FSCN1 Promotes Glycolysis and Epithelial-Mesenchymal Transition in Prostate Cancer through a YAP/TAZ Signaling Pathway.

Objective: The aim of the study is to investigate the role and possible mechanism of fascin-1 (FSCN1) in the invasion, migration, glycolysis, and epithelial-mesenchymal transition (EMT) of prostate cancer. Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to determine the mRNA expression level of FSCN1 in prostate cancer tissues and prostate cancer cells PC-3 and DU145. The transwell and the scratch test were applied to detect the invasion and migration abilities of cells, respectively. A metabolic assay was used for measuring the glucose consumption, lactate production, and the extracellular acidification rate (ECAR) in cells; western blot was used for checking FSCN1, EMT, and yes-associated protein/transcriptional co-activators with the PDZ-binding motif (YAP/TAZ) signaling pathway-related protein expression level in cells or tissues. Results: FSCN1 was significantly highly expressed in prostate cancer tissues and cells. On the one hand, interference with the expression of FSCN1 could inhibit the invasion, migration, EMT, and glycolysis of prostate cancer cells. On the other hand, overexpression of FSCN1 promoted the invasion, migration, EMT, and glycolysis of prostate cancer cells. Besides, further mechanistic studies revealed that FSCN1 could activate the YAP/TAZ signaling pathway in prostate cancer cells. Conclusion: FSCN1 promotes invasion, migration, EMT, and glycolysis in prostate cancer cells by activating the YAP/TAZ signaling pathway. FSCN1 may be used as a biomarker for the diagnosis or treatment in prostate cancer.

The design and synthesis of two imidazole fluorescent probes for the special recognition of HClO/NaHSO3 and their applications.

Two fluorescent probes (L1 and L2) based on an imidazole unit were synthesized for the specific detection of ClO- and HSO3-. Density functional theory (DFT) calculations were used to assist in designing the probes. As predicted, L1 could be used to detect ClO- in real water samples and in living cells. It was shown to be a quenching probe. L2 could be used to monitor HSO3- in living cells and is an enhanced fluorescence probe. Further details of the fluorescence recognition mechanism were obtained via HRMS analysis. Moreover, both fluorescent probes showed relatively low detection limits (0.96 and 0.59 µM, respectively), and fast and highly selective fluorescence responses.

Identification of potential core genes in metastatic renal cell carcinoma using bioinformatics analysis.

Most cases of mRCC without an early finding are not candidates for curative therapies, which may be one of the reasons for the poor patient prognosis. Therefore, candidate markers to diagnose the disease and treatment with high efficiency are urgently demanded. Three datasets of mRNA microarray have been assessed to discover DEGs between tissues from metastatic RCC and RCC. 111 DEGs in total were identified according to the expression profile result of genes in the database of GEO. Enrichment analyses for GO and KEGG have been conducted to reveal the interacting activities in the DEGs. A network of PPI has been established to reveal the interconnection among the DEGs, and we selected 10 hub genes. Subsequently, the disease-free survival rate and total survival rate analysis for the hub genes have been carried out with the method of Kaplan-Meier curve. RCC patients with CDH11, COL3A1, COL5A1, COL5A2, COL6A3 and COL11A1 alteration showed worse overall survival. Nonetheless, RCC patients with CDH11, COL3A1, COL5A1, COL5A2 and COL11A1 alteration showed worse disease-free survival. In the Jones Renal dataset, mRNA levels of 10 hub genes were associated with metastasis, and the gene expression level in patients with mRCC was higher than that in patients without metastasis. COL5A1, COL6A3 and COL11A1 expression levels were remarkably related to RCC patient survival rate using UALCAN. COL5A1, COL6A3 and COL11A1 were positively correlated with each other in RCC. These genes have been recognized as genes with clinical relevance, revealing that they might have important roles in carcinogenesis or development of mRCC.

Attenuated BK channel function promotes overactive bladder in a rat model of obesity.

Overactive bladder (OAB) is mostly observed in obese individuals, and is associated with enhanced excitability and contractility of the detrusor smooth muscle (DSM). Large-conductance voltage- and Ca2+-activated K+ (BK) channels reduce the excitability and contractility of the DSM. We tested whether obesity-induced OAB is associated with altered BK channel expression and activity in the DSM. Seven-week-old female Sprague-Dawley rats (N=80) were fed a normal or high-fat diet (HFD) for 12 weeks. HFD-fed rats exhibited a higher average bodyweight and urodynamically established detrusor overactivity. mRNA levels of the Kcnma1 (BKα subunit) and Kcnmb1 (BKß1 subunit) in whole tissues and cells from the DSM were reduced in HFD-fed rats. A selective BK channel opener, NS1619, was then applied to DSM cells from the two groups of rats. Patch-clamp techniques revealed that spontaneous transient outward currents, NS1619-induced activation of spontaneous transient outward currents, and whole-cell BK currents, as well as NS1619-induced membrane hyperpolarization, were attenuated in DSM cells from HFD-fed rats. The relaxation effect of NS1619 on contractility was reduced in DSM strips from HFD-fed rats. Thus, impaired expression of Kcnma1 and Kcnmb1 in the DSM contributes to obesity-induced OAB, suggesting that BK channels could be a useful treatment targets in OAB.

Two highly selective and sensitive fluorescent imidazole derivatives design and application for 2,4,6-trinitrophenol detection.

In this paper, two nanoparticle fluorescence sensors L1 and L2 were designed and synthesized for the detection of 2,4,6-trinitrophenol (TNP) in water. Density functional theory (DFT) calculations were used to assist in designing sensors and explaining the detection mechanism. A further illustration of the fluorescence quenching mechanism was also studied by 1H NMR titration and UV-Vis absorption spectroscopy. The Job's plot demonstrates the combined stoichiometry of the sensor and TNP. Both sensors show low detection limit apparently (0.17 and 0.49 µM), fast and highly selective fluorescence response to TNP compared to other nitro-compounds. Moreover, L1 and L2 were successfully applied for the determination of TNP in real water samples.

Effect of high-fat diet-induced obesity on the small-conductance Ca2+-activated K+ channel function affecting the contractility of rat detrusor smooth muscle.

PURPOSE: Obesity usually induces overactive bladder (OAB) associated with detrusor overactivity, which is related to increased contractility of the detrusor smooth muscle (DSM). Small-conductance Ca2+-activated K+ (SK) channels play a constitutive role in the regulation of DSM contractility. However, the role of SK channels in the DSM changes in obesity-related OAB is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM and that SK channels activation is a potential treatment for OAB. METHODS: Female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. Urodynamic studies, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and isometric tension recording were performed. RESULTS: Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. qRT-PCR experiments revealed a decrease in the mRNA expression level of SK channel in DSM tissue of the HFD rats. Isometric tension recordings indicated an attenuated relaxation effect of NS309 on the spontaneous phasic and electrical field stimulation-induced contractions that occurred via SK channel activation in HFD DSM strips. CONCLUSIONS: Reduced expression and activity of SK channels in the DSM contribute to obesity-related OAB, indicating that SK channels are a potential therapeutic target for OAB.

TRIP13 is a predictor for poor prognosis and regulates cell proliferation, migration and invasion in prostate cancer.

Thyroid hormone receptor interactor 13 (TRIP13) has been reported to be overexpressed in serval types of human cancers, and regulate tumor cell proliferation, migration and invasion. However, the role of TRIP13 in prostate cancer was still unclear. In our study, the correlation between TRIP13 expression and clinical parameters including prognosis was evaluated in 160 prostate cancer patients. Moreover, the MTT assay, cell migration and invasion assays were performed to assess the effect of TRIP13 on prostate cancer cell biological behaviour. In our results, the expression status of TRIP13 was observed to be elevated in prostate cancer tissue samples through analyzing microarray (GSE55945). Furthermore, mRNA and protein TRIP13 expression were confirmed to be overexpressed in prostate cancer tissue samples and cell lines. High-expression of TRIP13 was correlated with present lymph node involvement, distant metastasis, high Gleason score, levels of serum PSA and poor prognosis in prostate cancer patients. The gain-of-function and loss-of-function studies suggested that TRIP13 functioned as oncogene to regulate prostate cancer cell proliferation, migration, invasion through controlling YWHAZ and epithelial-mesenchymal transition (EMT)-associated genes. In conclusion, TRIP13 is correlated with clinical progression and poor prognosis, and serves as oncogene in prostate cancer.

The phosphodiesterase type 4 inhibitor roflumilast suppresses inflammation to improve diabetic bladder dysfunction rats.

PURPOSE: To demonstrate that phosphodiesterase type 4 (PDE4) inhibitors could potentially treat diabetic bladder dysfunction (DBD) through modulation of the systemic inflammatory response. METHODS: In this 6-week study, 60 female Sprague-Dawley rats were divided into three groups: (i) vehicle-treated control rats; (ii) vehicle-treated streptozocin (STZ)-injected rats; and (iii) roflumilast-treated STZ-injected rats. Oral roflumilast (5 mg/kg/day) was administered during the last 4 weeks of STZ injection to induce diabetes in the test group. At 6 weeks, a urodynamic study was performed in each group. The expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1ß in detrusor smooth muscle (DSM) was analyzed using quantitative reverse transcription-polymerase chain reaction and Western blotting. RESULTS: A significant decrease in bodyweight and significant increases in bladder weight and blood glucose level were observed in the diabetic rats and were not ameliorated by roflumilast treatment. Cystometry showed the increased bladder capacity, voiding volume, residual urine volume, and voiding interval in the diabetic rats and the prevention of these changes by roflumilast. These changes were accompanied by significantly enhanced expression of NF-κB, TNF-α, IL-6, and IL-1ß in DSM tissue from diabetic rats. Furthermore, roflumilast attenuated the expression of inflammatory factors in DSM tissue. CONCLUSIONS: Oral treatment with roflumilast in diabetic rats improves bladder function and inhibits the expression of inflammatory factors in DSM tissue, indicating that PDE4 is a potential therapeutic target for DBD.

LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer.

INTRODUCTION: Terminal differentiation-induced non-coding RNA (TINCR) has been suggested to have aberrant expression in multiple human cancers, and functions as tumor suppressor or promoter in various types of human tumors depending on the specific cancer types. The expression status and biological function of TINCR in prostate cancer is still unknown. MATERIALS AND METHODS: In our study, we detected TINCR expression in prostate cancer tissue samples and cell lines, and analyzed the association between TINCR expression and clinical parameters in 160 prostate cancer patients. Moreover, we conducted gain-of-function and loss-of-function studies in prostate cancer cell to explore the biological function and molecular mechanism of TINCR. RESULTS: In our results, low-expression TINCR was observed in prostate cancer, and correlated with advanced clinical T stage, lymph node involvement, distant metastasis, high Gleason score and poor prognosis in prostate cancer patients. Moreover, levels of TINCR expression were negatively associated with TRIP13 mRNA and protein expressions in prostate cancer tissues, and negatively regulated the TRIP13 mRNA and protein expressions in prostate cancer cell lines. TINCR inhibits prostate cancer cell proliferation, migration and invasion via suppressing TRIP13 expression. CONCLUSION: TINCR plays a tumor suppressive role in regulating prostate cancer cell proliferation, migration and invasion through modulating TRIP13 expression.

Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast.

PURPOSE: To prove that phosphodiesterase type-4 inhibitors could potentially treat obesity-associated overactive bladder through modulation of the systemic inflammatory response. METHODS: In this 12-week study, 90 female Sprague-Dawley rats were divided into three groups: (1) vehicle-treated normal diet (ND)-fed rats; (2) vehicle-treated high-fat diet (HFD)-fed rats; and (3) roflumilast-treated HFD-fed rats. Oral roflumilast (5 mg/kg/day) was administered during the last 4 weeks of HFD feeding in the test group. At 12 weeks, a urodynamic study was performed in ten rats of each group. Bladder tissue was extracted, the bladder mucosa was separated under microscopy, and bladder detrusor smooth muscle (DSM) expression of TNF-α, interleukin (IL)-6, IL-1ß, and nuclear factor kappa B (NF-κB) were analyzed using Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Bodyweights of the HFD-fed rats significantly increased and were not ameliorated by roflumilast treatment. Cystometry evidenced augmented frequency and non-void contractions in obese rats that were also prevented by roflumilast. These alterations were accompanied by a markedly increased expression of TNF-α, IL-6, IL-1ß, and NF-κB in DSM of obese rats. Furthermore, roflumilast decreased expression of inflammatory factors in DSM. CONCLUSIONS: Oral treatment with roflumilast in rats fed an HFD restores normal bladder function and downregulates expression of inflammatory factors in the bladder.

Expression and function of the small-conductance Ca2+-activated K+ channel is decreased in urinary bladder smooth muscle cells from female guinea pig with partial bladder outlet obstruction.

PURPOSE: Overactive bladder (OAB), usually accompanied by partial bladder outlet obstruction (PBOO), is associated with detrusor overactivity (DO) which is related to the increased urinary bladder smooth muscle (UBSM) cells excitability. Small-conductance Ca2+-activated K+ (SK) channels play a constitutive regulatory role of UBSM excitability and contractility. PBOO is associated with the decreased SK channels mRNA expression and the attenuated regulative effect of SK channels on UBSM contractility. However, the regulation of SK channels in PBOO UBSM cell excitability is less clear. Here, we tested the hypothesis that PBOO is associated with decreased expression and function of SK channels in UBSM cells and that SK channels are a potential target for the treatment of OAB. METHODS: Cystometry indicated that DO was achieved 2 weeks after PBOO in female guinea pigs. Using this animal model, we conducted single-cell quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and patch-clamp electrophysiology. RESULTS: The single-cell qRT-PCR experiments indicated the reduced SK channel mRNA expression in PBOO UBSM cells. Patch-clamp studies revealed that NS309 had a diminished effect on resting membrane potential hyperpolarization via the activation of SK channels in PBOO UBSM cells. Moreover, attenuated whole-cell SK channel currents were demonstrated in PBOO UBSM cells. CONCLUSIONS: The attenuated expression and function of SK channels, which results in the increased UBSM cells excitability and contributes to DO, was discovered in PBOO UBSM cells, suggesting that SK channels might be potential therapeutic targets for the control of OAB.

Growth characteristics of nanocrystalline silicon films fabricated by using chlorinated precursors at low temperatures.

We employed plasma enhanced chemical vapor deposition technique to fabricate nanocrystalline Si films at a low temperature of 250 degrees C by using SiCl4 and H2 as source gases. The evolution of microstructure of the films with deposition periods shows that nanocrystalline Si can be directly grown on amorphous substrate at the initial growth process, which is in contrast to the growth behavior observed in the SiH4/H2 system. Furthermore, it is interesting to find that the area density of nanocrystalline Si as well as grain size can be controlled by modulating the concentration of SiCl4. By decreasing the SiCl4 concentration, the area density of nanocrystalline Si can be enhanced up to 10(11) cm(-2), while the grain size is shown to decrease down to 10 nm. It is suggested that Cl plays an important role in the low-temperature growth of nanocrystalline Si.