Ultrasound and microbubble-mediated delivery of miR-424-5p has a therapeutic effect in preeclampsia.

OBJECTIVE: To determine the influence of ultrasound/microbubble-mediated miR-424-5p delivery on trophoblast cells and the underlying mechanism. METHODS: Blood pressure and 24-h proteinuria of patients with preeclampsia (PE) were measured as well as the levels of miR-424-5p and amine oxidase copper containing 1 (AOC1) in placental tissues. HTR-8/Svneo and TEV-1 cells were subjected to cell transfection or ultrasonic microbubble transfection for determination of the expression of miR-424-5p, AOC1, ß-catenin and c-Myc as well as cell proliferation, apoptosis, migration and invasiveness. The concentrations of placental growth factor (PLGF), human chorionic gonadotropin (ß-hCG) and tumor necrosis factor-α (TNF-α) were measured in HTR-8/Svneo and TEV-1 cells. RNA immunoprecipitation (RIP) and dual luciferase reporter assay detected the binding of miR-424-5p to AOC1. A PE mouse model was induced by subcutaneous injection of L-NAME, where the influence of ultrasound/microbubble-mediated miR-424-5p delivery was evaluated. RESULTS: miR-424-5p was downregulated while AOC1 was upregulated in the placental tissues from PE patients. Overexpression of miR-424-5p activated Wnt/ß-catenin signaling pathway and promoted the proliferation of HTR-8/Svneo and TEV-1 cells as well as enhanced the migratory and invasive behaviors. AOC1 overexpression partly eliminated the effects of miR-424-5p on HTR-8/Svneo and TEV-1 cells. Ultrasound and microbubble mediated gene delivery enhanced the transfection efficiency of miR-424-5p and further promoted the effects of miR-424-5p in trophoblast cells. Ultrasound/microbubble-mediated miR-424-5p delivery alleviated experimental PE in mice. CONCLUSION: Ultrasound and microbubble-mediated miR-424-5p delivery targets AOC1 and activates Wnt/ß-catenin signaling pathway, thus promoting the aggressive phenotype of trophoblast cells, which indicating that miR-424-5p/AOC1 axis might be involved with PE pathogenesis.

Value of dual Doppler echocardiography for prediction of atrial fibrillation recurrence after radiofrequency catheter ablation.

BACKGROUND: Increasing evidence has been presented which suggests that left ventricular (LV) diastolic dysfunction may play an important role in the development of atrial fibrillation (AF). However, the potential for LV diastolic dysfunction to serve as a predictor of AF recurrence after radiofrequency catheter ablation remains unresolved. METHODS: Dual Doppler and M-PW mode echocardiography were performed in 67 patients with AF before ablation and 47 patients with sinus rhythm. The parameters measured within identical cardiac cycles included, the time interval between the onset of early transmitral flow peak velocity (E) and that of early diastolic mitral annular velocity (e') (TE-e'), the ratio of E to color M-mode Doppler flow propagation velocity (Vp)(E/Vp), the Tei index, the ratio of E and mitral annular septal (S) peak velocity in early diastolic E/e'(S) and the ratio of E and mitral annular lateral (L) peak velocity E/e'(L). A follow-up examination was performed 1 year after ablation and patients were divided into two groups based on the presence or absence of AF recurrence. Risk estimations for AF recurrence were performed using univariate and multivariate logistic regression. RESULTS: TE-e', E/Vp, the Tei index, E/e'(S) and E/e'(L) were all increased in AF patients as compared with the control group (p <  0.05). At the one-year follow-up examination, a recurrence of AF was observed in 21/67 (31.34%) patients. TE-e' and the Tei index within the recurrence group were significantly increased as compared to the group without recurrence (p <  0.001). Results from multivariate analysis revealed that TE-e' can provide an independent predictor for AF recurrence (p = 0.001). CONCLUSIONS: Dual Doppler echocardiography can provide an effective and accurate technique for evaluating LV diastolic function within AF patients. The TE-e' obtained within identical cardiac cycles can serve as an independent predictor for the recurrence of AF as determined at 1 year after ablation.

Epigenetic modifications inhibit the expression of MARVELD1 and in turn tumorigenesis by regulating the Wnt/ß-catenin pathway in pan-cancer.

MARVEL domain-containing 1 (MARVELD1) is one of the MARVEL domain-containing proteins. Expression of MARVELD1 in tumor and non-tumor tissues, the relationship between its expression and cancer prognosis, and upstream regulation of MARVELD1 were examined using pan-cancer data from The Cancer Genome Atlas. MARVELD1 expression was significantly downregulated in tissues used for pan-cancer analysis compared to that in normal tissues. Low expression of MARVELD1 was associated with poor disease outcomes in pan-cancer. Colon cancer patients with low expression of MARVELD1 had worse progression free survival and overall survival than those with high expression levels in our cohort. Hypermethylation and histone modification in the MARVELD1 promoter locus synergistically affected its expression in pan-cancer. The function of MARVELD1 in colon cancer remains to be studied. Gene Ontology enrichment analysis revealed that MARVELD1 may modulate processes associated with inhibition of tumorigenesis in colon cancer. Both upstream transcription factors and downstream functional enrichment of MARVELD1 were related to the Wnt/ß-catenin signaling pathway. Overexpression of MARVELD1 inhibited the expression of ß-catenin and its entry into the nucleus. MARVELD1 also inhibited the proliferation, migration, and invasion of colon cancer cells. With Wnt/ß-catenin activator LiCl treatment, rescue experiments demonstrated that the role of MARVELD1 in colon cancer progression was dependent on the Wnt/ß-catenin pathway. These results indicate that MARVELD1 acts as a tumor suppressor and inhibits tumorigenesis via the Wnt/ß-catenin pathway.

A prediction model for major adverse cardiovascular events in patients with heart failure based on high-throughput echocardiographic data.

Background: Heart failure (HF) is a serious end-stage condition of various heart diseases with increasing frequency. Few studies have combined clinical features with high-throughput echocardiographic data to assess the risk of major cardiovascular events (MACE) in patients with heart failure. In this study, we assessed the relationship between these factors and heart failure to develop a practical and accurate prognostic dynamic nomogram model to identify high-risk groups of heart failure and ultimately provide tailored treatment options. Materials and methods: We conducted a prospective study of 468 patients with heart failure and established a clinical predictive model. Modeling to predict risk of MACE in heart failure patients within 6 months after discharge obtained 320 features including general clinical data, laboratory examination, 2-dimensional and Doppler measurements, left ventricular (LV) and left atrial (LA) speckle tracking echocardiography (STE), and left ventricular vector flow mapping (VFM) data, were obtained by building a model to predict the risk of MACE within 6 months of discharge for patients with heart failure. In addition, the addition of machine learning models also confirmed the necessity of increasing the STE and VFM parameters. Results: Through regular follow-up 6 months after discharge, MACE occurred in 156 patients (33.3%). The prediction model showed good discrimination C-statistic value, 0.876 (p < 0.05), which indicated good identical calibration and clinical efficacy. In multiple datasets, through machine learning multi-model comparison, we found that the area under curve (AUC) of the model with VFM and STE parameters was higher, which was more significant with the XGboost model. Conclusion: In this study, we developed a prediction model and nomogram to estimate the risk of MACE within 6 months of discharge among patients with heart failure. The results of this study can provide a reference for clinical physicians for detection of the risk of MACE in terms of clinical characteristics, cardiac structure and function, hemodynamics, and enable its prompt management, which is a convenient, practical and effective clinical decision-making tool for providing accurate prognosis.

The complete mitochondrial gemone of Phoxinus lagowskii (Teleostei, Cypriniformes: Cyprinidae).

In this paper, we determined the whole mitochondrial DNA (mtDNA) sequence of Phoxinus lagowskii, a small freshwater fish that is distributed in rivers of north China, Russia and North Korea. The entire sequence of P. lagowskii mitochondrial genome is 16,699 bp in size, consisting of 13 protein-coding genes, 2 ribosomal RNA genes (12S rRNA and 16S rRNA), 22 transfer RNA genes (tRNA) and 1 putative control region. Most of the genes are encoded on the heavy strand except ND6 and eight tRNA genes (Gln, Ala, Asn, Cys, Try, Ser, Glu and Pro) encoded on the light strand.