// Xiang Zhou 1 , Dimple Natino 2 , Zili Qin 3 , Dong Wang 1 , Zhen Tian 4 , Xuan Cai 1 , Bo Wang 5 and Xijing He 1 1 Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China 2 Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, USA 3 Department of Otolaryngology, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 4 Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China 5 Department of Pharmacology, School of Basic Medical Science, Xi'an Jiaotong University Health Science Center, Xi'an, China Correspondence to: Xijing He, email: xijing_h@vip.tom.com Keywords: osteosarcoma; circRNA-0008717; miR-203; Bmi-1 Received: September 11, 2017 Accepted: November 16, 2017 Epub: December 20, 2017 Published: April 27, 2018 ABSTRACT Circular RNA (circRNA) is a key regulator in the development and progression of human cancers, however its role in osteosarcoma tumorigenesis is not well understood. The present study aims to investigate the expression profiles and potential modulation of circRNA on osteosarcoma carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in osteosarcoma tissue and circRNA-0008717 was identified as one circRNA significantly upregulated in osteosarcoma tissue. Osteosarcoma patients with high circRNA-0008717 expression had shortened survival. Gain and loss functional assays suggested that knockdown of circRNA-0008717 suppressed cell proliferation, migration and invasion, but promoted cell apoptosis. By using biotin-labeled circRNA-0008717 probe to perform RNA precipitation in osteosarcoma cells, we identified miR-203 as the circ0008717-associated microRNA. Subsequently, Bmi-1 was identified as the functional target of miR-203. In addition, overexpression of circRNA-0008717 in osteosarcoma could elevate Bmi-1 expression, resulting in the promotion of osteosarcoma cell proliferation and invasion. Furthermore, the tumor promoting effect of circRNA-0008717 was abolished by miR-203 mimics or Bmi-1 silencing vector. In conclusion, circRNA-0008717 plays an oncogenic role in osteosarcoma and may serve as a promising prognostic biomarker for osteosarcoma patients. Therefore, silence of circRNA-0008717 could be a future direction to develop a novel treatment strategy.
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Asthma is affecting more than 300 million people worldwide, which represents the most common chronic disease among children. We previously found that mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) modulated the immune response on Th2-mediated asthma in vivo and in vitro. This study further evaluated the immunomodulatory effects of MSCs from human embryonic stem cells (hESCs) on asthma.Multipotent hESC-MSCs were obtained using a feeder-free method. The hESC-MSCs were analysed for the expression of stem cell surface markers by flow cytometry, their differentiation potentials were analysed using in vitro trilineage differentiation methods hESC-MSCs were transplanted into the murine model with ovalbumin (OVA)-induced airway allergic inflammation. The expression levels of allergic related genes were measured by the mRNA PCR arrays.The hESC-MSCs expressed classical MSC markers and held the capability of differentiation into multiple mesoderm-type cell lineages. hESC-MSCs were able to suppress allergic inflammation by modulating Th2 cells and eosinophils in the mice, and reversed the reduction of regulatory T cells. By using PCR array, 5 mRNAs- chemokine (C-C motif) ligand 11 (Ccl11), Ccl24, interleukin13 (Il13), Il33 and eosinophil-associated, ribonuclease A family, member 11 (Ear11) were identified the most relevant in murine airway allergic inflammation and hESC-MSCs treatment.The therapeutic effects of hESC-MSCs were identified in the murine model of airway allergic inflammation with key mRNAs involved. This study will provide a better understanding regarding the mechanisms underlying hESC-MSCs therapeutic application in airway allergic inflammation.
Abstract Background Standardized training allows more physicians to master otoendoscopic surgery. However, the lecture-based learning (LBL) applied in otoendoscopy teaching may not be conducive to training students in clinical thinking and surgical ability. It is necessary to explore innovative methods for otoendoscopy teaching. This study aimed to determine the effect of a step-by-step (SBS) method combined with case-based learning (CBL) in otoendoscopy teaching. Methods Fifty-nine physicians who participated in otoendoscopy training were selected as the study subjects and randomly divided into two groups (A and B). Group A underwent training with the SBS & CBL method, while Group B underwent training with the LBL & CBL method. The effects of these two methods for otoendoscopy training were compared by evaluation of professional skills and questionnaires before and after the training. Results Proficiency in otoendoscopic anatomy and grades for both professional knowledge and otoendoscopic skills were significantly higher in Group A than in Group B( P < 0.05). In terms of learning interest, surgical ability, acting capacity during surgery, reducing surgical complications, and satisfaction with learning experience, all responses from Group A were better than those from Group B( P < 0.05). Conclusions The SBS & CBL method may help to improve ability in otoendoscopic surgery and clinical thinking and appears suitable for endoscopy teaching.
miR-511-3p, encoded by CD206/Mrc1, was demonstrated to reduce allergic inflammation and promote alternative (M2) macrophage polarization. Here, we sought to elucidate the fundamental mechanism by which miR-511-3p attenuates allergic inflammation and promotes macrophage polarization. Compared with WT mice, the allergen-challenged Mrc1-/- mice showed increased airway hyperresponsiveness (AHR) and inflammation. However, this increased AHR and inflammation were significantly attenuated when these mice were pretransduced with adeno-associated virus-miR-511-3p (AAV-miR-511-3p). Gene expression profiling of macrophages identified Ccl2 as one of the major genes that was highly expressed in M2 macrophages but antagonized by miR-511-3p. The interaction between miR-511-3p and Ccl2 was confirmed by in silico analysis and mRNA-miR pulldown assay. Further evidence for the inhibition of Ccl2 by miR-511-3p was given by reduced levels of Ccl2 in supernatants of miR-511-3p-transduced macrophages and in bronchoalveolar lavage fluids of AAV-miR-511-3p-infected Mrc1-/- mice. Mechanistically, we demonstrated that Ccl2 promotes M1 macrophage polarization by activating RhoA signaling through Ccr2. The interaction between Ccr2 and RhoA was also supported by coimmunoprecipitation assay. Importantly, inhibition of RhoA signaling suppressed cockroach allergen-induced AHR and lung inflammation. These findings suggest a potentially novel mechanism by which miR-511-3p regulates allergic inflammation and macrophage polarization by targeting Ccl2 and its downstream Ccr2/RhoA axis.
The T helper 2 (Th2)-type response was considered the hypostasis of allergic airway diseases, including asthma and allergic rhinitis (AR). However, more recent studies have suggested that allergic airway inflammation also depends on innate immunity and is closely related to group 2 innate lymphoid cells (ILC2s). This study evaluated the ILC2 levels of asthma subjects, patients with asthma and AR, and healthy individuals, regarding how to investigate the relationship between clinical data and ILC2 levels. It was found that asthma patients and asthma with AR patients had higher ILC2 levels compared to healthy subjects. ILC2s were positively correlated with the percentage of eosinophils in patients with asthma and AR, but not with pulmonary function. ILC2 levels were higher in mild asthma subjects than in patients with severe asthma. This study provides a new interpretation of the pathogenesis of allergic airway inflammation and may provide a new direction for the diagnosis and assessment of allergic airway diseases.
Group 2 innate lymphoid cells (ILC2s) are essential in initiating and driving allergic immune responses. However, there were inconsistent findings of the ILC2 levels in allergic rhinitis (AR) patients. This study investigated the ILC2 levels in the peripheral blood of house dust mite (HDM)-sensitized AR patients and their ability to secrete type 2 cytokines. The levels of ILC2s with phenotypic ILC2 characteristics were increased in the HDM-AR patients. The AR patients' symptom score and IL-13 levels were positively associated with the ILC2s in HDM-AR patients. The epithelial cytokine stimulation induced dramatic production of IL-5 and IL-13 in PBMCs of AR patients. We successfully sorted ILC2s from AR patients and identified their ability of type 2 cytokines production. The number of ILC2s increased in the HDM-AR patients and ILC2s produced the amount of TH2 cytokines in the presence of epithelial cytokines, which suggested the important role of ILC2 in AR patients.
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