Yun-Fei Xu

Combination of quercetin and hyperoside has anticancer effects on renal cancer cells through inhibition of oncogenic microRNA-27a

Quercetin and hyperoside (QH) in combination (1:1 ratio) have previously been shown to inhibit the growth of human leukemia cells. Here, we investigated the anticancer activity of the same mixture in 786-O renal cancer cells. QH decreased the generation of reactive oxygen species (ROS) by up to 2.25-fold and increased the antioxidant capacity by up to 3-fold in 786-O cells (3.8-60 μg/ml), whereas IC50 values for viability were 18.2, 18.7 and 11.8 μg/ml, respectively. QH also induced caspase-3 cleavage (2-fold) and increased PARP cleavage. Specificity protein (Sp) transcription factors are overexpressed in cancer cells and regulate genes required for cell proliferation, survival and angiogenesis. QH treatment decreased the expression of Sp1, Sp3 and Sp4 mRNA and this was accompanied by decreased protein expression. Moreover, expression of the Sp-dependent anti-apoptotic survival gene survivin was also significantly reduced, both at the mRNA and protein levels. QH decreased microRNA-27a (miR-27a) and induced the zinc finger protein ZBTB10, an Sp-repressor, suggesting that interactions between QH and the miR-27a-ZBTB10 axis play a role in Sp downregulation. This was confirmed by transfection of cells with a specific mimic for miR-27a, which partially reversed the effects of QH. These findings are consistent with previous studies on botanical anticancer agents in colon cancer cells.

A comparative study of thulium laser resection of the prostate and bipolar transurethral plasmakinetic prostatectomy for treating benign prostatic hyperplasia

Thulium laser is a new generation of surgical laser. It is a minimally invasive technology with several advantages, including rapid vaporization and minimal tissue damage and bleeding. However, details regarding the safety and efficacy of thulium laser in treating BPH remains unknown. We performed a comparative study in 100 patients with BPH of the safety and efficacy of thulium laser resection of the prostate (TMLRP, n = 50) and bipolar transurethral plasmakinetic prostatectomy (TUPKP, n = 50). We found that the efficacy and indications were the same in TMLRP and TUPKP. In TUPKP, the morbidity of urethrostenosis was low, and was nearly bloodless in surgery and had higher safety. Nevertheless, TUPKP is more suitable for patients with larger prostate volume.

High Level of Circulating Endothelial Progenitor Cells Positively Correlates with Serum Vascular Endothelial Growth Factor in Patients with Renal Cell Carcinoma

PURPOSE Although accumulated evidence indicates that circulating endothelial progenitor cells contribute to tumor neovascularization, to our knowledge the level of these cells and its correlation with serum vascular endothelial growth factor in patients with renal cell carcinoma have not been studied. We measured this level and investigated its clinical significance in patients with renal cell carcinoma. MATERIALS AND METHODS The level of circulating endothelial progenitor cells (percent of total peripheral blood mononuclear cells) was quantified by assaying the CD45(-)CD34(+)vascular endothelial growth factor receptor 2(+) cell phenotype in 53 patients with renal cell carcinoma, 33 with benign renal tumors and 40 healthy controls. Serum vascular endothelial growth factor was quantified. RESULTS The mean circulating endothelial progenitor cell level in patients with renal cell carcinoma was 0.281%, significantly higher than in patients with benign renal tumors and healthy controls (0.073% and 0.076%, respectively, each p <0.001). Patients with stage III-IV renal cell carcinoma had a statistically higher level of these cells than those with stage I-II (0.339% vs 0.243%, p <0.001). The mean level in patients with renal cell carcinoma greater than 7 cm was 0.331%, significantly higher than in those with tumors 4 or less and 4 to 7 cm (0.225% and 0.231%, respectively, each p <0.001). Mean serum vascular endothelial growth factor in patients with renal cell carcinoma was higher than in patients with benign renal tumors and healthy controls (315.5 vs 34.6 and 26.9 pg/ml, respectively, each p <0.001). The preoperative circulating endothelial progenitor cell level positively correlated with serum vascular endothelial growth factor in patients with renal cell carcinoma (r = 0.710, p <0.001). Levels of these cells and of vascular endothelial growth factor significantly decreased postoperatively compared to preoperatively (0.081% vs 0.297% and 31.69 vs 310.70 pg/ml, respectively, each p <0.001). CONCLUSIONS A high circulating endothelial progenitor cell level was found in patients with renal cell carcinoma, which positively correlated with serum vascular endothelial growth factor. Results support the potential use of circulating endothelial progenitor cells as a novel biomarker for renal cell carcinoma.

Protective Effects of SP600125 on Renal Ischemia-Reperfusion Injury in Rats

BACKGROUND Ischemia/reperfusion injury (IRI) has a negative effect on renal allograft survival. Using a rat model of kidney IRI in this study, we investigated the overall effect of selective c-Jun N-terminal kinase (JNK) inhibitor SP600125 on renal IRI events. METHODS All 45 Fisher rats were anesthetized and renal IRI model was established by 45 min clamp of bilateral renal pedicles and 24 h reperfusion. Vehicle solution or SP600125 solution was intraperitoneally injected 45 min before ischemia, respectively. Analysis of renal histology, function, reactive oxygen species (ROS) expression, JNK phosphorylation status, as well as intra-renal pro-inflammatory cytokines expression was evaluated in this study. RESULTS After IRI, the levels of blood urea nitrogen, creatinine, tissue malondialdehyde, TNF-α, IL-1β, IL-6 were all elevated significantly, while superoxide dismutase, catalase activity were decreased. Histologic findings showed severe devastating lesions and increased rodent cell apoptosis; SP600125 effectively improved morphologic features, reversed above-mentioned parameters, and significantly attenuated c-Jun phosphorylation, as well as intra-renal pro-inflammatory cytokines expression compared with vehicle-treated group. CONCLUSION These data demonstrate that inhibition of c-Jun with SP600125 is capable of attenuating renal IRI, which might be a novel therapy target.

Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels

Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.

Coaxial electrospinning of P(LLA-CL)/heparin biodegradable polymer nanofibers: potential vascular graft for substitution of femoral artery

Electrospinning is one of the most simple and effective methods to prepare polymer fibers with the diameters ranging from nanometer to several micrometers. Poly(L-lactide)-co-poly (ɛ-caprolactone) (P(LLA-CL)) fibers and P(LLA-CL)/heparin coaxial composite fibers herein were successfully prepared by single electrospinning and coaxial electrospinning, respectively. The prepared endothelialized P(LLA-CL) and P(LLA-CL)/heparin vascular grafts were used in the Beagle dogs experiment to evaluate the feasibility of thus made different scaffolds for substitution of dog femoral artery in early period, medium term, and long term, meanwhile the pure P(LLA-CL) vascular graft was used as the control group during all the experiments. The animal model was established by using the graft materials to anastomose both femoral arteries of dogs. The vascular grafts patency rates (i.e., the unobstructed capacity of blood vessel) were detected by color Doppler flow imaging technology and digital subtraction angiography. To observe the histological morphology at different periods, the vascular grafts were removed after 7, 14, and 30 days, and the corresponding histological changes were evaluated by hematoxylin and eosin staining. The experimental results show that in the early period, the patency rates of pure P(LLA-CL) graft, endothelial P(LLA-CL) graft, and P(LLA-CL)/heparin graft were 75%, 75%, and 100%, respectively; in the medium term, the patency rates of pure P(LLA-CL) graft and endothelial P(LLA-CL) graft were 25%, whereas that of P(LLA-CL)/heparin graft was 50%; the patency rates of pure P(LLA-CL) graft and endothelial P(LLA-CL) graft were down to 0%, whereas the patency rate of P(LLA-CL)/heparin graft was 25% in the long term. This preliminary study has demonstrated that P(LLA-CL)/heparin coaxial composite fiber maybe a reliable artificial graft for the replacement of femoral artery.

miR-203a regulates proliferation, migration, and apoptosis by targeting glycogen synthase kinase-3β in human renal cell carcinoma

MicroRNAs play a crucial role in cancer progression and metastasis. miR-203a has been identified as a tumor suppressor in various cancers. However, its functions in renal cell carcinoma have not been illustrated. In this study, we detected the miR-203a expression in renal cell carcinoma and evaluated its association with clinical features. Overexpression of miR-203a was found in renal cell carcinoma tissues and renal cell carcinoma cells. High miR-203a expression is correlated with tumor stage and short overall survival time. Bioinformatics and luciferase assay confirmed that glycogen synthase kinase-3β was a target gene of miR-203a. Silencing of miR-203a could inhibit cell proliferation and migration, arrest them in G1 phase, and promote apoptosis in vitro. miR-203a promotes the progression of renal cell carcinoma and predicts a poor prognosis.

Elevated Levels of miR-155 in Blood and Urine from Patients with Nephrolithiasis

Background. Both circulating and urinary miRNAs may represent a potential noninvasive molecular biomarker capable of predicting chronic kidney disease, and, in the present study, we will investigate the serum and urinary levels of miR-155 in patients with nephrolithiasis. Methods. Serum and urinary levels of miR-155 are quantified in 60 patients with nephrolithiasis; the result was compared to 50 healthy volunteers. Estimated glomerular filtration (eGFR) was calculated and, by simple regression analysis, the correlations of miR-155/eGFR and miR-155/CRP (C-reactive protein) levels were analyzed as well. Results. The median levels of serum and urinary levels of miR-155 are significantly higher in nephrolithiasis patients than in controls. eGFR inversely correlates with urinary level of miR-155; CRP positively correlates with urinary miR-155. Urinary level of miR-155 inversely correlates with urinary expression of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α and positively correlates with urinary expression of regulated upon activation, normal T-cell expressed, and secreted (RANTES). Conclusion. Serum and urinary levels of miR-155 were significantly elevated in patients with nephrolithiasis, and the upregulation of miR-155 was correlated with decline of eGFR and elevation of CRP. Our results suggested that miR-155 might play important roles in the pathophysiology of nephrolithiasis via regulating inflammatory cytokines expression. Further study on the molecular pathogenic mechanism and larger scale of clinical trial are required.

The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma

The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.

A novel minimally invasive percutaneous nephrolithotomy technique: safety and efficacy report

Abstract Objective. The aim of this study was to evaluate the outcome and determine the complications of ultrasound-guided 16 F tract percutaneous nephrolithotomy (PCNL) by review of over 1000 cases in a Chinese hospital. Material and methods. A total of 1368 patients underwent 16 F tract PCNL in the hospital between March 2007 and July 2013. Surgery was performed under general anesthesia in all cases. Central venous puncture was chosen as a puncture device. Complications, residual stones, stone clearance and the need for auxiliary treatments were evaluated. Management experience was evaluated with respect to the complications. Results. Complications occurred in 275 out of 1368 patients (20.1%). There were 102 Clavien grade 1 (7.4%), 121 grade 2 (8.8%) and 48 grade 3 (3.5%) complications, but no grade 4 or 5 complications. Access to the kidney was established in 99.7% of cases and 82.0% of cases had complete stone clearance without undergoing further PCNL. Auxiliary treatments included shockwave lithotripsy in 135 patients, second-phase PCNL in 49 patients and ureteroscopy in 63 patients. Three cases of rare complications occurred, including a double-J stent translocated to the chest, and intraoperative acute pulmonary edema and heart failure. Severe intraoperative or postoperative complications should be managed immediately. Conclusion. An ultrasound-guided mini-tract PCNL is safe and convenient, even for patients with complicated stones.