Overexpression of HOXB9 promotes metastasis and indicates poor prognosis in colon cancer

Objective：Homeobox B9 （HOXB9） is proposed to be involved in tumor angiogenesis and metastasis.We investigated the role of HOXB9 in the progression of colon cancer.Methods：HOXB9 expression was investigated by immunohistochemically and Western blotting in 128 colon cancer patients and the results were analyzed statistically associated with clinicopathological data and survival of the patients.The effect of HOXB9 on cell invasion and metastases abilities were analyzed in vitro and in vivo.Results：HOXB9 is overexpressed in colon cancer tissues and significandy correlated with metastasis and poor survival of patients （P＜0.05,respectively）.Additionally,high levels of expression of HOXB9 were observed in metastatic lymph nodes.The down-regulation of HOXB9 expression can inhibit the migration and invasive ability of colon cancer cells,while exogenous expression of HOXB9 in colon cancer cells enhanced cell migration and invasiveness.Moreover,stable knockdown of HOXB9 reduced the liver and lung metastasis of colon cancer in vivo.Conclusions：HOXB9 may play an important role in the invasion and metastasis of colon cancer cells and may be a useful biomarker for metastasis and prognostic of colon cancer.

Detection of hTERT mRNA,CEA,CA19-9 in Pleural Effusion and Its Clinical Significance

OBJECTIVE To explore the clinical significance of the human telomerase reverse transcriptase(hTERT)mRNA,CEA and CA19-9 in differential diagnosis of benign and malignant pleural effusions. METHODS Concentrations of CEA and CA19-9 in pleural effusions were assayed using automated chemiluminescence,and expression of hTERT mRNA was detected by RT-PCR. RESULTS The positive rates of hTERT mRNA,CEA and CA19-9 expression in the group with malignant effusions were significantly higher compared to the group with benign effusion (P<0.05).The sensitivity(%),specificity(%)and diagnostic accordance rates(%)of the 3 tumor markers were as follows:i) hTERT mRNA:81.8/90.5/86.1;ii)CEA:52.3/92.9/72.1;iii)CA19-9: 34.1/90.5/61.6.The positive rates of hTERT mRNA+CEA(%) expression in the pleural effusions were 97.7. CONCLUSION All of these tumor markers can be helpful for differential diagnosis of pleural effusions.hTERT mRNA had more clinical value in differentiation of the pleural efffusions. CA19-9 is unfit to be as an optimal index.The combined assay of hTERT mRNA and CEA in pleural effusions can further raise the positive detection rate of the tumor markers and can be helpful in producing a diagnosis.

Rapamycin Protects Cardiomyocytes against Anoxia/Reoxygenation Injury by Inducing Autophagy through the PI3k/Akt Pathway

The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation（A/R） injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes（NRVM） as an in vitro model of ischemial/reperfusion（I/R） injury to the heart. NRVM were pretreated with four different concentrations of Rapamycin（20, 50, 100, 150 μmol/L）, and pretreated with 10 mmol/L 3-methyladenine（3MA） for inhibiting autophagy during A/R. Then, Western blot analysis was used to examine variation in the expression of LC3-Ⅱ, LC3-Ⅰ, Bim, caspase-3, p-PI3KⅠ, PI3KⅠ, p-Akt and Akt. In our model, Rapamycin had a preferential action on autophagy, increasing the expression of LC3-Ⅱ/ LC3-Ⅰ, whereas decreasing the expression of Bim and caspase-3. Moreover, our results also demonstrated that Rapamycin inhibited the activation of p-PI3KⅠ and enhanced the activation of p-Akt. It is concluded that Rapamycin has a cardioprotection effect by inducing autophagy in a concentration-dependent manner against apopotosis through PI3K/Akt signaling pathway during A/R in NRVM.

Low deceleration capacity is associated with higher stroke risk in patients with paroxysmal atrial fibrillation

Background: Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction;however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations between DC and stroke risk in paroxysmal atrial fibrillation (AF). We aimed to explore the influencing factors of abnormal DC and the relationships between DC and stroke risk in patients with paroxysmal AF. Methods: The study included hospitalized paroxysmal AF patients with DC measurements derived from 24-h Holter electrocardiography recordings taken between August 2015 and June 2016. Multivariable regression analysis was performed to evaluate the associations between correlated variables and abnormal DC values. The relationship between DC and ischemic stroke risk scores in patients with paroxysmal AF was analyzed. Results: We studied 259 hospitalized patients with paroxysmal AF (143 [55.2%] male, mean age 66.4 ± 12.0 years);38 patients of them showed abnormal DC values. In the univariate analysis, age, hypertension, heart failure, and previous stroke/transient ischemic attack (TIA) were significantly associated with abnormal DC values. Among these factors, a history of previous stroke/TIA (odds ratio = 2.861, 95% confidence interval: 1.356–6.039) were independently associated with abnormal DC values in patients with paroxysmal AF. The abnormal DC group showed a higher stroke risk with the score of congestive heart failure, hypertension, age >75 years, diabetes mellitus, previous stroke and TIA (CHADS2)(2.25 ± 1.48 vs. 1.40 ± 1.34, t =-4.907, P = 0.001) and CHA2DS2-vascular disease, age 65–74 years and female category (VASc)(3.76 ± 1.95 vs. 2.71 ± 1.87, t =-4.847, P = 0.001) scores. Correlation analysis showed that DC was negatively correlated with CHADS2 scores (r =-0.290, P < 0.001) and CHA2DS2-VASc scores (r =-0.263, P > 0.001). Conclusions: Lower DC is closely associated with previous stroke/TIA, and is also correlated negatively with higher stroke risk scores in patients with paroxysmal AF. It could be a potential indicator of stroke risk in paroxysmal AF patients.

PlaD： A Transcriptomics Database for Plant Defense Responses to Pathogens, Providing New Insights into Plant Immune System

High-throughput transcriptomics technologies have been widely used to study plant transcriptional reprogramming during the process of plant defense responses, and a large quantity of gene expression data have been accumulated in public repositories. However, utilization of these data is often hampered by the lack of standard metadata annotation. In this study, we curated2444 public pathogenesis-related gene expression samples from the model plant Arabidopsis and three major crops （maize, rice, and wheat）. We organized the data into a user-friendly database termed as PlaD. Currently, PlaD contains three key features. First, it provides large-scale curated data related to plant defense responses, including gene expression and gene functional annotation data.Second, it provides the visualization of condition-specific expression profiles. Third, it allows users to search co-regulated genes under the infections of various pathogens. Using PlaD, we conducted a large-scale transcriptome analysis to explore the global landscape of gene expression in the curated data. We found that only a small fraction of genes were differentially expressed under multiple conditions, which might be explained by their tendency of having more network connections and shorter network distances in gene networks. Collectively, we hope that PlaD can serve as an important and comprehensive knowledgebase to the community of plant sciences, providing insightful clues to better understand the molecular mechanisms underlying plant immune responses. PlaD is freely available at http：//systbio.cau.edu.cn/plad/index.php or http：//zzdlab.com/plad/index.php.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAHⅡ/eNOS/NO pathway

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine.Its primary therapies include clearing heat and detoxification,activating blood circulation,and removing blood stasis.Lonicera japonica flos(LJF)has long been known as an excellent antipyretic and antidote.Luteoloside(Lut)is one of the main components of LJF and exhibits antioxidant,anti-inflammatory,and cytoprotective properties.However,the protection of Lut against iron overload injury and its underlying mechanisms remain unclear.Therefore,HUVECs were exposed to 50μmol·L^(−1)iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed.Our results showed that 20μmol·L^(−1)Lut not only increased cell viability and weakened LDH activity,but also significantly up-regulated DDAHⅡexpression and activity,increased p-eNOS/eNOS ratio and NO content,and reduced ADMA content in HUVECs exposed to iron overload.Furthermore,Lut significantly attenuated intracellular/mitochondrial ROS generation,improved SOD,CAT,and GSH-Px activities,reduced MDA content,maintained MMP,inhibited mPTP opening,prevented cyt c from mitochondria released into cytoplasm,reduced cleaved-caspase3 expression,and ultimately decreased cell apoptosis induced by iron overload.The effects of Lut were similar to those of L-arginine(an ADMA competitive substrate),cyclosporin A(a mPTP blocker agent),and edaravone(a free radical scavenger)as positive controls.However,addition of pAD/DDAHⅡ-shRNA adenovirus reversed the above beneficial effects of Lut.In conclusion,Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAHⅡ/eNOS/NO pathway.The mitochondria are the target organelles of Lut’s protective effects.