Spatial heterogeneity of soil available medium- and micro-elements in evergreen-deciduous broadleaved forest in karst.

Understanding the spatial heterogeneity of soil available medium- and micro-elements in karst area can provide a valuable theoretical guideline for soil nutrient management of karst ecosystem. We collected soil samples at a soil depth of 0-10 cm using grid sampling (20 m×20 m) in a 25 hm2 (500 m×500 m) dynamic monitoring plot. We further analyzed the spatial variability of soil medium- and micro-elements and their drivers, with classic statistics analysis and geo-statistics analysis. The results showed that the average contents of exchangeable Ca and Mg and available Fe, Mn, Cu, Zn, and B were 7870, 1490, 30.24, 149.12, 1.77, 13.54, and 0.65 mg·kg-1, respectively. The coefficient of variation of the nutrients ranged from 34.5% to 68.8%, showing a medium degree of their spatial variation. The coefficient of determination of the best-fit semi-variogram models of each nutrient was higher than 0.90, except for available Zn (0.78), indicating a strong predictive power for the spatial variation of the nutrients. The nugget coefficients for all the nutrients were less than 50%, showing a moderate spatial correlation, and the structural factors played a pivotal role. The spatially autocorrelated variation was within the range of 60.3-485.1 m, among which available Zn showed the lowest range and the deepest fragmentation degree. The spatial distribution of exchangeable Ca, Mg, and available B were consistent, with contents in the depression being significantly lower than that in other habitats. The contents of available Fe, Mn, and Cu declined with the increases of altitude and were significantly lower on the hilltop than in other habitats. The spatial variation of soil medium- and micro-elements was closely related to topographic factors in karst forest. Elevation, slope, soil thickness, and rock exposure rate were the primary drivers of spatial variation of soil elements and need to be considered in soil nutrient management of karst forestlands.

[Corrigendum] MicroRNA­218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.

Subsequently to the publication of the above article, the authors have realized that the cell migration and tube formation assay data portrayed in Figs. 2 and 4 in their paper were published with some inadvertent errors. Specifically, the photograph selected for the ACHN-SFM group was accidentally misused for the 769P/LV-miR-218 group in Fig. 2F. Secondly, the photograph for the 786O/LV­NC group in Fig. 2F was accidentally misused as the image for the 786O/shNC group in Fig. 4E; and thirdly, the photograph selected for the ACHN/shNC group in Fig. 4C was inadvertently misused for the ACHN/shNC group in Fig. 4D. These errors arose inadvertently as a consequence of the authors' mishandling their data; however, the authors were able to retrieve their original data, and have been able to reassemble these figures to show the data as was originally intended. The revised versions of Figs. 2 and 4, featuring the corrected data panels for the 769P/LV­miR­218 group in Fig. 2F, the ACHN/shNC group in Fig. 4D and the 786O/shNC group in Fig. 4E, are shown on the next two pages. The revised data shown for these Figures do not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 44: 1961­1970, 2020; DOI: 10.3892/or.2020.7759].

Is there a place for extracorporeal shockwave lithotripsy (ESWL) in the endoscopic era?

This retrospective study aimed to evaluate whether there was still a place for ESWL therapy in the endourological era. From 1988 to 2018, ESWL therapy was performed with 3 successive types of lithotripters in our hospital. From 1988 to 1998, the electrohydraulic lithotripter NS-15 was used, and the electromagnetic lithotripter HK-V was put to use in 1999. Since 2010, the electromagnetic lithotripter HK-Vm has been used. Over the 30-year period, 16,969 urolithiasis patients underwent ESWL therapy, including 124 paediatric cases and 178 special cases. The stone clearance rate (SCR) and postoperative complications in the 3 lithotripter groups were recorded and analysed. The SCR was estimated by ultrasonography or plain X-ray, while the complications were recorded by the modified Clavien grading system. The primary stone clearance rate (pSCR) of ureteral and renal stones was significantly improved in the HK-Vm group compared with the NS-15 and HK-V groups. The final stone clearance rate (fSCR) of lower calyx stones was considerably higher in the HK-Vm group (55.9%) than in the NS-15 (41.1%) and HK-V (44.1%) groups. Most complications were grade I and II, while the incidence of grade III and above complications was less than 3%. Additionally, the fSCR in paediatric and special cases ranged from 66.5% to 83.5%, with no record of severe complications. As our data showed, ESWL was effective and safe for most urolithiasis patients, including paediatric patients and special cases. Therefore, ESWL is still the major treatment option in the current endourological era.

Chemical investigation and anti-inflammatory activities of the aerial part of Filipendula palmata.

ETHNOPHARMACOLOGICAL RELEVANCE: Filipendula palmata Maxim. as an ethnic herb is commonly used by Oroqen minority people in the treatment of rheumatism in China and as a wild vegetable is eaten by Russian in the Far East area. However, so far, the chemical constituents and bioactivity of this edible herb are still unclear, especially the anti-inflammatory constituents and action have not been elucidated despite the traditional folk use. AIM OF STUDY: The current study was conducted to investigate the main chemical components of the aerial part of F. palmata and evaluate the anti-inflammatory and antioxidant and cytotoxic activities of the extract and the isolated constituents. MATERIALS AND METHODS: Various chromatographic techniques including silica gel, ODS, HPLC were used to isolate the components and several spectroscopic methods such as UV, IR, MS and NMR were adopted to characterize the structures of the compounds. The inhibitory action of the extract and components on the production of nitric oxide stimulated by LPS in RAW264.7 cells was applied to evaluate the anti-inflammatory activity and the MTT method was used to investigate the cytotoxicity. In addition, the antioxidant capacity of F. palmata was measured in three in vitro assays including DPPH and hydroxyl radicals scavenging and FRAP experiments. RESULTS: The bioactivity research demonstrated that the EtOAc fraction and n-BuOH fraction of this ethnic herb possessed potent anti-inflammation activity in RAW264.7 macrophages and antioxidant activity in three in vitro assays. The chemical study on the EtOAc fraction led to a new dihydrophenanthrene derivative, filipendutin A (1), together with 9 known compounds from the herb, in which compound 4 could significantly inhibit the production of nitric oxide in RAW264.7 cells, while compounds 1 and 9 exhibited obvious cytotoxicity in cells. CONCLUSIONS: These results demonstrated that F. palmata had significant anti-inflammatory and antioxidant activities and could be used in the treatment of inflammatory diseases. Meanwhile, the cytotoxic activity of EtOAc fraction and its components also indicated the potential application in antitumor which remained the further study in the future.

DSPE-PEG polymers for improving pulmonary absorption of poorly absorbed macromolecules in rats and relative mechanism.

OBJECTIVE: This study aims to investigate the potential of DSPE-PEG polymers (DSPE-PEG-OH and DSPE-PEG-SH) on improving absorption of poorly absorbable macromolecules via intrapulmonary administration and underlying mechanism. METHODS: In situ pulmonary absorption experiments were performed to investigate the absorption of model compounds after intrapulmonary administration to rats. The local membrane damage induced by these DSPE-PEG polymers were evaluated based on morphological observation of lung tissues and measurement of biological toxic markers in bronchoalveolar lavage fluid (BALF) postintrapulmonary delivery of DSPE-PEG polymers to rats. The underlying enhancement mechanism of these polymers was explored by investigating their effects on the pulmonary membrane fluidity and gene expression of tight junction associated proteins with fluorescence polarization and western blotting, respectively. RESULTS: Intrapulmonary delivery of these DSPE-PEG polymers significantly enhanced absorptions of poorly absorbed model drugs and did not induce serious damage to the pulmonary membranes of rats. Mechanistic studies demonstrated unaffected pulmonary membrane fluidity and up-regulated expression levels of tight junction-associated proteins by DSPE-PEG polymers, thus indicating that paracellular pathways might be included in the underlying mechanisms by which DSPE-PEG polymers exerted their enhancing actions on drug absorption. CONCLUSIONS: These findings suggested that these DSPE-PEG polymers are potential for promoting absorptions of poorly absorbable macromolecules with no evidence of damage to the local pulmonary membranes of rats.Novelty statementIn this study, DSPE-PEG-OH and DSPE-PEG-SH polymers, two DSPE-PEG2000 conjugates with different terminal groups demonstrated significant promoting effects on the absorption of poorly absorbed macromolecular drugs after intrapulmonary delivery to rats, and did not induce serious damage to the pulmonary membranes of rats. These DSPE-PEG polymers could statistically downregulate expression levels of tight junction-associated proteins (ZO-1 and occludin), indicating the underlying mechanism by which these polymers exerted their absorption enhancing actions through pulmonary epithelial paracellular pathways. Thus, this study exhibited prospective potential of these DSPE-PEG polymers in developing into dosage forms with the aim to improve the poor bioavailability of some poorly absorbed macromolecular drugs.

FOXM1-Dependent Transcriptional Regulation of EZH2 Induces Proliferation and Progression in Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most commonly diagnosed cancers and one of the most common causes of cancer-related deaths among men worldwide. Patients who are diagnosed with localized prostate cancer and treated with radical prostatectomy often respond well to therapy. The current standard therapy for prostate cancer involves maximal surgical resection, followed by radiotherapy and chemotherapy. Clarifying the molecular mechanism of tumor proliferation and recurrence becomes more and more important for clinical therapies of prostate cancer. METHODS: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpress or knockdown the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In this study, we identified that FOXM1 expression was significantly enriched in prostate cancer compared with normal tissue. Additionally, FOXM1 was functionally required for tumor proliferation and its expression was associated with poor prognosis in prostate cancer patients. Mechanically, FOXM1-dependent regulation of EZH2 is essential for proliferation and progression in prostate cancer. CONCLUSION: Taken together, our data suggest that oncogenic transcription factor FoxM1 is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on FOXM1 activity. FOXM1 may serve as a clinical prognostic factor and a therapeutic target for prostate cancer.

PTPN13 acts as a tumor suppressor in clear cell renal cell carcinoma by inactivating Akt signaling.

Protein tyrosine phosphatase, nonreceptor type 13 (PTPN13), has emerged as a critical cancer-related gene that is implicated in a wide range of cancer types. However, the role of PTPN13 in clear cell renal cell carcinoma (ccRCC) is poorly understood. In the present study, we aimed to evaluate whether PTPN13 participates in the progression of ccRCC. Decreased expression of PTPN13 was found in ccRCC tissues, which predicted a shorter survival rate in ccRCC patients. PTPN13 expression was also lower in ccRCC cell lines, and the upregulation of PTPN13 repressed the proliferation, colony formation and invasion, but enhanced the apoptosis of ccRCC cells. In contrast, the silencing of PTPN13 produced the opposite effects. Further data showed that PTPN13 overexpression decreased the phosphorylation of Akt, while PTPN13 silencing increased the phosphorylation of Akt. Treatment with Akt inhibitor markedly abrogated the PTPN13 silencing-evoked oncogenic effect in ccRCC cells. Xenograft tumor experiments revealed that overexpression of PTPN13 remarkably restricted the tumor formation and growth of ccRCC cells in vivo associated with inactivation of Akt. In conclusion, our data demonstrated that overexpression of PTPN13 restricts the proliferation and invasion of ccRCC cells through inactivation of Akt. Our study suggests a tumor suppressive function of PTPN13 in ccRCC and highlights the potential role of PTPN13 in the progression of ccRCC.

MicroRNA­218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.

Renal cell carcinoma (RCC) is one of the most common malignant cancers in the adult urinary system worldwide. Tumor angiogenesis is a critical process during cancer progression, as it modulates carcinogenesis and metastasis. In recent years, microRNA­218 (miR­218) has been confirmed to play a crucial role in tumor suppression. However, the role of miR­218 in RCC angiogenesis remains unclear. In the present study, it was found that the expression of miR­218 was decreased in RCC tumor tissues and cell lines as detected by real­time PCR analysis. Tube formation assays and migration assays also confirmed that miR­218 inhibited the interaction between RCC cells and vascular endothelial cells by suppressing proangiogenic factor vascular endothelial growth factor A (VEGFA) in RCC cells. miR­218 also repressed the subcutaneous tumorigenesis of RCC cells in nude mice, and the corneal angiogenesis in rabbit eyes. The underlying molecular mechanism was elucidated; miR­218 targets GRB2­associated binding protein 2 (GAB2), thereby inhibiting the PI3K/AKT/mTOR/VEGFA pathway. These results provide new insights into the mechanism of RCC carcinogenesis and progression, suggesting that miRNA­218 may be a therapeutic target for the treatment of RCC.

BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK.

BACKGROUND: Prostate cancer remains one of the most common and deadliest forms of cancer, generally respond well to radical prostatectomy and associated interventions, up to 30% of individuals will suffer disease relapse. Although BUB1B was found to be essential for cell growth and proliferation, even in several kinds of tumor cells, the specific importance and mechanistic role of BUB1B in prostate cancer remain unclear. METHODS: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In the present report, we found BUB1B expression to be highly increased in prostate cancer tissues relative to normal controls. We further found BUB1B to be essential for efficient tumor cell proliferation, and to correlate with poorer prostate cancer patient outcomes. From a mechanistic perspective, the ability of BUB1B to regulate MELK was found to be essential for its ability to promote prostate cancer cell proliferation. CONCLUSION: Altogether, our data suggest that BUB1B is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on BUB1B-dependent regulation of MELK transcription. BUB1B may serve as a clinical prognostic factor and a druggable target for prostate cancer.

Robot-Assisted Radical Prostatectomy Is More Beneficial for Prostate Cancer Patients: A System Review and Meta-Analysis.

BACKGROUND Robot-assisted radical prostatectomy (RARP) is increasingly used worldwide, but comparisons of perioperative, functional, and oncologic outcomes among RARP, laparoscopic radical prostatectomy (LRP), and open radical prostatectomy (ORP) remain inconsistent. MATERIAL AND METHODS Systematic literature searches were conducted using EMBASE, PubMed, the Cochrane Library, CNKI, and Science Direct/Elsevier up to April 2017. A meta-analysis was conducted using Review Manager and Stata software. RESULTS We included 33 studies. Meta-analysis revealed that blood loss, transfusion rate, and positive surgical margin (PSM) rate were significantly lower following RARP compared with LRP (SMD (95% confidence interval [CI]) 0.31 [0.01, 0.61]; combined ORs (95% CI) 5.32 [1.29, 21.98]; 1.27 [1.10, 1.46]) and ORP (SMD (95% CI) 0.75 [0.30, 1.21]; and combined ORs (95% CI) 3.44 [1.21, 9.79]); positive surgical margin (PSM) rates were significantly lower following RARP compared with LRP (combined ORs (95% CI) 1.27 [1.10, 1.46]), but not ORP. Operation time was also shorter for RARP than for LRP. The rates of nerve-sparing, recovery of complete urinary continence, and recovery of erectile function were significantly higher following RARP compared with LRP (combined ORs (95% CI) 0.55 [0.31, 0.95]; 0.66 [0.55, 0.78]; 0.46 [0.30, 0.71]) and ORP (combined ORs (95% CI) 0.36 [0.21, 0.63]; 0.33 [0.15, 0.74]; 0.65 [0.37, 1.14]). CONCLUSIONS This meta-analysis demonstrates that RARP results in better overall outcomes than LRP and ORP in terms of blood loss, transfusion rate, nerve sparing, urinary continence and erectile dysfunction recovery, and suggests that RARP offers better results than LRP and ORP in treatment of prostate cancer. However, studies with larger sample sizes and long-term results are needed.

Assessment of the SonixGPS system for its application in real-time ultrasonography navigation-guided percutaneous nephrolithotomy for the treatment of complex kidney stones.

SonixGPS is a novel real-time ultrasonography navigation technology, which has been demonstrated to promote accuracy of puncture in surgical operations. The aim of this study is to evaluate its application in guiding the puncture during percutaneous nephrolithotomy (PCNL). We retrospectively reviewed our experience in treating a total of 74 patients with complex kidney stones with PCNL, in which puncture in 37 cases were guided by SonixGPS system, while the other 37 by conventional ultrasound. The effectiveness of operation was evaluated in terms of stone clearance rate, operation time, time to successful puncture, number of attempts for successful puncture and hospital stay. The safety of operation was examined by evaluating postoperative complications. Our retrospective review showed that although there were no significant differences in stone clearance rates between the groups, SonixGPS guidance resulted in more puncture accuracy with shorter puncture time and higher successful puncture rate. Under the help of SonixGPS, most patients (92 %) had no or just mild complications, compared to that (73 %) in conventional ultrasound group. Post-operative decrease of hemoglobin in SonixGPS group was 13.79 (7-33) mg/dl, significantly lower than that 20.97 (8-41) mg/dl in conventional ultrasound group. Our experience demonstrates that SonixGPS is superior to conventional ultrasound in guiding the puncture in PCNL for the treatment of complex kidney stone.

Autophagy activation protects shock wave induced renal tubular epithelial cell apoptosis may through modulation of Akt/ GSK-3ß pathway.

PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) is well documented to exert destructive effect to renal cells and its mechanism is not clear. Autophagy is one of cell basic response for stressful conditions and it is important to determine cell's fate. The aim of this study is to elucidate the role of autophagy in the process of shock wave-induced renal cells injury. METHODS: NRK-52E cell, a rat renal tubular epithelial cell, was exposed to shock wave at the voltage of 14KV. GFP-LC3 puncta was used to monitor Autophagy flux in the process of shock wave injury. Autophagic relative proteins, such as light chain 3 (LC3), beclin-1 and p62, were also examined. Cell variability and apoptosis were detected when inhibition autophagy with 3-methyladenine (3MA) or stimulating its activity with rapamycin during the process of shock wave injury. The role of Akt/ GSK-3ß and its connection with autophagy in the process of shock wave injury were also investigated. RESULTS: Shock wave was confirmed to activate autophagy in renal cells, which was manifested in LC3-II turnover, beclin-1 induction and degradation of p62. Inhibition autophagy enhanced cell damage or apoptosis, whereas its stimulating was able to exert protection from shock wave injury. Akt/ GSK-3ß, a cell-survival signaling pathway, can also be activated during the process. And its activation could be suppressed by blockade autophagy. CONCLUSION: Autophagy is a self-protective response for renal cells from shock wave injury. The cyto-protection of autophagy may be connected with modulation Akt/ GSK-3ß pathway.

Significant differences in struvite and cystine stone frequency seen among Chinese nephrolithiasis patients living in North America compared to those living in China.

BACKGROUND: Interracial disparities in nephrolithiasis prevalence have been reported, but the interplay between genetics and the environment for urinary stone disease risk factors is poorly understood. To examine how environment may alter genetic predisposition for stone formation, we established the International Chinese Consortium on Nephrolithiasis (ICCON) as a multi-institutional collaboration to examine patterns of nephrolithiasis presentation between Chinese patients living in different countries. METHODS: Chinese patients undergoing percutaneous nephrolithotomy (PCNL) at six participating institutions in China and North America over 4 years were reviewed retrospectively. Patient demographics and clinical data were compared between Chinese patients living in China and North America. RESULTS: A total of 806 patients were included, encompassing 721 Chinese patients living in China and 85 living in North America. Nephrolithiasis patients living in China were more likely to be male (67% vs. 56%, P=0.02), present at a younger age (48.6±15.0 vs. 55.0±13.0 years, P<0.01), and have a lower BMI (24.6±4.0 vs. 25.9±5.7, P=0.04) but were less likely to form struvite stones (5.5% vs. 14.1%, P<0.01). No cystine stone patients were seen in North American Chinese patients, whereas 1.8% of nephrolithiasis patients living in China presented with cystine stones. Similar rates of calcium-based and uric acid calculi as well as urinary pH were seen among both groups. CONCLUSIONS: Significant differences exist between Chinese nephrolithiasis patients living in China compared to those living in North America, highlighting the importance of environmental factors in addition to genetics in modulating risk for urinary stone disease.

Prognostic Value of High CXCR4 Expression in Renal Cell Carcinoma: A System Review and Meta-Analysis.

BACKGROUND: Recent studies have shown that CXC chemokine receptor 4 (CXCR4) is involved in the progression and metastasis of renal cell carcinoma (RCC). However, the prognostic value of CXCR4 expression in RCC remains controversial. The aim of our meta-analysis is to evaluate the prognostic value of high CXCR4 expression in RCC. METHODS: Relevant studies focused on the relationship between high CXCR4 expression and the outcome of RCC were searched in PubMed and EMBASE/Cochrane Library database. Hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were our evaluation index. The individual and pooled HRs with 95% confidence intervals (CIs) were analyzed. RESULTS: A total of 1068 patients from 7 studies were included in our meta-analysis. The results suggested that high CXCR4 expression predicted a poor OS (random effect model (REM) HR = 2.77, 95% CI = 1.80-4.27) and PFS (REM HR = 4.83, 95% CI = 2.30-10.15) for RCC patients. CONCLUSION: The results of meta-analysis indicated that high CXCR4 expression was correlated with worse OS and PFS for patients with RCC. However, some larger samples and well-matched studies should be designed to estimate the potential prognosis of RCC patients.

Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling.

Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.

Insulin-like growth factor binding protein-3 mediates interleukin-24-induced apoptosis through inhibition of the mTOR pathway in prostate cancer.

IGF-binding protein-3 (IGFBP-3) has been shown to induce apoptosis in an insulin-like growth factor (IGF)­independent manner in various cell systems, however, the underlying molecular mechanisms remain unknown. In the present study, we showed that IGFBP-3 significantly enhanced interleukin-24 (IL-24)-induced cell death in prostate cancer (PC) cell lines in vitro. Both the addition of IGFBP-3 to cell medium or the enforced expression of IGFBP-3 in the PC cell line inhibited activation of mammalian target of rapamycin (mTOR). Downregulation of mTOR/S6K reduced Mcl-1 protein expression and consequently promoted sensitization to IL-24 treatment. Overexpression of Mcl-1 reduced the level of cleaved poly(ADP-ribose) polymerase (PARP) induced by IL-24 and IGFBP-3, suggesting that the IL-24-induced apoptosis is realized by way of Mcl-1. We then showed that the combination of IL-24 and IGFBP-3 significantly suppressed PC tumor growth in vivo. We propose that the IGFBP-3 and IL-24 non-toxic mTOR inhibitors can be used as an adjuvant in the treatment of PC.

The effect of chronic prostatitis on zinc concentration of prostatic fluid and seminal plasma: a systematic review and meta-analysis.

BACKGROUND: Prostatitis is a common disease in urology departments. Prostatic zinc accumulation is connected with the secretory function of the prostate, and zinc concentrations present in prostatic diseases differ greatly from the normal level. Studies have investigated the effect of chronic prostatitis on zinc concentration of prostatic fluid and seminal plasma, but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the effect of chronic prostatitis on the zinc concentration of prostatic fluid and seminal plasma. METHODS: Systematic literature searches were conducted with PubMed, Embase, Science Direct/Elsevier, CNKI and the Cochrane Library up to March 2015 for case-control studies that involved the relationship between chronic prostatitis and zinc concentration of prostatic fluid and seminal plasma. Meta-analysis was performed with Review Manager and Stata software. Standard mean differences (SMDs) of zinc concentration were identified with 95% confidence intervals (95% CIs) in a random- or fixed-effects model. RESULTS: Our results illustrated that the zinc concentrations in prostatic fluid and seminal plasma from chronic prostatitis patients were significantly lower than normal controls (SMD [95% CI] -246.71 [-347.97, -145.44], -20.74 [-35.11, -6.37], respectively). LIMITATIONS: The sample size of each study was relatively small, and a total of 731 chronic prostatitis patients and 574 normal controls were investigated in all fourteen studies. Several studies related to the subject were excluded due to lack of control data or means and standard deviations. CONCLUSIONS: The present study illustrates that there was a significant negative effect of chronic prostatitis on zinc concentrations of prostatic fluid and seminal plasma. Further studies with larger sample sizes are needed to better illuminate the negative impact of chronic prostatitis on zinc concentrations.

miR-124 represses FZD5 to attenuate P-glycoprotein-mediated chemo-resistance in renal cell carcinoma.

Renal cell carcinoma (RCC) is one of most malignant neoplasms, exhibiting poor responsiveness to the conventional chemo-regime. Abnormal expression of P-glycoprotein (P-gp) has been implicated in the emergence of multiple-drug resistance (MDR) by reducing the accumulation of intracellular chemotherapy drugs. Wnt signaling plays critical roles in renal cancer and is triggered by binding of Wnt ligands to Frizzled (FZD) receptor proteins. miR-124 is a tumor suppressor associated with cancer relapse and MDR, whereas its role in P-gp-mediated MDR in refractory RCC is as yet unrevealed. Our study aimed to investigate the roles of miR-124 in chemo-resistant RCC cells and the potential targeted signaling paths in inducing P-gp expression. Doxorubicin (DOX)- and vinblastine (VBL)-resistant Caki-2 cells were developed by exposure of parental Caki-2 cells to the agents over a long period of time. In comparison with their parental cells, miR-124 was downregulated in Caki-2/DOX and Caki-2/VBL cells, accompanied by increased FZD5 and P-gp. IC50 values were reduced significantly after miR-124 mimics were introduced into Caki-2/DOX cells. In addition, miR-124 mimics significantly promoted apoptosis of Caki-2/DOX cells. miR-124 targeted to FZD5 and miR-124 mimics as well as FZD5 siRNA showed significant inhibitory effects on P-gp expression in Caki-2/DOX cells. Furthermore, Wnt-5a dose-dependently stimulated the presentation of p-PKCα/ßII and p-CamKII via activating FZD5, which was reversed by FZD5 silencing. Moreover, FZD5/protein kinase C (PKC) signaling is responsible for the elevation of P-gp and cancer cell survival. In conclusion, restoring miR-124 may function as a promising strategy to overcome P-gp-mediated MDR by inhibiting FZD5/PKC signaling.

Real-time ultrasound-guided PCNL using a novel SonixGPS needle tracking system.

SonixGPS is a successful ultrasound guidance position system. It helps to improve accuracy in performing complex puncture operations. This study firstly used SonixGPS to perform kidney calyx access in PCNL to investigate its effectiveness and safety. This was a prospectively randomized controlled study performed from September 2011 to October 2012. A total of 97 patients were prospectively randomized into two groups using random number generated from SAS software. 47 Patients were enrolled in conventional ultrasound-guided (US-guided) group and 50 patients were classified into SonixGPS-guided group. Nine patients were lost during follow-up. Hence, a total of 88 patients were qualified and analyzed. Preoperative examinations included urine analysis, urine culture, kidney function, coagulation profile and routine analysis of blood. Ultrasonography was used to evaluate the degree of hydronephrosis. The intraoperative findings, including blood loss, operating time, time to successful puncture, the number of attempts for successful puncture and hospital stay were recorded. The stone clearance rate and complications were analyzed. The present study showed no significant difference between the two groups in terms of demographic data, preoperative markers, stone clearance rate and the stone composition. However, the time to successful puncture, the number of trials for successful puncture, operating time and hospital length of stay were significantly decreased in the SonixGPS-guided group. Furthermore, the hemoglobin decrease was also obviously lower in the SonixGPS group than that in conventional US-guided group. SonixGPS needle tacking system guided PCNL is safe and effective in treating upper urinary tract stones. This novel technology makes puncturing more accuracy and can significantly decrease the incidence of relative hemorrhage and accelerate recovery.

Downregulation of mTOR by lentivirus inhibits prostate cancer cell growth.

Prostate cancer, one of the most lethal forms of urinary system cancer, remains resistant to currently available treatments. Therefore, novel mechanism and target-based approaches are needed for the management of this neoplasm. PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, the role of mTOR in prostate cancer is not well-established. Here, we demonstrate that mTOR is over-expressed in both clinical tissue specimens and cultured human prostate cancer cells when compared to normal prostate tissues, respectively. Further, mTOR gene knockdown via lentivirus mediated mTOR specific shRNA resulted in a significant decrease in the viability and growth of prostate cancer cells without affecting normal human prostate cells. In addition, mTOR inhibition resulted in a significant i) decrease in 4EBP1, S6K, PI3K and AKT protein, ii) increase in PARP protein of prostate cancer cells. Most importantly, mTOR inhibition triggered apoptosis and suppressed pancreatic carcinoma growth in vivo in a mouse xenograft model. We suggest that targeting of mTOR may be a viable approach for the treatment of prostate cancer.