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Mounting evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and tumor progression. SNHG12 has been identified in multiple types of malignant tumors. However, the role of SNHG12 in human non‐small cell lung cancer (NSCLC) is poorly characterized, and the relevant underlying mechanism remains unclear. The expression levels of SNHG12, miR‐101‐3p, and CUL4B in collected human NSCLC tumor tissues and NSCLC cell lines were tested via qRT‐PCR. Then, NSCLC cellular proliferation, migration and invasion were determined, followed by MTT, scratch and Transwell assays. Dual‐luciferase reporter assays and RNA pulldown assays were adopted to explore the target site. Moreover, western blotting was performed to detect the relevant protein expression concerning the CUL4B/PI3K/AKT pathway. This study clarified that SNHG12 knockdown significantly reduced proliferation, migration, invasion and EMT of NSCLC cells. Our data indicated that SNHG12 targeted and negatively regulated miR‐101‐3p, and this depletion reversed the inhibitory effect of si‐SNHG12 on NSCLC cells. Furthermore, CUL4B was confirmed as a functional target of miR‐101‐3p, and its knockdown resulted in a strong alleviation of the NSLCL cell phenotype, which was enhanced by the silencing of miR‐101‐3p. Mechanistically, we found that SNHG12 regulated miR‐101‐3p to modulate the PI3K/AKT pathway mediated by CUL4B.These observations suggested that lncRNA SNHG12‐mediated miR‐101‐3p downregulation regulated the malignant phenotype of NSCLC cells by targeting CUL4B through the PI3K/AKT pathway, which may present a path to novel therapeutic strategies for NSCLC therapy.

Currently, the role of Notch signaling during myocardial infarction (MI) remains controversy. In this study we used in vitro and in vivo approaches to investigate the role of Notch signaling in MI. Using cultured human umbilical vein endothelial cells exposed to hypoxia/reoxygenation (H/R), we demonstrated that H/R inhibited the proliferation, VEGF secretion, and tube formation of HUVECs, and these effects were correlated with the inhibition of Notch signaling. Furthermore, these effects were antagonized by overexpression of NICD but aggravated by knockdown of NICD. In addition, in MI model rats we found that heart dysfunction and angiogenesis in model rats was partly improved by NICD overexpression but was aggravated by knockdown of NICD. In conclusion, these data demonstrate that Notch signaling is downregulated in H/R injury in the hearts. Artificial activation of Notch signaling could promote myocardial survival and angiogenesis and improve cardiac function following H/R injury.

Reports have highlighted an association between connexins (CXs) or gap junction proteins and non-small cell lung cancer (NSCLC). In the present study, it was aimed to elucidate the regulatory mechanism of CX26 and CX43 under hypoxic conditions in NSCLC. Clinical samples were collected for analysis of CX26 and CX43 expression and clinical cancerization followed by quantification of CX26 and CX43 expression. Following the establishment of an in vitro hypoxia model, P53/murine double minute-2 (MDM2) signaling pathway-, proliferation- and epithelial-mesenchymal transition (EMT)-related genes were quantified to evaluate the influence of CX26 and CX43 on the biological functions of pulmonary epithelial cells in NSCLC. In addition, the proliferation and tumorigenicity of cancer cells were assessed by EdU staining and xenograft tumors, respectively. Decreased expression of CX26 and CX43 was found in cancer tissues compared with surrounding normal tissue. Hypoxia was shown to activate the P53/MDM2 axis and stimulate the downregulation, ubiquitination and degradation of CX26 and CX43, which were translocated from the membrane to the cytoplasm. Low levels of CX26 and CX43 were demonstrated to further promote EMT and the induction of the proliferation and tumorigenicity of cancer cells. These results were reflected by decreased E-cadherin expression and increased N-cadherin expression, along with increased cell migration, promoted cell proliferation ability and elevated relative protein expression of Oct4 and Nanog, and accelerated tumor growth, accompanied by a higher number of metastatic nodes. Taken together, the key observations of the present study demonstrate that the internalization of CX26 and CX43 promoted proliferation, EMT and migration and thus induced NSCLC via aberrant activation of the P53/MDM2 signaling pathway under hypoxic conditions.

To investigate in vitro effects of nicotine on the non-small-cell lung cancer line A549.The case-control study was conducted at the First Affiliated Hospital of Nanchang University from 1st January to 30th June, 2014 and comprised A549 cells which were treated with a series of concentrations of nicotine (0.01 µM, 0.1 µM, 1 µM and 10 µM) for 24 hours. Control cells were incubated under the same conditions without the addition of nicotine. Cell growth was detected by monotetrazolium salt [3-(4, 5-dimethyl-2-thiazolyl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. Cell apoptosis was detected by Haematoxylin and Eosin staining, immunofluorescence analysis of Filamentous actin and electron microscope observation.Nicotine had no significant effect on A549 cell growth at the dose of 0.01µM (p0.05), but had significant growth inhibitory effects at the doses of 0.1µM, 1µM and 10µM (p0.05 each). A significant decrease in cell numbers was observed on staining (p0.05). Significant changes in the size and shape of cells and concomitant changes in cytoskeletons and organelles were observed by immunofluorescence and electron microscope observation (p0.05).The growth inhibitory effects of nicotine on A549 cells were found to be dose-dependent.

Ischemic postconditioning (IPost), able to significantly attenuate myocardial ischemia reperfusion injury, is dependent on RISK signaling. Studies have shown that Notch signaling repairs damaged myocardium, and this study aimed to investigate the effect of Notch signaling in myocardial IPost.We used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation (H/R) model in vitro. which were randomly divided into control, H/R, IPost, Hepatocyte growth factor (HGF)+IPost and DAPT+IPost, N1ICD+IPost, miRNA+IPost, and Mock treatment groups. The myocardial cell viability was assessed by MTT, the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry analyses. The expression of N1ICD, Hes1, PTEN Phospho-Akt/Akt, Phospho-GSK-3β/GSK-3β were detected by Western blotting. Finally, we assessed the changes in ψm using the potential-sensitive dye JC-1 and measured using flow cytometry analyses.The Notch1 signaling is activated by HGF and ectopic expression of N1ICD during myocardial IPost, which increased myocardial cell viability, prevented cardiomyocyte apoptosis, and reduced loss of the mitochondrial membrane potential. However, myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by Notch1-miRNA. Western blotting found that PTEN was down-regulated by Hes1 when Notch1 was activated, which consequently promoted Akt and GSK-3β phosphorylation.Notch1 crosstalk with RISK signaling may be dependent on PTEN, which plays a cardioprotective role during IPost. This mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.

To investigate the impact of fluid resuscitation with different ratio of crystalloid-colloid in early resuscitation stage on prognosis of patients with severe acute pancreatitis (SAP).A retrospective analysis was made by reviewing clinical data of 47 patients with SAP from January 2001 to December 2011. According to crystalloid-colloid ratio 1.5 or 3, which was the input volume of crystalloid fluid versus colloid fluid in the first 24 hours, patients were divided into low ratio group (crystalloid-colloid ratio1.5, n=13), middle ratio group (crystalloid-colloid ratio 1.5-3, n=15) and high ratio group (crystalloid-colloid ratio3, n=19). Among the patients who had been successfully resuscitated, rate of mechanical ventilation, the oxygenation index, intra-abdominal pressure (IAP), and the amount of fluid retention in the third space within the first 24 hours, as well as the parameters of fluid resuscitation and the survival rate within 2 weeks were collected and analyzed.(1) In the first 24 hours, the rate of mechanical ventilation in the high ratio group was significantly higher than that in the middle ratio group and the low ratio group (68.4% vs. 20.0%, 23.1%, both P0.05); the oxygenation index was significantly lower than that in the middle ratio group and in the low ratio group (180.7±26.3 mm Hg vs. 280.6±24.8 mm Hg, 260.3±25.7 mm Hg, both P0.05); the IAP was significantly higher than that in the middle ratio group and the low ratio group (16.8±3.6 cm H(2)O vs. 13.4±3.5 cm H(2)O, 13.1±3.3 cm H(2)O, both P0.05); the amount of fluid retention in the third space was significant higher than that in the middle ratio group and the low ratio group (2834±631 ml vs. 1887±282 ml, 1865±300 ml, both P0.05). There was no significant difference in above indexes between middle ratio group and low ratio group (all P0.05). (2) In the first 24 hours, the volume of crystalloid in high ratio group was significantly larger than that in the middle ratio group and the low ratio group (3611±798 ml vs. 2308±416 ml, 2124±477 ml, both P0.05); and the volume of colloid in high ratio group and middle ratio group was significantly lower than that in the low ratio group (993±233 ml, 948±140 ml vs. 1506±332 ml, both P0.05); and the mean crystalloid-colloid rate in the high ratio group was significantly higher than that in the middle ratio group and the low ratio group (3.65±0.13 vs. 2.43±0.13, 1.41±0.08, both P0.05). The volume of infused fluid during the first 72 hours in the high ratio group was significantly higher than that in the middle and low ratio groups (11 941±1161 ml vs. 9036±982 ml, 9400±1051 ml, both P0.05). (3) The survival rate in the high ratio group (36.8%) was significantly lower than that in the middle ratio group (86.7%, P0.05) and the low ratio group (61.5%, P0.05).A suitable crystalloid-colloid ratio should be considered in the early stage of resuscitation in patients with severe acute pancreatitis, which would result in a decrease in the fluid retention in the third space as well as an improvement of survival rate in return. It is suggested that the middle ratio of crystalloid-colloid fluid resuscitation should be the optimal strategy.

Enteral feeding can be given either through the nasogastric or the nasojejunal route. Studies have shown that nasojejunal tube placement is cumbersome and that nasogastric feeding is an effective means of providing enteral nutrition. However, the concern that nasogastric feeding increases the chance of aspiration pneumonitis and exacerbates acute pancreatitis by stimulating pancreatic secretion has prevented it being established as a standard of care. We aimed to evaluate the differences in safety and tolerance between nasogastric and nasojejunal feeding by assessing the impact of the two approaches on the incidence of mortality, tracheal aspiration, diarrhea, exacerbation of pain, and meeting the energy balance in patients with severe acute pancreatitis. We searched the electronic databases of the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We included prospective randomized controlled trials comparing nasogastric and nasojejunal feeding in patients with predicted severe acute pancreatitis. Two reviewers assessed the quality of each study and collected data independently. Disagreements were resolved by discussion among the two reviewers and any of the other authors of the paper. We performed a meta-analysis and reported summary estimates of outcomes as Risk Ratio (RR) with 95% confidence intervals (CIs). We included three randomized controlled trials involving a total of 157 patients. The demographics of the patients in the nasogastric and nasojejunal feeding groups were comparable. There were no significant differences in the incidence of mortality (RR = 0.69, 95% CI: 0.37 to 1.29, P = 0.25); tracheal aspiration (RR = 0.46, 95% CI: 0.14 to 1.53, P = 0.20); diarrhea (RR = 1.43, 95% CI: 0.59 to 3.45, P = 0.43); exacerbation of pain (RR = 0.94, 95% CI: 0.32 to 2.70, P = 0.90); and meeting energy balance (RR = 1.00, 95% CI: 0.92 to 1.09, P = 0.97) between the two groups. Nasogastric feeding was not inferior to nasojejunal feeding. Nasogastric feeding is safe and well tolerated compared with nasojejunal feeding. Study limitations included a small total sample size among others. More high-quality large-scale randomized controlled trials are needed to validate the use of nasogastric feeding instead of nasojejunal feeding.