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INTRODUCTION: The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) and to provide a basis for clinical prevention of recurrence of NMIBC. METHODS: From January 2012 to December 2020, 592 patients with NMIBC who underwent TURBT attending the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively included in this study. Patients were divided into relapse and relapse-free groups according to whether relapse occurred within 2 years. Ultimately, 72 patients were included in the relapse group and 350 patients were included in the relapse-free group. Observation indicators included age, sex, smoking, underlying disease (hypertension, diabetes, coronary heart disease), two or more lesions, tumor size, hematuria, pathology grading (low, medium, high), staging (Ta, T1), muscular invasion in initial pathology, tumor base (sessile, pedunculated), use of intravesical drug (pirarubicin, bacillus Calmette-Guerin [BCG], mitomycin, hydroxycamptothecin, gemcitabine). RESULTS: In this study, the 2-year recurrence rate of NMIBC patients after TURBT was 17.06%. There were significant differences in comparison of pirarubicin, BCG, and mitomycin treatment between the two groups (p < 0.05). To avoid missing risk factors for recurrence, factors with p < 0.1 were analyzed. The results of univariate logistic regression analysis showed that NMIBC patients with BCG treatment (OR = 5.088, 95% CI = 1.444-17.73, p = 0.012), high pathology grading (OR = 0.415, 95% CI = 0.197-0.880, p = 0.023), T1 stage (OR = 2.097, 95% CI = 0.996-4.618, p = 0.059), mitomycin treatment (OR = 5.029, 95% CI = 1.149-21.77, p = 0.031), and pirarubicin treatment (OR = 1.794, 95% CI = 1.079-3.030, p = 0.024) had significantly higher risk of recurrence within 2 years after TURBT. The results of multivariate logistic regression analysis showed that NMIBC patients with high pathology grading (OR = 0.4030, 95% CI = 0.1702-0.8426, p = 0.0241), pirarubicin treatment (OR = 1.961, 95% CI = 1.159-3.348, p = 0.0125), and BCG treatment (OR = 6.201, 95% CI = 1.275-29.73, p = 0.0190) had significantly higher risk of recurrence within 2 years after TURBT. CONCLUSION: Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of mitomycin and BCG on recurrence rates.
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Doxorrubicina/análogos & derivados , Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Estudios de Seguimiento , Estudios Retrospectivos , Vacuna BCG/uso terapéutico , Resección Transuretral de la Vejiga , Recurrencia Local de Neoplasia/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Mitomicina/uso terapéutico , Factores de Riesgo , Recurrencia , Invasividad NeoplásicaRESUMEN
Background: Urethral stricture is a common disorder of the lower urinary tract in men. A complex network of pathways and interactions are involved in the pathogenesis of urethral fibrosis. However, the mechanisms underlying urethral fibrosis remain poorly understood. Objectives: To investigate the critical role of the canonical Wnt pathway in development of urethral fibrosis and explore DKK1, the endogenous inhibitor of Wnt pathway, as a potential target to prevent urethral fibrosis in vitro and in vivo. Methods: Urethral fibrosis tissue derived from patients and rat models were harvested to assess the activation of the canonical Wnt pathway by using western blot, qRT-PCR and immunohistochemistryWe performed histological staining, western blot, qRT-PCR and immunohistochemistry to examine the effects of DKK1 treatment on in vivo rat urethral fibrosis models. In vitro, human urethral fibroblasts (HUFs) were cultured to examine the effects of DKK1 in TGFß1-induced HUFs by CCK-8 assay, hydroxyproline assay, flow cytometry, cell migration assay, western blot, qRT-PCR and immunofluorescence. Results: The key components of Wnt signaling were upregulated in urethral fibrosis tissue derived from patients and rat models while DKK 1 was downregulated. DKK1 ameliorated TGFß1-induced urethral fibrosis in rats. TGFß1 induced myofibroblast differentiation by upregulating collagen I, collagen III, α-SMA, ß-catenin and p-GSK-3ß, while DKK1 was decreased. DKK1 significantly inhibited cell proliferation, collagen content, cell migration and promoted cell apoptosis in TGFß1-induced HUFs. DKK1 significantly suppressed myofibroblast differentiation of TGFß1-induced HUFs by downregulating collagen I, collagen III, α-SMA, ß-catenin and p-GSK-3ß with a mechanism independent of Smad2/3. Conclusions: Our study demonstrated that canonical Wnt pathway may be an essential mechanism underlying the pathogenesis of urethral fibrosis and explored the potential role of DKK1 participation in the development of urethral fibrosis.
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Vía de Señalización Wnt , beta Catenina , Animales , Humanos , Masculino , Ratas , beta Catenina/metabolismo , Diferenciación Celular/genética , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Fibrosis , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patologíaRESUMEN
Circular RNAs (circRNAs) take on regulatory roles in renal cell carcinoma (RCC). The research's goal was to figure out circ-CSPP1's role and molecular mechanism in RCC. The results clarified that circ-CSPP1 expression was enhanced in RCC. Down-regulating circ-CSPP1 refrained the proliferation, migration, invasion, and Warburg effect (aerobic glycolysis), but accelerated apoptosis of RCC cells. The luciferase activity assay exhibited that circ-CSPP1 could perform as an endogenous sponge for miR-493-5p. Elevating miR-493-5p repressed RCC progression. The bioinformatics website starBase confirmed that ras-related C3 botulinum toxin substrate 1 (RAC1) was a target gene of miR-493-5p. Circ-CSPP1 up-regulated RAC1 by sponging miR-493-5p, and elevating RAC1 could turn around the effect of down-regulating circ-CSPP1 on RCC cells. Taken together, circ-CSPP1 is identified as a novel RCC-promoting RNA that could serve as a latent therapeutic target for RCC therapy.
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Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Humanos , ARN Circular/genética , Carcinoma de Células Renales/genética , Carcinogénesis/genética , Neoplasias Renales/genética , MicroARNs/genética , Proteína de Unión al GTP rac1/genética , Proteínas Asociadas a Microtúbulos , Proteínas de Ciclo CelularRESUMEN
Urethral stricture secondary to urethral injury, afflicting both patients and urologists, is initiated by excessive deposition of extracellular matrix in the submucosal and periurethral tissues. Although various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, their clinical feasibility and effectiveness are limited. Here, to target the pathological state of the extracellular matrix, we design a protein-based nanofilm-controlled drug delivery system and assemble it on the catheter. This approach, which integrates excellent anti-biofilm properties with stable and controlled drug delivery for tens of days in one step, ensures optimal efficacy and negligible side effects while preventing biofilm-related infections. In a rabbit model of urethral injury, the anti-fibrotic catheter maintains extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation, resulting in a greater improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such facilely fabricated biocompatible coating with antibacterial contamination and sustained-drug-release functionality could not only benefit populations at high risk of urethral stricture but also serve as an advanced paradigm for a range of biomedical applications.
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Estrechez Uretral , Animales , Conejos , Estrechez Uretral/tratamiento farmacológico , Estrechez Uretral/patología , Estrechez Uretral/prevención & control , Catéteres Urinarios , Colágeno/metabolismo , Fibrosis , Matriz Extracelular/metabolismo , Sistemas de Liberación de MedicamentosRESUMEN
OBJECTIVE: To investigate the value of gemcitabine and pirarubicin in patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: 405 patients with non-muscle invasive bladder cancer admitted to our hospital from January 2012 to December 2020 who underwent transurethral bladder tumor electronic resection were studied. 177 patients were treated with gemcitabine (Gemcitabine group) and 228 patients were treated with pirarubicin (Pirarubicin group) after surgery. The efficacy and adverse effects of the two groups were observed and the patients were followed up. RESULTS: No differences were found when comparing age, gender, smoking, bladder mass, number of masses, hypertension, diabetes, coronary artery disease, hematuria and tumor diameter between the 2 groups (P > 0.05). In the Gemcitabine group, bladder irritation signs, meatus hematuria, fever, nausea and vomiting were lower than those in the Pirarubicin group (P < 0.05). The recurrence rates were 6.21% and 12.28% at 1 year, 11.86% and 23.68% at 2 years, 15.82% and 25.88% at 3 years in the Gemcitabine and Pirarubicin groups respectively, with the Gemcitabine group having a significantly lower recurrence rate than the Pirarubicin group (P < 0.05). The tumor recurrence-free survival rate for 5 years of gemcitabine was significantly higher than that of the Pirarubicin group (P < 0.05). CONCLUSION: Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Gemcitabina , Hematuria/inducido químicamente , Administración Intravesical , Neoplasias de la Vejiga Urinaria/patología , Recurrencia Local de Neoplasia/epidemiología , Invasividad NeoplásicaRESUMEN
Background: Flexible ureteroscopy (FURS) and holmium laser lithotripsy is considered one of the most minimally invasive and safe surgical methods for the treatment of renal calculi. Renal pseudoaneurysm is a rare complication after FURS holmium laser lithotripsy. We report a case of renal pseudoaneurysm after FURS and holmium laser lithotripsy and review the relevant literature to analyze the possible etiology and summarize the treatment. Case presentation: A 29-year-old male with a 2-year history of diabetes was admitted to the hospital because of right back pain for 5 days. A doppler ultrasound demonstrated bilateral renal calculi with bilateral mild hydronephrosis. The patient underwent one-stage right FURS and holmium laser lithotripsy and bilateral ureteral stent implantation. The urine was clear on the second day after the operation, and he was discharged from the hospital. Due to severe gross hematuria, he had to be hospitalized 28 days after the operation. A CT scan showed multiple blood clots in the right renal pelvis and bladder. An emergency blood transfusion and removal of the bladder blood clots and bilateral double J tubes were performed. His urine was clear for one week, and he was discharged from the hospital. He was hospitalized again 47 days after the operation because of fever and hematuria. A CT scan demonstrated blood clots in the bladder and right renal pelvis. Angiography showed a pseudoaneurysm in a small branch of the right renal artery, and hematuria stopped after selective renal artery embolization with microcoils. Conclusion: FURS and holmium laser lithotripsy is safe, but we should be aware of the possibility of renal artery pseudoaneurysms (RAP). Through careful operation during the surgery, avoiding kidney injury, reducing intrarenal pressure and controlling the time of operation may prevent the occurrence of this complication. Vascular embolization is the first choice for the treatment of pseudoaneurysms.
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Urethral stricture (US) is a common disorder of the lower urinary tract in men caused by fibrosis. The recurrence rate of US is high; however, there are no effective therapies to prevent or treat urethral fibrosis. The pathogenesis of urethral fibrosis involves myofibroblast activation and excessive extracellular matrix (ECM) deposition. The molecular mechanisms underlying this pathological activation are not completely understood. It has been demonstrated that Notch signalling contributes to the development of fibrosis and inflammation. However, whether this contributes to urethral fibrosis remains unclear. In this study, activation of Notch signalling was observed in patients with US. Additionally, it was noted that activation of Notch signalling promoted ECM production and myofibroblast activation in human urethral scar fibroblasts (HUSFs) treated with transforming growth factor (TGF) ß1. However, the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppressed activation of Notch signalling as well as proliferation and migration of the TGFß1-treated HUSFs. Additionally, DAPT ameliorated TGFß1-induced urethral fibrosis in Sprague Dawley rats by suppressing ECM production, myofibroblast activation and the TGFß signalling pathway. These findings demonstrate that Notch signalling may be a promising and potential target in the prevention or treatment of urethral fibrosis.
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Fibrosis/metabolismo , Receptores Notch/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Estrechez Uretral/metabolismo , Anciano , Animales , Células Cultivadas , Fibroblastos , Humanos , Masculino , Persona de Mediana Edad , Ratas , Ratas Sprague-Dawley , Estrechez Uretral/patologíaRESUMEN
Many studies have recognized that circular RNAs (circRNAs) can be promising targets for renal cell carcinoma (RCC) by acting as competing endogenous RNAs for miRNAs. This study intends to uncover the implication of a novel circRNA, circ_000926 in RCC, and how it affects tumorigenesis. Microarray-based circRNA/gene expression profiling of RCC was used to identify differentially expressed circRNAs/genes in RCC and normal tissues. miRNAs targeting the screened circRNAs/genes were predicted online, followed by analyzing circ_000926 expression in RCC. The crosstalk among circ_000926, miRNA-411 (miR-411), and CDH2 was then validated. The expression of circ_000926, miR-411, and cadherin 2 (CDH2) was up-regulated or down-regulated in RCC cells to unearth their effects on the biological behaviors of RCC cells. circ_000926 was highly expressed in RCC tissues and cell lines, whereas CDH2 was verified to be a target of miR-411. As a competing endogenous RNA, circ_000926 could directly bind to miR-411 to up-regulate CDH2. Down-regulation of circ_000926 resulted in inhibited growth, migration, and invasion abilities of RCC cells, as well as suppressed epithelial-mesenchymal transition and tumor growth. However, the inhibition of miR-411 or elevation of CDH2 reversed the antitumor effects induced by silencing circ_000926. Down-regulation of circ_000926 exerts an inhibitory effect on RCC progression through miR-411-dependent CDH2 inhibition, highlighting a potential target for RCC treatment.
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Antígenos CD/metabolismo , Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , MicroARNs/genética , ARN Circular/genética , Animales , Antígenos CD/genética , Apoptosis , Biomarcadores de Tumor/genética , Cadherinas/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Adhesión Celular , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: TGFß1 and mTOR are considered to play important roles in fibrotic diseases. Rapamycin has been reported to inhibit urethral stricture formation in a rabbit model of urethral fibrosis. AIM: To evaluate if dual mTOR inhibitor has a superior efficacy compared with rapamycin on inhibiting cell proliferation and collagen expression in human urethral scar fibroblasts (HUSFs). METHODS: We established HUSF cultures from fresh surgical specimen. The HUSFs were identified with typical fibroblast markers using immunofluorescence. Then we examined the effect of TGFß1 on HUSFs using Cell Counting Kit-8 and Western blot. The inhibiting effects of OSI-027 (a dual mTOR inhibitor) on cell proliferation and collagen expression in TGFß1-induced HUSFs were compared with rapamycin using Cell Counting Kit-8, Western blot, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: HUSFs were stained positive for vimentin, collagen I, and collagen III. TGFß1 had no effect on cell proliferation but increased collagen I and collagen III expressions in HUSFs. OSI-027 was more effective inhibiting cell proliferation and collagen expression compared with rapamycin in TGFß1-induced HUSFs. OSI-027 played a more important role in inhibiting TGFß1-induced mTOR pathway and phosphorylation of Smad2 compared with rapamycin in HUSFs. CONCLUSION: OSI-027 can inhibit the pro-fibrotic effects of TGFß1 significantly compared with rapamycin in HUSFs. These findings may provide a new therapy in the adjunctive treatment of urethral stricture disease.
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Cicatriz/tratamiento farmacológico , Fibroblastos/efectos de los fármacos , Imidazoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/farmacología , Triazinas/farmacología , Uretra/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cicatriz/enzimología , Cicatriz/patología , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo III/metabolismo , Relación Dosis-Respuesta a Droga , Fibroblastos/enzimología , Fibroblastos/patología , Fibrosis , Humanos , Fosforilación , Cultivo Primario de Células , Transducción de Señal , Proteína Smad2/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Uretra/enzimología , Uretra/patología , Vimentina/metabolismoRESUMEN
Rapamycin can inhibit fibroblast proliferation, collagen accumulation, and urethral stricture in rabbits. Transforming growth factor-beta-1 (TGF-ß1) signaling, with downstream recruitment of Smad2, is known to promote fibrosis. This in vitro study examined the effects of rapamycin on fibroblasts derived from human urethral scar tissue (FHUS) and investigated the possible mechanism with respect to regulation of TGF-ß1 signaling. FHUS were cultured from urethral scar tissues collected from four patients with urethral stricture. The cells were exposed to different concentrations of rapamycin (0, 10, 20, 40, 80, or 160 ng/ml) for 24 or 48 hours. Cell growth was assessed by the MTT assay. Collagen content was measured based on hydroxyproline levels. The mRNA expressions of Smad2, eIF-4E, and alpha-1 chains of collagen types I and III (Col1α1 and Col3α1) were determined by semiquantitative reverse-transcription PCR. The protein expressions of Smad2, phospho-Smad2, and eIF-4E were evaluated by western blot. Rapamycin caused a concentration-dependent inhibition of FHUS growth at 24 and 48 hours (P < 0.01). Rapamycin decreased total collagen content (P < 0.01), collagen content per 105 cells (P < 0.05), and mRNA expressions of Col1α1 and Col3α1 (P < 0.05) in a concentration-dependent manner. Rapamycin elicited concentration-dependent reductions in the mRNA (P < 0.05) and protein (P < 0.01) expressions of Smad2 and eIF-4E. The two highest concentrations of rapamycin also enhanced phospho-Smad2 levels (P < 0.01). In conclusion, the present study confirmed that rapamycin may reduce the growth and collagen production of FHUS, possibly through inhibition of TGF-ß1 signaling.
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Cicatriz/patología , Colágeno/biosíntesis , Fibroblastos/metabolismo , Fibroblastos/patología , Sirolimus/farmacología , Uretra/patología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Factor 4E Eucariótico de Iniciación/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Fosforilación/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína Smad2/genética , Proteína Smad2/metabolismoRESUMEN
PURPOSE: To present our single-center experience with retroperitoneal laparoscopic partial nephrectomy (LPN) and retroperitoneal laparoscopic radical nephrectomy (LRN) for T1 renal hilar tumors and evaluate which one is better. METHODS: A retrospective review of 63 patients with hilar tumors undergoing retroperitoneal LPN or LRN was performed. The perioperative characteristics, change in estimated glomerular filtration rate (eGFR) from baseline to month 3, and oncologic outcomes were summarized. RESULTS: In total, 25 patients underwent LPN, and 38 patients underwent LRN. The mean tumor size in the LPN and LRN groups was 4.5 and 4.9 cm, respectively. The mean operation time was longer in the LPN group than that in the LRN group (212.5 minutes versus 160.7 minutes, respectively; P < .05). Patients undergoing the LPN had a longer median length of hospital stay after surgery (9 days versus 7 days, P < .05). Four percent of patients in the LPN group experienced postoperative complications compared with 5% of patients in the LRN group, which was not significantly different. Compared with preoperative eGFR, postoperative eGFR at 3 months decreased by 15.2 mL/min/1.73 m2 and 27.8 mL/min/1.73 m2 in the LPN and the LRN groups, respectively (P < .05). There was one local recurrence in the LPN group and three local or distant recurrences in the LRN group (P > .05). CONCLUSIONS: In experienced hands, although retroperitoneal LRN can result in shorter operation times and shorter lengths of stay, retroperitoneal LPN can preserve renal function better than LRN. Retroperitoneal LPN should be the priority in selected patients with T1 renal hilar tumors, especially for patients with renal insufficiency.
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Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Conversión a Cirugía Abierta/estadística & datos numéricos , Femenino , Tasa de Filtración Glomerular , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Nefrectomía/efectos adversos , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Novel magnetic molecularly imprinted nanomaterials (DAâ¯+â¯BSA-MMIPs) were prepared adopting bovine serum albumin (BSA) and dopamine as bifunctional monomers for the first time. Besides the role of assistant functional monomer, BSA can exclude the proteins with like charges and promote low molecular weight tetracyclines to be adsorbed. Thus, the DAâ¯+â¯BSA-MMIPs could fulfil the selective separation of tetracyclines directly from milk samples. The characteristics, polymerization conditions, and adsorption performances of the resultant nanomaterials were investigated in detail. In addition of uniform imprinting layers, stable crystalline phase, and good magnetism of the DAâ¯+â¯BSA-MMIPs, they have rapid binding kinetic, high adsorption capacity, and favorable reusability. The imprinted nanomaterials were coupled with HPLC to selectively extract and determine trace tetracyclines from untreated milk samples. The recoveries of tetracyclines are in the range of 84.1-95.8% with relative standard deviations of less than 6.7%. The developed method is especially suitable for the selective enrichment and detection of target compounds directly from a complex sample with proteins.
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The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) gene has been recognized to be a protooncogene and to be linked to human malignancies. However, the additional functions of EZH2 in renal cell carcinoma (RCC) are not completely understood. In the present study, a possible role of EZH2 in RCC was identified. EZH2 was demonstrated to promote the cell proliferation and invasion potential of 769P cells, and inhibition of EZH2 was demonstrated to prevent these two processes in 786O cells. Mechanically, EZH2 was demonstrated to increase the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and upregulate 72 kDa type IV collagenase (MMP2) expression. When cells were treated with small interfering RNA targeting STAT3 or Stattic, a specific inhibitor of STAT3, the invasive ability of the cells was decreased and downregulation of MMP2 was observed. Based on these results, in the present study it was hypothesized that EZH2 may serve a critical role in the progression of RCC. Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC.
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Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Adhesión Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Proteína Potenciadora del Homólogo Zeste 2/antagonistas & inhibidores , Proteína Potenciadora del Homólogo Zeste 2/genética , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Fosforilación , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/genéticaRESUMEN
MicroRNAs (miRNAs) have been known to be implicated in tumorigenic programs. miR-1297 has been reported to be dysregulated and involved in cancer progression in many types of human cancers. However, the expression level and the role of miR-1297 in prostate cancer remain unclear. Herein, we aimed to investigate the potential role and molecular mechanism of miR-1297 in prostate cancer progression. We found that miR-1297 was significantly downregulated in human prostate cancer specimens as well as in several prostate cancer cell lines. In addition, functional experiments demonstrated that overexpression of miR-1297 remarkably inhibited prostate cancer cell proliferation and invasion whereas miR-1297 suppression significantly promoted prostate cancer cell proliferation and invasion. Bioinformatics analysis showed that the Astrocyte elevated gene-1 (AEG-1), a well-known oncogene, is a predicted target of miR-1297. Dual-luciferase reporter assay showed that miR-1297 was able to directly target the 3'-untranslated region of AEG-1. In addition, RT-qPCR and Western blot analysis showed that miR-1297 regulated the mRNA and protein expression levels of AEG-1. We also showed that miR-1297 was able to regulate the Wnt signaling pathway. Moreover, rescue assays indicated that AEG-1 contributed to miR-1297-endowed effects on cell proliferation and invasion as well as Wnt signaling pathway. Taken together, these findings suggest that miR-1297 inhibits prostate cancer proliferation and invasion by targeting AEG-1, thereby providing novel insight into understanding the pathogenesis of prostate cancer. Thus, miR-1297 may be a novel potential therapeutic candidate to treat prostate cancer.
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Moléculas de Adhesión Celular/metabolismo , MicroARNs/genética , Neoplasias de la Próstata/genética , Vía de Señalización Wnt/genética , Regiones no Traducidas 3' , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Proteínas de la Membrana , MicroARNs/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas de Unión al ARNRESUMEN
The insect pathogenic fungus Aschersonia placenta is a highly effective pathogen of whiteflies and scale insects. However, few genetic tools are currently available for studying this organism. Here we report on the conditions for the production of transformable A. placenta protoplasts using an optimized protocol based on the response surface method (RSM). Critical parameters for protoplast production were modelled by using a Box-Behnken design (BBD) involving 3 levels of 3 variables that was subsequently tested to verify its ability to predict protoplast production (R(2) = 0.9465). The optimized conditions resulted in the highest yield of protoplasts ((4.41 ± 0.02) × 10(7) cells/mL of culture, mean ± SE) when fungal cells were treated with 26.1 mg/mL of lywallzyme for 4 h of digestion, and subsequently allowed to recover for 64.6 h in 0.7 mol/L NaCl-Tris buffer. The latter was used as an osmotic stabilizer. The yield of protoplasts was approximately 10-fold higher than that of the nonoptimized conditions. Generated protoplasts were transformed with vector PbarGPE containing the bar gene as the selection marker. Transformation efficiency was 300 colonies/(µg DNA·10(7) protoplasts), and integration of the vector DNA was confirmed by PCR. The results show that rational design strategies (RSM and BBD methods) are useful to increase the production of fungal protoplasts for a variety of downstream applications.
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Algoritmos , Técnicas Genéticas , Hypocreales/genética , Protoplastos , Transformación Genética , ÓsmosisRESUMEN
Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.
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Dietilhexil Ftalato/administración & dosificación , Genisteína/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Animales , Femenino , Humanos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Testículo/efectos de los fármacos , Testículo/crecimiento & desarrollo , Testosterona/biosíntesisRESUMEN
INTRODUCTION: Urethral stricture, a frequent source of lower urinary tract disorders in men, is still a difficult problem for urologists. Based the anti-restenosis effect of paclitaxel on coronary artery, the role of docetaxel, a semi-synthetic analogue of paclitaxel, in limiting urethral stricture formation was studied. METHODS: Forty adult New Zealand male rabbits were involved in this study, which were randomly assigned into 3 groups, namely a high dose docetaxel (DH, 0.1 mg/d), a low dose docetaxel (DL, 0.01 mg/d) and a control (C) group, with 16, 16, 8 rabbits in each group, respectively. All animals underwent a 10 mm-long circumferential electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Drugs were given by urethral irrigation daily and continuous for 28 days. Stricture formation was assessed by retrograde urethrography and videourethroscopy. Urethra pathology was evaluated by hematoxylin and eosin staining and Sirius red staining. RESULTS: At the end of this study, 15, 14 and 7 rabbits remained for evaluation in DH, DL and C group, respectively. Urethral diameters in DH, DL and C group were (7.17±1.63) mm, (6.55±0.62) mm, (3.23±1.36) mm, with a normal urethral diameter of (9.08±1.29) mm. Lumen reduction in DH, DL and C group were (36.93±11.58)%, (48.03±7.89)% and (84.66±14.95)%, respectively. Statistically difference could be found between every two groups (p<0.05) both in urethral diameters and in lumen reduction, except for compare of urethral diameters between DH and DL group. Histological examination confirmed mass fibrous tissue and collagen content at the stricture sit in C group, whereas less in docetaxel treated rabbits. CONCLUSIONS: Docetaxel could limit urethral stricture formation, which may be due to inhibition of fibrous tissue and collagen expression. Docetaxel may become a new choice in the prevention of urethral stricture formation.
Asunto(s)
Taxoides/administración & dosificación , Estrechez Uretral/tratamiento farmacológico , Estrechez Uretral/patología , Animales , Colágeno/metabolismo , Modelos Animales de Enfermedad , Docetaxel , Esquema de Medicación , Masculino , Proyectos Piloto , Conejos , Taxoides/farmacología , Estrechez Uretral/prevención & controlRESUMEN
In the present study, we compared the expression of miRNAs and angiogenesis-related genes in the renal tumors and adjacent normal renal tissues of patients with clear cell renal cell carcinoma (ccRCC). The first part of the present study was a preliminary analysis of 4 patients with stage T1a/b ccRCC that measured the levels of angiogenesis and expression of angiogenesis-related genes and miRNAs in the tumors and adjacent normal renal tissues. The second part of this study was an analysis of 30 patients with stage T1, T2 or T3 ccRCC that employed qPCR to characterize expression of angiogenesis-related miRNAs in the tumors and adjacent normal tissues. The first part of this study indicated that all 4 patients had increased levels of CD34 in tumors, indicating elevated angiogenesis. However, quantitative analysis of microvessel density and expression of miRNAs indicated highly variable results among these patients. The data of all patients in the present study indicated that more patients with stage T1 ccRCC had higher expression of miR-126 and miR-378 in their normal tissues, whereas more patients with stage T2/3 ccRCC had higher expression of these miRNAs in their tumor tissues. The tumors of patients with ccRCC had lower expression of miR-126 and miR-378 during the early stages of disease (T1), but higher expression of these miRNAs during the later stages of disease (T2/T3).
Asunto(s)
Carcinoma de Células Renales/genética , Neoplasias Renales/genética , MicroARNs/genética , Neovascularización Patológica/genética , Anciano , Antígenos CD34/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Riñón/irrigación sanguínea , Riñón/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismoRESUMEN
PATIENT: Male, 24 FINAL DIAGNOSIS: Urethral stricture Symptoms: - MEDICATION: - Clinical Procedure: - Specialty: Urology. OBJECTIVE: Unusual or unexpected effect of treatment. BACKGROUND: The most dependable management of anterior urethral stricture is the complete excision of the area of fibrosis, with a primary reanastomosis of the normal ends of the anterior urethra. CASE REPORT: A 24-year-old man had urethral stricture in the penoscrotal junction caused by catheterization approximately 3 years ago. After the resection of the urethral stricture segment and the end-to-end anastomosis were performed, in addition to stricture, urethrocutaneous fistula formation as another complication in the penoscrotal junction was confirmed. The direct vision internal urethrotomy did not improve all the above symptoms. The retrograde urethrogram and voiding cysto-urethrogram showed complete obliteration in the penile urethra, urethrocutaneous fistula, and proximal urethral bifurcation singularity. Intraoperatively, we found that the distal urethral end had been anastomosed to the proximal false passage in the initial surgery and the proximal urethra was located in the dorsal side of the false passage. Then, tubularized preputial flap urethroplasty was performed. The patient was followed up for 10 months. His peak urinary flow was 18.3 milliliter per second. CONCLUSIONS: We would remind urologists that urethral end intraoperatively anastomosed to the false passage is a rare, serious, avoidable, and elementary medical error. Urethroplasty is one of the curative choices for treatment of this unexpected condition.
RESUMEN
Rapamycin has been reported to inhibit hepatic fibrosis, lung fibrosis, renal fibrosis, and subglottic stenosis. Fibrosis is also involved in urethral stricture. Therefore, we investigated the effect of rapamycin on the inhibition of urethral stricture formation in a rabbit model. First, models of urethral stricture were successfully established by electrocoagulation of the bulbar urethra in adult New Zealand male rabbits. Forty-six model rabbits were randomly assigned to four groups: high-dose rapamycin (R(H), 1.0 mg/day), low-dose rapamycin (R(L), 0.1 mg/day), dimethyl sulfoxide (DMSO) alone (DMSO, solvent control), and normal saline (NS). Urethral stricture was assessed by a retrograde urethrogram and video-urethroscopy. Urethra pathology was evaluated by hematoxylin and eosin and Sirius red staining. After 28 days of treatment, lumen reduction in the R(H), R(L), DMSO, and NS groups was 36.0, 56.5, 69.1, and 82.9, respectively. Comparison of the rapamycin groups (R(H) and R(L)) and control groups (DMSO and NS) indicated significantly less restriction in the rapamycin groups. Histopathological analysis confirmed the presence of fibroblasts and an increase in collagen at the stricture site in the two control groups but not in the R(H) or R(L) groups. These results indicate that rapamycin inhibits experimentally induced urethral stricture formation in rabbits. This effect may be due to its inhibition of fibroblast proliferation and collagen expression.