Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells

Bladder cancer, which can be divided into non‐muscle‐invasive and muscle‐invasive bladder cancer, is the most common urinary cancer in the United States. Caspase recruitment domain family member 10 (CARD10), also named CARD‐containing MAGUK protein 3 (CARMA3), is a member of the CARMA family and may activate the nuclear factor kappa B (NF‐κB) pathway. We utilized RNA sequencing and metabolic mass spectrometry to identify the molecular and metabolic feature of CARD10. The signalling pathway of CARD10 was verified by Western blotting analysis and functional assays. RNA sequencing and metabolic mass spectrometry of CARD10 knockdown identified the metabolic enzyme carbamoyl phosphate synthase 1 (CPS1) in the urea cycle as the downstream gene regulated by CARD10. We confirmed that CARD10 affected cell proliferation and nucleotide metabolism through regulating CPS1. We indicated that CARD10 promote bladder cancer growth via CPS1 and maybe a potential therapeutic target in bladder cancer.     

Whole-Organ Genomic Characterization of Mucosal Field Effects Initiating Bladder Carcinogenesis

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Urinary steroid evaluations to monitor ovarian function in exotic ungulates: VI. Pregnancy detection in exotic equidae

The measurement of serum and urinary estrone sulfate (ES) was evaluated on random single samples for the detection of pregnancy in the Przewalski's horse (PRZ) and Hartmann's mountain zebra (HMZ). Pregnancy was detected by ES analysis of urine or serum in the PRZ and HMZ by at least 8 and 10 months before delivery, respectively. The values of ES in both serum and urine are shown at various stages of gestation. Results indicate urinary ES analysis is a noninvasive early diagnosis for pregnancy in these species.     

Bladder exstrophy‐epispadias complex

The bladder exstrophy‐epispadias complex (BEEC) represents an anterior midline defect with variable expression comprising a spectrum of anomalies involving the abdominal wall, pelvis, urinary tract, genitalia, and occasionally the spine and anus. The vast majority of BEEC cases are classified as non‐syndromic and the etiology of this malformation is still unknown. This review presents the current state of knowledge on this multifactorial disorder, including historical retrospect, phenotypic and anatomical characterization, epidemiology, proposed developmental mechanisms, existing animal models, and implicated genetic and environmental components. These published lines of evidence argue strongly that BEEC occurs as a result of strong genetic predisposition that is yet to be deciphered. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

分枝杆菌Ag85A DNA疫苗对膀胱癌小鼠细胞免疫功能的影响

为探讨分枝杆菌Ag85A DNA疫苗能否提高荷膀胱癌小鼠保护性免疫应答水平,将1×10^6个MBT-2细胞注射于C3H/HeN小鼠的右侧背部皮内,待肿瘤长至直径约5～8 mm时,将动物随机分成实验组、空质粒组和空白对照组3组,分别于小鼠双侧股四头肌内注射Ag85A-V1 Jns.tPA质粒,V1 Jns.tPA质粒总量0.1 mL（100μg）,或生理盐水0.1 mL,每14 d 1次,共3次,末次免疫后第14天分别检测T细胞亚群数量、NK细胞活性、FasL mRNA表达情况、淋巴细胞增殖水平及肿瘤重量。结果显示,实验组较空白质粒组和空白对照组免疫指标均无明显增高（P〉0.05）,提示肌肉注射Ag85A DNA疫苗不能明显提高荷瘤小鼠免疫功能。     

Comparative gene expression analysis of genital tubercle development reveals a putative appendicular Wnt7 network for the epidermal differentiation

Here we describe the first detailed catalog of gene expression in the developing lower urinary tract (LUT), including epithelial and mesenchymal portions of the developing bladder, urogenital sinus, urethra, and genital tubercle (GT) at E13 and E14. Top compartment-specific genes implicated by the microarray data were validated using whole-mount in situ hybridization (ISH) over the entire LUT. To demonstrate the potential of this resource to implicate developmentally critical features, we focused on gene expression patterns and pathways in the sexually indeterminate, androgen-independent GT. GT expression patterns reinforced the proposed similarities between development of GT, limb, and craniofacial prominences. Comparison of spatial expression patterns predicted a network of Wnt7a-associated GT-enriched epithelial genes, including Gjb2, Dsc3, Krt5, and Sostdc1. Known from other contexts, these genes are associated with normal epidermal differentiation, with disruptions in Dsc3 and Gjb2 showing palmo-plantar keratoderma in the limb. We propose that this gene network contributes to normal foreskin, scrotum, and labial development. As several of these genes are known to be regulated by, or contain cis elements responsive to retinoic acid, estrogen, or androgen, this implicates this pathway in the later androgen-dependent development of the GT.     

Urinary zinc excretion is normalized in primary arterial hypertension after perindopril treatment

Increased or unchanged urinary zinc excretion has been reported in hypertension. In the present article, this observation was confirmed in a group of 10 untreated hypertensive patients of both sexes that had no diabetes or obesity. The 24-h zinc excretion was significantly different between the patients: 7.46±3.01 μmol and healthy controls: 5.19±2.19 μmol (p<0.025). After a 1-mo treatment with 4 mg perindopril per day, a decrease of urinary zinc was observed until it reached levels not significantly different from those of the healthy controls (5.98±2.13 μmol). The decrease was significantly different from that of the pretreatment values (p<0.05).     

Inhibitory effects of various L-type and T-type calcium antagonists on electrically generated, potassium-induced and carbachol-induced contractions of porcine detrusor muscle

The inhibitory effects of different calcium antagonists on contractions of isolated porcine detrusor muscle were investigated. Suppression of the maximum potassium-induced contraction and electrically generated contractions by nifedipine, verapamil and diltiazem were investigated. Furthermore, concentration–response curves of carbachol after pretreatment with the L-type antagonists nifedipine, verapamil, diltiazem, nimodipine and the T-type antagonist mibefradil at different concentrations were performed. Nifedipine significantly reduced the potassium-induced maximum contraction to 89, 60, 21, 8 and 4% (10⁻⁹–10⁻⁵ M). Verapamil and diltiazem significantly reduced it to 64, 30 and 5% (10⁻⁷–10⁻⁵ M) or 79, 27, 7 and 1% (10⁻⁷–10⁻⁴ M), respectively. Nifedipine, verapamil and diltiazem significantly reduced the electrically generated contraction to 55, 36, 34 and 25% (10⁻⁷–10⁻⁴ M), 71, 32 and 2% (10⁻⁶–10⁻⁴ M), 96, 78, 38 and 5% (10⁻⁷–10⁻⁴ M), respectively. pD2 values of nifedipine, verapamil and diltiazem amounted to 7.07, 5.56 and 5.40 and differed significantly. After pretreatment with nifedipine at 10⁻⁶ M, the concentration–response curve of carbachol was nearly suppressed. The effects of nimodipine, verapamil and diltiazem were smaller. Mibefradil caused only at 10⁻⁵ M a significant reduction. All investigated L-type calcium antagonists were strong inhibitors of the examined contractions. Nifedipine showed the biggest inhibitory effect.     

肌足蛋白的研究进展

肌足蛋白(myopodin)是新近发现的突足蛋白(synaptopodin)家族的第二个成员。除了突足蛋白外,它和其他已知的蛋白质没有明显的同源关系。肌足蛋白可以直接与肌动蛋白相互作用,因此它也是一种结构蛋白。研究发现,肌足蛋白在细胞中的分布受到细胞分化及胁迫的调控,并且它在细胞核中的定位对抑制膀胱癌有一定的作用;同时发现肌足蛋白基因在细胞中的部分或全部缺失与前列腺癌的发生有关,因此它也有可能作为前列腺癌的临床检测标记。     

Studies of sodium channels in rabbit urinary bladder by noise analysis

Summary Sodium channels in rabbit urinary bladder were studied by noise analysis. There are two components of short-circuit current (I _sc) and correspondingly two components of apical Na⁺ entry, one amiloride-sensitive (termedI _A and the A channel, respectively) and one amiloride-insensitive (I _L and the leak pathway, respectively). The leak pathway gives rise tol/f noise, while the A channel in the presence of amiloride gives rise to Lorentzian noise. A two-state model of the A channel accounts well for how the corner frequency and plateau value of Lorentzian noise vary with amiloride concentration. The single-channel current is 0.64 pA, and the conducting channel density is on the order of 40 copies per cell. Triamterene blocks the A channel alone, and increasing external Na⁺ decreases the number but not the single-channel permeability of the A channel. Hydrostatic pressure pulses (punching) increase the number of both pathways. Repeated washing of the mucosal surface removes most of the leak pathway without affecting the A channel.Properties of the A channel revealed by noise analysis of various tight epithelia are compared, and the mechanism ofl/f noise is discussed. It is suggested that the A channel is synthesized intracellularly, stored in intracellular vesicles, transferred with or from vesicular membrane into apical membrane under the action of microfilaments, and degraded into the leak pathway, which is washed out into urine or destroyed. The A channel starts withP _Na/P _K30 and loses selectivity in stages untilP _Na/P _K reaches the free-solution mobility ratio (0.7) for the leak pathway. This turnover cycle functions as a mechanism of repair and regulation for Na⁺ channels, analogous to the repair and regulation of most intracellular proteins by turnover. Vesicular delivery of membrane channels may be operating in several other epithelia.