Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia.

OBJECTIVE: To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models. METHODS: Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested. RESULTS: KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels. CONCLUSION: KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Prognostic significance of long noncoding RNA Z38 as a candidate biomarker in breast cancer.

BACKGROUND: Long noncoding RNA (lncRNA) Z38 has been shown to promote cell proliferation and tumorigenesis in breast cancer. However, expression pattern and prognostic value of lncRNA Z38 in breast cancer patients remain elusive. METHODS: The expression levels of SPRY4-IT1 in 110 self-paired specimens of breast cancer and adjacent normal breast tissues were measured by quantitative real-time PCR (qRT-PCR), and its correlation with overall survival of patients with breast cancer was further statistically analyzed. RESULTS: Compared with normal breast tissues, Z38 was upregulated in breast cancer tissues. Furthermore, of 110 breast cancer patients, high Z38 expression was significantly associated with tumor-node-metastasis stage and lymph node metastasis. Further analysis using the Cox regression model revealed that Z38 expression was an independent prognostic factor of overall survival in patients with breast cancer (hazard ratio=4.74, 95% confidence interval 2.41-9.32). The nomogram presents a good prediction of the probability of overall survival of breast cancer patients (c-index: 0.792), and its predictive efficiency was further confirmed by the calibration curve. CONCLUSION: Our data highlighted the potential of lncRNA Z38 as novel candidate biomarker to identify patients with breast cancer at high risk of tumor death.

Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma.

The pathogenesis of osteosarcoma involves complex genetic and epigenetic factors. This study was to explore the impact and clinical relevance of long non-coding RNA (lncRNA), Taurine up-regulated gene 1 (TUG1) on patients with osteosarcoma. Seventy-six osteosarcoma tissues and matched adjacent normal tissues were included for analysis. The plasma samples were obtained from 29 patients with osteosarcoma at pre-operation and post-operation, 42 at newly diagnosed, 18 who experienced disease progression or relapse, 45 post-treatment, 36 patients with benign bone tumor, and 20 healthy donors. Quantitative real-time reverse transcript polymerase chain reactions were used to assess the correlation of the expression levels of TUG1 with clinical parameters of osteosarcoma patients. TUG1 was significantly overexpressed in the osteosarcoma tissues compared with matched adjacent normal tissues (P < 0.01) and was closely correlated with tumor size, post-operative chemotherapy, and Enneking surgical stage. Upregulation of TUG1 strongly correlated with poor prognosis and was an independent prognostic indicator for overall survival (HR = 2.78, 95% CI = 1.29-6.00, P = 0.009) and progression-free survival (HR = 1.81, 95% CI = 1.01-3.54, P = 0.037). Our constructed nomogram containing TUG1 had more predictive accuracy than that without TUG1 (c-index 0.807 versus 0.776, respectively). In addition, for plasma samples, TUG1 expression levels were obviously decreased in post-operative patients (mean ΔCT -4.98 ± 0.22) compared with pre-operation patients (mean ΔCT -6.09 ± 0.74), and the changes of TUG1 expression levels were significantly associated with disease status. Receiver operating characteristic (ROC) curve analysis demonstrated that TUG1 could distinguish patients with osteosarcoma from healthy individuals compared with alkaline phosphatase (ALP) (the area under curve 0.849 versus 0.544). TUG1 was overexpressed in patients with osteosarcoma and strongly correlated with disease status. In addition, TUG1 may serve as a molecular indicator in maintaining surveillance and forecasting prognosis.

Association between Apolipoprotein E polymorphism and myocardial infarction risk: A systematic review and meta-analysis.

Published data regarding the association between Apolipoprotein E (ApoE) genetic variation and myocardial infarction (MI) risk were not always consistent. Therefore, the current meta-analysis was conducted to derive a more precise estimation of the association between ApoE polymorphism and MI risk. PubMed and Web of Science were searched to identify relevant studies. Summary odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. All the tests were performed using Stata 11.0. A total of 22 eligible studies were identified in this meta-analysis. The results show that ApoE ε2 and ε4 alleles were associated with MI risk. The study suggests that there is close association between ApoE polymorphism and MI risk. It shows that ApoE ε2 allele is a protective factor of MI, while ε4 allele is a risk factor of MI, especially in Caucasian and Asian population. Nevertheless, well-designed, unbiased and larger sample size studies are required to confirm the results.

Pre-operative lymphocyte-to-monocyte ratio as a predictor of overall survival in patients suffering from osteosarcoma.

Inflammatory markers have been proposed to predict clinical outcomes in many types of cancers. The purpose of this study was to explore the influence of the lymphocyte-to-monocyte ratio (LMR) on clinical prognosis of patients with osteosarcoma. This study collected 327 patients who underwent surgical treatment for osteosarcoma during the period 2006-2010. LMR was calculated from pre-operative peripheral blood cells counts. The optimal cut-off value of LMR was determined based on receiver operating characteristic curve analysis. Overall survival (OS) and event free survival (EFS) was plotted using the Kaplan-Meier method and evaluated by the log-rank test. A predictive model was established to predict clinical prognosis for OS, and the predictive accuracy of this model was determined by concordance index (c-index). Our results showed that young age, elevated alkaline phosphatase, metastasis at diagnosis, chemotherapy, lymphocyte and monocyte counts were significantly associated with LMR. Low LMR was associated with shorter OS and EFS (P < 0.001), and was an independent predictor of both OS and EFS (HR = 1.72, 95% CI = 1.14-2.60, P = 0.010; HR = 1.89, 95% CI = 1.32-2.57, P = 0.009). The nomogram performed well in the prediction of overall survival in patients with osteosarcoma (c-index 0.630). In conclusion, low pre-operative LMR is associated with a poor prognosis in patients suffering from osteosarcoma. A prospective study is warranted for further validation of our results.