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Yang G.,Chinese Institute of Basic Medical Sciences | Wang Y.,U.S. Center for Disease Control and Prevention | Wu Y.,Think Tank Research Center for Health Development | Yang J.,U.S. Center for Disease Control and Prevention | Wan X.,Chinese Institute of Basic Medical Sciences
The Lancet | Year: 2015

The non-communicable disease burden in China is enormous, with tobacco use a leading risk factor for the major non-communicable diseases. The prevalence of tobacco use in men is one of the highest in the world, with more than 300 million smokers and 740 million non-smokers exposed to second-hand smoke. In the past decade public awareness of the health hazards of tobacco use and exposure to second-hand smoke has grown, social customs and habits have changed, aggressive tactics used by the tobacco industry have been revealed, and serious tobacco control policies have been actively promoted. In 2014, national legislators in China began actively considering national bans on smoking in public and work places and tobacco advertising. However, tobacco control in China has remained particularly difficult because of interference by the tobacco industry. Changes to the interministerial coordinating mechanism for implementation of the WHO Framework Convention on Tobacco Control are now crucial. Progress towards a tobacco-free world will be dependent on more rapid action in China. © 2015 Elsevier Ltd.


Liu J.,Second Military Medical University | Cao X.,Second Military Medical University | Cao X.,Chinese Institute of Basic Medical Sciences
Journal of Autoimmunity | Year: 2015

Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to maintain immune homeostasis. The regulatory capacity of DCs depends on their immature state and distinct subsets, yet not restricted to the immature state and one specialized subset. The tolerogenicity of DC is controlled by a complex network of environmental signals and cellular intrinsic mechanisms. Regulatory DCs play an important role in the maintenance of immunological tolerance via the induction of T cell unresponsiveness or apoptosis, and generation of regulatory T cells. DCs play essential roles in driving autoimmunity via promoting the activation of effector T cells such as T helper 1 and T helper 17 cells, and/or suppressing the generation of regulatory T cells. Besides, a breakdown of DCs-mediated tolerance due to abnormal environmental signals or breakdown of intrinsic regulatory mechanisms is closely linked with the pathogenesis of autoimmune diseases. Novel immunotherapy taking advantage of the tolerogenic potential of regulatory DCs is being developed for treatment of autoimmune diseases. In this review, we will describe the current understanding on the generation of regulatory DC and the role of regulatory DCs in promoting tolerogenic immune responses and suppressing autoimmune responses. The emerging roles of DCs dysfunction in the pathogenesis of autoimmune diseases and the potential application of regulatory DCs in the treatment of autoimmune diseases will also be discussed. © 2015 Elsevier Ltd.


Yang G.,Chinese Institute of Basic Medical Sciences
Tobacco Control | Year: 2014

While the 'low-tar' scheme has been widely recognised as a misleading tactic used by the tobacco industry to deceive the public about the true risks of cigarette smoking, a similar campaign using the slogan of 'less harmful, low tar' was launched by the Chinese tobacco industry, that is, State Tobacco Monopoly Administration/ China National Tobacco Corporation and began to gain traction during the last decade. Despite the fact that no sufficient research evidence supports the claims made by the industry that these cigarettes are safer, the Chinese tobacco industry has continued to promote them using various health claims. As a result, the production and sales of 'less harmful, low-tar' cigarettes have increased dramatically since 2000. Recently, a tobacco industry senior researcher, whose main research area is 'less harmful, low-tar' cigarettes, was elected as an Academician to the prestigious Chinese Academy of Engineering for his contribution to developing 'less harmful, low-tar' cigarettes. The tobacco researcher's election caused an outcry from the tobacco control community and the general public in China. This paper discusses the Chinese tobacco industry's 'less harmful, low-tar' initiatives and calls for the Chinese government to stop the execution of this deceptive strategy for tobacco marketing.


Cao X.,Chinese Institute of Basic Medical Sciences | Cao X.,Second Military Medical University
Nature Reviews Immunology | Year: 2016

In the initiation of innate immune responses against pathogens, pattern-recognition receptors (PRRs) have an essential role in recognizing specific components of microorganisms and triggering responses that eliminate the invading microorganisms. However, inappropriate activation of PRRs can lead to prolonged inflammation and even to autoimmune and inflammatory diseases. Thus, PRR-triggered responses are regulated through the degradation or translocation of the innate receptors themselves and through the involvement of intracellular regulators or amplifiers. In addition, a complex interplay between PRRs and/or other immune pathways finely tunes the outcome of host immune defence responses. In this Review, I describe many of the numerous distinct mechanisms for the self-regulation and cross-regulation of innate immune receptor signalling. © 2015 Macmillan Publishers Limited.


Liu W.X.,Chinese Institute of Basic Medical Sciences | Wang R.,Chinese Institute of Basic Medical Sciences
Medicinal Research Reviews | Year: 2012

The application of endomorphins as clinical available analgesic drugs has been impeded by their relatively poor receptor selectivity compared with alkaloid analgesics, rapid degradation in vivo, inefficient to penetrate the blood-brain barrier (BBB), and undesirable or toxic effects, such as acute tolerance and physical dependence, respiratory depression, and inhibition of gastrointestinal motility. Extensive studies have been performed so far striving to conquer these problems. In this article we review and discuss conformational and topographical modifications of the peptide amide bond and amino acid side groups to attain the most appropriate receptor binding affinity and high receptor selectivity; diverse strategies such as insertion of unnatural amino acids, covalent or noncovalent constraints as well as cyclization of linear peptides to enhance the enzymatic stability; designing of peptidomimetic ligands, glycopeptides, and N-terminal amidinationed analogues (such as incorporating guanidine into endomorphins) to penetrate the BBB. Also, several pertinent examples of bivalent and/or multivalent (such as mixed μ-agonist/δ-antagonist profile) compounds are discussed based on the existing literature and current data intending to give an insight into the development of opioid peptides expressing low tendency to produce acute tolerance and physical dependence. © 2011 Wiley Periodicals, Inc.


Li M.,Chinese Institute of Basic Medical Sciences
Advances in Experimental Medicine and Biology | Year: 2015

The most important of nature of biomarker is changes. Blood is under strict homeostatic control which means changes tend to be removed from blood. Urine is a partial filtrate of blood, reflects systemic physiology but with no homeostatic mechanism. However, changes induced directly into the blood can be more sensitively detected in urine than in blood itself. This indicates that urine may serve as a source for more sensitive detection of protein biomarkers than blood. © 2015, Springer Science+Business Media Dordrecht.


Lung cancer is the leading cause of cancer mortality worldwide, yet the therapeutic strategy for advanced non-small cell lung cancer (NSCLC) is limitedly effective. In addition, validated histone deacetylase (HDAC) inhibitors for the treatment of solid tumors remain to be developed. Here, we propose a novel HDAC inhibitor, OSU-HDAC-44, as a chemotherapeutic drug for NSCLC. The cytotoxicity effect of OSU-HDAC-44 was examined in three human NSCLC cell lines including A549 (p53 wild-type), H1299 (p53 null), and CL1-1 (p53 mutant). The antiproliferative mechanisms of OSU-HDAC-44 were investigated by flow cytometric cell cycle analysis, apoptosis assays and genome-wide chromatin-immunoprecipitation-on-chip (ChIP-on-chip) analysis. Mice with established A549 tumor xenograft were treated with OSU-HDAC-44 or vehicle control and were used to evaluate effects on tumor growth, cytokinesis inhibition and apoptosis. OSU-HDAC-44 was a pan-HDAC inhibitor and exhibits 3-4 times more effectiveness than suberoylanilide hydroxamic acid (SAHA) in suppressing cell viability in various NSCLC cell lines. Upon OSU-HDAC-44 treatment, cytokinesis was inhibited and subsequently led to mitochondria-mediated apoptosis. The cytokinesis inhibition resulted from OSU-HDAC-44-mediated degradation of mitosis and cytokinesis regulators Auroroa B and survivin. The deregulation of F-actin dynamics induced by OSU-HDAC-44 was associated with reduction in RhoA activity resulting from srGAP1 induction. ChIP-on-chip analysis revealed that OSU-HDAC-44 induced chromatin loosening and facilitated transcription of genes involved in crucial signaling pathways such as apoptosis, axon guidance and protein ubiquitination. Finally, OSU-HDAC-44 efficiently inhibited A549 xenograft tumor growth and induced acetylation of histone and non-histone proteins and apoptosis in vivo. OSU-HDAC-44 significantly suppresses tumor growth via induction of cytokinesis defect and intrinsic apoptosis in preclinical models of NSCLC. Our data provide compelling evidence that OSU-HDAC-44 is a potent HDAC targeted inhibitor and can be tested for NSCLC chemotherapy.


Zhou T.,Chinese Institute of Basic Medical Sciences
Methods in Molecular Biology | Year: 2013

Reconstruction of metabolic networks from metabolites, enzymes, and reactions is the foundation of the network-based study on metabolism. In this chapter, we describe a practical method for reconstructing metabolic networks from KEGG. This method makes use of organism-specific pathway data in the KEGG/PATHWAY database to reconstruct metabolic networks on pathway level, and the pathway hierarchy data in the KEGG/ORTHOLOGY database to guide the network reconstruction on higher levels. By calling upon the KEGG Web services, this method ensures the data used in the reconstruction are correct and up-to-date. The incorporation of a local relational database allows caching of pathway data improves performance and speeds up network reconstruction. Some applications of reconstructed networks on network alignment and network topology analysis are exampled and notes are stated in the end. © 2013 Springer Science+Business Media, LLC.


Patent
Chinese Institute of Basic Medical Sciences | Date: 2016-04-13

A portable paper-based device capable of visually detecting chlorine ion content in sweat, which is provided with a double-layer structure of paper (3) capable of generating color or fluorescence changes according to pH and anion exchange paper which is arranged on the lower surface of the paper. The paper-based device can be used to visually detect chlorine ion content in sweat. The chloride ion content can be quantified by taking an image of the paper after sufficient contact with the sweat with a digital imaging device, followed by analyzing the color image using an appropriate software or application. The device can be used in monitoring physiological status and diagnosing cystic fibrosis diseases.


Patent
Chinese Institute of Basic Medical Sciences | Date: 2012-10-26

The present invention provides a humanized monoclonal antibody against extracellular domain of human death receptor 5, comprising a light chain variable region, whose amino acid sequence has at least 90% identity with the amino acid sequence shown as SEQ ID NO: 1, a heavy chain variable region, whose amino acid sequence has at least 90% identity with the amino acid sequence shown as SEQ ID NO: 2, and constant region derived from human antibody. The present invention also provides nucleotide sequence encoding said humanized monoclonal antibody, a recombinant eukaryotic expression vector, a process for preparing the humanized monoclonal antibody, and the composition and use therefore. Said humanized monoclonal antibody of the present invention shows specific apoptosis-inducing activity against various cancer cells both in vivo and in vitro, and thus it can be used alone or in combination with natural ligand of DR5, apoptosis-inducing ligand associated with tumor nerosis factor or other medicaments for the treatment of a variety of cancers as well as other diseases associated with high DR5 expression.

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