Nonenveloped Avian Reoviruses Released with Small Extracellular Vesicles Are Highly Infectious.

Vesicle-encapsulated nonenveloped viruses are a recently recognized alternate form of nonenveloped viruses that can avoid immune detection and potentially increase systemic transmission. Avian orthoreoviruses (ARVs) are the leading cause of various disease conditions among birds and poultry. However, whether ARVs use cellular vesicle trafficking routes for egress and cell-to-cell transmission is still poorly understood. We demonstrated that fusogenic ARV-infected quail cells generated small (~100 nm diameter) extracellular vesicles (EVs) that contained electron-dense material when observed by transmission electron microscope. Cryo-EM tomography indicated that these vesicles did not contain ARV virions or core particles, but the EV fractions of OptiPrep gradients did contain a small percent of the ARV virions released from cells. Western blotting of detergent-treated EVs revealed that soluble virus proteins and the fusogenic p10 FAST protein were contained within the EVs. Notably, virus particles mixed with the EVs were up to 50 times more infectious than virions alone. These results suggest that EVs and perhaps fusogenic FAST-EVs could contribute to ARV virulence.

Long-noncoding RNA LINC00461 promotes proliferation and invasion of nonsmall cell lung cancer cells via targeting miR-518a-3p/WDR1 pathway.

Long noncoding RNAs (lncRNAs) are a class of RNAs participating in many biological processes such as imprinting, alternative splicing and RNA decay. Recently, lncRNAs have drawn a great deal of attention for their critical role in cancer progression. LINC00461, a newly identified lncRNA, has been reported to be significantly overexpressed in breast cancer and markedly expedited breast cancer progression. However, the specific role of LINC00461 in nonsmall cell lung cancer (NSCLC) remains unknown. In this study, we for the first time showed the biological functions of LINC00461 in NSCLC. Our results demonstrated that LINC00461 was significantly up-regulated in NSCLC tissues and cell lines. Furthermore, knockdown of LINC00461 inhibited NSCLC cell proliferation and invasion in vitro as well as suppressed tumor growth and metastasis in vivo. We also performed luciferase reporter assays and found that LINC00461 functioned as a sponge for miR-518a-3p and WDR1 was a target of miR-518a-3p. Taken together, we suggested an essential role of LINC00461/miR-518a-3p/WDR1 axis in NSCLC, which could be used as a potential therapeutic target for NSCLC treatment.

Expression analysis and tissue localization of IgZ in the grouper Epinephelus coioides after Vibrio alginolyticus infection and vaccination.

The orange-spotted grouper (Epinephelus coioides) is an important marine farmed fish in China. It is affected by the bacterial pathogen Vibrio alginolyticus, which causes high mortality and substantial economic losses. We studied the transcriptional changes of the IgZ gene in E. coioides following V. alginolyticus stimulation and investigated the distribution of IgZ in different tissues. The highest expression level of IgZ occurred in the head kidney. When fish were stimulated with live and inactivated V. alginolyticus, the expression levels of IgZ in the head kidney, spleen, intestine, gills and blood cells were significantly upregulated. In an in situ hybridization study, IgZ mRNA-positive cells were detected in the head kidney, spleen and gill, but positive signals were not detected in the liver and intestine. IgZ-labelled cells increased in the head kidney, spleen and gills post-infection with V. alginolyticus for 21 days. The present study provides additional evidence that IgZ is involved in mucosal immune responses and helps explain the role of IgZ in E. coioides defence against V. alginolyticus infection.

Catalpol inhibits TGF-ß1-induced epithelial-mesenchymal transition in human non-small-cell lung cancer cells through the inactivation of Smad2/3 and NF-κB signaling pathways.

Catalpol, one of the main active ingredients isolated from Rehmannia glutinosa, was reported to possess anticancer activity. However, the role of catalpol in transforming growth factor ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in human non-small-cell lung cancer (NSCLC) cells has not been elucidated. The objective of this study was to investigate the effect of catalpol on EMT in human NSCLC cells. Our results showed that catalpol significantly inhibited the TGF-ß1-induced cell migration and invasion of A549 cells, as well as repressed matrix metalloproteinase (MMP)2 and MMP9 expression induced by TGF-ß1 in A549 cells. In addition, catalpol markedly repressed the EMT process in A549 cells in response to TGF-ß1. Furthermore, catalpol prevented the activation of Smad2/3 and nuclear factor κB (NF-κB) signaling pathways induced by TGF-ß1 in A549 cells. In conclusion, these findings indicated that catalpol inhibits TGF-ß1-induced EMT in human NSCLC cells through the inactivation of Smad2/3 and NF-κB signaling pathways. Thus, catalpol may be a promising agent for the treatment of NSCLC.

Silencing TRIM37 inhibits the proliferation and migration of non-small cell lung cancer cells.

Tripartite motif containing 37 (TRIM37), a member of the tripartite motif (TRIM) family, has been involved in the development and progression of several tumors. However, its role in non-small cell lung cancer (NSCLC) is still unclear. Therefore, the aim of this study was to investigate the expression pattern and role of TRIM37 in NSCLC. Our results showed that TRIM37 was highly expressed in human NSCLC cell lines. Knockdown of TRIM37 obviously inhibited the proliferation in vitro and xenografted tumor growth in vivo. Furthermore, knockdown of TRIM37 suppressed NSCLC cell migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) phenotype. Lastly, knockdown of TRIM37 greatly down-regulated the protein expression levels of ß-catenin, cyclinD1 and c-myc in A549 cells. In conclusion, the present study revealed that TRIM37 plays an important role in the development and progression of NSCLC. Thus, TRIM37 may act a potential therapeutic target for treating NSCLC.

LncRNA CCAT1/miR-130a-3p axis increases cisplatin resistance in non-small-cell lung cancer cell line by targeting SOX4.

BACKGROUND: Colon cancer-associated transcript-1 (CCAT1) has been demonstrated to act as an oncogene and promote chemoresistance in several cancers. However, little is known about the underlying mechanism of CCAT1 in cisplatin (DDP) resistance of non-small-cell lung cancer (NSCLC) cells. METHODS: qRT-PCR was performed to detect the expression levels of CCAT, miR-130a-3p, or sex-determining region Y-box 4 (SOX4) mRNA. Luciferase reporter assay, RNA immunoprecipitation (RIP), and qRT-PCR analysis were carried out to explore the potential targets of CCAT1 or miR-130a-3p. Effect of CCAT1, miR-130a-3p, or SOX4 on IC50 value of DDP and ATP binding cassette subfamily G member 2 (ABCG2) level in NSCLC cells were determined by cell counting kits-8 (CCK-8) assay and western blot, respectively. RESULTS: CCAT1 and SOX4 were up-regulated, and miR-130a-3p was down-regulated in DDP-resistant NSCLC cells compared with their parental NSCLC cells. CCAT1 directly interacted with miR-130a-3p and negatively regulated miR-130a-3p expression. CCAT1 contributed to DDP resistance of A549/DDP cells by down-regulating miR-130a-3p. miR-130a-3p was found to directly target SOX4 to suppress its expression. SOX4 knockdown reversed miR-130a-3p-inhibition-induced increase of DDP resistance and ABCG2 expression in NSCLC cells. Exogenous expression of SOX4 abrogated CCAT1-knockdown-mediated decrease of DDP resistance and ABCG2 expression in DDP-resistant NSCLC cells. CONCLUSION: CCAT1/miR-130a-3p axis enhanced DDP resistance of NSCLC cells by targeting SOX4, providing potential targets to overcome DDP resistance and improve efficacy of chemotherapy for patients with NSCLC.

miR-181c contributes to cisplatin resistance in non-small cell lung cancer cells by targeting Wnt inhibition factor 1.

PURPOSE: miRNAs are implicated in drug resistance of multiple cancers including non-small cell lung cancer (NSCLC), highlighting the potential of miRNAs as chemoresistance regulators in cancer treatment. This study aims to explore the relationship between miR-181c and chemoresistance of NSCLC cells. METHODS: qRT-PCR was conducted to examine the expression of miR-181c in NSCLC tissues, and parental and cisplatin (DDP)-resistant NSCLC cells. MTT assay and flow cytometry were performed to detect the survival rate and apoptosis in NSCLC cells. Luciferase reporter assay was performed to confirm the potential target of miR-181c. Xenograft tumor experiment was applied to confirm the effect of miR-181c on DDP sensitivity of DDP-resistant NSCLC cells in vivo. RESULTS: miR-181c was upregulated in NSCLC tissues, and parental and DDP-resistant NSCLC cells. miR-181c downregulation or WIF1 overexpression increased DDP sensitivity of DDP-resistant NSCLC cells by decreasing survival rate and promoting DDP-induced apoptosis. miR-181c was demonstrated to be able to bind to WIF1 and negatively regulate the expression of WIF1. WIF1 knockdown abolished anti-miR-181c-induced DDP sensitivity. Moreover, anti-miR-181c suppressed the Wnt/ß-catenin pathway by regulating WIF1. XAV939 treatment reversed miR-181c-induced increase in IC50 value and miR-181c-triggered decrease in apoptosis. Finally, anti-miR-181c improved DDP sensitivity of DDP-resistant NSCLC cells in vivo. CONCLUSION: miR-181c contributed to DDP resistance in NSCLC cells through activation of the Wnt/ß-catenin pathway by targeting WIF1, providing a potential therapeutic application for the treatment of patients with DDP-resistant NSCLC in the future.

Does adenomatous polyposis coli gene promoter 1A methylation increase non-small cell lung cancer risk? A meta-analysis.

BACKGROUND: The promoter region of the adenomatous polyposis coli (APC) gene is hypermethylated in several types of cancers, including non-small cell lung cancer (NSCLC). The prevalence of methylation in the promoter region of this gene in tumor tissues and autologous controls has not been consistent in previous studies. We evaluated the frequency of APC gene promoter 1A methylation between tumor tissues and autologous controls in NSCLC patients by meta-analysis. METHODS: Open published studies of APC gene promoter 1A methylation between tumor tissues and autologous samples in NSCLC patients were identified using a systematic search. Odds ratios (OR) and 95% confidence intervals (CI) of APC gene promoter 1A methylation in lung cancer tissues versus autologous controls were calculated. Fourteen studies, involving a total of 1345 patients and 2182 samples, were finally included. RESULTS: The pooled proportion of APC promoter 1A methylation was 0.62 (95% CI 0.52-072) and 0.34 (95% CI 0.21-0.50) in cancer tissues and autologous controls, respectively. The APC gene promoter 1A methylation rate in cancer tissues was much higher than in autologous controls, with a pooled OR of 3.66 (95% CI 2.12-6.33). A strong and significant correlation of APC gene promoter 1A methylation between tumor tissues and autologous controls was detected (correlation coefficient rpearson = 0.77; P = 0.0013). CONCLUSION: The proportion of APC promoter 1A methylation in lung cancer tissues was higher than in autologous controls, indicating that promoter 1A methylation of the APC gene may play an important role in NSCLC carcinogenesis.

Bevacizumab did not reduce the risk of anemia associated with chemotherapy: an up-to-date meta-analysis.

PURPOSE: The risk of anemia due to bevacizumab-based chemotherapy has not been well described, and new randomized controlled trials (RCTs) have been reported in recent years. We therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of anemia with bevacizumab. METHODS: We carried out an electronic search of Medline, Embase, and The Cochrane Central Register of Controlled Trials to investigate the effects of RCTs on bevacizumab treatment on cancer patients up to October 2014, and random or fixed-effect meta-analytical models were used to assess the risk ratio (RR) of anemia due to the use of bevacizumab according to the heterogeneity of included studies. RESULTS: A total of 13,173 patients were included in this analysis from 18 RCTs. Among those patients receiving bevacizumab and chemotherapy, the incidences of all-grade and high-grade (grade 3 and above) anemia were 24% (95% confidence interval (CI) 13-41%) and 4.0% (95% CI 3.0-6.0%), respectively. Bevacizumab-containing therapy did not significantly decreased the risk of developing all-grade anemia (RR 0.872, 95% CI 0.739-1.029, P = 0.104) and high-grade anemia (RR 0.850, 95% CI 0.720-1.002, P = 0.053), which is not in agreement with previous meta-analysis. On subgroup analysis, we did not find significant risk differences based on bevacizumab dosage, tumor types, and concomitant drugs. When stratified by dose level, a significantly decreased risk of high-grade anemia with bevacizumab was obtained in a lower dose level (2.5 mg/kg/week, RR 0.773, 95% CI 0.611-0.978, P = 0.031) compared to control group. CONCLUSIONS: Bevacizumab did not significantly reduce the risk of anemia with chemotherapy in cancer patients.

[Treatment of cicatricial stricture subsequent to esophageal chemical burns with transverse colon replacing esophagus in children].

OBJECTIVE: To study the validity of transplanting transverse colon to replace esophagus in treating cicatricial stricture resulting from severe esophageal chemical burns in children. METHODS: A retrospective study was carried out on the clinical data of 46 patients with severe chemical esophageal burns who were treated from November 1972 to September 2008. The transverse colon with the ascending branch of the left colic artery was brought through a retrosternal tunnel to replace strictured esophagus. Thirty-two patients underwent colon-esophageal anastomosis and 14 patients underwent colon-pharyngeal anastomosis. RESULTS: All patients survived after surgery, but complications occurred in 7 cases, including leakage of anastomosis in cervical region in 4 cases, stenosis of anastomosis in 2 cases, and dyspnea in 1 case, and they were cured after due treatment. Follow-up study (1 - 26 years) in 39 patients revealed that there was no difference in growth, development and diet between the patients and the normal children of the same age. CONCLUSIONS: Esophageal reconstruction with transverse colon together with the ascending branch of the left colic artery through a retrosternal tunnel is a valuable method for treating cicatricial stricture of the esophagus secondary to severe chemical burns of the esophagus in children.