , Hematospermia/etiología , Hernia Inguinal/cirugía , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Radiografía/métodos , Conducto Deferente/lesiones , Adulto JovenRESUMEN
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.
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Rechazo de Injerto/patología , Trasplante de Riñón , ARN Largo no Codificante/sangre , Enfermedad Aguda , Área Bajo la Curva , Biomarcadores/sangre , Estudios de Cohortes , Rechazo de Injerto/genética , Rechazo de Injerto/metabolismo , Humanos , Curva ROC , Transcriptoma , Trasplante HomólogoRESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de los Músculos/genética , Neoplasias de los Músculos/mortalidad , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Carcinoma Papilar/genética , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de los Músculos/patología , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
AIM: To analyze the clinicopathological features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 RCC) in our institution. MATERIALS & METHODS: We screened 983 RCC specimens. TFE3 immunohistochemical staining and FISH assay confirmed 22 Xp11.2 RCCs out of 65 suspicious cases. Clinicopathological and treatment outcomes of 22 patients were retrospectively analyzed. RESULTS: In total, 22 patients included 13 females and nine males with a mean age of 27 years. Ten patients showed gross hematuria. Treatments included surgeries, immunotherapy and molecular-targeted therapy. Seven cases were at stage III/IV and four cases had tumor thrombosis or distant metastasis. During a median follow-up of 34 months, 19 patients were alive while three died of distant metastasis. CONCLUSION: Xp11.2 RCC is rare and FISH proved a useful diagnostic tool. Surgical resection achieved favorable outcome for early disease. Adult patients at advanced stage had poorer outcomes even with postoperative adjuvant therapy.
Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/genética , Cromosomas Humanos X , Neoplasias Renales/genética , Proteínas de Fusión Oncogénica/genética , Translocación Genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/terapia , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Renales/diagnóstico , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas de Fusión Oncogénica/metabolismo , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVE: To explore the pneumoperitoneum-mediated renoprotective effects of preconditioning, mobilizing and homing of endothelial progenitor cells (EPCs) in rats. METHODS: A total of 40 rats were randomized by a numerical table into 5 groups of gasless (C), pneumoperitoneum injury (Pp), long-term pneumoperitoneum preconditioning (P-L), mid-term pneumoperitoneum preconditioning (P-M) and short-term pneumoperitoneum preconditioning (P-S). C group had a pneumoperitoneum pressure of 0 mmHg; Pp group 15 mmHg, time 60 min; P-L, P-M, P-S groups were deflated and deflated preconditioning before pneumoperitoneum, then the same as Pp group, P-L group: inflation time was 25 min, gas discharge time 10 min; P-M group: 15 min, 10 min; P-S group: 5 min, 10 min. At 24 h post-operation, the animals were sacrificed by destroying cervical spine. And the specimens of venous blood and kidneys were harvested. Also the extent of renal injury, the homing of EPCs, the proliferation and angiogenesis of renal endothelial cell and the expression of angiogenic growth factor were analyzed. RESULTS: Compared with Pp group, P-L, P-M and P-S groups exhibited significant improvements in renal function, morphology and histological score (1.88 ± 0.35, 1.63 ± 0.52, 1.75 ± 0.46 vs 2.38 ± 0.52, all P < 0.05). The histological scores of P-M and P-S groups improved significantly versus P-L group (both P < 0.05). P-M and P-S groups showed no significant difference in histological score (P > 0.05). The number of EPCs in kidneys increased in P-L, P-M and P-S groups versus Pp group (2.18% ± 0.14%, 2.87% ± 0.29%, 2.90% ± 0.24% vs 1.73% ± 0.19%, all P < 0.05). The EPCs numbers of P-M and P-S groups were more than that of P-L group (both P < 0.05). And no significant difference existed between P-M and P-S groups (P > 0.05). Compared with Pp group, EPCs of P-L, P-M and P-S groups markedly increased in kidneys. No significant difference existed between P-M and P-S groups, but P-L group was the lowest. Also there was an up-regulated expression of stromal cell derived factor 1-α in pretreated kidneys versus Pp group (all P < 0.05). And P-M and P-S groups increased markedly. CONCLUSIONS: Pneumoperitoneum-mediated preconditioning protects against kidney injury by promoting EPC homing and enhancing endothelial cell and vascular proliferations. And short and medium-term preconditioning protocols are more effective for protecting kidneys.