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C3G and PCA enhanced testicular heat stress tolerance, and alleviated oxidative stress and ER stress so as to guarantee the orderly progress of spermatogenesis.

Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been shown to play critical regulatory roles in clear cell renal cell carcinoma (ccRCC). Metastasis is the main contributor to the poor prognosis of patients with ccRCC. However, the role of circRNAs in ccRCC metastasis has not been fully elucidated. In this study, microarray and RNA-seq analyses revealed that circPSD3 (hsa_circ_0002111) was dramatically downregulated in ccRCC tissues compared to adjacent nontumor tissues. A qRT-PCR analysis performed on our ccRCC cohorts confirmed the downregulation of circPSD3 in ccRCC tissues and further suggested that a low level of circPSD3 expression was associated with tumor metastasis in patients with ccRCC. Based on the results of functional studies, circPSD3 significantly inhibited cell migration, invasion, and the epithelial-mesenchymal transition (EMT) in vitro and blocked pulmonary metastasis in vivo. Mechanistically, circPSD3 functioned as a competing endogenous RNA for microRNA 25-3p (miR-25-3p) to regulate F-box and WD repeat domain-containing 7 (FBXW7) expression. Further verification indicated that circPSD3 overexpression restrained an EMT-like phenotype in cells, while miR-25-3p partially rescued these effects. In summary, circPSD3 inhibits tumor metastasis by repressing the miR-25-3p/FBXW7-EMT axis and might be developed as a potential diagnostic and therapeutic target for ccRCC.

Metastatic prostate cancer (PCa) remains incurable and fatal. Previous studies have proven that circulating tumor cells (CTCs) and Ezrin are involved in PCa progression, metastasis, diagnosis, and prognosis. Therefore, we aimed to investigate the roles of CTCs and Ezrin in PCa metastasis. The expression of Ezrin was measured by qRT-PCR and immunohistochemical staining. The migration and invasion of PCa cells were evaluated. Additionally, clinical data from PCa patients were collected to analyze the potential roles of Ezrin expression in CTCs of PCa. The results showed that Ezrin expression was significantly upregulated in PCa tissues and 22RV1 and PC-3 cell samples. The overexpression of Ezrin promoted the migratory and invasive abilities of 22RV1 and PC-3 cells. Finally, the clinical data revealed that the expression of Ezrin in CTCs of PCa patients was significantly upregulated with the metastatic degree. Furthermore, after radical prostatectomy, CTCs from Ezrin-positive PCa patients were susceptible to tumor metastasis. Therefore, these results indicated that Ezrin expression in CTCs may offer novel insights into the prognosis and management of PCa.

Ribonucleotide reductase (RNR) is the key enzyme that catalyzes the production of deoxyribonucleotides (dNTPs) for DNA replication and it is also essential for cancer cell proliferation. As the RNR inhibitor, Gemcitabine is widely used in cancer therapies, however, resistance limits its therapeutic efficacy and curative potential. Here, we identified that mTORC2 is a main driver of gemcitabine resistance in non-small cell lung cancers (NSCLC). Pharmacological or genetic inhibition of mTORC2 greatly enhanced gemcitabine induced cytotoxicity and DNA damage. Mechanistically, mTORC2 directly interacted and phosphorylated RNR large subunit RRM1 at Ser 631. Ser631 phosphorylation of RRM1 enhanced its interaction with small subunit RRM2 to maintain sufficient RNR enzymatic activity for efficient DNA replication. Targeting mTORC2 retarded DNA replication fork progression and improved therapeutic efficacy of gemcitabine in NSCLC xenograft model in vivo. Thus, these results identified a mechanism through mTORC2 regulating RNR activity and DNA replication, conferring gemcitabine resistance to cancer cells.

Alpha-ketoglutarate (AKG) or 2-oxoglutarate is a key substance in the tricarboxylic acid cycle (TCA) and has been known to play an important role in cancerogenesis and tumor progression. Renal cell carcinoma (RCC) is the most common type of kidney cancer, and it has a high mortality rate. Autophagy is a phenomenon of self-digestion, and its significance in tumor genesis and progression remains debatable. However, the mechanisms underlying how AKG regulates autophagy in RCC remain unknown. Thus, the purpose of this study was to assess the therapeutic efficacy of AKG and its molecular mechanisms.RCC cell lines 786O and ACHN were treated with varying doses of AKG for 24 h. CCK-8, Transwell, and scratch wound healing assays were utilized to evaluate the role of AKG in RCC cells. Autophagy protein and PI3K/AKT/mTOR pathway protein levels were analyzed by Western blot.AKG inhibited the proliferation of RCC cells 786O and ACHN in a dose-dependent manner according to the CCK-8 assay. In addition, flow cytometry and Western blot analysis revealed that AKG dose-dependently triggered apoptosis and autophagy in RCC cells. By promoting cell apoptosis and autophagy, AKG dramatically suppressed tumor growth. Mechanistically, AKG induces autophagy by promoting ROS generation and inhibiting the PI3K/AKT/mTOR pathway.The anti-tumor effect of AKG promotes autophagy in renal cancer cells via mediating ROS-PI3K/Akt/mTOR, and may be used as a potential anticancer drug for kidney cancer.

As one of the most common cancer chemotherapy drugs, cisplatin is widely used in cancer management. However, cisplatin-induced nephrotoxicity occurs in patients who receive this drug. This study is aimed at developing therapeutic agents that effectively alleviate the nephrotoxic effects during cisplatin treatment. We identified a compound named pyrocatechol (PCL) from a natural product library that significantly alleviated cisplatin-induced cytotoxicity in vitro. Pyrocatechol treatment substantially ameliorated cisplatin (20 mg · kg-1) treatment-induced neuropathological indexes, including inflammatory cell infiltration and apoptosis, in vivo. Mechanistically, pyrocatechol significantly prevented oxidative stress-induced apoptosis by activating glutathione peroxidase 4 (GPX4) to reduce reactive oxygen species (ROS) accumulation in cisplatin-treated cells. In addition, pyrocatechol significantly inhibited ROS-induced JNK/P38 activation. Thus, we found that pyrocatechol prevents ROS-mediated JNK/P38 MAPK activation, apoptosis, and cytotoxicity through GPX4. Our study demonstrated that pyrocatechol is a novel therapeutic agent against cisplatin-induced kidney injury.

Introduction: The aim of this study was to implement our technique for the initial dissection of the inferior hypogastric plexus and protection of the autonomic nerve supply to the corpora cavernosa in laparoscopic radical cystoprostatectomy with an orthotopic ileal neobladder and report the initial outcomes. Methods: Eleven normally potent patients with preoperative cT2N0 bladder cancer who underwent bilateral nerve-sparing laparoscopic cystoprostatectomy performed by the same surgeon were selected from May 2018 to September 2020. In this procedure, the anterior part of the inferior hypogastric plexus was dissected first between the prehypogastric nerve fascia and rectal proper fascia medial to the distal ureter. Then the Denonvilliers’ fascia and the nerves around the prostate were preserved according to current intrafascial principles. The preliminary operative, oncologic, and functional results are presented. Results: The median follow-up duration was 18 months. We observed early and late complications in 5 patients, but none exceeded grade III. Of the 11 patients, ten gained daytime continence (90.9%), and 8 (72.7%) showed nocturnal continence at the last follow-up. Regarding postoperative potency, 10 of the 11 patients (90.9%) remained potent with or without oral medications, excluding one who had partial tumescence but did not follow our recommendations regarding medication use. No local recurrence or positive surgical margins were noted. Conclusion: In addition to emphasizing our cavernosal nerve-sparing procedure, this report on the precise dissection and protection of the inferior hypogastric plexus could be of clinical significance, providing potentially ideal short-term functional results.

Objective: The aim of the objective was to present our initial experience and evaluate the feasibility of the novel comprehensive modified laparoscopic pyeloplasty (CMLP) technique based on membrane anatomy. Materials and Methods: Forty-eight patients underwent CMLP from February 2016 to October 2020. CMLP involves the following: dissection of the ureter was based on the fascia or fusion fascia formed by embryonic development. The ureter was separated from the ureteral sheath, and the pelvis and ureter were incised with incomplete amputation. The first stitch was placed between the lower point of the spatulated ureter and the lowest corner of the renal pelvis to ensure correct orientation of the anastomosis; anastomosis of the renal pelvis and ureter was performed using the touchless technique. Results: All CMLPs were completed successfully without conversion. The mean overall operating time was 230.96 min. The median estimated blood loss was 50.00 (interquartile range 20.00–57.50) mL. The average postoperative hospital stay was 9.31 days. The average follow-up time was 24.73 months. No major complications occurred. In 1 case, revision laparoscopic pyeloplasty was performed, but the obstruction persisted after double J stent removal, so ultimately, the double J stent required regular replacement. Another asymptomatic patient with hydronephrosis experienced failed treatment and is still under follow-up. The overall success rate was 95.83% (46/48). The success rate in patients with recurrent ureteropelvic junction obstruction (UPJO) was 87.5% (7/8). Conclusions: CMLP is a practical and effective treatment option for UPJO with a high success rate. An advantage of CMLP is the clear surgical field.

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that play important roles in germline development and carcinogenesis. In this study, we used the deep sequencing of small RNA Transcriptome to explore the piRNA expression in six clear cell renal carcinoma (ccRCC) tissues and matched adjacent normal tissues and found that six piRNAs were upregulated and sixteen were downregulated in ccRCC tissues. Among them, piRNA-31115 (NCBI accession number: DQ571003) was the most upregulated piRNA in ccRCC tissues compared with matched adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to confirm piR-31115 expression in other ccRCC tissues ( n = 40 ) and ccRCC cell lines. Besides, function analysis demonstrated that silencing of piR-31115 inhibited ccRCC cell proliferation, motility, and invasiveness. Mechanistic investigations showed that piRNA-31115 may activate epithelial-mesenchymal transition (EMT) via the PI3K/AKT signaling pathway. Hence, piR-31115 may represent an oncogene in the development of ccRCC.

BACKGROUND: The treatment of ketamine-induced bladder contractures remains poorly studied. We therefore evaluated the efficacy of cystectasia with a sodium hyaluronate balanced solution in this kind of bladder contracture. METHODS: Eighteen patients presenting with ketamine-induced bladder contracture between July 2010 and February 2018 were selected and analysed. Ketamine was discontinued in all patients, who were then treated with weekly cystectasia (0.09% sodium hyaluronate balanced solution) 3 times. The volume of the first perfusion was twice the preoperatively measured bladder capacity, and the volume of the subsequent two perfusions was increased by 100 mL each time. The Pelvic Pain and Urgency/Frequency (PUF) symptom score, O’Leary-Sant Interstitial Cystitis (IC) Symptom Index (ICSI), IC Problem Index (ICPI), Quality of Life (QOL) score, and bladder capacity were recorded before surgery and 3 and 12 months after the 3(rd) expansion. RESULTS: No significant complications were observed during the 3 expansions. Fourteen patients completed the full follow-up schedule. Preoperatively and at the 3- and 12-month follow-up evaluations performed after the 3(rd) expansion, the PUF symptom scores were 20.4±3.6, 11.5±3.1, and 13.2±3.3, respectively; the mean ICSI was 13.6±2.8, 7.7±2.3, and 8.2±2.5, respectively; the mean ICPI was 10.6±2.6, 7.3±2.1, and 7.7±2.5, respectively; and the mean QOL scores were 6.0±0, 2.1±0.5, and 2.7±0.8, respectively; and the mean bladder catheter volume was 83±27, 234±56, and 228±52 mL, respectively. There were significant differences between all preoperative and postoperative values. CONCLUSIONS: Cystectasia with a sodium hyaluronate balanced solution is an effective treatment modality for ketamine-induced bladder contracture.

Purpose To evaluate the association between the use of statins and/or metformin and patient survival in prostate cancer patients in Taiwan. Subjects and methods Newly diagnosed prostate cancer patients who had hyperlipidemia and received radiotherapy were identified from the National Health Insurance Research Database 2000-2010. The survival rate was estimated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to examine the association of mortality. Sensitivity analysis was performed to assess the risk of mortality in patients with diabetes. Results The study included 567 patients. Patients who used statins or metformin after prostate cancer diagnosis had longer average survival times (9.3 years and 8.1 years, respectively; P=0.001) compared with patients who persistently used or used the medicines prior to cancer diagnosis. Multivariate Cox regression analysis found that patients treated with statins after cancer diagnosis were significantly associated with a lower risk of mortality (aHR =0.24, 95% CI =0.09-0.66) compared to patients who did not use statins during the study period. Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45-18.77) compared to patients who did not use metformin during the study period. Sensitivity analysis revealed that the average survival time was similar among different medicine use groups in patients with diabetes. Conclusion The finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.

BACKGROUND Renal fibrosis is a common consequence of chronic kidney disease (CKD) and is the mechanism by which various forms of CKD progress to endstage renal failure. Accurate assessment of renal fibrosis is important for treatment. PURPOSE To measure longitudinal changes of intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) before and after reversible unilateral ureteral obstruction in an animal model. STUDY TYPE Self-controlled animal study. ANIMAL MODEL Surgical obstruction of the ureters was performed and then removed after 5 days. Rats were scanned on Days 0, 1, 3, and 5 after creating the obstruction and on Days 4, 7, and 12 after releasing the obstruction. FIELD STRENGTH/SEQUENCE 3.0T/IVIM/ASL. ASSESSMENT The apparent diffusion coefficient (ADC), pure molecular diffusion (D), perfusion fraction (f), pseudodiffusion (D*), and renal blood flow (RBF) obtained from the ASL were measured. STATISTICAL TESTS Using SPSS v. 20.0 software, P

Background/aim Epigenetic inactivation of tumor suppressor genes is an important molecular mechanism in the formation and development of human tumors. The purpose of our study was to evaluate the correlation between the methylation level of the secreted frizzled-related protein 1 (SFRP1) gene and the risk of renal cell carcinoma (RCC). Methods The relevant literature was searched in detail in several electronic databases. The methodological heterogeneity was analyzed by meta-regression and subgroup analyses. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to summarize the dichotomous outcomes of our meta-analysis. Results The ten included articles contained 535 RCC samples and 475 normal controls. The results demonstrated that the methylation level of the SFRP1 promoter region was significantly correlated with an increased incidence of RCC (OR=13.72; 95% CI: 6.01-31.28; P=0.000). Furthermore, the eligible studies that had sufficient clinical data about the RCC cases were included in the analysis, and the results indicated that the frequency of SFRP1 promoter methylation was associated with a higher histological grade (P=0.000), tumor stage (P=0.033), tumor size (≥5 cm; P=0.029), and distant metastasis (P=0.047). Conclusion Our results indicate that the methylation level of the SFRP1 promoter region is increased in patients with RCC compared to normal controls and might be involved in the occurrence and development of RCC. Additional well-designed studies are needed to further verify our conclusions.

Increasing evidence has indicated that circular RNAs (circRNAs) play a key role in the development and progression of diverse cancers, but their role in clear cell renal carcinoma (CCRCC) tumorigenesis is not well understood. In this study, we firstly performed comprehensive circRNA-seq from CCRCC tissues and pair-matched adjacent normal tissues. In total, 1184 circRNAs were dysregulated in human CCRCC tissues compared with those in adjacent normal tissues. We randomly selected four circRNAs, including circHIPK3 (circBase ID: hsa_circ_0000284), to test the circRNA-seq data in another 40 CCRCC tissues by quantitative real-time PCR (qRT-PCR). Furthermore, we found that circHIPK3 was downregulated in CCRCC tissues and cell lines. Overexpression of circHIPK3 effectively suppressed CCRCC cell invasion and migration in vitro, and inhibited CCRCC cell proliferation in vitro and in vivo. Moreover, bioinformatic analysis and luciferase reporter assay showed that circHIPK3 targeted miR-637 in CCRCC cells. Hence, CircHIPK3 may represent a tumor suppressor and target miR-637 in clear cell renal carcinoma.

Solanine, a naturally steroidal glycoalkaloid in nightshade (Solanum nigrum Linn.), can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism of solanine‐suppressing prostate cancer cell growth remains to be elucidated. This study investigates the inhibition mechanism of solanine on cancer development in vivo and in cultured human prostate cancer cell DU145 in vitro. Results show that solanine injection significantly suppresses the tumor cell growth in xenograft athymic nude mice. Solanine regulates the protein levels of cell cycle proteins, including Cyclin D1, Cyclin E1, CDK2, CDK4, CDK6, and P21 in vivo and in vitro. Also, in cultured DU145 cell, solanine significantly inhibits cell growth. Moreover, the administration of NAC, an active oxygen scavenger, markedly reduces solanine‐induced cell death. Blockade of P38 MAPK kinase cannot suppress reactive oxygen species (ROS), but can suppress solanine‐induced cell apoptosis. Also, inhibition of ROS by NAC inactivates P38 pathway. Taken together, the data suggest that inhibition of prostate cancer growth by solanine may be through blocking the expression of cell cycle proteins and inducing apoptosis via ROS and activation of P38 pathway. These findings indicate an attractive therapeutic potential of solanine for suppression of prostate cancer.

Purpose To evaluate the association between the use of statins and/or metformin and patient survival in prostate cancer patients in Taiwan. Subjects and methods Newly diagnosed prostate cancer patients who had hyperlipidemia and received radiotherapy were identified from the National Health Insurance Research Database 2000–2010. The survival rate was estimated by the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to examine the association of mortality. Sensitivity analysis was performed to assess the risk of mortality in patients with diabetes. Results The study included 567 patients. Patients who used statins or metformin after prostate cancer diagnosis had longer average survival times (9.3 years and 8.1 years, respectively; P=0.001) compared with patients who persistently used or used the medicines prior to cancer diagnosis. Multivariate Cox regression analysis found that patients treated with statins after cancer diagnosis were significantly associated with a lower risk of mortality (aHR =0.24, 95% CI =0.09–0.66) compared to patients who did not use statins during the study period. Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45–18.77) compared to patients who did not use metformin during the study period. Sensitivity analysis revealed that the average survival time was similar among different medicine use groups in patients with diabetes. Conclusion The finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.

Background Previous studies have reported that granzyme B (GZMB) and perforin (PRF) could serve as noninvasive biomarkers in the diagnosis of acute rejection (AR) after kidney transplant. Yet, their noninvasive diagnostic value in clinical practice is still unknown. Methods To assess the noninvasive diagnostic performance of GZMB and PRF for AR, we performed a systematic search. After reviewing published studies in which both GZMB and PRF were detected, data on the diagnostic accuracy of separate and combined evaluation of GZMB and PRF were pooled. Results Across 16 studies (680 subjects), summary sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios with 95% confidence intervals were calculated. For overall GZMB analysis, the indices were 0.76 (0.71-0.81), 0.86 (0.82-0.89), 4.58 (3.36-6.25), and 0.32 (0.22-0.47), respectively. For overall PRF analysis, the indices were 0.83 (0.78-0.88), 0.86 (0.82-0.89), 4.82 (3.66-6.35), and 0.26 (0.18-0.37), respectively. Subgroup analyses showed similar results compared to overall study analyses. In analyses of combined evaluation of GZMB and PRF, the above indices were 0.65 (0.53-0.76), 0.96 (0.91-0.98), 12.66 (5.83-27.50), and 0.40 (0.23-0.69), respectively, when both markers were positive. The probability of developing AR in kidney transplant recipients increased from 15% to 73% when both GZMB and PRF tests were positive and was reduced to 2% if that were negative. Conclusions Currently, neither GZMB nor PRF, if evaluated alone, could be a convincing noninvasive diagnostic marker for AR in clinical practice. Combined use of PRF and GZMB post-kidney transplant may be a better choice in AR evaluation to direct allograft biopsy execution and earlier therapeutic intervention.

Engrailed 2 (EN2) is a member of the homeobox gene family. Many studies suggest that overexpression of EN2 protein may be associated with tumor development, including bladder cancer (BC). However, to date, the mechanisms of how EN2 functions to promote BC progression remain elusive. The present study introduced RNAi to silence the expression of EN2 in BC cell lines. In vitro invasion and migration assays and in vivo experiments were carried out to examine the functions of EN2 in BC invasion and metastasis. The results of the present study indicated that EN2 was significantly expressed in BC cells. Ectopic expression of EN2 in normal urothelial cells significantly enhanced cellular proliferation and invasion, but inhibited cellular apoptosis. EN2 knockdown significantly promoted cell cycle arrest and apoptosis of BC cells with inhibition of proliferation and invasion in vitro as well as EN2 knockdown decreased the tumor growth of BC. The tumor growth was decreased by regulation of the cell cycle, apoptosis and epithelial-mesenchymal transition-related proteins, with inhibition of metastasis to the liver and lung in vivo. Furthermore, EN2 knockdown significantly decreased the levels of pAkt-473, pAkt-308 and phosphatidylinositol 3-kinase (PI3K), whereas EN2 knockdown increased the expression of PTEN in vitro. Taken together, EN2 may be a candidate oncogene in BC by activating the PI3K/Akt pathway and inhibiting PTEN, and may be a potential therapeutic target for the treatment of BC.

Rationale and Objectives The aim of this study was to investigate the potential of magnetic resonance imaging (MRI) T1 mapping and T1 relaxation time in the rotating frame (T1rho) for assessment of renal fibrosis in a rat model of unilateral ureteral obstruction (UUO). Materials and Methods UUO was created in 36 rats. Six rats were scanned at each of the six time points (on days 0, 1, 3, 5, 10, and 15 after UUO). The contralateral kidneys were examined as controls. Hematoxylin-eosin, Masson's trichrome, and alpha-smooth muscle actin (α-SMA) antibody staining assays were performed. MRI data obtained with a 3.0T scanner were analyzed with α-SMA expression and Masson's staining. Results The T1 relaxation times and T1rho values increased, and the mean apparent diffusion coefficient (ADC) values decreased with time after UUO. Simple regression analysis indicated that the mean ADCs, T1 relaxation times, and T1rho values had strong correlations with the α-SMA expression levels (R2 = 0.34, R2 = 0.66, R2 = 0.71, respectively; P Conclusions The T1 mapping and T1rho parameters had better correlations with α-SMA expression and Masson's staining than ADC values.

Reactive oxygen species (ROS) is an important regulator in cellular signaling transduction, and many previous studies have indicated that acute ROS stimulation improves insulin sensitivity in skeletal muscle. In the study, we found that chronic ROS treatment caused serious insulin resistance in C2C12 myotubes. Glucose uptake and consumption assay indicated that pretreatment with 80 μM H2O2 for 2 h inhibited insulin-stimulated glucose uptake in C2C12 myotubes, and the reason for it, is that chronic H2O2 treatment decreased insulin-induced glucose transporter 4 (GLUT4) translocation from cell plasma to cell membrane. Moreover, Akt2 phosphorylation depended on insulin was reduced in C2C12 myotubes of chronic H2O2 treatment. Together, this study provides further demonstration that chronic ROS stress is associated with insulin resistance of skeletal muscle in the progression of type 2 diabetes.

Our preliminary study indicated that Engrailed-2 (EN2) is downregulated but also ectopically expressed in clear-cell renal cell carcinoma (CCRCC), and the absence of EN2 expression was associated with poor histological grade. However, the specific roles of EN2 in CCRCC have yet to be elucidated. In the present study, we examined the effects of inhibiting EN2 expression by human renal tubular epithelial cells (HK-2) and overexpressing EN2 by human clear-cell renal cells (786-O). Results showed that EN2 inhibition accelerated HK-2 cell proliferation, shortened the cell cycle, reduced apoptosis, and acted more invasively. By contrast, EN2 overexpression in 786-O cells decelerated the proliferative ability of 786-O, increased the percentage of cell apoptosis, and weakened the invasive ability. Overall, the results demonstrated that EN2 might play an anti-oncogenic role in oncogenesis and development of CCRCC, thereby maintaining the normal growth of human renal tubular epithelial cells.

Centromere protein H (CENPH), one of the essential component of active kinetochore, plays an important role in carcinogenesis of many cancer types. However, its expression signature and prognostic significance of renal cell carcinoma (RCC) are unclear. In the present study, we concluded that the expression of CENPH was prominently upregulated in RCC specimens and three RCC cell lines (ACHN, 786-O and A704). Immunohistochemical analysis revealed that RCCs exhibited higher levels of CENPH expression than normal renal tissues in paraffin-embedded archival specimens. Further statistical analysis suggested the upregulation of CENPH was positively correlated with the Fuhrman grade (P = 0.001), distant metastasis (P = 0.024) and clinical stage (P = 0.014). In addition, the CENPH served as an independent predictor of overall survival of RCC patients in multivariate analysis (P = 0.018). Furthermore, our in vitro assays of RCC cell lines indicated that knockdown of CENPH reduced cell proliferation, inhibited cell growth, and increased cell apoptosis. In conclusion, our data suggest that CENPH is a novel molecule involved in RCC progression, which provides a potential biomarker and therapeutic target.

Various rat kidney transplantation models have been introduced over the decades and the study on the models seems to lack novelty and necessity. However, vascular anastomosis, especially renal vein, is still very difficult for trainees. The aim of this study was to provide the modified renal venous anastomosis of rat kidney transplantation to substitute the current method for trainees.Male Wistar rats were used as donors and recipients, respectively. Left orthotopic transplantation was performed with a modified technique of renal vein anastomosis, combining the end-to-end sutures with epidural catheter. Meanwhile, the survival rate, warm ischemia time, renal venous anastomosis time, and complications were recorded to evaluate the merits of the modified technique compared with the current recommended technique of rat renal vein. Two trainees took part in the learning of the models in two methods for performing 30 operations, respectively.The difference in warm ischemia time (from (57.25 ± 7.30) minutes in the first 10 operations to (30.05 ± 1.85) minutes in the third 10 operations) and renal vein anastomosis time (from (32.80 ± 3.80) minutes in the first 10 operations to (19.30 ± 0.98) minutes in the third 10 operations) was significantly short (P0.01) and the survival rate was statistically high (from (25 ± 7)% in the first 10 operations to 70% in the third 10 operations) in equal number of operations (P0.01) by comparing with the current recommended method ((47.60 ± 7.19) minutes to (22.8 ± 1.85) minutes, (22.40 ± 3.10) minutes to (9.95 ± 1.50) minutes, 45%± 7% to 80%± 0, respectively). The intraoperative complications and postoperative complications of renal venous anastomosis were also significantly decreased (P0.01).The technique with epidural catheter can shorten the learning curve of the trainee learning rat kidney transplantation. It may replace the currently recommended technique of rat renal vein for trainees.

To investigate the expressions of Engrailed-2 (EN2) and β-catenin in bladder urothelial carcinoma and explore their significance.Sixty bladder urothelial carcinoma samples of different grades and stages and 10 normal bladder mucosal tissues were examined for expressions of EN2 and β-catenin proteins and mRNA using immunochemistry, Western blotting and RT-PCR. RESULTS Compared to normal bladder mucosa, bladder urothelial carcinoma tissues showed significantly increased expressions of EN2 and β-catenin proteins (P0.05), and the high-grade carcinoma tissues exhibited significantly stronger expressions than the low-grade ones (P0.05); the expressions of the proteins increased also significantly with advanced pathological stages of bladder urothelial carcinoma (P0.05). The expressions of EN2 and β-catenin mRNAs showed a consistent pattern of changes with their protein expressions.The expressions of EN2 and β-catenin are significantly increased in bladder urothelial carcinoma. EN2 may contribute to the development and progression of bladder urothelial carcinoma by activating Wnt/β-catenin signal pathway.

We investigate the role of the Lin28/let-7a/c-Myc pathway in non-muscle invasive bladder cancer (NMIBC). Using RT-PCR, western blot and immunohistochemistry techniques, the levels of pre-let-7a, let-7a, Lin28 and c-Myc RNA and/or proteins were determined in samples of normal bladder tissue and bladder cancer. Expression of pre-let-7a was found to be negatively correlated with the pathological grade of bladder cancer, while let-7a showed a positive correlation with bladder cancer pathological grade. Expression of Lin28 RNA and protein was not significantly different between normal bladder tissue and low-grade transitional cell carcinoma of bladder (TCC) but the expression levels in high-grade TCC were remarkably increased. Expression of c-Myc RNA and protein was significantly higher in bladder cancer samples in comparison to normal bladder tissue without correlation with cancer differentiation. Expression of all the above RNAs and proteins showed no significant difference in Ta and T1 stages. The Lin28/let-7a/c-Myc pathway plays an important role in NMIBC. In particular, expression levels of let-7a correlate with the degree of cancer differentiation but not cancer stage.

Engrailed-2 (EN2), a member of the homeobox family of genes, encodes a homeodomain-containing transcription factor that is thought to be a potential oncogene in a number of cancers. Because the role of EN2 in clear cell renal cell carcinoma (CCRCC) has not been determined, we investigated its expression in CCRCC tissues and cell lines. Using immunohistochemical (IHC) staining, we found that EN2 protein was expressed in normal renal cells and tubules, but was frequently down-regulated in tissues from patients with CCRCC and in CCRCC cell lines. In addition, we found that EN2, which functions in the nucleus, was completely localized to the cytoplasm of CCRCC cells as detected by IHC and immunofluorescence staining. Furthermore, expression of EN2 protein was negatively correlated with increasing histological grade of CCRCC tumors (P = 0.003). The exact role of EN2 expression in renal carcinoma carcinogenesis requires further investigation.

Transurethral enucleation resection of the prostate is safe and feasible for the treatment of symptomatic benign prostatic hyperplasia (BPH). However, long-term results of this treatment in patients with BPH have not been reported. To assess the efficacy and safety of this procedure, this study retrospectively evaluated long-term outcomes in 1400 consecutive patients who underwent transurethral enucleation resection of the prostate for BPH between 2008 and 2014. Patients were followed up at 1, 3, 6, and 12 months, and every year thereafter. At a median follow-up of 70.1 months, mean Qmax increased from 6.43 to 22.1 ml/s and mean IPSS decreased from 22.3 to 2.9. PVR decreased from 123.0 to 12.0 cc, and mean TRUS volume decreased from 65.4 to 21.4 ml (P