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Roles of autophagy in lymphocytes： reflections and directions

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Cellular & Molecular Immunology 2010年第2期7卷 104-107页

作者： Ian X McLeod Youwen He Department of Immunology Duke University Medical Center Durham NC USA

Recent studies have revealed that autophagy, a fundamental intracellular process, plays many different roles in lymphocyte development and function. Autophagy regulates naive T-lymphocyte homeostasis, specifically by regulating mitochondrial quality and turnover, and is necessary for the proliferation of mature T cells. Autophagy also acts as a cellular death pathway in lymphocytes, both upon prolonged cytokine withdrawal and during acute antigen-receptor stimulation if improperly regulated. Furthermore, during HIV infection, hyperinduction of autophagy leads to massive T-cell death in uninfected CD4＋ T cells, and is rescued by inhibiting autophagic initiation. Constitutively high levels of autophagy in thymic epithelial cells are necessary for optimal processing and presentation of endogenous antigens, and required for proper positive and negative selection of developing thymocytes. Autophagy also promotes the survival of B lymphocytes, as well as the development of early B-cell progenitors. In B cells, autophagy is an alternative death pathway, as antigen-receptor stimulation in the absence of costimulation induces a potent autophagic death. Thus, autophagy plays a complex role in lymphocytes and is regulated during their lifespan to ensure a healthy immune system.

关键词： apoptosis autophagy homeostasis lymphocytes

Antibacterial and angiogenic dual-functional fibrous membrane dressing for infected wound healing

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Biomedical Engineering Communications 2024年第1期3卷 4-14页

作者： Chao Zhou Che Zhao Hao-Yu Dai Tian-Jun Zhu Jia-Pei Yao Li Chen Jing-Jing Wen Jia Ling Celestine Loh Xin-Die Zhou Yong Huang School of Medical and Health Engineering Changzhou UniversityChangzhouJiangsu 213164China School of Aerospace and Mechanical Engineering Changzhou Institute of TechnologyChangzhouJiangsu 213032China Department of Orthopedics The Affiliated Changzhou Second People's Hospital of Nanjing Medical UniversityChangzhou Medical CenterNanjing Medical UniversityChangzhou 213000China duke-NUS Graduate Medical School National University of SingaporeKent Ridge 169547Singapore

Background:Skin,being a vital organ that regulates physiological responses in the human body,is prone to injury from external environmental *** full-thickness skin defects becomes especially challenging when infections and vascular injuries are *** wound dressings with single functions,such as antibacterial or angiogenic properties,fall short in achieving rapid wound *** address this,there is a need to develop wound dressing materials that possess both effective antibacterial and angiogenic ***:In this study,we utilized electrospinning technology to fabricate hyaluronic acid-cellulose acetate fibrous membrane dressings,incorporating poly(ionic liquid)as an antibacterial polymer and deferoxamine as an angiogenic ***:The resulting fibrous membrane dressing contained poly(ionic liquid)and deferoxamin showcased a microporous structure,drug-releasing capabilities,and excellent air *** not only demonstrated highly effective antibacterial properties but also exhibited remarkable angiogenesis,thereby promoting the healing of full-thickness skin defect wounds in both in vitro and in vivo ***:These findings highlight the immense potential of this wound dressing material for future clinical applications.

关键词： electro spinning antibacterial polymer angiogenesis wound healing membrane dressing

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7

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Neuroscience Bulletin 2018年第1期34卷 22-41页

作者： Sangsu Bang Jiho Yoo Xingrui Gong Di Liu Qingjian Han Xin Luo Wonseok Chang Gang Chen Sang-Taek Im Yong Ho Kim Judith A.Strong Ma-Zhong Zhang Jun-Ming Zhang Seok-Yong Lee Ru-Rong Ji Department of Anesthesiology Duke University Medical Center Department of Biochemistry Duke University Medical Center Pain Research center Department of AnesthesiologyUniversity of Cincinnati Department of Anesthesiology Shanghai Children's Medical Center Department of Physiology and Biophysics College of Medicine Eulji University Department of Physiology College of Medicine Gachon University

Abstract The voltage-gated Na＋ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody （SVmab） reduces Na＋ currents and pain and itch responses in mice. Here, we investigated whether recom- binant SVmab （rSVmab） binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltagesensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na＋ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7- expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na＋ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.

关键词： Primary afferent neuron Patch clamping (electrophysiology) Sodium channels Animal models

Lymphocyte phenotypes in wild-caught rats suggest potential mechanisms underlying increased immune sensitivity in post-industrial environments

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Cellular & Molecular Immunology 2012年第2期9卷 163-174页

作者： Ashley M Trama Zoie E Holzknecht Anitra D Thomas Kuei-Ying Su Sean M Lee Emily E Foltz Sarah E Perkins Shu S Lin William Parker Department of Surgery Duke University Medical Center Durham NC 27710 USA Cardiff School of Biosciences Cardiff CFIO 3AX UK Department of Immunology Duke University Medical Center Durham NC 27710 USA

The immune systems of wild rats and of laboratory rats can been utilized as models of the human immune system in pre-industrial and post-industrial societies, respectively. In this study, lymphocyte phenotypes in wild rats were broadly characterized, and the results were compared to those obtained by us and by others using cells derived from various strains of laboratory rats. Although not expected, the production of regulatory T cells was not apparently different in wild rats compared to laboratory rats. On the other hand, differences in expression of markers involved in complement regulation, adhesion, signaling and maturation suggest increased complement regulation and decreased sensitivity in wild-caught rats compared to laboratory rats, and point toward complex differences between the maturation of T cells. The results potentially lend insight into the pathogenesis of post-industrial epidemics of allergy and autoimmune disease.

关键词： allergy autoimmunity biome hygiene immune regulation

Adaptive Design of Fluorescence Imaging Systems for Custom Resolution, Fields of View, and Geometries

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Biomedical Engineering Frontiers 2023年第1期4卷 260-273页

作者： Roujia Wang Riley J.Deutsch Enakshi D.Sunassee Brian T.Crouch Nirmala Ramanujam Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Pharmacology and Cancer Biology Duke University Medical CenterDurhamNCUSA

Objective and Impact Statement:We developed a generalized computational approach to design uniform,high-intensity excitation light for low-cost,quantitative fluorescence imaging of in vitro,ex vivo,and in vivo samples with a single ***:Fluorescence imaging is a ubiquitous tool for biomedical *** extensively modify existing systems for tissue imaging,increasing the time and effort needed for translational research and thick tissue *** modifications are applicationspecific,requiring new designs to scale across sample ***:We implemented a computational model to simulate light propagation from multiple *** a global optimization algorithm and a custom cost function,we determined the spatial positioning of optical fibers to generate 2 illumination *** results were implemented to image core needle biopsies,preclinical mammary tumors,or tumor-derived *** were stained with molecular probes and imaged with uniform and nonuniform ***:Simulation results were faithfully translated to benchtop *** demonstrated that uniform illumination increased the reliability of intraimage analysis compared to nonuniform illumination and was concordant with traditional histological *** computational approach was used to optimize the illumination geometry for the purposes of imaging 3 different fluorophores through a mammary window chamber *** specifically designed for intravital tumor imaging generated higher image contrast compared to the case in which illumination originally optimized for biopsy images was ***:We demonstrate the significance of using a computationally designed illumination for in vitro,ex vivo,and in vivo fluorescence *** illumination increased the reliability of intraimage analysis and enhanced the local contrast of biological *** approach is generalizable across light sources,biological appl

关键词： illumination Fluorescence image

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome

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World Journal of Gastroenterology 2014年第39期20卷 14172-14184页

作者： Carly E Kelley Ann J Brown Anna Mae Diehl Tracy L Setji Department of Medicine Division of Endocrinology Duke University Medical Center Durham NC 27710 United States Department of Medicine Division of Gastroenterology Duke University Medical Center Durham NC 27710 United States

Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance(IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease(NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis(NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.

关键词： Polycystic ovary syndrome Fatty liver Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis

Targeting the SUMO pathway for neuroprotection in brain ischaemia

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Stroke & Vascular Neurology 2016年第3期1卷 101-107页

作者： Wei Yang Huaxin Sheng Haichen Wang Multidisciplinary Neuroprotection Laboratories Department of AnesthesiologyDuke University Medical CenterDurhamNorth CarolinaUSA Multidisciplinary Neuroprotection Laboratories Department of NeurologyDuke University Medical CenterDurhamNorth CarolinaUSA

Small ubiquitin-like modifier(SUMO)conjugation(SUMOylation)is a post-translational protein modification that modulates almost all major cellular processes,and has been implicated in many human diseases.A growing body of evidence from in vitro and in vivo studies demonstrates that increasing global levels of SUMO conjugated proteins(global SUMOylation)protects cells against ischaemia-induced damage,while suppressing global SUMOylation promotes cell injury after ***,SUMOylation has emerged as a potential therapeutic target for neuroprotection in brain ischaemia,including global brain ischaemia and focal brain ischaemia(ischaemic stroke).Here,we summarise findings on the role of SUMOylation in human diseases,brain ischaemia in particular,and review recent developments in drug discovery targeting SUMOylation with a major focus on its neuroprotective applications.

关键词： protective diseases SUMO

Mechanism of hamstring muscle strain injury in sprinting

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Journal of Sport and Health Science 2017年第2期6卷 130-132页

作者： Bing Yu Hui Liu William E.Garrett center for Human Movement Science The University of North Carolina at Chapel Hill Biomechanics Laboratory Beijing Sport University duke Sports Medicine center Duke University

Hamstring muscle strain injury is one of the most common injuries in sports involving sprinting and *** muscle strain injuries occur at a high rate and have a high re-injury rate,which results in loss of training and competition time,which has a significant impact on the quality of life of the injured athletes.~1Preventing and rehabilitating hamstring muscle strain injury is an important task for clinicians and scientists in sports *** the mechanisms underlying hamstring injury is critical for developing appropriate strategies to prevent and rehabilitate hamstring *** the

关键词：拉伤短跑肌机制时间损失质量产生运动医学临床医生

Resistance to receptor tyrosine kinase inhibition in cancer： molecular mechanisms and therapeutic strategies

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Frontiers of Medicine 2015年第2期9卷 134-138页

作者： Peter B. Alexander Xiao-Fan Wang Department of Pharmacology and Cancer Biology Duke University Medical Center Durham NC 27710 USA

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

关键词： targeted therapy drug resistance receptor tyrosine kinases cancer