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Toosky M.,Tsinghua University | Javid B.,Tsinghua University | Javid B.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease | Javid B.,University of Cambridge
British Medical Bulletin | Year: 2014

Introduction Drug-resistant tuberculosis (DR-TB) is associated with increased mortality and morbidity. This is at least partly due to late diagnosis and ineffective treatment of drug-resistant status. Sources of data Selective search of the literature on DR-TB supplemented by recent guidelines from the World Health Organization. Areas of agreement Better and more rapid diagnosis of DR-TB by new techniques such as Xpert Mtb/RIF are likely to make a substantial impact on the disease. New therapeutics for DR-TB are entering, or about to enter the market for the first time in decades. Areas of controversy It is not clear whether new treatments should be restricted for DR-TB or also used for drug-susceptible tuberculosis. Growing points With several new agents on the horizon, there is the real possibility of an entirely new regimen for tuberculosis. Areas timely for developing research An inexpensive 'near-patient' diagnostic test is still needed. Optimizing new drug combination regimens in a timely manner is urgently required. © The Author 2014.


Ribas de Pouplana L.,Barcelona Institute for Research in Biomedicine | Ribas de Pouplana L.,Catalan Institution for Research and Advanced Studies | Santos M.A.S.,University of Aveiro | Zhu J.-H.,Tsinghua University | And 3 more authors.
Trends in Biochemical Sciences | Year: 2014

The translation of genes into functional proteins involves error. Mistranslation is a known cause of disease, but, surprisingly, recent studies suggest that certain organisms from all domains of life have evolved diverse pathways that increase their tolerance of translational error. Although the reason for these high error rates are not yet clear, evidence suggests that increased mistranslation may have a role in the generation of diversity within the proteome and other adaptive functions. Error rates are regulated, and there appears to be an optimal mistranslation rate that varies by organism and environmental condition. Advances in unbiased interrogation of error types and experiments involving wild organisms may help our understanding of the potentially adaptive roles for protein translation errors. © 2014 Elsevier Ltd.


Wan Q.,Zhejiang University | Zhou Z.,Zhejiang University | Ding S.,Zhejiang University | Ding S.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease | And 2 more authors.
Journal of Interferon and Cytokine Research | Year: 2015

Interleukin-17 (IL-17) has been proved to be involved in the pathogenesis of several autoimmune diseases, including lupus, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. The regulation of IL-17 signal transduction is less studied. miR-30a has been identified to be downregulated in these human autoimmune diseases and their related animal models. However, how it functions in IL-17-mediated inflammation and the pathogenesis of these diseases remain unknown. In this study, we showed that miR-30a inhibits IL-17-mediated NF-κB and MAPK activation, leading to the reduced production of inflammatory cytokines and chemokines. miR-30a also reduced mRNA stability triggered by IL-17 stimulation. These suppressive effects of miR-30a were mediated by directly targeting Traf3ip2 mRNA (coding for Act1). Thus, we concluded that the downregulation of miR-30a in autoimmune diseases may exacerbate IL-17-mediated inflammation, which may serve as a potential target for the therapy of these diseases. © Copyright 2015, Mary Ann Liebert, Inc.


Wang L.,Institute of Translational Hepatology | Sun Y.,Beijing 302 Hospital | Zhang Z.,Institute of Translational Hepatology | Jia Y.,Institute of Translational Hepatology | And 15 more authors.
Hepatology | Year: 2015

There is increasing interest in the role of T follicular helper (Tfh) cells in autoimmunity from the perspective of both their role in breach of tolerance and their effects on the natural history of disease progression. Indeed, the critical role of Tfh cells in autoimmunity is further highlighted based on their location in the germinal center (GC), a pathogenic hot spot for development of autoreactivity. To address the role of Tfh cells in primary biliary cirrhosis (PBC), we comprehensively evaluated the immunobiology of CXCR5+CD4+ Tfh cells in 69 patients with PBC, including a nested subgroup of 16 autoimmune hepatitis (AIH) and 20 healthy controls (HC), followed for 1 year. We report herein several key observations. First, there was an increased frequency of circulating Tfh cells in patients with PBC compared to AIH (P<0.05) and HC (P<0.01). Second, the function of circulating Tfh cells from PBC patients, including interleukin (IL)-21 production (P<0.05), the ability to promote B-cell maturation, and autoantibody production, were greater than HC. Third, the frequency of these cells was significantly decreased in ursodeoxycholic acid (UDCA) responders compared to UDCA-treated nonresponders, in both cross-sectional (P=0.023) and longitudinal studies (P=0.036), respectively. Indeed, similar increases of Tfh cells were noted in liver and spleen. Conclusion: These results significantly extend our understanding of lymphoid subpopulations in PBC and their relative role in disease expression. Our data also provide a novel biomarker for evaluation of the effectiveness of new therapeutic approaches. © 2014 by the American Association for the Study of Liver Diseases.


Zhang M.,State Key Laboratory for Infectious Disease Prevention and Control China CDC | Zhang M.,Chinese National Institute for Communicable Disease Control and Prevention | Zhang M.,Beijing Institute of Technology | Zhang M.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease | And 9 more authors.
Analytical Methods | Year: 2014

The CP4 EPSPS gene is widely used in herbicide-tolerant crops/plants all over the world. In this study, a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and validated to quantify the amount of CP4 EPSPS expression in Nicotiana tabacum leaves. The quantification of protein was used to measure the unique peptides of the CP4 EPSPS protein. Two peptides unique to CP4 EPSPS were synthesized and labelled in H 2 18O to give 18O stable isotope labelled peptides which served as internal standards. The validated method resulted in good specificity and linearity. The intra- and inter-day precisions and accuracy for all samples were satisfactory. The results demonstrated that the novel method was sensitive and selective to quantify CP4 EPSPS in the crude extract without time-consuming pre-separation or purification procedures. © the Partner Organisations 2014.

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