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Converted neural cells: induced to a cure?

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Protein & Cell 2012年第2期3卷 91-97页

作者： Weiqi Zhang Shunlei Duan Ying Li Xiuling Xu Jing Qu Weizhou Zhang Guang-Hui Liu National laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China laboratory of gene regulation and signal transduction Department of PharmacologySchool of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA

Many neurodegenerative disorders such as Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS)and others often occur as a result of progressive loss of structure or function of ***,many groups were able to generate neural cells,either differentiated from induced pluripotent stem cells(iPSCs)or converted from somatic *** in converted neural cells have opened a new era to ease applications for modeling diseases and screening *** addition,the converted neural cells also hold the promise for cell replacement therapy(Kikuchi et al.,2011;Krencik et al.,2011;Kriks et al.,2011;Nori et al.,2011;Rhee et al.,2011;Schwartz et al.,2012).Here we will mainly discuss most recent progress on using converted functional neural cells to treat neurological diseases and highlight potential clinical challenges and future perspectives.

关键词： converted neural cell pluripotent stem cell transdifferentiation transplantation neurodegenerative diseases

Inflammation and liver tumorigenesis

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Frontiers of Medicine 2013年第2期7卷 242-254页

作者： Beicheng Sun Michael Karin Liver Transplantation Center of the First Affiliated Hospital and Cancer Center Nanjing Medical UniversityNanjing 210029China laboratory of gene regulation and signal transduction Department of Pharmacology and PathologyCancer CenterUCSD School of MedicineLa JollaCA 92093-0723USA

Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver *** review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research,including cellular interaction,cytokines,microRNA and stem *** of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.

关键词： hepatocellular carcinoma hepatitis cytokine stem cell miRNA

New insights into the pathogenesis and treatment of non-viral hepatocellular carcinoma:a balancing act between immunosuppression and immunosurveillance

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Precision Clinical Medicine 2018年第1期1卷 21-28页

作者： Michael Karin laboratory of gene regulation and signal transduction UC San Diego School of MedicineDepartment of Pharmacology9500 Gilman DriveLaJollaCA92093USA

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths *** initiates as a consequence of chronic liver damage and inflammation caused by hepatitis B and C virus infections,excessive alcohol con sumption,or non-alcoholic fatty liver disease(NAFLD).Until recently,no effective treat-ments for advanced HCC were available and the 5-year survival rate had remained below 8%for many *** insights into the mechanisms that drive the development of NAFLD-related HCC indicate that loss of T-cell-mediated immunosurveillance plays a cardinal role in tumor growth and malignant progression,in addition to previously identifhed inflammation-driven compensatory *** completed groundbreaking clinical studies have shown that treatments that restore antitumor immunity represent a highly effective therapeutic option for approximately 20%of advanced HCC *** the causes of inflammation-driven immunosuppression and immune system dysfunction in the 80%of patients who fail to reignite antitumor immunity despite treatment with checkpoint inhibitors should lead to further and even more dramatic improvements in HCC immunotherapy.

关键词： inflammation immunity treatment

Non-viral iPSCs:a safe way for therapy?

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Protein & Cell 2012年第4期3卷 241-245页

作者： Weiqi Zhang Di Guan Jing Qu Weizhou Zhang Guang-Hui Liu National laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China laboratory of gene regulation and signal transduction Department of PharmacologySchool of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA

Patients-derived induced pluripotent stem cells(iPSCs)pro-vide an invaluable tool to study mechanisms of human dis-eases and also a limitless cellular source for clinical trans-plantation(Takahashi et al.,2007;Yu et al.,2007;Liu et al.,2011a,2011b;Zhang et al.,2012).Retrovirus-or lenti-virus-based delivery systems have been serving as main-stream methods to generate patients-derived ***-ever,genomic integrations of reprogramming factors in virally generated iPSCs not only cause insertional mutagenesis but also lead to residual expression of reprogramming factors in iPSCs and their derivatives.

关键词： al. clinical programming

regulation of antitumor immunity by inflammation-induced epigenetic alterations

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Cellular & Molecular Immunology 2022年第1期19卷 59-66页

作者： Michael Karin Shabnam Shalapour Department of Pharmacology School of MedicineUniversity of California San DiegoLa JollaCAUSA laboratory of gene regulation and signal transduction Department of PharmacologySchool of MedicineUniversity of California San DiegoLa JollaCAUSA Department of Cancer Biology University of Texas MD Anderson Cancer CenterHoustonTXUSA

Chronic inflammation promotes tumor development,progression,and metastatic dissemination and causes treatment *** accumulation of genetic alterations and loss of normal cellular regulatory processes are not only associated with cancer growth and progression but also result in the expression of tumor-specific and tumor-associated antigens that may activate antitumor *** antagonism between inflammation and immunity and the ability of cancer cells to avoid immune detection affect the course of cancer development and treatment *** inflammation,particularly acute inflammation,supports T-cell priming,activation,and infiltration into infected tissues,chronic inflammation is mostly ***,the main mechanisms that dictate the outcome of the inflammation-immunity interplay are not well *** data suggest that inflammation triggers epigenetic alterations in cancer cells and components of the tumor *** alterations can affect and modulate numerous aspects of cancer development,including tumor growth,the metabolic state,metastatic spread,immune escape,and immunosuppressive or immunosupportive leukocyte *** this review,we discuss the role of inflammation in initiating epigenetic alterations in immune cells,cancer-associated fibroblasts,and cancer cells and suggest how and when epigenetic interventions can be combined with immunotherapies to improve therapeutic outcomes.

关键词： Inflammation Epigenetics Antitumor immunity Immunotherapy

regulation of antiviral innate immunity by deubiquitinase CYLD

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Cellular & Molecular Immunology 2011年第6期8卷 502-504页

作者： Minying Zhang Andrew J Lee Xuefeng Wu Shao-Cong Sun Department of Immunology The University of Texas MD Anderson Cancer CenterHoustonTXUSA Department of Melanoma Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA laboratory of gene regulation and signal transduction Department of PharmacologySchool of MedicineUniversity of California at San DiegoLa JollaCAUSA

An antiviral innate immune response involves induction of type I interferons(IFNs)and their subsequent autocrine and paracrine actions,but the underlying regulatory mechanisms are incompletely *** we report that CYLD,a deubiquitinase that specifically digests lysine 63-linked ubiquitin chains,is required for antiviral host *** of CYLD renders mice considerably more susceptible to infection by vesicular stomatitis virus(VSV).Consistently,CYLD-deficient dendritic cells are more sensitive to VSV *** functional defect was not due to lack of type I IFN production but rather because of attenuated IFN receptor *** the absence of CYLD,IFN-b is ineffective in the induction of antiviral genes and protection of cells from viral *** findings establish CYLD as a novel regulator of antiviral innate immunity and suggest a role for CYLD in regulating IFN receptor signaling.

关键词： antiviral innate immunity CYLD deubiquitinase interferon VSV

Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein

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World Journal of Biological Chemistry 2010年第11期1卷 327-337页

作者： Koichi Sato Fumikazu Okajima laboratory of signal transduction Institute for Molecular and Cellular RegulationGunma University

The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed.

关键词： High-density lipoprotein Sphingosine 1-phosphate Scavenger receptor class B type I Anti-atherogenic actions

Cloning and expression of MXR7 gene in human HCC tissue

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World Journal of Gastroenterology 2000年第1期6卷 57-60页

作者： Zhou XP Wang HY Yang GS Chen ZJ Li BA Wu MC The International Cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery Hospitalthe Second Military Medical UniversityShanghai 200438China

AIM To clone and identify the whole cDNA ofMXR7 gene and to find out its expression inhuman HCC,and normal *** The DNA primers were designed andsynthesized according to the whole cDNAsequence of MXR? *** cDNA of humanHCC was taken as the template while the cDNA ofMXR7 gene was synthesized by polymerasechain reaction（PCR）.Recombinant DNAconforming to reading frame was constructed byconnecting purified PCR product of the cDNA ofMXR? gene with expression vector pGEX-5X-1 offusion *** plasmid MXRT/pGEX-5X-1was identified by *** 32p labeledMXR? cDNA as probe,MXR7 mRNA expressionwas detected by Northern blot analysis in 12different human normal tissues,7 preoperativelyuntreated non-liver tumor tissues,30preoperatively untreated HCC,theparacancerous liver tissues and 12 normal livertissues *** Restriction enzyme and sequenceanalysis confirmed that the insertion sequence invector pGEX-5X-1 was the same as the cDNAsequence of MXR7 *** blot analysisshowed no expression of MXR? mRNA in 12 kindsof normal human tissues including liver,7 tumortissues in other sites and 12 normal livertissues,the frequencies of MXR7 mRNA expression in HCC and paracancerous livertissues were 76.6% and 13.3%,*** frequency of MXR7 mRNA expression in HCCwithout elevation of serum AFP and in HCC<5cm was 90%（9/10）and 83.3%（5/6）,*** MXR7 mRNA is highly expressedin human HCC,which is specific and occurs at anearly stage of HCC,suggesting MXR7 mRNA canbe a tumor biomarker for *** detection ofMXR7 mRNA expression in the biopsied livertissue is helpful in discovering early subclinicalliver cancer in those with negative serum AFP.

关键词： Subject headings human HCC tissues MXR7 gene gene expression cDNA mRNA

regulation of Actin Dynamics in Pollen Tubes:Control of Actin Polymer Level

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Journal of Integrative Plant Biology 2009年第8期51卷 740-750页

作者： Naizhi Chen Xiaolu Qu Youjun Wu Shanjin Huang Center for signal transduction and Metabolomics Key Laboratory of Photosynthesis and Environmental Molecular Physiology Institute of Botany the Chinese Academy of Sciences Beijing 100093 China

Actin cytoskeleton undergoes rapid reorganization in response to internal and external cues. How the dynamics of actin cytoskeleton are regulated, and how its dynamics relate to its function are fundamental questions in plant cell biology. The pollen tube is a well characterized actin-based cell morphogenesis in plants. One of the striking features of actin cytoskeleton characterized in the pollen tube is its surprisingly low level of actin polymer. This special phenomenon might relate to the function of actin cytoskeleton in pollen tubes. Understanding the molecular mechanism underlying this special phenomenon requires careful analysis of actin-binding proteins that modulate actin dynamics directly. Recent biochemical and biophysical analyses of several highly conserved plant actin-binding proteins reveal unusual and unexpected properties, which emphasizes the importance of carefully analyzing their action mechanism and cellular activity. In this review, we highlight an actin monomer sequestering protein, a barbed end capping protein and an F-actin severing and dynamizing protein in plant. We propose that these proteins function in harmony to regulate actin dynamics and maintain the low level of actin polymer in pollen tubes.

关键词： actin-binding proteins actin dynamics pollen tube