Inhibition of Endothelial Cell Proliferation and Tumor Angiogenesis by Up-Regulating NDRG2 Expression in Breast Cancer Cells

The N-myc downstream-regulated gene 2 (NDRG2) is involved in tumor cell differentiation and apoptosis, but its function in tumor angiogenesis remains to be established. Here, we employed adenovirus overexpressing NDRG2 (Ad-NDRG2) to efficiently up-regulate target gene expression in the NDRG2-low-expressing, breast cancer cell line MCF-7. Moreover, VEGF secretion was decreased in MCF-7 cells infected by Ad-NDRG2, and medium conditioned by these infected cells could significantly inhibit the proliferation, tube formation and invasion of human umbilical vein endothelial cells (HUVECs). Further study indicated that the angiogenesis promoting factors VEGF and HIF-1α were down-regulated, whereas the angiogenesis suppressing factors p53 and VHL were up-regulated in MCF-7 cells infected by Ad-NDRG2. Finally, in a nude mouse model, intratumoral injections of Ad-NDRG2 every 3 days for 20 days significantly inhibited the growth and angiogenesis of xenografted MCF-7 tumors. In summary, these data indicate that NDRG2 may be involved in angiogenesis by impacting the expression of angiogenesis related factors. Thus, specific overexpression of NDRG2 by adenovirus represents a promising approach for the treatment of tumor angiogenesis

ODAD1 variants resulting from splice-site mutations retain partial function and cause primary ciliary dyskinesia with outer dynein arm defects

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused by defects in motile ciliary function and/or structure. Outer dynein arm docking complex subunit 1 (ODAD1) is an important component of the outer dynein arm docking complex (ODA-DC). To date, 13 likely pathogenic mutations of ODAD1 have been reported. However, the pathogenesis of ODAD1 mutations remains elusive. To investigate the pathogenesis of splice-site mutations in ODAD1 discovered in this study and those reported previously, molecular and functional analyses were performed. Whole-exome sequencing revealed a compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) in a patient with PCD, with c.598-2A>C being a novel mutation that resulted in two mutant transcripts. The compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) led to aberrant splicing that resulted in the absence of the wild-type ODAD1 and defects of the outer dynein arm in ciliary axonemes, causing a decrease in ciliary beat frequency. Furthermore, we demonstrated that the truncated proteins resulting from splice-site mutations in ODAD1 could retain partial function and inhibit the interaction between wild-type ODAD1 and ODAD3. The results of this study expand the mutational and clinical spectrum of PCD, provide more evidence for genetic counseling, and offer new insights into gene-based therapeutic strategies for PCD

Angiotensin II induces the secretion of ICAM-1 and MCP-1 in human airway smooth muscle cells in vitro

Background: Angiotensin [1] II is known to cause human airway smooth muscle (HASM) contraction and closely relate to asthma, however, the effect of Ang II on HASM cells (HASMCs) secretion function is still unclear. Methods: Primary cultured HASMCs were treated with Ang II, Ang II + Ang-(1–7), and Ang II + irbersatan (IRB), respectively. The nuclear translocation of the NF-κB p65 in HASMCs in each group was analyzed performed with Immunofluorescence. The expression levels of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were evaluated by Real-time polymerase chain reaction (PCR) and Enzyme linked immunosorbent assay (ELISA). Results: Ang II caused sharply increase of the nuclear translocation of NF-κB p65, also, Ang II significantly increased expression of ICAM-1 and MCP-1 secreted by HASMCs, this effect could be inhibited by Ang-(1–7) and IRB. Conclusion: These data may indicate the effect of Ang II on inducing HASMCs to secret ICAM-1 and MCP-1, which might be through the NF-κB p65 pathway by AT-1 receptor

Association between β2-Adrenoceptor Gene Polymorphisms and Asthma Risk: An Updated Meta-Analysis

<div><p>Background</p><p>Evidence is increasingly accumulated about multiple roles for the β2-adrenoceptor gene in asthma. The results were inconsistent partly due to small sample sizes. To assess the association between β2-adrenoceptor gene polymorphisms and asthma risk, a meta-analysis was performed.</p><p>Methods</p><p>We comprehensively searched the PubMed, EMBASE, BIOSIS Previews databases and extracted data from all eligible articles to estimate the association between β2-adrenoceptor gene polymorphisms and asthma risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.</p><p>Results</p><p>Thirty-seven studies involving 6648 asthma patients and 15943 controls were included in the meta-analysis. Overall, significant associations were found in allelic genetic model (OR = 1.06, 95% CI = 1.01∼1.12), recessive genetic model (OR = 1.11, 95% CI = 1.02∼1.21) for Arg/Gly16. Stratified by ethnicity and age, significant associations were also found in Asian population in allelic genetic model, recessive genetic model and addictive model. For Gln/Glu27, no significant association was found when we combined all eligible studies. Age stratification showed significant associations in adults in allelic genetic model and recessive genetic model, but no significant association was found among Asians and Caucasians in ethnicity stratification.</p><p>Conclusions</p><p>This meta-analysis implied that the β2-adrenoceptor Arg/Gly16 polymorphism was likely to contribute to asthma risk in Asian population. Gln/Glu27 polymorphism might be a contributor to asthma susceptibility for adults.</p></div

Galbraith plots of the association between β2AR Arg16Gly polymorphism and asthma.

<p>A) Asian population subgroup; B) caucasian population subgroup. Four studies# maybe the main contributors to the heterogeneity Asian population subgroup; One studies# maybe the main contributors to the heterogeneity Asian population subgroup.</p

Results of the pooled analyses and subgroup analyses for the β2AR Arg/Gly16 polymorphism and asthma risk.

<p>n, number of studies.</p

Results of the pooled analyses and subgroup analyses for the β2AR Gln/Glu27 polymorphism and asthma risk.

<p># Pooled result not included study of Santilan, A A#, n, number of studies.</p

Fatty acid composition analyses of commercially important fish species from the Pearl River Estuary, China.

Evaluation of fish nutritional content information could provide essential guidance for seafood consumption and human health protection. This study investigated the lipid contents, fatty acid compositions, and nutritional qualities of 22 commercially important marine fish species from the Pearl River Estuary (PRE), South China Sea. All the analyzed species had a low to moderate lipid content (0.51-7.35% fat), with no significant differences in fatty acid profiles among fishes from different lipid categories (p > 0.05). Compared with previous studies from other regions, the examined fish species exhibited higher proportions of saturated fatty acids (SFAs, 39.1 ± 4.00%) and lower contents of polyunsaturated fatty acids (PUFAs, 21.6 ± 5.44%), presumably due to the shifted diet influence from increased diatoms and decreased dinoflagellate over the past decades in the PRE. This study further revealed that there was a significantly negative correlation between the trophic levels and levels of PUFAs in the examined species (Pearson's r = -0.42, p = 0.04), likely associated with their differed dietary composition. Considering the health benefit of PUFAs, a few marine fish in PRE with low levels of PUFAs might have no significant contribution to the cardiovascular disease prevention, although fish with different fatty acid profiles most likely contribute differently towards human health. Additional studies are needed in order to comprehensively analyze the nutritional status of fish species in the PRE

Funnel plot of publication bias for β2AR polymorphism under recessive genetic model.

<p>A) Arg/Gly16; B) Gln/Glu27. Funnel plot with pseudo 95% confidence limits was used.</p

Flow Diagram for Inclusion of Studies in Meta-analysis.

<p>The initial search identified 2205 articles, of which, 37 were included in the final analysis.</p