MiR-6838-5p facilitates the proliferation and invasion of renal cell carcinoma cells through inhibiting the DMTF1/ARF-p53 axis.

Renal cell carcinoma (RCC) is one of the most common renal malignancies in the urinary system. Numerous studies have demonstrated that miRNAs can regulate tumorigenesis and progression. This study aims to investigate the role and regulatory mechanism of miR-6838-5p in RCC. Our study confirmed that miR-6838-5p was upregulated in human RCC tissues (30/42, 77.43%, P < 0.01) and RCC cell lines (P < 0.05) compared to adjacent non-neoplastic tissues and normal renal epithelial cells. In vitro, overexpression of miR-6838-5p enhanced cell proliferation and invasion in human RCC cell lines (ACHN and 786-O), which were detected by CCK-8, Transwell and Colony formation assays (P < 0.05), and knockdown of miR-6838-5p suppressed cell proliferation and invasion (P < 0.05). Results of Bioinformatics analysis combined with Dual-luciferase reporter gene assay demonstrated that miR-6838-5p could bind to Cyclin D binding myb-like transcription factor 1 (DMTF1). In addition, RT-qPCR and Western blotting confirmed that DMTF1 was downregulated in RCC tissues and cell lines. Meanwhile, it was demonstrated that overexpression of miR-6838-5p inhibited DMTF1 level in ACHN cells. Next, we confirmed that DMTF1 overexpression reversed the inhibitory effects of overexpression of miR-6838-5p on phosphatase and tensin homolog (PTEN), tumor protein 53(p53), murine double minute 2 (MDM2) and alternative reading frame (ARF) protein levels in the ARF-p53 signaling pathway. In conclusion, our research showed that miR-6838-5p enhanced the proliferation and invasion of RCC cells by inhibiting the DMTF1/ARF-p53 axis.

TMEM88 exhibits an antiproliferative and anti-invasive effect in bladder cancer by downregulating Wnt/ß-catenin signaling.

Transmembrane protein 88 (TMEM88) acts as a novel tumor-associated protein. The dysregulation of TMEM88 has been observed in several tumor types. However, the relevance of TMEM88 in tumorigenesis is still contradictory. This study assessed the relevance of TMEM88 in bladder cancer. TMEM88 levels were found to be significantly lower in bladder cancer tissue. Upregulation of TMEM88 resulted in a dramatic decrease in the cellular proliferative and invasive abilities of bladder cancer. Upregulation of TMEM88 decreased the level of active ß-catenin and prohibited the activation of the Wnt/ß-catenin pathway, an effect that was associated with downregulation of glycogen synthase kinase-3ß (GSK-3ß) phosphorylation. Suppression of GSK-3ß or overexpression of ß-catenin reversed the TMEM88-induced tumor-inhibiting effects in bladder cancer. Overexpression of TMEM88 prohibited the tumor formation and growth of bladder cancer cells in nude mice. In conclusion, this study demonstrates that TMEM88 exerts an antitumor function in bladder cancer through downregulation of Wnt/ß-catenin signaling.

[Seminal vesiculoscopy in the treatment of refractory hemospermia and ejaculatory duct obstruction].

Objective: To summarize the experience in the diagnosis and treatment of refractory hematospermia and ejaculatory duct obstruction by seminal vesiculoscopy. METHODS: We retrospectively analyzed the clinical data about 42 cases of refractory hematospermia and 6 cases of ejaculatory duct obstruction with azoospermia. We investigated the diagnosis, treatment, and prognosis of the diseases. RESULTS: All the patients underwent pelvic MRI and seminal vesiculoscopy. MRI for the 42 refractory hematospermia patients showed that 21 (50.0%) had cystic dilatation in the uni- or bilateral seminal vesicles, 25 (59.5%) had abnormal internal signal intensity in the uni- or bilateral seminal vesicles, 12 (28.6%) had both the problems above, and 4 (9.52%) had no obvious abnormality in the seminal vesicle area. The bilateral seminal vesicles were <1 cm in width in 3 of the 6 cases of ejaculatory duct obstruction, and obviously enlarged in the other 3, but without abnormal internal signals. No recurrence was found during the 3－36 months follow-up. CONCLUSIONS: The history and physical examination play important roles in the diagnosis of refractory hemospermia, and MRI is more valuable than TRUS in the diagnosis of seminal vesicle diseases. Seminal vesiculoscopy is an effective option for the management of persistent hematospermia and ejaculatory duct obstruction.

Over-expression of a poor prognostic marker in prostate cancer: AQP5 promotes cells growth and local invasion.

BACKGROUND: The aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they also exhibit several properties related to tumor development. The aim of the present study is to elucidate whether the expression of AQP5 is a strong prognostic biomarker for prostate cancer, and the potential role in the progression of prostate cancer cells. METHODS: AQP5 expression was measured in 60 prostate cancer tissues and cells (both PC-3 and LNCaP) by immunohistochemistry and immunofluorescence assay. AQP5 gene amplification was detected with FISH (fluorescence in situ hybridization). Proliferation and migration of cells and AQP5 siRNA cells were detected with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Boyden chambers. Circulating tumor cells (CTCs) were detected by imFISH staining (CEP8-CD45-DAPI) assay. RESULTS: The results showed that in 60 tumor specimens, 19 (31.7%) patients showed high level of AQP5 expression, while 30 (50.0%) showed a moderate, intermediate level of staining, and 11 (18.3%) showed an absence of AQP5 staining, respectively. High-expression of AQP5 protein frequently accompanied gene amplification detection with FISH. The AQP5 over-expression was also associated with TNM stage (P=0.042), and lymph node metastasis (P=0.001). The relationships between age or tumor size with the expression of AQP5 were not significant (P>0.05). A positive correlation between the number of CTCs and AQP5 expression (P<0.05) was demonstrated. In addition, patients who were negative for AQP5 had superior cumulative survival rate than those who were positive for it. Over-expression of AQP5 protein was also found in prostate cancer cells and cell proliferation and migration were significantly attenuated by AQP5-siRNA. CONCLUSIONS: We concluded that AQP5 in prostate cancer was an independent prognostic indicator. AQP5 over-expression was likely to play a role in cell growth and metastasis. These conclusions suggest that AQP5 may be an effective therapeutic target for prostate cancer.

Experimental Study on Adsorption of SO2 and NH3 by Activated Carbon with Monometallic Active Sites at Low Concentration under Room Temperature.

SO2 and NH3 are toxic compounds and are the main sources of airborne molecular contaminants (AMCs). Even at low concentrations, they can cause equipment corrosion and reduce product yield. Therefore, it is crucial to develop a combined SO2 and NH3 capture material with a simple process and a high adsorption capacity. In this study, dynamic adsorption breakthrough experiments were conducted at 23 °C under an air pollutant concentration of 90 ppm. The synergistic adsorption results showed that Cu/AC-0.05 had a high adsorption capacity of 1.03 mmol of SO2/g and 1.45 mmol of NH3/g. Furthermore, to confirm the rationality of the modification method, characterization methods such as BET, SEM-EDX, XRD, and TG-DSC were used to study the new adsorbent and spent adsorbent. The results showed that copper was successfully attached to the activated carbon and distributed uniformly. In this study, efficient coremoval performance of SO2 and NH3 was achieved by modifying single metal active sites. Through a comprehensive analysis of the characterization results, the surface reaction mechanism of SO2 and NH3 on the prepared material was further determined. This work provides a feasible option for a highly efficient adsorbent for both SO2 and NH3 capture at low concentrations under room temperature.

High ligation of the hernia sac in open nonmesh inguinal herniorrhaphy is an important cause of iatrogenic vas deferens injury.

Vasectomy damage is a common complication of open nonmesh hernia repair. This study was a retrospective analysis of the characteristics and possible causes of vas deferens injuries in patients exhibiting unilateral or bilateral vasal obstruction caused by open nonmesh inguinal herniorrhaphy. The site of the obstructed vas deferens was intraoperatively confirmed. Data, surgical methods, and patient outcomes were examined. The Anderson-Darling test was applied to test for Gaussian distribution of data. Fisher's exact test or Mann-Whitney U test and unpaired t-test were used for statistical analyses. The mean age at operation was 7.23 (standard deviation [s.d.]: 2.09) years and the mean obstructive interval was 17.72 (s.d.: 2.73) years. Crossed (n = 1) and inguinal ( n = 42) vasovasostomies were performed. The overall patency rate was 85.3% (29/34). Among the 43 enrolled patients (mean age: 24.95 [s.d.: 2.20] years), 73 sides of their inguinal regions were explored. The disconnected end of the vas deferens was found in the internal ring on 54 sides (74.0%), was found in the inguinal canal on 16 sides (21.9%), and was found in the pelvic cavity on 3 sides (4.1%). Location of the vas deferens injury did not significantly differ according to age at the time of hernia surgery ( ≥ 12 years or <12 years) or obstructive interval (≥15 years or <15 years). These results underscore that high ligation of the hernial sac warrants extra caution by surgeons during open nonmesh inguinal herniorrhaphy.

Resveratrol inhibits TRAF6/PTCH/SMO signal and regulates prostate cancer progression.

Prostate cancer (PC) is one of the most common types of cancers among men, referring to the uncontrolled growth of the prostate gland. It is increasingly recognized that the interaction of the glioma-associated oncogene (GLI) pathway and androgen receptor affects PC progression. Nevertheless, the effects of resveratrol on PC progression via Hedgehog (HH) signaling remain unexplored. In this study, the castration-sensitive and castration-resistant xenograft models in mice are systematically established using two different PC cell lines (LNCaP and PC-3). Further, the Western blotting, immunohistochemistry, MTT, Transwell, and RT-qPCR analyses are performed to verify the mechanistic views of resveratrol on PC and HH signals in vitro and in vivo. Resveratrol showed epithelial-mesenchymal transition (EMT) progression, inhibiting the tumor size and expression levels of vimentin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) 7, as well as upregulating the expression profiles the E-cadherin and Annexin 2. Moreover, resveratrol inhibited the hedgehog (HH) signals and tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) levels exhibiting the therapeutic action on castration-sensitive and castration-resistant PC cell lines. In summary, the overexpression of TRAF6 enhanced the viability and EMT progression of cancer cells. The resveratrol could alleviate the TRAF6 effect and regulate the HH signal to affect PC progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00544-0.

Elevated free testosterone levels and reduced very low-density lipoprotein levels in men with lifelong premature ejaculation: a preliminary study.

OBJECTIVE: To investigate sex hormone and blood lipid levels in patients with lifelong premature ejaculation (LPE) in China. METHODS: Sex hormone and blood lipid levels were measured in 156 patients with LPE and 76 healthy controls. The Premature Ejaculation Diagnostic Tool (PEDT) and Chinese Index of Sexual Function for Premature Ejaculation-5 Questionnaires (CIPE-5) were applied to diagnose and grade LPE. RESULTS: PEDT and CIPE-5 scores were significantly altered in the LPE group compared with the control group. Free testosterone levels were significantly higher in the LPE group than in the control group. Free testosterone levels were also significantly higher in the mild, moderate, and severe LPE subgroups than in the control group. Total testosterone and prolactin levels tended to be lower in the control group than in the LPE group. Very low-density lipoprotein levels were significantly lower in the LPE group and LPE subgroups than in the control group. Triglyceride levels were highest in controls and decreased with progression of LPE. CONCLUSIONS: Patients with LPE have higher free testosterone levels and lower very low-density lipoprotein levels than controls. These findings indicate that these factors might be indices for LPE. However, the reasons for these phenomena need to be further investigated.

Long Noncoding RNA LINC01133 Promotes the Malignant Behaviors of Renal Cell Carcinoma by Regulating the miR-30b-5p/Rab3D Axis.

Renal cell carcinoma (RCC) is the most common type of kidney cancer with rising incidence. Long noncoding RNA (lncRNA) LINC01133 is a novel lncRNA that is involved in the development of several types of cancers. However, the role of LINC01133 in RCC has not been reported. Thus, in this study, we investigated the functions of LINC01133 in RCC. The qualitative real-time polymerase chain reaction analysis was performed to examine the levels of LINC01133 in RCC tissues and adjacent tissues, as well as RCC cell lines. The results showed that LINC01133 was highly expressed in RCC tissue specimens and cell lines. Downregulation of LINC01133 significantly inhibited the proliferation, migration, and invasion of RCC cells. Further mechanistic investigations proved that LINC01133 directly interacted with microRNA (miR)-30b-5p and regulated the miR-30b-5p expression in RCC cell lines. Moreover, miR-30b-5p exhibited tumor-suppressive activity in RCC cell lines, which was mediated by targeting Ras-related protein Rab-3D (Rab3D). In vivo study showed that LINC01133 knockdown suppressed tumor growth in the nude mice. Taken together, these findings indicated that LINC01133 might be an oncogene in RCC through regulation of the miR-30b-5p/Rab3D axis. Thus, LINC01133 might serve as a potential therapeutic target for the treatment of RCC.

Anatomic characteristics of epididymis based on histology, proteomic, and 3D reconstruction.

BACKGROUND: The epididymis is a popular research topic in urology and reproduction. OBJECTIVES: To explore and identify the anatomical characteristics of the epididymis based on histology, proteomics, and 3D reconstruction of epididymal tubules. MATERIALS AND METHODS: A 3D reconstruction of epididymal tubules was generated based on 7-µm-thick transverse serial sections of an epididymis. The proteins in the subcompartments of the epididymis were obtained and analyzed by non-labeled sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS). Protein function, signaling pathways, protein expression, and the histology in different subcompartments were analyzed. RESULTS: The caput (Cap), corpus (Cor), and cauda (Cau) of the epididymis were divided into 6, 10, and 4 subcompartments, respectively, and the subcompartment between the Cap and Cor is mixed together. A total of 3411 proteins were identified, and 854 proteins were accurately quantified after screening. When the subcompartment Cap 5 transitioned to Cap 6 and Cap 6 to Cap 7, 87 and 52 proteins were upregulated and 14 and 7 proteins were downregulated, respectively. The Cor 9 transition to Cau 1 was marked by 230 proteins that were downregulated, while 74 proteins were upregulated. At the junction of the cauda and the vas deferens, 57 proteins were downregulated, and 410 proteins were upregulated. Cap 6 histology was consistent with that of Cor 1. DISCUSSION AND CONCLUSION: The epididymis contains distinct connective tissue septa that can be identified under a surgical tabletop microscope, enabling it to be divided into 20 subcompartments.

Knockdown of MSP58 inhibits the proliferation and metastasis in human renal cell carcinoma cells.

The 58-kDa microspherule protein (MSP58) has been reported to play an important role in the tumorigenesis and progression of cancers. However, little is known about the role of MSP58 in human renal cell carcinoma (RCC). In this study, we investigated the expression and biological roles of MSP58 in RCC. The results indicated that the expressions of MSP58 at both mRNA and protein levels were greatly up-regulated in human RCC tissues and cell lines. Down-regulation of MSP58 significantly suppressed the proliferation, migration/invasion of RCC cells, as well as attenuated tumor growth in a 786-O xenograft model in vivo. Mechanistically, knockdown of MSP58 expression sharply down-regulated the protein expression levels of ß-catenin, c-myc and cyclin D1 in 786-O cells. Taken together, these findings showed that MSP58 downregulation suppressed the proliferation and invasion of RCC cells, at least in part, through regulating the Wnt/ß-catenin signaling pathway. Thus, MSP58 may act as a novel therapeutic target for the treatment of RCC.

Protective Effects of Genistein against Mono-(2-ethylhexyl) Phthalate-Induced Oxidative Damage in Prepubertal Sertoli Cells.

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein are two of the most prevalent endocrine-disrupting chemicals (EDCs) that present in the environment and food. However, how these two EDCs would affect prepubertal Sertoli cells development was rarely studied. In this study, primary prepubertal Sertoli cells were isolated from 22-day-old Sprague Dawley rats and exposed to MEHP at 1 µmol/L, 10 µmol/L, and 100 µmol/L (M1, M10, and M100), genistein at 10 µmol/L (G), and their combination (G + M1, G + M10, and G + M100). Cell proliferation inhibition rate, apoptosis and necrosis rate, and cellular redox state were evaluated. Our results revealed that MEHP could significantly increase cell proliferation inhibition rate, apoptosis rate, necrosis rate, and intracellular reactive oxidative species level. However, coadministration of genistein could partially alleviate MEHP-induced prepubertal Sertoli cells oxidative injuries via enhancement of testicular antioxidative enzymes activities and upregulation of Nrf2 and HO-1, indicating that genistein could partially attenuate MEHP-induced prepubertal Sertoli cells damage through antioxidative action and may have promising future on its curative role for attenuating other EDCs-induced reproductive disorders.