BackgroundStem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model.MethodsA DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy.ResultsInjection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity.ConclusionsIntramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0472-y) contains supplementary material, which is available to authorized users.

Otomycosis accounts for over 15% of cases of external otitis worldwide. It is common in humid regions and Chinese cultures with ear-cleaning custom. Aspergillus and Candida are the major pathogens causing long-term infection. Early endoscopic and microbiological examinations, performed by otologists and microbiologists, respectively, are important for the appropriate medical treatment of otomycosis. The deep-learning model is a novel automatic diagnostic program that provides quick and accurate diagnoses using a large database of images acquired in clinical settings. The aim of the present study was to introduce a machine-learning model to accurately and quickly diagnose otomycosis caused by Aspergillus and Candida. We propose a computer-aided decision-making system based on a deep-learning model comprising two subsystems: Java web application and image classification. The web application subsystem provides a user-friendly webpage to collect consulted images and display the calculation results. The image classification subsystem mainly trained neural network models for end-to-end data inference. The end user uploads a few images obtained with the ear endoscope, and the system returns the classification results to the user in the form of category probability values. To accurately diagnose otomycosis, we used otoendoscopic images and fungal culture secretion. Fungal fluorescence, culture, and DNA sequencing were performed to confirm the pathogens Aspergillus or Candida spp. In addition, impacted cerumen, external otitis, and normal external auditory canal endoscopic images were retained for reference. We merged these four types of images into an otoendoscopic image gallery. To achieve better accuracy and generalization abilities after model-training, we selected 2,182 of approximately 4,000 ear endoscopic images as training samples and 475 as validation samples. After selecting the deep neural network models, we tested the ResNet, SENet, and EfficientNet neural network models with different numbers of layers. Considering the accuracy and operation speed, we finally chose the EfficientNetB6 model, and the probability values of the four categories of otomycosis, impacted cerumen, external otitis, and normal cases were outputted. After multiple model training iterations, the average accuracy of the overall validation sample reached 92.42%. The results suggest that the system could be used as a reference for general practitioners to obtain more accurate diagnoses of otomycosis.

Indole-3-carbinol (I3C) is an active component of cruciferous vegetables and has been shown to markedly inhibit the growth of a variety of tumors. However, the role of I3C in nasopharyngeal carcinoma (NPC) remains unclear. Thus, the aim of the present study was to investigate the inhibition of NPC cells by I3C in vitro and in vivo. The human CNE2 NPC cell line was treated with various concentrations (0, 100, 200 and 300 μM) of I3C and analysis of cell proliferation after 0, 24, 48 and 72 h, apoptosis after 48 h and expression levels of phosphatidylinositol 3-kinase (PI3K)/Akt pathway-associated proteins in vitro was performed. BALB/c nude mice were divided into the following groups: Prevention, treatment and control. In vivo, all the nude mice were inoculated with CNE2 NPC cells and the mice in the prevention and treatment groups were administered a diet containing 0.5% I3C prior to and following inoculation, respectively. The tumoricidal effect of I3C was investigated in the nude mice. After eight weeks, the expression levels of PI3K/Akt pathway-associated proteins were analyzed in the tumors from the nude mice in each group. The results demonstrated that with increasing I3C concentrations, cell proliferation decreased and apoptosis increased significantly. In addition, the expression levels of PI3K/Akt pathway-associated proteins decreased. In the animal experiments, the prevention and treatment groups developed smaller tumors and the expression levels of PI3K/Akt pathway-associated proteins were reduced when compared with those in the control group. In addition, very few changes to the heart, liver and kidney tissues were observed with hematoxylin and eosin staining in all the groups. Therefore, the results of the present study indicated that I3C inhibited the growth of NPC cells and induced apoptosis effectively in vivo and in vitro. The underlying mechanism may be that I3C suppresses the PI3K/Akt pathway.

None of the four polymorphisms in ADRB2 gene were associated with a risk of asthma in a current children population.

Background: The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in several cancer types. However, the expression and biological function of Evi5 in human laryngeal squamous cell carcinoma (LSCC) are still unknown.Methods: Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Evi5 knockout (KO) LSCC cells. The proliferation and cell cycle distribution of LSCC cells was determined. The effect of Evi5 on LSCC tumor growth in vivo was studied in a tumor xenograft model in mice. The interaction between Evi5 and c-Myc was detected by immunoprecipitation (IP) assay. Luciferase assay was used to determine the transcriptional activity of c-Myc.Results: Here, we show that Evi5 controls LSCC tumorigenesis via the stabilization of c-MYC oncogene. CRISPR-mediated knockout (KO) of Evi5 decreased the proliferation and decreased colony formation ability of LSCC cells. Knockout of Evi5 caused increased G1 phase and decreased S phase cells. In the tumor-bearing nude mice, The transplanted tumors originated from Evi5-KO TU212 cells were significantly decreased when compared with control TU212 cells. At the molecular level, we found that Evi5 interacted with c-MYC and Evi5 antagonized E3 ligase FBXW7-mediated ubiquitination and degradation of c-Myc protein, and promoted c-Myc-dependent transactivation. Conclusion:Given the critical role of c-Myc in tumorigenesis, our data suggest that Evi5 is a potential therapeutic target in LSCC, and inhibition of Evi5 should be a prospective strategy for LSCC therapy.