The Role of Prostatitis in Prostate Cancer: Meta-Analysis

Objective

Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model.

Evidence Acquisition

Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. Selection criteria: the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases.

Evidence Synthesis

In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62), and random effects model (OR=1.64, 95%CI: 1.36-1.98). Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29), compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45). Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990’s: OR=1.58, 95% CI: 1.35-1.84; 2000’s: OR=1.59, 95% CI: 1.40-1.79; 2010’s: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990’s: OR=1.98, 95% CI: 1.08-3.62; 2000’s: OR=1.64, 95% CI: 1.23-2.19; 2010’s: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90.CONCLUSIONS: the present meta-analysis provides the statistical evidence that the association between prostatitis and prostate cancer is significant.     

Magnetic protein microbead-aided indirect fluoroimmunoassay for the determination of canine virus specific antibodies

Rabies, canine distemper, and canine parvovirus are common contagious viral diseases of dogs and many other carnivores, and pose a severe threat to the population dynamics of wild carnivores, as well as endangering carnivore conservation. However, clinical diagnosis of these diseases, especially canine distemper and canine parvovirus, is difficult because of the broad spectrum of symptoms that may be confused with other respiratory and enteric diseases of dogs. The most frequently used and proven techniques for diagnosing viral diseases include the conventional enzyme-linked immunosorbent assay (ELISA), rapid fluorescent focus inhibition test (RFFIT), mouse neutralisation test (MNT), and fluorescent antibody virus neutralization (FAVN) test. However, these methods still have some inherent limitations. In this study, a magnetic protein microbead-aided indirect fluoroimmunoassay was developed to detect canine virus specific antibodies, human rabies immunoglobulin, CDV McAbs, and CPV McAbs. In this assay, an avidin-biotin system was employed to combine magnetic microbeads and virus antigens (rabies virus, canine distemper virus, and canine parvovirus). Quantification of the targeted virus antibodies was analyzed through indirect fluoroimmunoassay using the specific antigen-antibody reaction, as well as their corresponding FITC-labeled detection antibodies (mouse anti-human IgG/FITC conjugate or rabbit anti-dog IgG/FITC conjugate). The results indicated that the fluorescence intensity increased when a higher concentration of the targeted analyte was used, but the control had almost no fluorescence, much like the conventional ELISA. For human rabies immunoglobulin, CDV McAbs, and CPV McAbs, the minimum detectable concentrations were 0.2 IU/mL, 0.3 ng/mL, and 0.5 ng/mL, respectively. All of these results indicate that this assay can be employed to determine the presence of canine virus specific antibodies. In addition, the method devised here can be utilized as a general protocol in other bacterial and viral marker analysis.     

T cell responses in mammalian diaphanous-related formin mDia1 knock-out mice

Activated T cells rapidly assemble filamentous (F-) actin networks in response to ligation of the T cell receptor or upon interaction with adhesive stimuli in order to facilitate cell migration and the formation of the immune synapse. Branched filament assembly is crucial for this process and is dependent upon activation of the Arp2/3 complex by the actin nucleation-promoting factor Wiskott-Aldrich Syndrome protein (WASp). Genetic disruption of the WAS gene has been linked to hematopoietic malignancies and various cytopenias. Although the contributions of WASp and Arp2/3 to T cell responses are fairly well characterized, the role of the mammalian Diaphanous (mDia)-related formins, which both nucleate and processively elongate non-branched F-actin, has not been demonstrated. Here, we report the effects on T cell development and function following the knock out of the murine Drf1 gene encoding the canonical formin p140mDia1. Drf1(-/-) mice develop lymphopenia characterized by diminished T cell populations in lymphoid tissues. Consistent with a role for p140mDia1 in the regulation of the actin cytoskeleton, isolated Drf1(-/-) splenic T cells adhered poorly to extracellular matrix proteins and migration in response to chemotactic stimuli was completely abrogated. Both integrin and chemokine receptor expression was unaffected by Drf1(-/-) targeting. In response to proliferative stimuli, both thymic and splenic Drf1(-/-) T cells failed to proliferate; ERK1/2 activation was also diminished in activated Drf1(-/-) T cells. These data suggest a central role for p140mDia1 in vivo in dynamic cytoskeletal remodeling events driving normal T cell responses.     

E3 ligase activity of XIAP RING domain is required for XIAP-mediated cancer cell migration, but not for its RhoGDI binding activity

Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored. To verify the specific structural basis of XIAP for regulation of cancer cell migration, we introduced different XIAP domains into XIAP(-/-) HCT116 cells, and found that reconstitutive expression of full length HA-XIAP and HA-XIAP ΔBIR, both of which have intact RING domain, restored β-Actin expression, actin polymerization and cancer cell motility. Whereas introduction of HA-XIAP ΔRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a crucial role of XIAP in regulation of cancer cell motility. Moreover, RING domain rather than BIR domain was required for interaction with RhoGDI independent on its E3 ligase activity. To sum up, our present studies found that role of XIAP in regulating cellular motility was uncoupled from its caspase-inhibitory properties, but related to physical interaction between RhoGDI and its RING domain. Although E3 ligase activity of RING domain contributed to cell migration, it was not involved in RhoGDI binding nor its ubiquitinational modification.     

斑胸草雀的鸣声学习

鸣声是鸟类重要的生物学特征和分类特征。由于生理结构和神经控制方面的差异,不同种群和同一种群的不同个体都有自己特有的鸣声特征,正是利用这些特征,鸟类才能在集群、取食、迁徙、喂雏、御敌和求偶等行为中进行通讯。作为一种能够利用语音信息进行交流的高等脊椎动物,斑胸草雀的鸣声特别是鸣啭能力获得,需要有一个适宜的学习对象,并在一段特定的时间内,经历复杂的学习过程才能实现。     

PKC-dependent extracellular signal-regulated kinase 1/2 pathway is involved in the inhibition of Ib on AngiotensinII-induced proliferation of vascular smooth muscle cells

AngiotensinII (AngII) induces vascular smooth muscle cell (VSMC) proliferation, which plays an important role in the development and progression of hypertension. AngII-induced cellular events have been implicated, in part, in the activation of protein kinase C (PKC) and extracellular signal-regulated kinases 1/2 (ERK1/2). In the present study, we investigated the effect of Ib, a novel nonpeptide AngII receptor type 1 (AT₁) antagonist, on the activation of PKC and ERK1/2 in VSMC proliferation induced by AngII. MTT, and [³H]thymidine incorporation assay showed that AngII-induced VSMC proliferation was inhibited significantly by Ib. The specific binding of [¹²⁵I]AngII to AT₁ receptors was blocked by Ib in a concentration-dependent manner with IC₅₀ value of 0.96 nM. PKC activity assay and Western blot analysis demonstrated that Ib significantly inhibited the activation of PKC and phosphorylation of ERK1/2 induced by AngII, respectively. Furthermore, AngII-induced ERK1/2 activation was obviously blocked by GF109203X, a PKC inhibitor. These findings suggest that the suppression of Ib on AngII-induced VSMC proliferation may be attributed to its inhibitory effect on PKC-dependent ERK1/2 pathway.     

山杏苹果酸酶基因的克隆与生物信息学分析

三羧酸转运体系(柠檬酸,苹果酸和丙酮酸)可为脂肪酸生物合成提供原料乙酰辅酶A与还原力NADPH;而苹果酸酶可催化苹果酸发生氧化脱羧而产生NADPH,是调控脂肪酸代谢的重要酶。山杏种子脂肪酸含量丰富、产油率高,是研究植物油脂代谢的良好材料。本研究以山杏为试材,采用RACE克隆和电子拼接相结合的方法,首次从山杏种子中克隆得到苹果酸酶基因(命名为SaME,GenBank上登记号为JX262381),该基因的cDNA编码区全长1923bp、编码640个氨基酸,预测其编码蛋白分子量为70.15kD、等电点为6.38;同时,运用生物信息学方法对SaME基因编码蛋白的理化特性、结构域和亚细胞定位等方面进行预测分析,结果显示,该蛋白定位在细胞的质体膜上,具有苹果酸酶活性,属于NADP-ME超家族。本文对山杏SaME基因的克隆与分析,为进一步探究苹果酸酶对油脂代谢的调控机制奠定了基础。