Glucocorticoid receptor (GR) is identified as a member of nuclear receptor family. To exert its biological action, the ligand bound GR is translocated from the cytoplasm into the nucleus by regulating transcriptional signals of related genes. In clinical practice, the effects of glucocorticoid are often mediated by GR signaling pathways. An increasing number of studies have indicated that GR signaling pathways play an essential role in the proliferation, invasion and prognosis of bladder cancer. Meanwhile, the new-generation selective GR activator improves its anti-tumor effects, and at the same time reduces the adverse reactions of hormones, which probably raises the prospect for the treatment of bladder cancer.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Nucleus ; genetics ; Humans ; Prognosis ; Protein Transport ; genetics ; Receptors, Glucocorticoid ; agonists ; physiology ; Signal Transduction ; genetics ; Transcriptional Activation ; drug effects ; physiology ; Urinary Bladder Neoplasms ; genetics ; physiopathology

To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg · kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g · kg(-1) · d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g · kg(-1) · d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P <0.05, P <0.01), declines in Na+ and Cl- concentrations in urine (P <0.01), notable rises in plasma ALD and ADH contents (P <0.05, P <0.01) and remarkable down-regulations in the P2X1 and P2X3 mRNA expressions in bladder tissues (P <0.01). The ZYJCW low dose group revealed obvious reductions in Na+ and Cl- concentrations in urine (P <0.01). The results indicated that ZYJCW may show the urination-reducing effect by down-regulating the P2X1 and P2X3 mRNA expressions in bladder tissues of rats with diuresis caused by kidney deficiency.
Aging ; physiology ; Animals ; Diuresis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression Regulation ; Kidney Diseases ; drug therapy ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X1 ; genetics ; Receptors, Purinergic P2X3 ; genetics ; Urinary Bladder ; metabolism

OBJECTIVETo observe the relaxant effect of Aike Mixture (AKM) on isolated bladder and prostatic urethral smooth muscle of rabbits.

METHODSThe isolated bladder and prostatic urethral smooth muscle from male rabbits were placed in a Magnus bath and smooth muscle contraction was measured using a biological signal acquisition and analysis system. The effects of AKM in combination with methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips were determined by cumulative dosing.

RESULTSAKM dose-dependently reduced contractile tension of bladder trigone smooth muscle (r=0.831, P<0.05), reduced contractile wave amplitude (r=0.837, P<0.05) and decreased contractile frequency (r=-0.917, P<0.01). AKM significantly inhibited the increases in smooth muscle contraction induced by methoxyamine, carbachol and CaCl2.

CONCLUSIONAKM dose-dependently inhibited the contraction of rabbit isolated bladder and prostatic urethral smooth muscle by antagonizing α1-adrenergic receptors and M-cholinergic receptors.

Animals ; Calcium Chloride ; pharmacology ; Carbachol ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Hydroxylamines ; pharmacology ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Neuromuscular Agents ; pharmacology ; Prostate ; drug effects ; physiology ; Rabbits ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Muscarinic ; metabolism ; Urethra ; drug effects ; physiology ; Urinary Bladder ; drug effects ; physiology

OBJECTIVETo explore the role of autophagy in quercetin (Que)-induced apoptosis in human bladder carcinoma BIU-87 cells in vitro.

METHODSTo determine the proliferative inhibition by MTT colorimetric assay after treating BIU-87 cells with quercetin at various concentrations. To identify autophagy and apoptosis in the BIU-87 cells after Que treatment by monodansylcadaverin (MDC) and Hoechst 33258 fluorescent staining, respectively. To examine the cytotoxic effect of Que and influence of autophagy on apoptosis by studying LDH leakage rate and flow cytometry, after blocking the autophagy with 3-methlyadenine (3-MA), a specific autophagy inhibitor.

RESULTSThere was an obvious inhibitory effect of Que on the proliferation of BIU-87 cells in a time- and dose-dependent manner. The inhibition rate of BIU-87 cells after 200 µmol/L Que treatment for 72 hours was 89.2%. Autophagy and apoptosis were induced and detected in Que-treated BIU-87 cells and autophagy occurred earlier than apoptosis. The apoptosis peak became much higher after the autophagy was blocked. Whenever the autophagy was blocked before or after Que treatment, the Que-induced cytotoxicity in BIU-87 cells was enhanced.

CONCLUSIONSQuercetin significantly inhibits the proliferation of BIU-87 cells, and the autophagy is induced earlier than apoptosis. In the process of Que-induced apoptosis of BIU-87 cells, autophagy may play a protective role at the initiation phase, delay apoptosis and reduce the Que-induced death of BIU-87 cells.

Adenine ; analogs & derivatives ; pharmacology ; Antioxidants ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; physiology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Humans ; L-Lactate Dehydrogenase ; drug effects ; metabolism ; Quercetin ; administration & dosage ; pharmacology ; Urinary Bladder Neoplasms ; pathology

BACKGROUNDIncreased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells.

METHODSIn the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2), with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting.

RESULTST24 cell proliferation was promoted by PD98059 at 5 - 20 µmol/L, inhibited by siMEK2 at 25 - 100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected.

CONCLUSIONMEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.

Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Flavonoids ; pharmacology ; Humans ; Insulin ; pharmacology ; Insulin Glargine ; Insulin, Long-Acting ; pharmacology ; MAP Kinase Kinase 1 ; antagonists & inhibitors ; metabolism ; MAP Kinase Kinase 2 ; genetics ; metabolism ; MAP Kinase Signaling System ; drug effects ; genetics ; Phosphorylation ; drug effects ; RNA, Small Interfering ; genetics ; physiology ; Urinary Bladder Neoplasms ; metabolism

BACKGROUNDThe neurogenic bladder dysfunction caused by spinal cord injury is difficult to treat clinically. The aim of this research was to establish an artificial bladder reflex arc in rats through abdominal reflex pathway above the level of spinal cord injury, reinnervate the neurogenic bladder and restore bladder micturition.

METHODSThe outcome was achieved by intradural microanastomosis of the right T13 ventral root to S2 ventral root with autogenous nerve grafting, leaving the right T13 dorsal root intact. Long-term function of the reflex arc was assessed from nerve electrophysiological data and intravesical pressure tests during 8 months postoperation. Horseradish peroxidase (HRP) tracing was performed to observe the effectiveness of the artificial reflex.

RESULTSSingle stimulus (3 mA, 0.3 ms pulses, 20 Hz, 5-second duration) on the right T13 dorsal root resulted in evoked action potentials, raised intravesical pressures and bladder smooth muscle, compound action potential recorded from the right vesical plexus before and after the spinal cord transaction injury between L5 and S4 segmental in 12 Sprague-Dawley rats. There were HRP labelled cells in T13 ventral horn on the experimental side and in the intermediolateral nucleus on both sides of the L6-S4 segments after HRP injection. There was no HRP labelled cell in T13 ventral horn on the control side.

CONCLUSIONUsing the surviving somatic reflex above the level of spinal cord injury to reconstruct the bladder autonomous reflex arc by intradural microanastomosis of ventral root with a segment of autologous nerve grafting is practical in rats and may have clinical applications for humans.

Anastomosis, Surgical ; Animals ; Atropine ; pharmacology ; Male ; Models, Theoretical ; Rats ; Rats, Sprague-Dawley ; Reflex, Abdominal ; drug effects ; physiology ; Trimethaphan ; pharmacology ; Urinary Bladder, Neurogenic ; physiopathology

To investigate the efficacy and safety of desmopressin in patients with mixed nocturia, Patients aged > or =18 yr with mixed nocturia (> or =2 voids/night and a nocturnal polyuria index [NPi] >33% and a nocturnal bladder capacity index [NBCi] >1) were recruited. The optimum dose of oral desmopressin was determined during a 3-week dose-titration period and the determined dose was maintained for 4 weeks. The efficacy was assessed by the frequency-volume charts and the sleep questionnaire. The primary endpoint was the proportion of patients with a 50% or greater reduction in the number of nocturnal voids (NV) compared with baseline. Among 103 patients enrolled, 94 (79 men and 15 women) were included in the analysis. The proportion of patients with a 50% or greater reduction in NV was 68 (72%). The mean number of NV decreased significantly (3.20 to 1.34) and the mean nocturnal urine volume, nocturia index, NPi, and NBCi decreased significantly. The mean duration of sleep until the first NV was prolonged from 118.4+/-44.1 to 220.3+/-90.7 min (P<0.001). The overall impression of patients about their quality of sleep improved. Adverse events occurred in 6 patients, including one asymptomatic hyponatremia. Desmopressin is an effective and well-tolerated treatment for mixed nocturia.
Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Antidiuretic Agents/*administration & dosage ; Deamino Arginine Vasopressin/*administration & dosage ; Drug Administration Schedule ; Female ; Humans ; Male ; Middle Aged ; Nocturia/complications/*drug therapy ; Polyuria/complications/*drug therapy ; Prospective Studies ; Questionnaires ; Sleep/drug effects/physiology ; Urinary Bladder/*physiopathology ; Urodynamics/physiology

OBJECTIVETo discuss the influence of Suoquan capsule (SQJN) on the detrusor of D-galactose mimetic rats, and to explore the mechanism of reducing urine.

METHODInvestigate the enzymes (ATPase, SDH, SOD, MDA, Na+ -K+ -ATPase, Ca2+ - Mg2+ -ATPase) which influence the production and excretion of urine and the reactivity of urinary detrusor strips to different concentrations of ISO and ATP.

RESULTCompared with the model group, the activity of SOD, Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase and SDH increased significantly in aging rats after administrating SQJN (P < 0.01); the complaisance and elasticity of bladder also increased (P < 0.05). The frequency of spontaneous contraction and the MDA decreased significantly (P < 0.05-0.01). The decreased relaxation response to ISO and increased contractile response to ATP were also changed after administrating SQJN.

CONCLUSIONSQJN can regulate the metabolism of fluid through recovering the normal physiologic function of the detrusor of bladder.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Galactose ; adverse effects ; Humans ; Male ; Muscle Contraction ; Muscle, Smooth ; physiology ; Rats ; Urinary Bladder ; drug effects ; metabolism ; physiopathology ; Urinary Incontinence, Urge ; chemically induced ; drug therapy ; metabolism ; physiopathology ; Urination ; drug effects

Acetylcholine ; metabolism ; physiology ; Animals ; Cholinergic Agonists ; pharmacology ; Male ; Muscle Contraction ; drug effects ; physiology ; Muscle Relaxation ; drug effects ; physiology ; Muscle, Smooth ; drug effects ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Receptors, Cholinergic ; physiology ; Synaptic Transmission ; drug effects ; Urinary Bladder ; drug effects ; innervation ; physiopathology

OBJECTIVETo evaluate the anticancer effects of exogenous human WT-PTEN overexpression on bladder transitional carcinoma cell line EJ.

METHODSThe plasmid containing WT-PTEN or mutant PTEN was separately transfected into bladder transitional carcinoma cell line EJ, and the protein expression of PTEN in the EJ cells was detected by Western blot. Cell morphological changes were observed under the inverted microscope and transmission electron microscope. MTT test was used to assess the effect of PTEN on proliferation and anticancer effects for mitomycin and theraubicin. The change of bcl-2 expression in the cells was measured by Western blot. The empty plasmid was used as control.

RESULTSWestern blot analysis showed that EJ cells expressed high level of PTEN protein after transfection with WT-PTEN or mutant PTEN plasmid. Abnormal morphological changes of the cells were observed in WT-PTEN transfected groups. The growth of EJ cells treated with WT-PTEN was significantly inhibited by 40.1% and anticancer effects were enhanced by mitomycin and theraubicin, but the cells transfected with mutant PTEN plasmid did not show such similar biological behavior.

CONCLUSIONWT-PTEN gene transfection can suppress the in vitro growth and induce apoptosis of bladder transitional carcinoma cell line EJ cells. Mutant PTEN does not show similar biological behavior. Overexpression of WT-PTEN inhibits cancer cell proliferation by down-regulating bcl-2 expression in the cells.

Antibiotics, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Carcinoma, Transitional Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Doxorubicin ; analogs & derivatives ; pharmacology ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Microscopy, Electron, Transmission ; Mitomycin ; pharmacology ; Mutation ; PTEN Phosphohydrolase ; genetics ; metabolism ; physiology ; Plasmids ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; physiology ; Transfection ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology