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Yang D.,Chongqing Medical University | Yang W.,181 st Hospital of PLA | Tian Z.,Chongqing Medical University | van Velkinburgh J.C.,van Velkinburgh Initiative for Collaboratory BioMedical Research | And 3 more authors.
Obesity Reviews | Year: 2016

Summary: The increased prevalence of obesity worldwide has been accompanied by increases in risk and rates of obesity-associated metabolic dysfunctions, such as insulin resistance. The chronic, low-grade inflammatory condition of obesity highlights the pathophysiological link between the immune system and the metabolic system, which has yet to be fully understood. Recent studies of obesity have started to uncover potential regulatory roles for the innate lymphoid cells (ILCs), which under normal conditions serve to regulate development of lymphoid tissue and function of the mucosal immune system. The ILCs are a newly identified immune cell population with complicated composition and subsequently diverse and dynamic functions. Studies to determine the distribution profile of the various ILCs in adipose tissue provide intriguing clues as to their regulatory capacity in obesity and its associated metabolic dysfunctions. Here, we review the recent findings supporting a role for ILCs as regulators of obesity or its associated insulin resistance, and discuss the potential underlying molecular mechanism as well as its promise as a therapeutic target for clinical applications. © 2016 World Obesity.


Ahmed M.O.,University of Liverpool | Williams N.J.,University of Liverpool | Clegg P.D.,University of Liverpool | Van Velkinburgh J.C.,Van Velkinburgh Initiative for Collaboratory BioMedical Research | And 2 more authors.
Microbial Drug Resistance | Year: 2012

Antimicrobial-resistant bacteria represent a major threat to human and animal health. We compared equine fecal samples (n=264) from 138 horses from hospital and nonhospital (livery stable and riding school) premises in North West England to determine the prevalence of Escherichia coli, Salmonella, and Campylobacter and rates of antimicrobial-resistant E. coli strains. Campylobacter jejuni was detected only in hospitalized horses (1.1%), and no Salmonella was identified. Data analysis of the horses' management and veterinary treatments (Tx) identified risk factors associated with shedding of antimicrobial-resistant E. coli. The hospital was the major source of resistant and multi-drug-resistant (MDR) E. coli. Moreover, shedding of antimicrobial-resistant E. coli was associated significantly with hospitalization for a gastrointestinal problem (odds ratio [OR]:±95% confidence intervals=8.50:1.79-40.32), receipt of oral antimicrobial Tx (OR=3.52:1.11-11.10), multiple antimicrobial Tx in hospital (OR/Tx=1.05:1.01-1. 09), or geldings (OR=4.62:1.23-17.46). Interestingly, intravenous antimicrobial Tx was negatively associated with shedding of antimicrobial-resistant E. coli (OR=0.18:0.04-0.76). MDR E. coli was associated with hospitalization, antimicrobial Tx in hospital (OR/Tx=3.65:1.54-8.68), and increased age (OR/year=1.11:1.03-1.19). Thus, equine hospitals in this geographic location appear to be an important source of antimicrobial-resistant and MDR E. coli strains, but unlikely reservoirs of Salmonella or Campylobacter. Thus, it is important to moderate antimicrobial Tx given to hospitalized horses to lessen exposure and fecal shedding of resistant pathogens. © 2012 Mary Ann Liebert, Inc.


Tian Y.,Chongqing Medical University | Ni D.,Chongqing Medical University | Yang W.,The 181th Hospital of PLA | Zhang Y.,Chongqing Medical University | And 8 more authors.
Carcinogenesis | Year: 2014

Hepatitis B virus (HBV) alters the expression of host cellular genes to support its replication and survival and to promote the liver cell injury. However, the underlying mechanism remained incompletely understood. In this study, we investigated HBV-induced epigenetic changes in HepG2 cells by profiling the landscapes of the active histone modification mark H3K4me3 and repressive mark H3K27me3 using chromatin immunoprecipitation-sequencing. HBV caused the altered histone modifications at thousands of genomic loci, which are critically involved in HBV entry, inflammation, fibrosis and carcinogenesis of host cells. Interestingly, treatment of the HBVtransformed HepG2 cells with the anti-HBV drug Telbivudine substantially restored the H3K4me3 level to that of untransformed HepG2 cells. More importantly, our analysis of liver samples from control and chronic hepatitis B patients revealed that treatment of the patients with Telbivudine not only corrected the target gene expression but also the epigenetic modification of critical genes. In addition, the expression of the histone methyltransferases SMYD3 and EZH2 that regulate histone H3-specific methylation showed no difference in HepG2 cell with or without HBV existence. Thus, our data suggest that abnormal histone modifications might critically involved in HBV-mediated liver pathogenesis and Telbivudine therapy might benefit patients with HBV-related chronic infection, liver cirrhosis and even hepatic carcinoma. Summary: Telbivudine substantially restores in vitro and in vivo HBV-caused abnormal expressions and histone H3K4me3 and H3K27me3 modifications at thousands of genomic loci that are involved in the pathogenesis of liver cells, revealing a novel mechanism for HBV-mediated liver damage. © The Author 2013. Published by Oxford University Press. All rights reserved.


Huang Z.,Chongqing Medical University | van Velkinburgh J.C.,Van Velkinburgh Initiative for Collaboratory BioMedical Research | Ni B.,Chongqing Medical University | Wu Y.,Chongqing Medical University
Liver International | Year: 2012

T helper 17 (Th17) cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria, as well as in the pathogenesis of autoimmune disease. Research interest in these cells was piqued when hepatitis B virus (HBV)-infected patients were found to have significantly elevated Th17 cell frequency, and it was proposed that these proinflammatory effectors may promote the HBV disease process. Subsequent studies have revealed that Th17 cells drive immune-mediated pathology of HBV infection, and that IL-23 amplifies the Th17 cell responses and liver inflammation. As a result, new pathways of HBV-mediated liver damage have been elucidated, along with promising new targets of molecular therapeutic strategies. Ongoing research is also providing significant insights into the target cells and underlying mechanisms of Th17-secreted cytokines, including IL-17A, IL-21 and IL-22. Future studies are expected to fully uncover the cytokine-related mechanisms mediating HBV-induced liver inflammation, and to determine the yet unknown cell source of IL-23. This review will draw upon the most up-to-date available data to discuss the putative roles and detailed mechanisms of IL-23/Th17 cell axis in HBV infection-mediated liver pathogenesis. © 2012 John Wiley & Sons A/S.


Zhang Y.,Chongqing Medical University | Tang J.,105th Hospital of PLA | Tian Z.,Chongqing Medical University | van Velkinburgh J.C.,Van Velkinburgh Initiative for Collaboratory BioMedical Research | And 3 more authors.
International Reviews of Immunology | Year: 2015

Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic. © 2015 Informa Healthcare USA, Inc.


Yang S.,Chongqing Medical University | Tian Z.,Chongqing Medical University | Wu Y.,Chongqing Medical University | Van Velkinburgh J.C.,Van Velkinburgh Initiative for Collaboratory BioMedical Research | Ni B.,Chongqing Medical University
International Reviews of Immunology | Year: 2015

Innate lymphoid cells (ILCs) are involved in the development of mucosal-associated lymphoid tissues and serve as a rapid and early source of the effector cytokines that are typically associated with the T helper cell subsets in response to pathogen-induced changes in the microenvironment. Recent research has implicated ILCs as potential contributing factors to the spectrum of inflammation-related hepatic diseases, particularly hepatitis, fibrosis and carcinoma. In this review, we summarize the current knowledge on the roles of ILCs in these hepatic pathogeneses, providing insights into the underlying cellular and signaling mechanisms to help guide the future research to elucidate the ILCs characters under normal and diseased conditions and provide interventional targets with therapeutic potential. Copyright © Taylor & Francis Group, LLC.


Chen S.,Wenzhou Medical College | Ou R.,Wenzhou Medical College | Tang J.,The 105th Hospital of PLA | Deng X.,Wenzhou Medical College | And 4 more authors.
Cancer Epidemiology | Year: 2013

Background: It is well known that both heat shock protein (HSP) and Toll-like receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable of promoting the antigen-specific immune responses. In the current study, we assessed whether the anti-tumor effects of the HPV16E749-57-based vaccine can be elevated by combined applications of poly(I:C) and oxygen-regulated protein 150 (ORP150) in a mouse cervical cancer model. Methods: Recombinant mouse ORP150 and HPV E749-57 peptide were combined to passively form the ORP150-E749-57 complex under heat shock conditions. The effects of ORP150-E749-57 complex plus poly(I:C) adjuvant on lymphocyte proliferation and functional cytotoxic T cells were investigated by methyl thiazolyl tetrazolium (MTT), ELISPOT, and non-radioactive cytotoxicity assays. Finally, the complex's therapeutic anti-tumor effects with and without adjuvant therapy were observed in a tumor challenge experiment. Results: This combination vaccine approach significantly enhanced the proliferation of splenocytes and induced strong E749-57-specifi{ligature}c CTL responses. More importantly, the ORP150-E749-57 complex plus poly(I:C) vaccine format demonstrated more potent anti-tumor effects than ORP150-E749-57 complex alone or E749-57 plus poly(I:C) in TC-1 tumor-bearing mice. Conclusion: Both poly(I:C) and ORP150 chaperone can synergistically enhance the anti-tumor effects of the HPV16E749-57-based vaccine in vitro and in vivo. This strategy provides a platform for the design of a tumor therapeutic vaccine capable of inducing an effective anti-tumor immune response. © 2012 Elsevier Ltd.


Liu M.,Chongqing Medical University | Gao W.,Chongqing Medical University | van Velkinburgh J.C.,van Velkinburgh Initiative for Collaboratory BioMedical Research | Wu Y.,Chongqing Medical University | And 2 more authors.
Medicinal Research Reviews | Year: 2016

Through positive selection, double-positive cells in the thymus differentiate into CD4+ or CD8+ T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes and CD4+ and CD8+ T cells are controlled by a multitude of secreted and intracellular factors, ranging from cytokine signaling modules to transcription factors and epigenetic modifiers. Members of the E26 transformation specific (Ets) family of transcription factors, in particular, are potent regulators of these CD4+ or CD8+ T-cell processes. In this review, we summarize and discuss the functions and underlying mechanisms of the Ets family members that have been characterized as involved in these processes. Ongoing research of these factors is expected to identify practical applications for the Ets family members as novel therapeutic targets for inflammation-related diseases. © 2016 Wiley Periodicals, Inc.


Wang Q.,Chongqing Medical University | Zhou J.,Chongqing Medical University | Zhang B.,Qingdao University | Tian Z.,Chongqing Medical University | And 12 more authors.
PLoS Pathogens | Year: 2013

IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs) and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg) efficiently induces IL-23 secretion in a mannose receptor (MR)-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg) can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis. © 2013 Wang et al.


PubMed | van Velkinburgh Initiative for Collaboratory BioMedical Research and Chongqing Medical University
Type: Journal Article | Journal: Medicinal research reviews | Year: 2016

Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, ranging from cytokine signaling modules to transcription factors and epigenetic modifiers. Members of the E26 transformation specific (Ets) family of transcription factors, in particular, are potent regulators of these CD4(+) or CD8(+) T-cell processes. In this review, we summarize and discuss the functions and underlying mechanisms of the Ets family members that have been characterized as involved in these processes. Ongoing research of these factors is expected to identify practical applications for the Ets family members as novel therapeutic targets for inflammation-related diseases.

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