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Cytosolic DNA sensing by cGAS:regulation,function,and human diseases

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1483-1497页

作者： Le Yu Pengda Liu lineberger comprehensive cancer center The University of North Carolina at Chapel HillChapel HillNCUSA department of biochemistry and biophysics The University of North Carolina at Chapel HillChapel HillNCUSA

Sensing invasive cytosolic DNA is an integral component of innate *** was identified in 2013 as the major cytosolic DNA sensor that binds dsDNA to catalyze the synthesis of a special asymmetric cyclic-dinucleotide,2/3/-cGAMP,as the secondary messenger to bind and activate STING for subsequent production of type I interferons and other immune-modulatory *** of cGAS signaling contributes to autoimmune diseases but serves as an adjuvant for anticancer immune *** the other hand,inactivation of cGAS signaling causes deficiency to sense and clear the viral and bacterial infection and creates a tumor-prone immune microenvironment to facilitate tumor evasion of immune ***,cGAS activation is tightly *** this review,we summarize up-to-date multilayers of regulatory mechanisms governing cGAS activation,including cGAS pre-and post-translational regulations,cGAS-binding proteins,and additional cGAS regulators such as ions and small *** will also reveal the pathophysiological function of cGAS and its product cGAMP in human *** hope to provide an up-to-date review for recent research advances of cGAS biology and cGAS-targeted therapies for human diseases.

关键词： diseases function cGAS

HIV-1 immunopathogenesis in humanized mouse models

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Cellular & Molecular Immunology 2012年第3期9卷 237-244页

作者： Liguo Zhang Lishan Su Key Laboratory of Immunity and Infection Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China lineberger comprehensive cancer center Department of Microbiology and Immunology School of Medicine University of North Carolina at Chapel Hill Chapel Hill NC USA

In recent years, the technology of constructing chimeric mice with humanized immune systems has markedly improved. Multiple lineages of human immune cells develop in immunodeficient mice that have been transplanted with human hematopoietic stem cells. More importantly, these mice mount functional humoral and cellular immune responses upon immunization or microbial infection. Human immunodeficiency virus type I （HIV-1） can establish an infection in humanized mice, resulting in CD4＋ T-cell depletion and an accompanying nonspecific immune activation, which mimics the immunopathology in HIV-l-infected human patients. This makes humanized mice an optimal model for studying the mechanisms of HIV-1 immunopathogenesis and for developing novel immune-based therapies.

关键词： HIV humanized mice pathogenesis immune activation

Metabolic alteration in tumorigenesis

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Science China(Life Sciences) 2013年第12期56卷 1067-1075页

作者： YANG Hui XIONG Yue GUAN KunLiang Molecular and Cell Biology Lab Institutes of Biomedical SciencesShanghai Medical College School of Life Sciences Fudan University department of biochemistry and biophysics and lineberger comprehensive cancer center University of North Carolina at Chapel HillNorth Carolina 27599USA department of Pharmacology and Moores cancer center University of California San DiegoLa JollaCA 92093USA

Altered metabolism in cancer was first discovered by Otto Warburg early last *** the Warburg Effect has been widely used in tumor detection,relatively little progress had been made in mechanistic understanding of cancer metabolism in the subsequent eight *** studies have recently identified mutations in human cancer targeting multiple enzymes involved in intermediate *** emerging mechanism common to these mutant enzymes is the accumulation of a metabolite that alters the epigenetic control.

关键词： metabolite epigenetic tumorigenesis

Lenalidomide downregulates ACE2 protein abundance to alleviate infection by SARS-CoV-2 spike protein conditioned pseudoviruses

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1664-1667页

作者： Siyuan Su Jianfeng Chen Ying Wang Lilly M.Wong Zhichuan Zhu Guochun Jiang Pengda Liu lineberger comprehensive cancer center The University of North Carolina at Chapel HillChapel HillNCUSA department of biochemistry and biophysics The University of North Carolina at Chapel HillChapel HillNCUSA UNC HIV Cure center Institute of Global Health and Infectious DiseasesThe University of North Carolina at Chapel HillChapel HillNCUSA

Dear Editor,The recent health emergency caused by SARS-CoV-2 created a global *** to other CoVs,SARS-CoV-2 utilizes its Spike(S)protein to specifically recognize the human angiotensin converting enzyme 2(ACE2)membrane... 详细信息

关键词： ACE2 infection utilize

Control of Stem and Progenitor Cell Cycle by INK4 Genes

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Control of Stem and Progenitor Cell Cycle by INK4 Genes

A mouse model for HBV immunotolerance and immunotherapy

2009医学前沿论坛暨第十一届全国肿瘤药理与化疗学术会议

作者：熊跃 department of biophysics and biochemistry Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillNC 27599-7295

The INK4-RB pathway plays a key role in controlling entry into the cell division cycle and is functionally disrupted in most human *** the biochemical mechanisms of this pathway are relatively well understood,both the cellular function and regulation of INK4 genes are less *** and loss of expression of three INK4 genes,p16,p15 and p18,are

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Cellular & Molecular Immunology 2014年第1期11卷 71-78页

作者： Dan Yang Longchao Liu Danming Zhu Hua Peng Lishan Su Yang-Xin Fu Liguo Zhang BP-UC Group for Immunotherapy CAS Key Laboratory for Infection and Immunity Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China lineberger comprehensive cancer center University of North Carolina at Chapel Hill Chapel Hill NC USA department of Pathology the University of Chicago 924E 57 Street Chicago IL60637

Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus （HBV） infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus （AAV） carrying a replicable HBV genome （AAV/ HBV）. Similar to the clinical HBV carriers, the mice infected with AAV/H BV were sero-negative for antibodies against HBV surface antigen （HBsAg）. Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/H BV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism（s） of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections.

关键词： AAV vector HBV immunotherapy immunotolerance mouse model

Microbiota for production of wine with enhanced functional components

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Food Science and Human Wellness 2023年第5期12卷 1481-1492页

作者： Armachius James Ting Yao Hengming Ke Yousheng Wang Beijing Advanced Innovation Centre for Food Nutrition and Human Health Beijing Technology and Business UniversityBeijing 100048China Tanzania Agricultural Research Institute Makutupora Centre P.O.Box 1676DodomaTanzania Rizhao HUAWEI Institute of comprehensive Health Industries Shandong KEEPFIT Biotech.Co.Ltd.Rizhao 276800China department of biochemistry and biophysics and lineberger comprehensive Centre The University of North CarolinaChapel Hill 27599USA

Microbial communities during winemaking are diverse and change throughout the fermentation process. Microorganisms not only drive alcohol fermentation, flavor and aroma, but also enhance wine functional components such as extraction of polyphenols from the berries, production of γ-aminobutyric acid, hydroxytyrosol and melatonin. Polyphenols such as resveratrol, catechin and quercetin determine the functional quality of the wine. Moderate wine consumption, particularly red wine has been associated with functional benefits to human health, which includes anti-inflammation, promoting healthy aging, prevention of cardiovascular diseases, cancers, type 2 diabetes and metabolic syndrome. Indeed, the management of microbiota allows the production of wine with distinct features and functional components that benefits human health. This review scrutinizes the possible contributions of wine microbiota to the production of wine with enhanced functional components and highlights the contributions of Saccharomyces and non-Saccharomyces yeasts and bacteria to enhance wine functional components during winemaking. Thus, contributing to the dissemination of the benefits of light to moderate wine intake to human health.

关键词： Wine Polyphenols Resveratrol Oenococcus oeni Non-Saccharomyces yeast

Acetylation regulation of metabolism

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Acetylation regulation of metabolism

Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice

中国生物化学与分子生物学会第十届会员代表大会暨全国学术会议

作者： Yue Xiong Molecular & Cell Biology Lab Fudan UniversityShanghaiChina department of biophysics and biochemistry Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillNC 27599-7295

Alterations in cell growth and cell cycle regulations are commonly associated with the development of several human proliferative diseases,in particular cancer,and are believed to link with changes in cellular *** most metabolic pathways have been well established several decades ago,how extracellular metabolic fuels signal to different metabolic pathways remain poorly understood. Recent proteomic analyses on protein acetylation identified potentially a large number of acetylated proteins in the

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Virologica Sinica 2014年第6期29卷 393-402页

作者： Zhangsheng Yang Jun Du Gang Chen Jie Zhao Xuanming Yang Lishan Su Genhong Cheng Hong Tang Key Laboratory of Infection and Immunity (CASKLII) Institute of BiophysicsChinese Academy of Sciences Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Institute of BiotechnologyShanxi University department of Microbiology and Immunology and lineberger comprehensive cancer center University of North Carolina at Chapel Hill School of MedicineNC 27599-7295USA department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095USA

It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome cornavirus(MERS-Co V) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59(MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Inflammatory leukocyte infiltrations, hemorrhages and fibrosis of alveolar walls can be observed 2-11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections.

关键词： coronavirus MHV-A59 pneumonia inflammation cytokine