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Shenzhen, China

Wu W.,Tongji University | Sun M.,Tongji University | Zhang H.-P.,Shanxi Medical University | Chen T.,Tongji University | And 8 more authors.
Gut | Year: 2014

Objective: The dysfunction of immune regulation plays a critical role in the pathogenesis of a number of chronic inflammatory disorders, such as IBD. A close relationship between psychological stress and intestinal inflammation has been noted; the underlying mechanism remains elusive. This study aims to elucidate a pathological pathway between psychological stress and the dysfunction of regulatory T cells (Treg), and its effect on facilitating intestinal inflammation. Design: A restraint stress model was employed to induce psychological stress in mice. The functions of Tregs were determined by assessing the immune suppressor effects in the intestine. A mouse model of intestinal inflammation was established using a low dose of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) together with the challenge of chronic stress. Results: After treating mice with restraint stress, the suppressor function of intestinal Treg was compromised, although the frequency of Treg was not changed in the intestine. Further observation revealed that stress induced Tregs in the intestine to differentiate into foxhead box P3+ interleukin (IL)-17+ tumour necrosis factor (TNF)-α+ T cells. We also observed that exposure to stress-derived prolactin induced dendritic cells (DC) to produce IL-6 and IL-23 in vitro and in vivo, which played a critical role in altering Treg's phenotypes. Treating mice with chronic stress facilitated the initiation of intestinal inflammation by a low dose of TNBS or DSS, which was abolished by pretreatment with an inhibitor of prolactin, the cabergoline. Conclusions: Psychological stress-derived prolactin alters DC and Treg's properties to contribute to intestinal inflammation. © 2014 BMJ Publishing Group Ltd & British Society of Gastroenterology.


He W.,Shenzhen University | Yang C.,Shenzhen University | Xia L.,Shenzhen University | Zhao M.-Z.,ENT Hospital | And 5 more authors.
Cytokine | Year: 2014

Background: CD4+ T cell polarization plays a critical role in the pathogenesis of allergy. How to modulate the skewed CD4+ T cell polarization is less clear. The specific immunotherapy (SIT) is the only specific remedy for the treatment of allergic diseases; the therapeutic effect is to be improved. Objectives: This study aims to investigate the role of interleukin (IL)-18 in enhancing the therapeutic effect of SIT. Methods: A peanut allergy mouse model was developed and treated with SIT or/and IL-18. CD4+ T cell apoptosis was assessed by flow cytometry. The expression of Fas ligand (FasL) was observed by quantitative real time RT-PCR and Western blotting. Interferon-γ in the culture medium was determined by enzyme-linked immunosorbent assay. The fasL gene promoter methylation in CD4+ T cells was assessed by methylation specific PCR. Results: The results showed that lower levels of IL-18 were detected in allergic mice; administration of IL-18 significantly enhanced the therapeutic effect of SIT on suppressing the allergic inflammation in the mouse intestine. In the cell culture studies, IL-18 increased the TCR-dependent CD4+ T cell apoptosis, the expression of FasL in CD4+ T cells, the production of Interferon-γ and the demethylation of the FasL promoter in CD4+ T cells. Conclusions: Administration of IL-18 enhances the effect of SIT on suppressing allergic inflammation in the mouse intestine via enhancing the TCR-dependent CD4+ T cell apoptosis. © 2014 Elsevier Ltd.


Mahadevan M.,Starship Childrens Hospital | Navarro-Locsin G.,Rush University Medical Center | Tan H.K.K.,KK Womens and Childrens Hospital | Yamanaka N.,Wakayama Medical University | And 6 more authors.
International Journal of Pediatric Otorhinolaryngology | Year: 2012

Objective: The burden of disease due to otitis media (OM) in Asia Pacific countries was reviewed to increase awareness and raise understanding within the region. Methods: Published literature and unpublished studies were reviewed. Results: In school-age children, OM prevalence varied between 3.25% (Thailand) and 12.23% (Philippines) being highest (42%) in Aboriginal Australian children. OME prevalence at school age varied between 1.14% (Thailand) and 13.8% (Malaysia). Higher prevalence was reported in children with hearing impairment, HIV, pneumonia and rhinitis. CSOM prevalence was 5.4% in Indonesia (all ages), 15% in Aboriginal Australian children and 2-4% in Thailand, Philippines, Malaysia and Vietnam (WHO estimate). OM prevalence/incidence and service utilisation were highest in children 2-5 years of age. The disease burden was substantially higher in Pacific Island children living in New Zealand (25.4% with OME), and was highest in indigenous Australians (>90% with any OM). Streptococcus pneumoniae and Haemophilus influenzae dominated as primary causes of AOM in all studies. Few studies examined pneumococcal serotype distribution. Health-related cost estimates for OM, when available, were substantial. In developing countries, significant investment is needed to provide facilities for detection and treatment of ear disease in children, if long term hearing deficits and other sequelae are to be prevented. Conclusion: The available evidence suggests an important burden of disease and economic cost associated with OM in most Asia Pacific countries and a potential benefit of prevention through vaccination. Large, prospective community-based studies are needed to better define the prevalence of ear disease in children, and to predict and track pneumococcal conjugate vaccine impacts. AOM prevention through vaccination may also provide a means of reducing antibiotic use and controlling antibiotic-resistant disease in children. This review highlights the need for additional research, and provides a basis on which to build and develop regional guidelines for OM management. © 2012 Elsevier Ireland Ltd.


Ledeboer N.A.,Medical College of Wisconsin | Lopansri B.K.,Intermountain Medical Center | Dhiman N.,Med fusion | Cavagnolo R.,Med fusion | And 15 more authors.
Journal of Clinical Microbiology | Year: 2015

Bloodstream infection is a serious condition associated with significant morbidity and mortality. The outcome of these infections can be positively affected by the early implementation of effective antibiotic therapy based on the identification of the infecting organism and genetic markers associated with antibiotic resistance. In this study, we evaluated the microarray-based Verigene Gram-negative blood culture (BC-GN) assay in the identification of 8 genus or species targets and 6 genetic resistance determinants in positive blood culture broths. A total of 1,847 blood cultures containing Gram-negative organisms were tested using the BC-GN assay. This comprised 729 prospective fresh, 781 prospective or retrospective frozen, and 337 simulated cultures representing 7 types of aerobic culture media. The results were compared to those with standard bacterial culture and biochemical identification with nucleic acid sequence confirmation of the resistance determinants. Among monomicrobial cultures, the positive percent agreement (PPA) of the BC-GN assay with the reference method was as follows; Escherichia coli, 100%; Klebsiella pneumoniae, 92.9%; Klebsiella oxytoca, 95.5%; Enterobacter spp., 99.3%; Pseudomonas aeruginosa, 98.9%; Proteus spp., 100%; Acinetobacter spp., 98.4%; and Citrobacter spp., 100%. All organism identification targets demonstrated>99.5% negative percent agreement (NPA) with the reference method. Of note, 25/26 cultures containing K. pneumoniae that were reported as not detected by the BC-GN assay were subsequently identified as Klebsiella variicola. The PPA for identification of resistance determinants was as follows; blaCTX-M, 98.9%; blaKPC, 100%; blaNDM, 96.2%; blaOXA, 94.3%; blaVIM, 100%; and blaIMP, 100%. All resistance determinant targets demonstrated>99.9% NPA. Among polymicrobial specimens, the BC-GN assay correctly identified at least one organism in 95.4% of the broths and correctly identified all organisms present in 54.5% of the broths. The sample-to-result processing and automated reading of the detection microarray results enables results within 2 h of culture positivity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.


Geng X.-R.,Shenzhen University | Geng X.-R.,ENT Hospital | Yang G.,Shenzhen University | Yang G.,ENT Hospital | And 8 more authors.
Journal of Biological Chemistry | Year: 2014

Regulatory B cells (Bregs) are important in immune regulation. The factors that regulate Breg functions are less clear. Insulin-like growth factor 2 (IGF2) is capable of inducing hematopoietic stem cell differentiation. This study aimed to investigate the role of IGF2 in the development of Bregs and the enhancement of their function. In this study, the expression of IGF1 receptor (IGF1R) and IGF2R in ovalbumin (OVA)-specific B cells (OVAsBCs) was assessed by real time RT-PCR and Western blotting. The release of interleukin (IL)-10 from OVAsBCs and OVAsBC proliferation were assessed by enzyme-linked immunoassay and proliferation assay. The role of IGF2 in enhancing the function of OVAsBCs was tested with an intestinal allergic inflammation mouse model. The results showed that OVAsBCs expressed high levels of IGF2R. Exposure to both IGF2 and a specific antigen (Ag), OVA, markedly enhanced the expression of IL-10 in OVAsBCs as well as enhanced the IL-10+ OVAsBC proliferation. The concurrent exposure to IGF2 and specific Ag markedly induced the IL-10 promoter DNA demethylation via activating the STAT5 pathway. IGF2 also enhanced both the OVAsBC proliferation in vivo and the effect of Ag-specific immunotherapy on inhibiting allergic inflammation in the intestine. We conclude that OVAsBCs express high levels of IGF2R and that IGF2 increases the expression of IL-10 in OVAsBCs and enhances OVAsBC proliferation and the inhibitory effect on allergic inflammation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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