CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells.

Circular RNAs (circRNAs) have important potential in modulating vascular smooth muscle cell (VSMC) activity, but their roles in abdominal aortic aneurysm (AAA) are unknown. We performed in situ hybridization and immunohistochemistry and determined that circChordc1 (cysteine and histidine-rich domain containing 1) was markedly downregulated in aneurysm tissue compared with normal arteries. A gene gain and loss strategy was used to confirm that circChordc1 transformed VSMCs into a contracted phenotype and improved their growth, which significantly suppressed aneurysm formation and reduced the risk of rupture in mouse models of angiotensin (Ang) II- and CaCl2-induced AAA. RNA pull-down, immunoprecipitation, and immunoblotting indicated that circChordc1 facilitated the VSMC phenotype and growth determination by binding to vimentin and ANXA2 (annexin A2), which not only increased vimentin phosphorylation to promote its degradation but also promoted the interaction between ANXA2 and glycogen synthase kinase 3 beta (GSK3ß) to induce the nuclear entry of ß-catenin. Thus, our present study revealed that circChordc1 optimized the VSMC phenotype and improved their growth by inducing vimentin degradation and increasing the activity of the GSK3ß/ß-catenin pathway, thereby extenuating vascular wall remodeling and reversing pathological aneurysm progression.

Epithelial-myoepithelial carcinoma originating from minor salivary gland in the inferior turbinate: A case report and literature review.

Epithelial-myoepithelial carcinoma (EMC) is a rare tumor that occurs mainly in the major salivary glands. Cases occurring in the nasal cavity are rarely reported. The patient was a 48-year-old woman with a postoperative pathological diagnosis of EMC. The patient recovered well after surgery. We consulted and summarized all previous cases of nasal EMC. We also discuss the clinical presentation, treatment, and prognosis of EMC of the nasal cavity and paranasal sinuses.

Myocardial fibrosis combined with NT-proBNP improves the accuracy of survival prediction in ADHF patients.

BACKGROUND: Soluble suppression of tumorigenesis-2 (sST2), Procollagen Type III N-Terminal Peptid (PIIINP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been verified their role in predicting survival in acutely decompensated heart failure (ADHF). However, whether their combination could improve more specific and sensitive prognostic information than NT-proBNP alone remains unclear. METHODS: This was a prospective study, in which 217 ADHF patients at admission were enrolled from November 2018 and August 2019 (mean age 66.18 years ± 13.60, 63.98% male). The blood samples were collected to measure the concentrations of NT-proBNP, sST2 and PIIINP in the first 24 h of hospitalizations. All-cause mortality was registered for all patients after they were discharge over a median period of 339 days. RESULTS: In univariate Cox analysis, the three biomarkers were predictive of short-term mortality of ADHF patients. After adjusted for some clinical variables including age, admission systolic blood pressure, peripheral edema on admission, history of chronic obstructive pulmonary disease, admission sodium < 135 mmol/L, admission hemoglobin, NT-proBNP, sST2 and PIIINP was significantly associated with the poor outcome (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14-1.53, P < 0.01; HR 1.21, 95% CI 1.03-1.43, P = 0.020; HR 1.40, 95% CI 1.08-1.81, P = 0.011). After added with Log2 PIIINP, but not Log2 sST2, the area under the curves (AUC) in the model of clinical variables and Log2 NT-proBNP could increase from 0.79 to 0.85 (95% CI 0.0071-0.10, P = 0.024). Furthermore, compared with the model of clinical variables, Log2 NT-proBNP, the improvement in the prognostic model of clinical variables, Log2 NT-proBNP and Log2 PIIINP had statistical significance [net reclassification improvement (NRI) 0.31, P = 0.018; integrated discrimination improvement (IDI) 0.068, P < 0.01]. CONCLUSIONS: NT-proBNP, sST2 and PIIINP are independent prognostic factors for all-cause mortality in ADHF patients. Furthermore, the combination of NT-proBNP and PIIINP may provide incremental prognostic value over NT-proBNP in the survival of ADHF patients.

Engineered Nanotopography on the Microfibers of 3D-Printed PCL Scaffolds to Modulate Cellular Responses and Establish an In Vitro Tumor Model.

Scaffold-based three-dimensional (3D) cell culture systems have gained increased interest in cell biology, tissue engineering, and drug screening fields as a replacement of two-dimensional (2D) monolayer cell culture and as a way to provide biomimetic extracellular matrix environments. In this study, microscale fibrous scaffolds were fabricated via electrohydrodynamic printing, and nanoscale features were created on the fiber surface by simply leaching gliadin of poly(ε-caprolactone) (PCL)/gliadin composites in ethanol solution. The microstructure of the printed scaffolds could be precisely controlled by printing parameters, and the surface nanotopography of the printed fiber could be tuned by varying the PCL/gliadin ratios. By seeding mouse embryonic fibroblast (NIH/3T3) cells and human nonsmall cell lung cancer (A549) cells on the printed scaffolds, the cellular responses showed that the fiber nanotopography on printed scaffolds efficiently favored cell adhesion, migration, proliferation, and tissue formation. Quantitative analysis of the transcript expression levels of A549 cells seeded on nanoporous scaffolds further revealed the upregulation of integrin-ß1, focal adhesion kinase, Ki-67, E-cadherin, and epithelial growth factor receptors over what was observed in the cells grown on the pure PCL scaffold. Furthermore, a significant difference was found in the relevant biomarker expression on the developed scaffolds compared with that in the monolayer culture, demonstrating the potential of cancer cell-seeded scaffolds as 3D in vitro tumor models for cancer research and drug screening.

Long noncoding RNA GAS5 induces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis.

Objective: Long noncoding RNAs (lncRNAs) may serve as specific targets for the treatment of abdominal aortic aneurysms (AAAs). LncRNA GAS5, functionally associated with smooth muscle cell (SMC) apoptosis and proliferation, is likely involved in AAA formation, but the exact role of GAS5 in AAA is unknown. We thus explored the contribution of GAS5 to SMC-regulated AAA formation and its underlying mechanisms. Methods: Human specimens were used to verify the diverse expression of GAS5 in normal and AAA tissues. The angiotensin II (Ang II)-induced AAA model in ApoE-/- mice and the CaCl2-induced AAA model in wild-type C57BL/6 mice were used. RNA pull-down and luciferase reporter gene assays were performed in human aortic SMCs to detect the interaction between GAS5 and its downstream targets of protein or microRNA (miR). Results: GAS5 expression was significantly upregulated in human AAA specimens and two murine AAA models compared to human normal aortas and murine sham-operated controls. GAS5 overexpression induced SMC apoptosis and repressed its proliferation, thereby promoting AAA formation in two murine AAA models. Y-box-binding protein 1 (YBX1) was identified as a direct target of GAS5 while it also formed a positive feedback loop with GAS5 to regulate the downstream target p21. Furthermore, GAS5 acted as a miR-21 sponge to release phosphatase and tensin homolog from repression, which blocked the activation and phosphorylation of Akt to inhibit proliferation and promote apoptosis in SMCs. Conclusion: The LncRNA GAS5 contributes to SMC survival during AAA formation. Thus, GAS5 might serve as a novel target against AAA.

LncRNA H19 promotes vascular inflammation and abdominal aortic aneurysm formation by functioning as a competing endogenous RNA.

Abdominal aortic aneurysm (AAA) is accepted as a chronic vascular inflammatory disease. However, how the inflammatory response is regulated during AAA formation is not fully understood. This study was undertaken to determine whether the long noncoding RNA (lncRNA) H19 (H19) promotes AAA formation by enhancing aortic inflammation. qRT-PCR detected the upregulation of H19 in human and mouse AAA tissue samples. Co-staining for H19 and the macrophage marker MAC-2 showed that H19 was located in vascular smooth muscle cells (VSMCs) and infiltrating aortic macrophages. In vivo overexpression of H19 increased vascular inflammation and induced AAA formation, which was supported by exacerbated aortic morphology, maximum aortic diameter values, elastin degradation, expression of interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1), and macrophage infiltration. H19 suppression resulted in the opposite effects. A rescue experiment indicated that IL-6 neutralization significantly mitigated the aortic inflammation and AAA formation evoked by H19 overexpression. Luciferase reporter assays and ex vivo experiments using VSMCs and macrophages confirmed that H19 induced aneurysm formation in part via endogenous competition with the let-7a microRNA to induce the transcription of its target gene, IL-6. This mechanism was further validated by in vivo experiments using a mutant H19 that could not effectively bind let-7a. Collectively, our study revealed a pathogenic H19/let-7a/IL-6 inflammatory pathway in AAA formation, which offers a new potential therapeutic strategy for AAA.

LncRNA Expression Profile of Human Thoracic Aortic Dissection by High-Throughput Sequencing.

BACKGROUND/AIMS: In this study, the long non-coding RNA (lncRNA) expression profile in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. METHODS: Human TAD (n=3) and normal aortic tissues (NA) (n=3) were examined by high-throughput sequencing. Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results. RESULTS: A total of 269 lncRNAs (159 up-regulated and 110 down-regulated) and 2, 255 mRNAs (1 294 up-regulated and 961 down-regulated) were aberrantly expressed in human TAD (fold-change> 1.5, P< 0.05). QRT-PCR results of five dysregulated genes were consistent with HTS data. A lncRNA-mRNA coexpression analysis showed positive correlations between the up-regulated lncRNA (ENSG00000269936) and its adjacent up-regulated mRNA (MAP2K6, R=0.940, P< 0.01), and between the down-regulated lncRNA_1421 and its down-regulated mRNAs (FBLN5, R=0.950, P< 0.01; ACTA2, R=0.96, P< 0.01; TIMP3, R=0.96, P< 0.05). The lncRNA-miRNA-mRNA network indicated that the up-regulated lncRNA XIST and p21 had similar sequences targeted by has-miR-17-5p. The results of luciferase assay and fluorescence immuno-cytochemistry were consistent with that. And qRT-PCR results showed that lncRNA XIST and p21 were expressed at a higher level and has-miR-17-5p was expressed at a lower level in TAD than in NA. The predicted binding motifs of three up-regulated lncRNAs (ENSG00000248508, ENSG00000226530, and EG00000259719) were correlated with up-regulated RUNX1 (R=0.982, P< 0.001; R=0.967, P< 0.01; R=0.960, P< 0.01, respectively). CONCLUSIONS: Our study revealed a set of dysregulated lncRNAs and predicted their multiple potential functions in human TAD. These findings suggest that lncRNAs are novel potential therapeutic targets for human TAD.

Loss of AZIN2 splice variant facilitates endogenous cardiac regeneration.

Aims: Long noncoding RNAs (lncRNAs) are critical regulators of cardiovascular lineage commitment and heart wall development, but their roles in regulating endogenous cardiac regeneration are unclear. The present study investigated the role of human-derived lncRNA in regulating endogenous cardiac regeneration as well as the underlying mechanisms. Methods and results: We compared RNA sequencing data from human foetal and adult hearts and identified a novel lncRNA that was upregulated in adult hearts (Genesymbol NONHSAG000971/NONHSAT002258 or ENST00000497710.5), which was a splice variant of the AZIN2 gene (AZIN2-sv). We used quantitative PCR to confirm the increased expression of AZIN2-sv in adult rat hearts. Coexpression network analysis indicated that AZIN2-sv could regulate proliferation. Loss- and gain-of-function approaches demonstrated that AZIN2-sv negatively regulated endogenous cardiomyocyte proliferation in vitro and in vivo. Knockdown of AZIN2-sv attenuated ventricular remodelling and improved cardiac function after myocardial infarction. Phosphatase and tensin homolog (PTEN) was identified as a target of AZIN2-sv, their direct binding increased PTEN stability. Furthermore, AZIN2-sv acted as a microRNA-214 sponge to release PTEN, which blocked activation of the PI3 kinase/Akt pathway to inhibit cardiomyocyte proliferation. Conclusions: The newly discovered AZIN2-sv suppressed endogenous cardiac regeneration by targeting the PTEN/Akt pathway. Thus, AZIN2-sv may be a novel therapeutic target for preventing and treating heart failure.

Impact of remote ischaemic preconditioning on major clinical outcomes in patients undergoing cardiovascular surgery: A meta-analysis with trial sequential analysis of 32 randomised controlled trials.

BACKGROUND: The impact of remote ischaemic preconditioning (RIPC) on major clinical outcomes in patients undergoing cardiovascular surgery remains controversial. We systematically reviewed the available evidence to evaluate the potential benefits of RIPC in such patients. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant randomised controlled trials (RCTs) conducted between January 2006 and March 2016. The pooled population of patients who underwent cardiovascular surgery was divided into the RIPC and control groups. Trial sequential analysis was applied to judge data reliability. The pooled relative risks (RRs) with 95% confidence intervals (CIs) between the groups were calculated for all-cause mortality, major adverse cardiovascular and cerebral events (MACCEs), myocardial infarction (MI), and renal failure. RESULTS: RIPC was not associated with improvement in all-cause mortality (RR, 1.04; 95%CI, 0.82-1.31; I2=26%; P>0.05) or MACCE incidence (RR, 0.90; 95%CI, 0.71-1.14; I2=40%; P>0.05) after cardiovascular surgery, and both results were assessed by trial sequential analysis as sufficient and conclusive. Nevertheless, RIPC was associated with a significantly lower incidence of MI (RR, 0.87; 95%CI, 0.76-1.00; I2=13%; P≤0.05). However, after excluding a study that had a high contribution to heterogeneity, RIPC was associated with increased rates of renal failure (RR, 1.53; 95%CI, 1.12-2.10; I2=5%; P≤0.05). CONCLUSIONS: In patients undergoing cardiovascular surgery, RIPC reduced the risk for postoperative MI, but not that for MACCEs or all-cause mortality, a discrepancy likely related to the higher rate of renal failure associated with RIPC.

[Intratympanic versus systemic steroid initial treatment for idiopathic sudden hearing loss: a Meta-analysis].

OBJECTIVE: To assess the efficacy and safety of glucocorticoid in initial treatment of sudden hearing loss with intratympanic (IT) and systemic ways. METHOD: We searched the database of PubMed, Cochrane, Embase,CBM, CNKI, VIP, Wanfang systematically. Literatures were screened according to the preestablished inclusion and exclusion standards,and all the RCT literatures associated with intratympanic and systemic glucocorticoid in the initial treatment of sudden hearing loss before may 2015 were collected. All the data, which meet the inclusion standards, were analyzed by using Meta-analysis software. RESULT: Among all the qualified literatures, 11 randomized controlled trials were included. A total of 1298 cases were involved, including 521 cases with intratympanic administration, 410 with IV-therapy, and 201 with oral therapy. Meta analysis results showed that there was significant difference of the total effective rate and improvement rate between the intratympanic and systemic administration. Intratympanic injection (P > 0.05) was more effective than systemic administration. There was no significant difference between intratympanic group and oral group (RR = 1.15, 95% CI: 0.92-1.42, P > 0.05). A significant difference of the effective rate occurred between intratympanic group and IV therapy group (RR = 1.17, 95% CI: 1.02-1.34, P < 0.05). The major complications of intratympanic were pain, dizziness/vertigo, which occurred more frequently than systemic therapy group; The major complications of systemic therapy group were hyperglycaemia, loss of appetite and insomnia. CONCLUSION: This study shows that the intratympanic (IT) glucocorticoid for sudden deafness is more effective than the systemic administration. But it was not the first choice in clinical treatment. Further studies are warranted.