MicroRNA MiR-490-5p suppresses pancreatic cancer through regulating epithelial-mesenchymal transition via targeting MAGI2 antisense RNA 3.

Pancreatic cancer with about 5% five-year overall survival rate remains a challenge. Invasion and migration of pancreatic cancer cells are the main factors leading to poor prognosis. MicroRNA-490-5p (miR-490-5p) has anti-cancer effects in a variety of tumors, but its role in pancreatic cancer has not been reported. The mRNA expressions of miR-490-5p, MAGI2 antisense RNA 3 (MAGI2-AS3), Matrix metalloproteinase (MMP)2, MMP9, N-cadherin, and E-cadherin were detected by quantitative real-time PCR, while the protein expressions of these genes except miR-490-5p were measured by Western blot analysis. The cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), apoptosis and transwell assays. MiR-490-5p was abnormally low-expressed in pancreatic cancer, whose down-regulation generated enhanced effects on viability, migration and invasion in pancreatic cancer cells, as well as MAGI2-AS3 expression. MiR-490-5p mimic exerted the opposite effect on cells, which also down-regulated MMP2, MMP9, and N-cadherin protein expressions, while up-regulating E-cadherin protein expression. MAGI2-AS3, which was the targeted binding site of miR-490-5p, promoted viability, migration and invasion, and inhibited apoptosis of cancer cells. More importantly, miR-490-5p played an anti-cancer role in pancreatic cancer by targeting MAGI2-AS3 and regulating epithelial-mesenchymal transition (EMT), which was partially offset by MAGI2-AS3.

Changes in Expressions of HSP27, HSP70, and Soluble Glycoprotein in Heart Failure Rats Complicated with Pulmonary Edema and Correlations with Cardiopulmonary Functions.

The study is aimed at investigating the changes in expressions of heat shock protein 27 (HSP27), HSP70, and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema and exploring their potential correlations with cardiopulmonary functions. The rat model of HF was established, and the rats were divided into HF model group (model group, n = 15) and normal group (n = 15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α) in the blood was measured. The partial pressure of oxygen (PaO2) and oxygenation index (OI) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70, and SGP130. The levels of serum creatine kinase (CK), creatine (Cr), and blood urea nitrogen (BUN) were increased markedly in model group (p < 0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group (p < 0.05), while the opposite results of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP-9, and TNF-α was raised remarkably (p < 0.05), OI and PaO2 were reduced notably (p < 0.05), the airway resistance was increased (p < 0.05), and the lung compliance was decreased (p < 0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70, and SGP130 were detected in model group (p < 0.05). The expressions of HSP27, HSP70, and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.

Targeted destruction of cancer stem cells using multifunctional magnetic nanoparticles that enable combined hyperthermia and chemotherapy.

Cancer stem cells (CSCs) have been implicated in cancer recurrence and therapy resistance. Therefore, a CSC-targeted therapy that disrupts the maintenance and survival of CSCs may offer an effective approach in killing tumor cells in primary tumors and preventing the metastasis caused by CSCs. Nanoparticles (NPs)-based thermotherapy and/or chemotherapy are promising therapeutic methods for cancer treatment. Methods: A silica-based multifunctional NP system was present, which encapsulated a chemotherapeutic agent and magnetic cores and coated with a specific antibody against the lung CSCs. The efficacy of this novel therapeutic strategy was systematically studied both in vitro and in vivo by simultaneous activating the combined thermotherapy and chemotherapy via CSC-targeted NPs. Results: These NPs were systematically administered and activated for targeted chemotherapy and thermotherapy by using an externally applied alternating magnetic field (AMF). The antibody-modified NPs targeted to lung CSCs with enhanced cellular uptake in vitro and extended accumulation in tumor in vivo. Up to 98% of lung CSCs was killed in vitro with 30-min application of AMF, due to the combined effects of hyperthermia and chemotherapeutic drug treatment. In in vivo models, this combined therapy significantly suppressed tumor growth and metastasis in lung CSC xenograft-bearing mice, with minimal side effects and adverse effects. Conclusion: With good biocompatibility and targeting capability, the nanodrug delivery system may offer a promising clinical platform for the combined thermotherapy and chemotherapy. This work demonstrated the feasibility of developing multifunctional nanomedicine targeting CSCs for effective cancer treatment.

MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF.

MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional and mechanistic impacts of a novel miRNA on GC cellular process. The significant down-regulation of miR-876-5p in GC cells attracted our attention. In function, we performed gain-of-function assays and found that miR-876-5p overexpression repressed proliferative, anti-apoptotic and migratory abilities and epithelial-mesenchymal transition (EMT) of GC cells. By applying bioinformatics prediction and mechanism experiments, we verified that miR-876-5p could double-bind to the 3' untranslated regions (3'UTRs) of Wnt family member 5A (WNT5A) and melanogenesis associated transcription factor (MITF), thus regulating their mRNA and protein levels. Both WNT5A and MITF were highly expressed in GC cells. Additionally, we conducted loss-of-function assays and confirmed the oncogenic roles of WNT5A and MITF in GC. Finally, rescue assay uncovered a fact that miR-876-5p suppressed GC cell viability and migration, but induced cell apoptosis via targeting WNT5A and MITF. Taken together, we might offer a valuable evidence for miR-876-5p role in GC development.

BAG2 Overexpression Correlates with Growth and Poor Prognosis of Esophageal Squamous Cell Carcinoma.

Previous studies have suggested that Bcl2-associated athanogene 2 (BAG2) serves as a crucial regulator for tumorigenesis in multiple tumors. However, little is known about the effect of BAG2 on esophageal squamous cell carcinoma (ESCC). This study focused on investigating whether BAG2 functions as a cancer-promoting gene in ESCC. In this work, gene expression data and clinical information from the NCBI Gene Expression Omnibus (GEO), Oncomine and The Cancer Genome Atlas (TCGA) were collected and analyzed. Expression of BAG2 in ESCC was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). BAG2 was knocked down using small interference RNA (si-RNA) approach. Cell proliferation, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8) and transwell assays. Molecular mechanism was detected by western blotting assay. The expression of BAG2 both in ESCC tissues and cells was upregulated and overexpression was associated with worsened prognosis. BAG2 silencing inhibited ESCC cell proliferation, migration and invasion, which was regulated by the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. These results reveal contributions of BAG2 as a predictor and potential therapeutic target in ESCC.

In vitro study on the role of SOX9 in trastuzumab resistance of adenocarcinoma of the esophagogastric junction.

Trastuzumab is recommended for the treatment of human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagogastric junction (AEG) in combination with chemotherapy; however, drug resistance has severely affected its clinical application. The present study aimed to investigate the effect of sex determining region Y-box 9 (SOX9), a prognostic marker in adjuvant oncological settings, on AEG cell proliferation and apoptosis in the presence or absence of trastuzumab. Furthermore, the molecular mechanism underlying the role of SOX9 in trastuzumab resistance was explored. ESO26 cells were treated with various concentrations of trastuzumab, and trastuzumab induced SOX9 expression in a concentration-dependent manner, as determined by reverse transcription-quantitative polymerase chain reaction and western blotting analyses. Transfection of ESO26 cells with SOX9 small interfering RNA was conducted to knock down SOX9 expression, and the results of MTT and flow cytometry assays demonstrated that SOX9 knockdown sensitized ESO26 cells to trastuzumab by inhibiting cell proliferation and enhancing cell apoptosis. In addition, it was observed that the trastuzumab-induced phosphorylation of AKT was suppressed by SOX9 knockdown. In conclusion, the present study demonstrated that SOX9 participated in trastuzumab resistance by affecting cell proliferation and apoptosis, and indicated that SOX9 may exert its effect on trastuzumab resistance via activation of the phosphatidylinositol-3-kinase/AKT signaling pathway. This study identified a novel mechanism underlying trastuzumab resistance in vitro and may be useful in improving the efficacy of trastuzumab treatment.

Single-blinded, randomized, and controlled clinical trial evaluating the effects of Omega-3 fatty acids among septic patients with intestinal dysfunction: A pilot study.

Sepsis is a systemic inflammatory reaction, which is aggravated by aspects of the immune response that are thought to be inhibited by Omega-3 fatty acids. The aim of the present study was to determine if Omega-3 fatty acid could modulate immunological function and improve survival rate among septic patients with intestinal dysfunction. A total of 48 mechanically ventilated patients with intestinal dysfunction were included in this prospective, randomized and single-blind clinical study. Patients were randomly divided into control (group A) and treatment groups (group B). The treatment protocol for all the participants followed the Sepsis Survival Campaign guidelines, and group B received total parenteral nutrition containing 100 ml of Omega-3 fatty acids (containing 10 g refined fish oil) per day in addition to the standard treatment applied in group A. Group B had a significantly lower mortality rate compared with group A (12.5 vs. 41.7%, P<0.05) during the 28-day follow-up. Group B also had lower Acute Physiology and Chronic Health Evaluation II scores (P<0.05) and lower Marshall scores (P<0.05) at day 7. In addition, group B had a higher ratio of T helper to inducer lymphocytes as well as a higher ratio of CD4 to CD8 lymphocytes (P<0.01 for both) than group A. It was concluded that Omega-3 fatty acids improved T helper/inducer and CD4/CD8 ratios, and may have reduced mortality, among septic patients with intestinal dysfunction.

Omega-3 Fish Oil Reduces Mortality Due to Severe Sepsis with Acute Gastrointestinal Injury Grade III.

BACKGROUND: Sepsis plays an important role in acute gastrointestinal injury (AGI). Our research was designed to determine the effects of omega-3 fish oil (FO) in patients suffering from severe sepsis combined with AGI III, and the ability of FO to modulate immune function. METHODS: Seventy-eight patients diagnosed with severe sepsis with AGI III and a need for mechanical ventilation were randomized to two groups. In the FO group, 50 g of long chain fatty acid soybean oil (n = 6) and 10 g of FO (n = 3) were administered as total parenteral nutrition (TPN). The control group was treated with 50 g of long chain fatty acid soybean oil without addition of FO to TPN. RESULTS: At baseline, there were no significant differences between the two groups. The 60-day mortality was lower in the FO group. Multiple factor logistic regression analysis revealed that intra-abdominal pressure (IAP) and abdominal infection were correlated with the FO intervention. The patients with abdominal infection demonstrated a lower mortality rate, fewer CD3 T lymphocytes, and fewer helper/inducer T lymphocytes in the FO group compared with the control group. After 7 days, the Marshall Score was lower in the FO group than in the control group. CONCLUSION: FO has positive effects in terms of improving the long-term prognosis of patients with severe sepsis with AGI III. Patients with a high IAP and abdominal infection might experience greater benefit from FO. This effect might be due, in part, to immunomodulation. SUMMARY: Fish oil (FO) has positive effects in terms of improving the long-term prognosis of patients with severe sepsis with acute gastrointestinal injury Grade IIIPatients with a high intra-abdominal pressure and abdominal infection might experience greater benefit from FOThis effect might be due, in part, to immunomodulation. Abbreviations used: AGI: Acute gastrointestinal injury; FO: Fish oil; TPN: Total parenteral nutrition; IAP: Intra-abdominal pressure; ICU: Intensive Care Unit; MODS: Multiple organ dysfunction syndrome; TLR4: Toll-like receptor 4; DNR: Do Not Resuscitate; WGAP: Working Group of Abdominal Problem; EN: Enteral nutrition; BP: Low blood pressure; CRI: Catheter-related infection; PBS: Phosphate-buffered saline; ELFA: Enzyme-linked fluorescent assay; SD: Standard deviation; PUFAs: Polyunsaturated fatty acids; EPA: Eicosapentenoic acid; DHA: Docosahexaenoic acid.

Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma.

Sex-determining region Y-box 9 (SOX9), a vital transcription factor, play important roles in numerous biological and pathological processes. However, the clinical significance and biological role of SOX9 expression has not been characterized in human esophageal squamous cell cancer (ESCC). Herein, we found that SOX9 was markedly upregulated, at both mRNA and protein level, in ESCC cell lines and ESCC tissues and that SOX9 expression was significantly correlated with tumor clinical stage, T classification, N classification, M classification, pathological differentiation, and shorter overall survival. The proliferation and tumorigenicity of ESCC cells were dramatically induced by SOX9 overexpression but were inhibited by SOX9 knockdown both in vitro and in vivo. Moreover, we demonstrated that upregulation of SOX9 increased the expression of phosphorylated Akt, the cyclin-dependent kinase (CDK) regulator cyclin D1, phosphorylated forkhead box O (FOXO)1, and phosphorylated FOXO3, but SOX9 downregulation decreased their expression, whereas the levels of the CDK inhibitors p21Cip1 and p27Kip1 were attenuated in SOX9-transduced cells. Taken together, our results suggest that SOX9 plays an important role in promoting the proliferation and tumorigenesis of ESCC and may represent a novel prognostic marker for the disease.