Sodium tanshinone IIA sulfonate inhibits tumor growth via miR-138 upregulation in intermittent hypoxia-induced xenograft mice.

PURPOSE: We studied the functions of sodium tanshinone IIA sulfonate (TSA) in inducing tumor growth in obstructive sleep apnea (OSA)-mimicking intermittent hypoxia (IH) xenograft mice and the underlying potential molecular mechanism. METHODS: RNA sequencing was conducted to screen the differentially expressed microRNAs in cell lines exposed to IH with or without TSA treatment. As part of the 5-week in vivo study, we treated xenograft mice with 8-h IH once daily. TSA and miR-138 inhibitors or mimics were administrated appropriately. In addition, we performed real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), microvessel density (MVD), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. RESULTS: RNA sequencing and RT-PCR results demonstrated that TSA increased the levels of miR-138 under IH conditions in vitro. TSA reduced the IH-stimulated high levels of hypoxia-induced factor-1α and vascular endothelial growth factor. Furthermore, IH contributed to high tumor migration, invasion, MVD, and low apoptosis. TSA attenuated IH-mediated tumor proliferation, migration, invasion, MVD, and increased apoptosis, whereas miR-138 inhibitor interrupted the effect of TSA on treating IH-induced tumor behaviors. CONCLUSIONS: OSA mimicking IH facilitates tumor growth and reduces miR-138 levels. TSA inhibits IH-induced tumor growth by upregulating the expression of miR-138.

Atorvastatin attenuates intermittent hypoxia-induced myocardial oxidative stress in a mouse obstructive sleep apnea model.

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), is associated with various cardiovascular diseases. In the present study, we assessed the effect of the lipid reducing agent atorvastatin on CIH-induced myocardial oxidative stress and apoptosis in a mouse OSA model. Forty-eight C57BL/6J mice were evenly divided among normoxia + vehicle, normoxia + atorvastatin, CIH + vehicle, and CIH + atorvastatin groups. CIH consisted of a hypoxia-reoxygenation cycle in which oxygen concentrations fluctuated from 21% to 6% and back over two minutes for 8 hours each day (30 events/hour). CIH exposure continued for 12 weeks. Atorvastatin (5 mg/kg) was administered from week 6 through the end of the experiment. CIH increased malondialdehyde levels and decreased superoxide dismutase activity, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2 levels in cardiac tissue, indicating a reduction in antioxidant activity. Atorvastatin significantly reversed those effects (p < 0.05). CIH also increased B-cell lymphoma 2-associated protein X and cleaved caspased-3 levels as well as the myocardial apoptotic rate, as indicated by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Atorvastatin had no effect on those changes (p > 0.05). Thus, atorvastatin administration exerts antioxidant but not anti-apoptotic effects after CIH and may therefore have therapeutic potential in OSA patients with cardiovascular comorbidities.

Phylogenetic studies of two Anas platyrhynchos (Anatini: Anatinae) in Hunan province of China based on complete mitochondrial DNA sequences.

In this study, we cloned and sequenced the complete mitochondrial DNAs of Chinese duck, Anas platyrhynchos, population from two different areas of Hunan province in China. The Anas platyrhynchos breed Linwu duck (LW) sample was taken from the Linwu county of Chenzhou city, and the Anas platyrhynchos breed Youxian duck (YX) sample was taken from the Youxian county of Zhuzhou city. The lengths of their complete mitochondrial genome were 16,604 bp (LW) and 16,606 bp (YX), respectively. The organization of the two Anas platyrhynchos breed mitochondrial genomes was similar to those reported from other duck mitochondrial genomes. Phylogenetic analyses using N-J computational algorithms showed that the analyzed species are divided into four major clades: Anatinae, Anserinae, Dendrocygninae and Anseranatidae. Also, the Linwu duck and Youxian duck have highly similar phylogenetic relationship.

Efficacy of positive airway pressure on brain natriuretic peptide in patients with heart failure and sleep-disorder breathing: a meta-analysis of randomized controlled trials.

OBJECTIVE: Positive airway pressure (PAP) has been recognized as an effective therapeutic option for sleep-disordered breathing (SDB) in patients with heart failure (HF), and it can improve left ventricular function. Whether PAP can ameliorate serum brain natriuretic peptide (BNP) levels, a biomarker of HF, is controversial. The purpose of the present study was to quantitatively assess the efficacy of PAP on BNP in patients with HF and SDB. METHODS: A systematic search of PubMed, Embase, Web of Science and Cochrane library identified six randomized controlled trials (RCTs), in which PAP was compared with medical therapy, subtherapeutic PAP or different types of PAP. The data of BNP were extracted and pooled into meta-analysis using STATA 12.0. RESULTS: Totally 6 RCT studies (7 cohorts) with 222 patients were enrolled into analysis. The quality of each study was high and the heterogeneity (I(2) = 58.1%) was noted between studies. A significant reduction of BNP was observed after PAP treatment in patients with HF and SDB (SMD -0.517, 95% CI -0.764 to -0.270, z = 4.11, p = 0.000). CONCLUSION: Our meta-analysis of RCTs demonstrated that PAP elicits significant reduction of BNP in patients with HF and SDB.

Efficacy of continuous positive airway pressure on testosterone in men with obstructive sleep apnea: a meta-analysis.

OBJECTIVE: To evaluate the efficacy of continuous positive airway pressure (CPAP) on serum testosterone in men with obstructive sleep apnea (OSA). METHODS: Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before June 2014. Information on characteristics of subjects, study design, pre- and post-CPAP treatment of serum total testosterone, free testosterone and sexual hormone blinding protein (SHBG) was extracted for analysis. RESULTS: A total of 7 studies with 9 cohorts that included 232 men were pooled into meta-analysis. There was no change of total testosterone levels before and after CPAP treatment in OSA men (standardized mean difference (SMD) = -0.14, 95%CI: -0.63 to 0.34, z = 0.59, p = 0.558), even subdivided by CPAP therapeutic duration (>3 months). Meanwhile, no significant differences in free testosterone and SHBG were detected after CPAP treatment (SMD =  0.16, 95%CI: -0.09 to 0.40, z = 1.25, p = 0.211 and SMD = -0.58, 95%CI: -1.30 to 0.14, z = 1.59, p = 0.112, respectively). CONCLUSION: CPAP has no influence on testosterone levels in men with OSA, further large-scale, well-design interventional investigation is needed.

[Influence of mutations in epidermal growth factor receptor gene on growth, metastasis and survival rate of non-small cell lung carcinoma].

OBJECTIVE: To evaluate the influence of mutations in epidermal growth factor receptor (EGFR) gene on the prognosis of non-small cell lung cancer (NSCLC). METHODS: A total of 107 NSCLC patients undergoing tumor resection from December 2005 to August 2009 at our hospital were recruited. Mutations of exons 18 - 21 of EGFR gene in patients were detected by polymerase chain reaction (PCR) amplification and gene sequencing. The influence of mutations in EGFR gene on the growth, metastasis and survival rate of NSCLC was evaluated. RESULTS: EGFR mutations were detected in 30 (28.0%) of 107 patients. The mutation distribution was as follows: exon 18 (n = 1), exon 19 (n = 8), exon 21 (n = 20), and exons 18 and 19 multiple (triple mutations, n = 1). NSCLC with EGFR mutations had a higher growth velocity than that without EGFR mutations [M(Q(1-3)): 0.42 (0.17 - 1.04) mm/d vs 0.21 (0.19 - 1.00) mm/d, P < 0.05]. EGFR mutations had no significant impaction on neither the lymph node metastasis of NSCLC (P > 0.05) nor on the tumor metastasis to other organs (P > 0.05). The mean survival time of patients with and without EGFR mutations were (18.2 ± 8.9) and (25.5 ± 7.8) months respectively. The 1, 2 and 3-year survival rate were 62.2% vs 72.2%, 47.7% vs 57.3% and 46.9% vs 56.3% respectively between patients with and without EGFR mutations. Log-rank test didn't show a significant difference among them (χ(2) = 0.59, P > 0.05). CONCLUSIONS: The EGFR mutations promote the growth of NSCLC. But it may not be a factor of predicting prognosis.