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TNF-α Induces Transient Resistance to Fas-Induced Apoptosis in Eosinophilic Acute Myeloid Leukemia Cells

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Cellular & Molecular Immunology 2007年第1期4卷 43-52页

作者： Yimin Qin Sogyong Auh Lyubov Blokh Catherine Long Isabelle Gagnon Kimm J. Hamann Pulmonary ＆ Critical care medicine Department of Medicine Universityof Chicago Chicago IL 60637 USA Department of Pathology University of Chicago Chicago IL 60637 USA

Tumor necrosis factor α （TNF-α） has been recognized as an activator of nuclear factor kB （NF-kB）, a factor implicated in the protection of many cell types from apoptosis. We and others have presented evidence to suggest that Fas-induced apoptosis may be an important aspect of the resolution of inflammation, and that delayed resolution of inflammation may be directly associated with NF-kB-dependent resistance to Fas. Because TNF-α activates NF-kB in many cell types including inflammatory cells such as eosinophils, we examined effects of TNF-α signaling on the Fas-mediated killing of an eosinophilic cell line AML14. While agonist anti-Fas （CHII） treatment induced apoptosis in AML14 cells, no significant cell death occurred in response to TNF-α alone. Electrophoretic mobility shift assay （EMSA） revealed that TNF-α induced NF-kB transactivation in AMLI4 cells in a time- and dose-dependent fashion, and subsequent supershift assays indicated that the translocated NF-kB was the heterodimer p65 （RelA）/p50. Pre-treatment of cells with TNF-α dramatically decreased the CHll-induced cell death in a transient fashion, accompanied by suppression of activation of caspase-8 and caspase-3 activation. Inhibition of NF-kB transactivation by inhibitors, BAY 11-7085 and parthenolide, reversed the suppression of Fas-mediated apoptosis by TNF-α. Furthermore, TNF-α up-regulated X-linked inhibitor of apoptosis protein （XIAP） transiently and XIAP levels were correlated with the temporal pattern of TNF-α protection against Fas-mediated apoptosis. This finding suggested that TNF-α may contribute to the prolonged survival of inflammatory cells by suppression of Fas-mediated apoptosis, the process involved with NF-kB transactivation, anti-apoptotic XIAP up-regulation and caspase suppression. Cellular ＆ Molecular Immunology. 2007;4（1）：43-52.

关键词： TNF-α NF-kB transactivation apoptosis XIAP inflammatory cell resolution

Stem cell gene therapy:the risks of insertional mutagenesis and approaches to minimize genotoxicity

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Frontiers of Medicine 2011年第4期5卷 356-371页

作者： Chuanfeng Wu Cynthia E.Dunbar Hematology Branch National HeartLung and Blood InstituteNational Institutes of HealthBethesdaMD 20892USA

Virus-based vectors are widely used in hematopoietic stem cell(HSC)gene therapy,and have the ability to integrate permanently into genomic DNA,thus driving long-term expression of corrective genes in all hematopoietic *** date,HSC gene therapy has been successfully employed in the clinic for improving clinical outcomes in small numbers of patients with X-linked severe combined immunodeficiency(SCID-X1),adenosine deaminase deficiency(ADA-SCID),adrenoleukodystrophy(ALD),thalassemia,chronic granulomatous disease(CGD),and Wiskott-Aldrich syndrome(WAS).However,adverse events were observed during some of these HSC gene therapy clinical trials,linked to insertional activation of proto-oncogenes by integrated proviral vectors leading to clonal expansion and eventual development of *** studies have been performed to understand the molecular basis of vector-mediated genotoxicity,with the aim of developing safer vectors and lower-risk gene therapy *** review will summarize current information on the mechanisms of insertional mutagenesis in hematopoietic stem and progenitor cells due to integrating gene transfer vectors,discuss the available assays for predicting genotoxicity and mapping vector integration sites,and introduce newlydeveloped approaches for minimizing genotoxicity as a way to further move HSC gene therapy forward into broader clinical application.

关键词： gene therapy hematopoietic stem cells insertional mutagenesis genotoxicity induced pluripotent stem cell

HMGB1, IL-1α, IL-33 and S100 proteins： dual-function alarmins

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Cellular & Molecular Immunology 2017年第1期14卷 43-64页

作者： Damien Bertheloot Eicke Latz Institute of Innate Immunity University Hospitals University of Bonn 53127 Bonn Germany German Center for Neurodegenerative Diseases (DZNE) 53117 Bonn Germany Department of Infectious Diseases and Immunology University of Massachusetts Medical School Worcester MA 01605 USA

Our immune system is based on the close collaboration of the innate and adaptive immune systems for the rapid detection of any threats to the host. Recognition of pathogen-derived molecules is entrusted to specific germline- encoded signaling receptors. The same receptors have now also emerged as efficient detectors of misplaced or altered self-molecules that signal tissue damage and cell death following, for example, disruption of the blood supply and subsequent hypoxia. Many types of endogenous molecules have been shown to provoke such sterile inflammatory states when released from dying cells. However, a group of proteins referred to as alarmins have both intracellular and extracellular functions which have been the subject of intense research. Indeed, alarmins can either exert beneficial cell housekeeping functions, leading to tissue repair, or provoke deleterious uncontrolled inflammation. This group of proteins includes the high-mobility group box 1 protein （HMGB1）, interleukin （IL）-1α, IL-33 and the Ca^2＋-binding S100 proteins. These dual-function proteins share conserved regulatory mechanisms, such as secretory routes, post-translational modifications and enzymatic processing, that govern their extracellular functions in time and space. Release of alarmins from mesenchymal cells is a highly relevant mechanism by which immune cells can be alerted of tissue damage, and alarmins play a key role in the development of acute or chronic inflammatory diseases and in cancer development.

关键词： alarmin HMGB1 IL-1α IL-33 inflammation S100 proteins

Opportunistic and other intestinal parasites among HIV/AIDS patients attending Gambi higher clinic in Bahir Dar city,North West Ethiopia

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Asian Pacific Journal of Tropical Medicine 2011年第8期4卷 661-665页

作者： Abebe Alemu Yitayal Shiferaw Gebeyaw Getnet Aregaw Yalew Zelalem Addis Department of Medical Laboratory Sciences College of Medicine and Health SciencesUniversity of GondarGondarEthiopia

Objective:To determine the magnitude of opportunistic and non-opportunistic intestinal parasitic infections among HTV/AIDS patients in Bahir ***:Cross-sectional study was conducted among HIV/ AIDS patients attending Gambi higher clinic from Aprill- May 30,2009. Convenient sampling technique was employed to identify the study subjects and hence a total of 248 subjects were included.A pre-tested structured questionnaire was used to collect sociodemographic data of *** samples were examined by direct saline,iodine wet mount, formol-ether sedimentation concentration and modified Ziehl-Neelsen staining technique. Results:Out of 248 enrolled in the study,171(69.0%)(90 males and 81 females) were infected with one or more intestinal *** highest rate of intestinal parasites were observed among HIV/AIDS patients(80.3%,151/188),and the infection rate of HIV negative individuals was 33.3%(20/60).Cryptosporidum parvum(43.6%),Isospora belli(15.5%) and Blastocystis hominis (10.5%) were opportunistic parasites that were found only in HIV/AIDS ***: Opportunistic parasite infections are common health problem among HIV/ AIDS patients in the study ***,early detection and treatment of these parasites are important to improve the quality of life of HIV/AIDS patients.

关键词： Opportunistic parasites Non-opportunistic parasites HIV/AIDS Ethiopia

Molecular signal transduction in vascular cell apoptosis

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Cell Research 2001年第4期11卷 253-264页

作者： GENG YONG JIAN Center for Cardiovascular Biology and Atherosclerosis Research, Division of Cardiology, Department of Internal Medicine, University of Texas Houston Health Science Center Medical School, 6431 Fannin Street, MSB 6.045, Houston, TX 77030, USA Division of Cardiology Department of Internal Medicine Center for Cardiovascular Biology and Atherosclerosis Research University of Texas Houston Health Science Center Medical School Houston USA

Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., ma influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and ii major complication, the acute vascular syndromes.

关键词： Apoptosis vascular cells caspases atherosclerosis cytokines.

Therapeutic targets of Traditional Chinese Medicine for colorectal cancer

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Journal of Traditional Chinese Medicine 2016年第2期36卷 243-249页

作者： Li Weidong Li Chunsheng Zheng Honggang Chen Guohong Hua Baojin Oncology Department Guang'anmen Hospital China Academy of Chinese Medical Sciences Nephrology department Taizhou Central Hospital Urinary surgery Department Guang'anmen Hospital China Academy of Chinese Medical Sciences

OBJECTIVE: To explore the role of Traditional Chinese Medicine(TCM) in the prevention and treatment of colorectal cancer and identify possible therapeutic targets of TCM to provide clues for the use of TCM for colorectal cancer prevention and treatment in the clinic and to find novel directions for new drug discovery for colorectal ***: We used Pub Med and Google to search for and collect scientific publications for a full evaluation of current evidence in the literature indicating the potential role of Chinese herbal medicines and their respective ingredients as effective ***: We extracted a detailed description of potential therapeutic Chinese herbal medicines and their constituent ingredients that target different mechanisms in colorectal cancer such as gene mutation, dysregulation of signaling pathways, metabolism disorders, and the inflammatory microenvironment, including both conventional and non-conventional ***: TCM may be a promising complementary and alternative therapy for the treatment of colorectal cancer.

关键词： Colorectal neoplasms Medicine Chi nese traditional Prevention and control Therapeu tics Drug delivery systems

Histone/protein deacetylase 3 dictates critical aspects of regulatory T cell development and function

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Cellular & Molecular Immunology 2016年第4期13卷 415-417页

作者： Benjamin D. Singer Franco R. D'Alessio Johns Hopkins University Division of Pulmonary and Critical Care Medicine Baltimore MD USA

Regulatory T cells （Tregs） comprise a subset of CD4＋ T lymphocytes that holds promise as immunotherapy for inflammat- ory disease states including autoimmune disorders, solid organ allograft rejection, graft-versus-host disease, and acute inflam- matory conditions. However, limited availability of Treg numbers restricts their usefulness in cell transfer applications, particularly as patients may need multiple infusions for chronic diseases.

关键词： HISTONE DEACETYLASES

Risk of Active Pulmonary Tuberculosis among Patients with Coal Workers'Pneumoconiosis:A Case-control Study in China

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Biomedical and Environmental Sciences 2018年第6期31卷 448-453页

作者： JIN Yan FAN Jing Guang PANG Jing WEN Ke ZHANG Pei Ying WANG Huan Qiang LI Tao National Institute of Occupational Health and Poison Control Chinese Center for Disease Control and PreventionBeijing 100050China Department of Infectious Disease Taizhou Center for Disease Control and PreventionTaizhou 318000ZhejiangChina Research Center for Occupational Safety and Health State Administration of Work SafetyBeijing 102308China Department of Orthopedics and Chinese-Western Medicine Hunan Institute for Tuberculosis ControlChangsha 410013HunanChina

The aim of this study was to estimate the association between occupational, environmental, behavioral risk factors, and active pulmonary tuberculosis（PTB） among coal workers＇ pneumoconiosis（CWP） patients. A matched case-control study was conducted in 86 CWP patients with active PTB and 86 CWP controls without TB. A standardized questionnaire was used for risk factors assessment. Conditioned logistic regression analysis was used to identify associations between the risk factors and active PTB among CWP patients. The results showed that the stage of CWP, poor workplace ventilation, family history of TB, and exposure to TB were independent risk factors for active PTB in patients with CWP with which recommendations for improving work environments, and for case finding activities in patients with CWP could be made.

关键词： Pulmonary tuberculosis Coal workers' pneumoconiosis Risk Case-control study

A new guideline for diagnosis and treatment of syncope in children and adolescents that stimulates further thought and discussion

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Science Bulletin 2018年第23期63卷 1527-1528页

作者： Julian M.Stewart Physiology and Medicine Center for HypotensionThe New York Medical CollegeValhallaNY 10595USA

A new guideline for diagnosis and treatment of syncope in children and adolescents was published by Chinese Pediatric Cardiology Society (CPCS)[1].This guideline admirably outlines a differential diagnosis of syncope in the Chinese population,placing appropriate emphasis on vasovagal syncope (VVS,simple faint), the most common *** authors appropriately discuss other more ominous causes of syncope such as cardiogenic syncope and neurogenic orthostatic *** particular,cardiogemc syncope can have lethal consequences if not promptly treated.

关键词： Children Adolescent syncope CPCS