Expression of survivin and patients survival in non-small cell lung cancer: a meta-analysis of the published studies

Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed oncogenes, however, its role in NSCLC remains controversial. We performed a systematic review of the literature with meta-analysis to clarify this issue. Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association of survivin expression with survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Overall 29 relevant published studies including 2,517 lung cancer patients were identified from electronic databases. We found that overexpression of survivin in NSCLC patients might be a poor prognostic factor for survival 1.95 (95 % CI: 1.65-2.29; P < 0.001). Heterogeneity testing indicated that there was heterogeneity among studies. When stratified by histology types, the heterogeneity was absent. We should point out that the publication bias may partly account for the result, but the conclusion might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results remained significant (HR = 1.71, 95 % CI: 1.44–2.02, P < 0.001), suggesting the stability of our results. Therefore, our study suggested that survivin overexpression had a poor prognosis value in patients with NSCLC.     

Role of autophagy in early brain injury after subarachnoid hemorrhage in rats

Early brain injury (EBI) occurred after aneurismal subarachnoid hemorrhage (SAH) strongly determined the patients’ prognosis. Autophagy was activated in neurons in the acute phase after SAH, while its role in EBI has not been examined. This study was designed to explore the effects of autophagy on EBI post-SAH in rats. A modified endovascular perforating SAH model was established under monitoring of intracranial pressure. Extent of autophagy was regulated by injecting autophagy-regulating drugs (3-methyladenine, wortmannin and rapamycin) 30 min pre-SAH intraventricularly. Simvastatin (20 mg/kg) was prophylactically orally given 14 days before SAH induction. Mortality, neurological scores, brain water content and blood–brain barrier (BBB) permeability were evaluated at 24 h post-SAH. Microtubule-associated protein light chain-3 (LC3 II/I) and beclin-1 were detected for monitoring of autophagy flux. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, expression of cleaved caspase-3 and cytoplasmic histone-associated DNA fragments were used to detect apoptosis. The results showed that mortality was reduced in rapamycin and simvastatin treated animals. When autophagy was inhibited by 3-methyladenine and wortmannin, the neurological scores were decreased, brain water content and BBB permeability were further aggravated and neuronal apoptosis was increased when compared with the SAH animals. Autophagy was further activated by rapamycin and simvastatin, and apoptosis was inhibited and EBI was ameliorated. The present results indicated that activation of autophagy decreased neuronal apoptosis and ameliorated EBI after SAH. Aiming at autophagy may be a potential effective target for preventing EBI after SAH.     

Molecular character of a phosphatase 2C (PP2C) gene relation to stress tolerance in Arabidopsis thaliana

Protein phosphatases type 2C (PP2Cs) from group A, which includes the ABI1/HAB1 and PP2CA branches, are key negative regulators of ABA signaling. HAI-1 gene had been shown to affect both seed and vegetative responses to ABA, which is one of PP2Cs clade A in Arabidopsis thaliana. Transgenic plants containing pHAI-1::GUS (β-glucuronidase) displayed GUS activity existing in the vascular system of leave veins, stems and petioles. Green fluorescent protein fused HAI-1 (HAI-1-GFP) was found in the nucleus through transient transformation assays with onion epidermal cells. The water-loss assays indicated the loss-of-function mutants did not show symptoms of wilting and they had still turgid green rosette leaves. The assays of seed germination by exogenous ABA and NaCl manifested that the loss-of-function mutants displayed higher insensitivity than wild-type plants. Taken together, the final results suggest that the HAI-1 (AT5G59220) encoded a nuclear protein and it can be highly induced by ABA and wound in Arabidposis, the stress-tolerance phenotype showed a slightly improvement when HAI-1 gene was disrupted.     

Overexpression of Smad7 suppressed ROS/MMP9-dependent collagen synthesis through regulation of heme oxygenase-1

We previously reported that AngiotensinII receptor blocker effectively inhibited TGF-β1-mediated epithelial-to-mesenchymal transition progress through regulating Smad7. However, the underlying mechanism by which Smad7 exerted in regulating MMP9 and fibrogenic response has not been fully elucidated. In the current study, we proved that NADPH p47^phox-dependent reactive oxygen species (ROS) production contributed to MMP9 activation and collagen expression, which was suppressed by transfecting pcDNA3–Smad7 in cardiac fibroblasts. The effect of Smad7 overexpression on MMP9 activity and collagen expression was further reversed by adding H₂O₂ (10 μmol/L). In contrast, knockdown of Smad7 caused the enhanced collagen synthesis in cardiac fibroblasts, which was also reversed by treating cells with a ROS inhibitor, YCG063 (2 μmol/L). Further investigation showed that Smad7 regulated NADPH-mediated ROS production through activating Heme oxygenase-1 (HO-1). Meanwhile, the intercellular level of bilirubin (product of hemin) and nitric oxide (NO) in cell supernatant were not significantly increased in cells treated with AngII or transfected with Smad7. Knockdown of HO-1 in Smad7-overexpressed cardiac fibroblasts or cells pretreated with SnPP IX, a competitive inhibitor of HO-1 activity, resulted in increased productions of ROS and NADPH p47^phox, and abolished the inhibitory effects of Smad7 on MMP9 activity and collagen expression. Our results indicated that HO-1 might be critically involved in Smad7-mediated regulation of MMP9 activity and fibrogenic genes expression via antagonizing the enhanced myocardial oxidative stress.     

Relationship between CCR2-V64I polymorphism and cancer risk: A meta-analysis

Background and objectives

The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism.

Methods

Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association.

Results

Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR = 1.84, 95% CI = 1.35–2.51, AA vs GA/GG, P = 0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR = 2.06, 95% CI = 1.02–4.15, AA vs GA/GG, P = 0.11), cervical cancer (OR = 3.34, 95% CI = 1.48–7.50, AA vs GG, P = 0.56), and oral cancer (OR = 2.04, 95% CI = 1.46–2.84, GA vs GG, P = 0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR = 2.31, 95% CI = 1.45–3.68, AA vs GA/GG, P = 0.16) and Asians (OR = 1.88, 95% CI = 1.12–3.16, AA vs GA/GG, P = 0.92).

Conclusion

This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.     

A Parvancorina-like arthropod from the Cambrian of South China

Constraining the origin of animal groups is allowed, to some extent, by discoveries of Cambrian Lagerstätten that preserve both mineralizing and nonmineralizing organisms. A new species is reported here of the Cambrian arthropod Skania, which bears an exoskeleton that shares homologies with the Neoproterozoic (Ediacaran) organism Parvancorina and firmly establishes a Precambrian root for arthropods. A new monophyletic group, Parvancorinomorpha, is proposed as the first clade within the arthropod crown group demonstrably ranging across the Neoproterozoic–Paleozoic transition. The Parvancorinomorpha is interpreted to be the sister group of the Arachnomorpha. Incipient cephalization in Skania and related genera represents a step in the progression toward division of a cephalon from a large posterior trunk as shown in Cambrian arachnomorphs such as naraoiids and the addition of a pygidium and thoracic tergites as shown in the arachnomorph clade basal to trilobites. This evidence can serve as a new calibration point for estimating the divergence time for the last common ancestor of arthropods and priapulids based on molecular clock methods.