BackgroundLong noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of cancers. In this study, we described lncRNAs profiles in 6 pairs of human renal clear cell carcinoma (RCCC) and the corresponding adjacent nontumorous tissues (NT) by microarray.Methodology/Principal FindingsWith abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 17157. From the data we found there were thousands of lncRNAs that differentially expressed (≥2 fold-change) in RCCC tissues compared with NT and 916 lncRNAs differentially expressed in five or more of six RCCC samples. Compared with NT, many lncRNAs were significantly up-regulated or down-regulated in RCCC. Our data showed that down-regulated lncRNAs were more common than up-regulated ones. ENST00000456816, X91348, BC029135, NR_024418 were evaluated by qPCR in sixty-three pairs of RCCC and NT samples. The four lncRNAs were aberrantly expressed in RCCC compared with matched histologically normal renal tissues.Conclusions/SignificanceOur study is the first one to determine genome-wide lncRNAs expression patterns in RCCC by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in RCCC compared with NT samples, which revealed that lncRNAs differentially expressed in tumor tissues and normal tissues may exert a partial or key role in tumor development. Taken together, this study may provide potential targets for future treatment of RCCC and novel insights into cancer biology.

Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury.

Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a cesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of the present study was to determine if increasing the number of doses of MSCs improves urethral and pudendal nerve function and anatomy. We hypothesized that increasing the number of MSC doses would accelerate recovery from SUI compared with vehicle treatment. Rats underwent pudendal nerve crush and vaginal distension or a sham injury and were treated intravenously with vehicle or one, two, or three doses of 2 × 106 MSCs at 1 h, 7 days, and 14 days after injury. Urethral leak point pressure testing with simultaneous external urethral sphincter electromyography and pudendal nerve electroneurography were performed 21 days after injury, and the urethrovaginal complex and pudendal nerve were harvested for semiquantitative morphometry of the external urethral sphincter, urethral elastin, and pudendal nerve. Two and three doses of MSCs significantly improved peak pressure; however, a single dose of MSCs did not. Single, as well as repeated, MSC doses improved urethral integrity by restoring urethral connective tissue composition and neuromuscular structures. MSC treatment improved elastogenesis, prevented disruption of the external urethral sphincter, and enhanced pudendal nerve morphology. These results suggest that MSC therapy for postpartum incontinence and SUI can be enhanced with multiple doses.

Stress urinary incontinence (SUI) in women is strongly associated with childbirth which injures the pudendal nerve (PN) and the external urethral sphincter (EUS) during delivery. Electrical stimulation (ES) can increase brain-derived neurotrophic factor (BDNF) expression in injured neurons, activate Schwann cells and promote neuroregeneration after nerve injury. The aim of this study was to determine if more frequent ES would increase recovery from SUI in a rat model. Forty female Sprague–Dawley rats underwent either sham injury or pudendal nerve crush (PNC) and vaginal distention (VD) to establish SUI. Immediately after injury, electrodes were implanted at the pudendal nerve bilaterally. Each injured animal underwent sham ES, twice per week ES (2/week), or daily ES of 1 h duration for two weeks. Urethral and nerve function were assessed with leak point pressure (LPP), EUS electromyography and pudendal nerve sensory branch potential (PNSBP) recordings two weeks after injury. LPP was significantly increased after daily ES compared to 2/week ES. EUS neuromuscular junction innervation was decreased after injury with sham ES, but improved after 2/week or daily ES. This study demonstrates that daily bilateral ES to the pudendal nerve can accelerate recovery from SUI. Daily ES improved urethral function more than 2/week ES.

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Purpose of Review: The present review highlights regenerative electrical stimulation (RES) as a potential future treatment options for patients with nerve injuries leading to urological dysfunction, such as urinary incontinence, voiding dysfunction or erectile dysfunction. Additionally, it will highlight highlights the mechanism of nerve injury and regeneration as well as similarities and differences between RES and current electrical stimulation treatments in urology, functional electrical stimulation (FES) and neuromodulation. Recent Findings: It has been demonstrated that RES upregulates brain derived neurotrophic factor (BDNF) and its receptor to facilitate neuroregeneration, facilitating accurate reinnervation of muscles by motoneurons. Further, RES upregulates growth factors in glial cells. Within the past two years, RES of the pudendal nerve upregulated BDNF in Onuf's nucleus, the cell bodies of motoneurons that course through the pudendal nerve and accelerated functional recovery in an animal model of stress urinary incontinence. Additionally, ES of the vaginal tissue in an animal model of stress urinary incontinence accelerated functional recovery.

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Highlights The bladder cavernous hemangioma (BCH) is a benign non-urothelial tumor rarely occurred in the urinary bladder. Treatment options are vary for individuals and most are with favorable follow-ups. A history of cancer related radiation therapy seems to be a risk factor for BCH. It is important to differentiate them from malignant neoplasms since they have extremely different prognostic features and therapeutic strategies.