Case report: Partial cystectomy for pheochromocytoma of the urinary bladder: A case report and review of literature.

Pheochromocytomas are neuroendocrine tumors that produce catecholamines and can be difficult to diagnose. Bladder involvement is uncommon with pheochromocytoma. Hypertension (sometimes with hypertensive crisis coinciding with micturition), headache, hematuria and syncope, which are commonly associated with voiding, are the most prevalent symptoms. While transurethral resection may be performed in roughly 20% of patients, 70% require partial cystectomy and 10% require radical cystectomy. We present a case of pheochromocytoma with hypertension and syncope that was often associated with voiding, satisfactorily treated by partial cystectomy.

Inhibition of FSTL3 abates the proliferation and metastasis of renal cell carcinoma via the GSK-3ß/ß-catenin signaling pathway.

Renal cell carcinoma (RCC) is a lethal malignancy of the genitourinary system. Follistatin-like 3 (FSTL3), which mediates cell differentiation and growth, acts as a biomarker of tumors and participates in cancer development and progression. Presently, the FSTL3's functions in RCC were investigated. Quantitative reverse transcription PCR (qRT-PCR), Western Blot, and enzyme linked immunosorbent assay (ELISA) were conducted to verify FSTL3 expression in RCC tissues and cell lines. BrdU assay and CCK8 experiment were made to monitor cell proliferation. Transwell was implemented to examine the invasion of the cells. Flow cytometry analyzed cell apoptosis, and Western Blot evaluated the protein levels of E-cadherin, Twist, and Slug. In the meantime, the protein profiles of the GSK-3ß, ß-catenin, and TGF-ß signaling pathways were ascertained. Moreover, the Xenograft tumor model was constructed in nude mice for measuring tumor growth in vivo. The statistics showed that FSTL3 presented an overexpression in RCC, and patients with a lower expression of FSTL3 manifested a better prognosis. Down-regulated FSTL3 hampered the proliferation, invasion, EMT, and tumor growth of RCC cells and caused cell apoptosis. On the contrary, FSTL3 overexpression enhanced the malignant behaviors of RCC cells. Furthermore, FSTL3 knockdown bolstered GSK-3ß, suppressed ß-catenin, and reduced BMP1-SMAD pathway activation. Inhibited ß-catenin substantially mitigated FSTL3-mediated promoting functions in RCC. In short, FSTL3 functions as an oncogene in RCC by modulating the GSK-3ß/ß-catenin signaling pathway.

FAST1 Predicts Poor Survival of Renal Carcinoma and Promotes Its Progression Through the TGF-ß/Smad Pathway.

PURPOSE: Renal carcinoma (RC) originates in the renal tubular epithelial system, among which renal cell carcinoma (RCC) is the most frequent one. The forkhead activin signal transducer 1 (FAST1) has been shown to interfere with tumor progression as an oncogene, while its role in RC is limited. Therefore, this paper explored the prognostic significance, specific effects, and related mechanisms of FAST1 on RC. PATIENTS AND METHODS: Cell colony formation assay, cell counting kit-8 (CCK8) assay, flow cytometry and Transwell assay were used to test cell proliferation, viability, apoptosis, migration and invasion, respectively. Western blot (WB) was employed to determine the protein level of FAST1. RESULTS: Our study confirmed that FAST1 was up-regulated in RC tissues and cell lines, and its overexpression often represented a poor prognosis of RC patients. Meanwhile, the in vitro experiments showed that overexpressing FAST1 facilitated RC cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and repressed cell apoptosis. In addition, the in vivo experiments illustrated that the up-regulation of FAST1 strengthened tumor growth. On the contrary, knocking down FAST1 had the opposite effects. Mechanistically, The TGF-ß/Smad pathway contributed to RC evolvement and was activated by FAST1 both in vitro and in vivo. CONCLUSION: This article suggests that FAST1 exerts a carcinogenic role in RC by regulating the TGF-ß/Smad signaling.

Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway.

BACKGROUND: Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is a fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs. METHODS: In vivo study, a total of forty-eight 10-week-old male Sprague-Dawley (SD) rats were used. Twelve rats received intraperitoneal injection of PBS as the sham group; the rest received intraperitoneal injection of 60 mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM group), MSCs (M group), or administrated probucol after intracavernosal injection of MSCs (P + M group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In in vitro experiment, H2O2 was used to create oxidative stress environment to detect changes in cell viability. CCK8 was used to measure cell viability of MSCs treated with or without probucol. Intracellular ROS changes were detected by flow cytometry. Autophagy and apoptosis were detected by Western blotting and confocal microscopy. RESULTS: Recovery of erectile function was observed in the P + M group. The combination therapy decreased fibrosis and increased endothelial function compared with MSC therapy alone. Western blotting results confirmed the increased expression of Nrf2 and HO-1 in cavernous body. H2O2 induced high oxidative stress and reduced cell viability in vitro, which was gradually reversed with increased concentration of probucol. H2O2 reduced Nrf2 expression, which was reversed by probucol's intervention. Furthermore, the expression of Bax, Caspase3, and Cleaved-Caspase3 decreased, and the expression of Bcl-2 increased in a dose-dependent manner because of probucol's intervention. In addition, Beclin1 and LC3II both increased in a dose-dependent manner. Meanwhile, the expression of P62 decreased. In the study of autophagy flux, we found probucol did not block it. CONCLUSION: Probucol enhanced therapeutic efficiency of MSCs in DMED by prolonging their survival time, which mediated through improving the transplanted microenvironment of MSCs, increasing self-antioxidant ability of MSCs, strengthening protective autophagy, and inhibiting apoptosis of MSCs via Nrf2 pathway. Schematic model showing combined probucol and MSCs to improve DMED. Probucol increases self-antioxidant ability of MSCs, strengthening protective autophagy and inhibiting apoptosis via Nrf2/HO-1 and Nrf2/autophagy pathways.

Enhanced complex local frequency elastography method for tumor viscoelastic shear modulus reconstruction.

BACKGROUND AND OBJECTIVES: The Mayo Clinic provides a magnetic resonance (MR) elastography software named MRE Wave, which uses the conventional local frequency elastography (LFE) method. However, MRE Wave is unable to supply complex viscoelasticity maps for elastography. We sought to improve the local frequency estimation algorithm used in LFE, which we refer to as the Enhanced Complex Local Frequency Elastography (EC-LFE) algorithm. METHODS: The proposed algorithm uses wave equations under the hypotheses of being linear, isotropic, and locally homogeneous. Two 2D simulation models were used to investigate the accuracy and sensitivity of the EC-LFE algorithm for detecting small tumors. The corresponding statistical parameters were the relative root mean square (RMS) error and contrast-to-noise ratio (CNR). EC-LFE was investigated with two different parameter sets, one with an optimally chosen parameter ξ (EC-LFE Adj, for short) and the other with ξ = 0 (EC-LFE0). We compared the MRE Wave and the EC-LFE using series signal-to-noise (SNR) wave data. RESULTS: The elasticity RMS error of the MRE Wave software was about 1%, and that of the EC-LFE0 and EC-LFE Adj were about 0.2%. The elasticity standard deviation of the MRE Wave software was about 3% of the mean value, and those of the EC-LFE0 and EC-LFE Adj were about 1% of the mean value. The elasticity CNR value of EC-LFE0 reached 1.93 times that of the MRE Wave in the region of small tumors (less than 10-point sampling). The viscosity RMS errors of the EC-LFE0 could be less than 5%. CONCLUSION: Compared to conventional methods, the EC-LFE was more accurate and sensitive for small tumor detection and exhibited higher noise immunity. The improved algorithm output more parameters and outperformed than the MRE Wave, thereby rendering them more suitable for clinical applications.

Requirements for accurate estimation of shear modulus by magnetic resonance elastography: A computational comparative study.

BACKGROUND: Magnetic resonance (MR) elastography is a non-destructive method of measuring biological tissue and is conducive to the early detection of tumors. Researchers usually set different assumptions according to different research objects, then establish and solve wave equations to estimate the shear modulus. Establishing a more reasonable model for a measured object estimates a more accurate shear modulus. Different assumptions of the mathematical model, and the method used to solve the wave equation causes deviation of the estimation. OBJECTIVE: This study focused on shear modulus deviations caused by differences in calculation methods. The author demonstrated a method to ensure that the measuring range of the selected reconstruction algorithm with selected drive frequency covers the elasticity range of the target tissue. It is hoped to arouse the interest of researchers to introduce new transform domain methods to the field of MR elastography. METHOD: In linear, isotropic and local homogeneity assumptions, the typical representative of two different calculation methods are algebraic inversion of the differential equation (AIDE) algorithm and local frequency elastography (LFE) algorithm. To compare the accuracy of these calculation methods, the author adopted a digital phantom that can set the parameter values accurately. It is assumed that the phantom tissue was linear and isotropic, and that the driving wave was sinusoidal. The displacement distribution of waves in the tissue was calculated by the finite element simulation method in two different resolutions with the signal-to-noise ratio (SNR) set to 40 dB and the threshold of relative mean error (RME) no more than 10%. The wavelength-to-pixel-size ratios of the two methods under the setting threshold of RME were compared. RESULTS: The lower threshold of wavelength-to-pixel-size ratio for AIDE was close to 10, while that for LFE was nearly 2 (the limitation of Shannon's law) under the setting precision. Thus, the measuring range of the AIDE method was less than that of LFE at the same experimental conditions. CONCLUSION: The driving frequency selection range of the spatial frequency domain method is wider than that of the spatial domain method. It is worthwhile for researchers to devote more time to introducing new transformation domain method for MR elastography.

A mutation in CsHD encoding a histidine and aspartic acid domain-containing protein leads to yellow young leaf-1 (yyl-1) in cucumber (Cucumis sativus L.).

Leaf color mutants are an ideal tool to study chlorophyll biosynthesis, chloroplast development and photosynthesis. In this study, we identified an EMS-induced yellow young leaf mutant C777. The mutant exhibited yellow cotyledons and emerging true leaves with stay-green dots that turn green gradually with leaf growth. Segregation analysis in several populations indicated that the mutant C777 was controlled by a recessive gene yyl-1. Fine mapping delimited the yyl-1 locus to a 45.3 kb region harboring 8 putative genes, but only one SNP (G to A) was identified between C777 and its wild-type parental line in this region which occurred in the 13th exon of CsHD that encodes a histidine and aspartic acid (HD) domain containing protein. This nonsense mutation introduced a stop codon and thus a premature protein. Uniqueness of this mutant allele was verified in 515 cucumber lines. Quantitative real-time PCR revealed significantly reduced expression of CsHD gene in the mutant. Further, silencing the NbHD gene by VIGS in tobacco resulted in virescent young leaves and significantly down-regulated expression of HD gene. These results strongly supported the association of the CsHD gene with the virescent young leaf phenotype in C777. This is the first report to clone and characterize the CsHD gene in the horticultural crops. The results may help understand the functions of the HD gene in chloroplast development and chlorophyll biosynthesis in plants.

Impact on sexual function of plasma button transurethral vapour enucleation versus plasmakinetic resection of the large prostate >90 ml: Results of a prospective, randomized trial.

To compare the impact of plasma button transurethral vapour enucleation of the prostate (PVEP) and plasmakinetic resection of the prostate (PKRP) on lower urinary tract symptoms and sexual function in patients with benign prostatic enlargement (BPE) >90 ml. Between July 2017 and August 2018, 101 patients with symptomatic BPE were randomly, prospectively assigned to either PKRP or PVEP in our department. The clinical characteristics and sexual function were evaluated before and after surgery. Post-void residual volume, IPSS and QoL were all significantly decreased compared with baseline data in each group, while Qmax was significantly increased. The IIEF-5 score showed a slight but nonsignificant increase in both groups at 3 and 6 months after surgery, and there was no significant difference between the two groups. The post-operative rate of reduced ejaculate volume was significantly higher than the pre-operative rate in PKRP group, while there was no significant difference in PVEP group. PVEP had an attenuated effect on no ejaculate compared with PRKP, and they both had a significantly negative effect on no ejaculate. PVEP is an effective and minimally invasive procedure for large prostate. Compared with PKRP, PVEP has no effect on erectile dysfunction and has a lower negative impact on ejaculation.

Effect of probucol on autophagy and apoptosis in the penile tissue of streptozotocin-induced diabetic rats.

Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction (DMED). Probucol is considered to have anti-apoptotic effects, but its relationship with autophagy has not been reported. The aim of this study was to investigate the effects and mechanisms of probucol on erectile function. Thirty Sprague-Dawley (SD) male rats (12 weeks old) were fasted for 12 h. Twenty SD rats were injected with a single intraperitoneal injection of 60 mg kg-1 streptozotocin (STZ). Ten rats were given vehicle only and used as a sham group. After 72 h, 20 STZ-treated rats with random blood glucose concentrations consistently greater than 16.7 mmol l-1 were used as successfully established diabetic rats. The diabetic rats were divided randomly into two groups and treated with a daily gavage of probucol at a dose of 0 or 500 mg kg-1 for 12 weeks. After treatment, the intracavernous pressure (ICP) was used to measure erectile function upon electrical stimulation of the cavernous nerve. After euthanasia, penile tissue was examined using immunohistochemistry and Western blot to assess the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), microtubule-associated protein light chain 3-II (LC3-II), mammalian target of rapamycin (mTOR), and sequestosome 1 (P62). Caspase-3 activity was measured to determine apoptosis using a caspase-3 assay kit. After 12 weeks of treatment, the erectile function of the probucol group was significantly better than that of the DM group (P < 0.05). Bax and LC3-II protein expression and caspase-3 activity were significantly lower in the probucol group than those in the DM group (all P < 0.05), while Bcl-2, mTOR, and P62 protein expression levels were significantly higher than those in the DM group (all P < 0.05). We demonstrated that probucol inhibited apoptosis and autophagy in STZ-induced diabetic rats.

MicroRNA-204-5p Inhibits Ovarian Cancer Cell Proliferation by Down-Regulating USP47.

Ovarian cancer (OC) is the most lethal gynecologic cancer, and the incidence of OC has risen steadily worldwide. Numerous microRNAs (miRNAs) have been found to be involved in the progression of OC. miR-204-5p is down-regulated and functions as a tumor suppressor in various types of human malignant tumors. However, the biological roles and molecular mechanisms of miR-204-5p in OC still remain unclear. In this study, the aberrant down-regulation of miR-204-5p was detected in OC tissues. We also observed that miR-204-5p overexpression represses OC cell proliferation. Ubiquitin-specific peptidase 47 (USP47) is verified as the functional target of miR-204-5p, through which it plays an important biological role in OC. Our results uncover new functions and mechanisms for miR-204-5p in the progression of OC, and provide a potential therapeutic target for the treatment of OC.

MCT4 promotes cell proliferation and invasion of castration-resistant prostate cancer PC-3 cell line.

Prostate cancer (PCa) is one of the leading causes of cancer-related death in men. Blocking androgen receptor (AR) signaling is an effective treatment strategy for the treatment of advanced metastatic disease of PCa in men. However, the method of blocking AR signaling is not suitable for castration-resistant prostate cancer (CRPC), and the treatment of CRPC is still clinically difficult. It has recently been reported that MCT4 is a plasma membrane transporter that mediates the secretion of lactic acid from aerobic glycolysis by cancer cells. Its expression is up-regulated in PCa and plays an important role in the carcinogenesis of PCa, but the underlying mechanism is hardly known. The MCT4 gene of PC-3 cell line was knocked down by siRNA, then MCT4 mRNA and protein was detected by real-time PCR and western blotting, respectively. CCK-8, Transwell migration assay, Flow cytometry, and TUNEL methods were used to detect the proliferation, invasion and apoptosis of PC-3 cells by MCT4 knockdown, and the expression of invasion-related proteins (MCT4) was detected by western blot analysis. The treatment of PC-3 with candidate MCT4 siRNAs led to marked inhibition of MCT4 expression in both mRNA and protein level. MCT4 knockdown inhibits PC-3 cell proliferation and facilitates apoptosis. Furthermore, MCT4 promoted the invasion capabilities of PC-3 cells by regulating invasion-related genes, such as VEGF, CD147, MMP2 and MMP9. In conclusion, MCT4 promotes oncogenic process of PCa may, as least partially, by inhibiting cell apoptosis and accelerating cell proliferation as well as invasion abilities of PC-3 cells. VEGF, CD147, MMP2 and MMP9 are important downstream genes of MCT4 in facilitating cell invasion.

Legumes can increase cadmium contamination in neighboring crops.

Legumes are widely used in many cropping systems because they share their nitrogen fixation products and phosphorus mobilization activities with their neighbors. In the current study, however, we showed that co-cultivation with legumes increased cadmium (Cd) contamination in the adjacent crops. Both field and mesocosm experiments indicated that legumes increased Cd levels in edible parts and shoots of four neighboring crops and five maize varieties tested, regardless of the Cd levels in the soil. This enhanced Cd accumulation in crops was attributed to root interactions that alter the rhizosphere environment. Co-cultivation with legumes reduced soil pH, which somewhat increased the exchangeable forms of Cd. Our results have demonstrated the inevitable increases in Cd levels of crops as a direct result of co-cultivation with legumes even under situations when these levels are below the permissible threshold. With this new revelation, we need to consider carefully the current cropping systems involving legumes and perhaps to re-design the current and future cropping systems in view of avoiding food contamination by Cd.

Plant coexistence can enhance phytoextraction of cadmium by tobacco (Nicotiana tabacum L.) in contaminated soil.

A mesocosm experiment was conducted to investigate whether plant coexistence affects cadmium (Cd) uptake by plant in contaminated soil. Tobacco (Nicotiana tabacum L. var. K326) and Japanese clover (Kummerowia striata (Thunb.) Schindl.) were used. Cadmium was applied as 3CdSO4 x 8H2O in solution at three levels (0, 1, and 3 mg/kg soil) to simulate an unpolluted soil and soils that were slightly and moderately polluted with Cd. Tobacco (crop), Japanese clover (non-crop), and their combination were grown under each Cd treatment. Compared to monoculture and under all Cd treatments, co-planting with Japanese clover did not affect tobacco biomass but significantly increased Cd concentration in all tobacco tissues and enhanced Cd accumulation in tobacco shoots and roots. Compared to monoculture, co-planting reduced soil pH and increased Cd bioavailability. For tobacco, co-planting with Japanese clover increased the Cd bioconcentration factor (BCF) in Cd contaminated soil. Japanese clover also accumulated substantial quantities of Cd in shoots and roots. Thus, total Cd uptake by the plants was much greater with co-planting than with monoculture. The results suggested that phytoextraction can be effectively increased through tobacco co-planting with Japanese clover in mildly Cd-contaminated soil.