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| 1 | Neutrophil chemoattractant receptors in health and disease: double-edged swords显示文摘Neutrophils are frontline cells of the innate immune system.These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential.Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis,for inflammation modulation and resolution,wound healing and tissue repair.After fulfilling the appropriate effector functions,however,dampening neutrophil activation and infiltration is crucial to prevent damage to the host.In humans,chemoattractant molecules can be categorized into four biochemical families,i.e.,chemotactic lipids,formyl peptides,complement anaphylatoxins and chemokines.They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs.Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors(GPCRs).In addition,emerging evidence suggests an important role for atypical chemoattractant receptors(ACKRs)that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses.The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation,with a pivotal modulatory role for the(inflammatory)environment.Here,we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease.Depending on the(patho)physiological context,specific chemoattractant receptors may be up-or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences,thus opening new windows for the identification of disease biomarkers and potential drug targets. | Mieke Metzemaekers Mieke Gouwy Paul Proost | 2020 | Cellular & Molecular Immunology2020，17，5： | 8 |
| 2 | 钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。 | Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无 郭鹤鸣(译) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 3 | 【特刊综述】骨骼两性异形中的雄激素和雌激素显示文摘骨骼是表达雄激素、雌激素受体以及类固醇代谢酶的一种内分泌组织。循环性激素的生物活性通过六种性激素结合球蛋白以及在骨组织中的局部转变来进行调节,例如,睾酮通过芳香酶转变成雌二醇,或通过5α还原酶转变成双氢睾酮。由于高分辨外周CT应用的增多,我们对造成骨骼强度性别差异的结构基础的认识在近几年有很大进步。这些对微小结构的观察是理解性激素对男性峰值骨量及对骨皮质和骨小梁之间转变的影响的基础。最近的研究利用Cre/LoxP技术使我们在整体基因敲除小鼠上机械的认识精确到性激素及其在成骨细胞、破骨细胞、骨细胞以及其它造成男性骨质疏松的细胞上的核受体的直接作用。同时,这些研究加强了这样的观点:雄激素和雌激素的缺乏通过与例如胰岛素样生长因子1、炎症、氧化应激、骨骼代谢的中枢神经系统控制、机械负荷的适应等的交互作用发挥直接和多种效应。这篇综述将总结性激素在男性骨骼自身平衡作用这个领域有关方面最近的进展。 | Michael Laurent Leen Antonio Mieke Sinnesael Vanessa Dubois Evelien Gielen Frank Classens Dirk Vanderschueren | 2014 | Asian Journal of Andrology2014，16，2： | 4 |
| 4 | The chemokines CXCL8 and CXCL12:molecular and functional properties,role in disease and efforts towards pharmacological intervention显示文摘Chemokines are an indispensable component of our immune system through the regulation of directional migration and activation of leukocytes.CxCL8 is the most potent human neutrophil-attracting chemokine and plays crucial roles in the response to infection and tissue injury.CXCL8 activity inherently depends on interaction with the human CXC chemokine receptors CXCR1 and CXCR2,the atypical chemokine receptor ACKR1,and glycosaminoglycans.Furthermore,(hetero)dimerization and tight regulation of transcription and translation,as well as post-translational modifications further fine-tune the spatial and temporal activity of CXCL8 in the context of inflammatory diseases and cancer.The CxCL8 interaction with receptors and glycosaminoglycans is therefore a promising target for therapy,as illustrated by multiple ongoing clinical trials.CXCL8-mediated neutrophil mobilization to blood is directly opposed by CXCL12,which retains leukocytes in bone marrow.CXCL12 is primarily a homeostatic chemokine that induces migration and activation of hematopoietic progenitor cells,endothelial cells,and several leukocytes through interaction with CXCR4,ACKR1,and ACKR3.Thereby,it is an essential player in the regulation of embryogenesis,hematopoiesis,and angiogenesis.However,CXCL12 can also exert inflammatory functions,as illustrated by its pivotal role in a growing list of pathologies and its synergy with CXCL8 and other chemokines to induce leukocyte chemotaxis.Here,we review the plethora of information on the CXCL8 structure,interaction with receptors and glycosaminoglycans,different levels of activity regulation,role in homeostasis and disease,and therapeutic prospects.Finally,we discuss recent research on CXCL12 biochemistry and biology and its role in pathology and pharmacology. | Seppe Cambier Mieke Gouwy Paul Proost | 2023 | Cellular & Molecular Immunology2023，20，3： | 4 |
| 5 | Chemoattractants and cytokines in primary ciliary dyskinesia and cystic fibrosis: key players in chronic respiratory diseases显示文摘Patients with primary ciliary dyskinesia(PCD)and cystic fibrosis(CF),two inherited disorders,suffer from recurrent airway infections characterized by persistent bacterial colonization and uncontrollable inflammation.Although present in high counts,neutrophils fail to clear infection in the airways.High levels of C-X-C motif chemokine ligand 8/interleukin-8(CXCL8/IL-8),the most potent chemokine to attract neutrophils to sites of infection,are detected in the sputum of both patient groups and might cause the high neutrophil influx in the airways.Furthermore,in CF,airway neutrophils are highly activated because of the genetic defect and the high levels of proinflammatory chemoattractants and cytokines(e.g.,CXCL8/IL-8,tumor necrosis factor-αand IL-17).The overactive state of neutrophils leads to lung damage and fuels the vicious circle of infection,excessive inflammation and tissue damage.The inflammatory process in CF airways is well characterized,whereas the lung pathology in PCD is far less studied.The knowledge of CF lung pathology could be useful to guide molecular investigations of the inflammatory processes in PCD lungs.Current available therapies can not completely remedy the chronic airway infections in these diseases.This review gives an overview of the role that chemoattractants and cytokines play in these neutrophil-dominated lung pathologies.Finally,the most frequently applied treatments in CF and PCD and new experimental therapies to reduce neutrophil-dominated airway inflammation are described. | Maaike Cockx Mieke Gouwy Jo Van Damme Sofie Struyf | 2018 | Cellular & Molecular Immunology2018，15，4： | 3 |
| 6 | Carcinoma-associated fibroblasts provide operational flexibility in metastasis显示文摘 | Olivier De Wever Mieke Van Bockstal Marc Mareel An Hendrix Marc Bracke | 2014 | Seminars in Cancer Biology2014，，： | 2 |
| 7 | 基因序列比对法验证实时荧光定量PCR阳性结果真伪显示文摘实时荧光定量PCR(q PCR)是检测食源性病毒的常用方法,其高度的灵敏性导致检测过程中容易产生假阳性结果。基因序列比对法是比利时根特大学食品微生物与食品保藏实验室新近建立的验证q PCR阳性结果真伪的一种方法。本研究以检测贝类诺如病毒GII.4(No V GII.4)为例,采用基因序列比对法验证q PCR阳性结果的真伪。在q PCR检测时添加102copies/m L的No V GII.4质粒作为标准阳性对照,旨在排除由于q PCR的高灵敏性而产生的假阳性结果。研究结果表明,在8份No V阳性的贝类样品中,2份为No V GII.4真阳性,2份可能为No V GII.4的变异株,1份为受到质粒污染的假阳性,其余3份为引物二聚体所致假阳性。基因序列比对法作为一种验证q PCR阳性结果真伪的高效、可行的方法,值得推广。 | 武娟 曹斌斌 李丹 张祺 左涛 赵玉然 Uyttendaele Mieke 薛长湖 唐庆娟 | 2016 | 中国食品学报2016，16，4： | 2 |
| 8 | Serum Lipid Profiles and Cancer Risk in the Context of Obesity: Four Meta-Analyses显示文摘 | Jennifer C. Melvin Lars Holmberg Sabine Rohrmann Massimo Loda Mieke Van Hemelrijck Thomas E. Rohan | 2013 | Journal of Cancer Epidemiology2013，，： | 2 |
| 9 | Experimental models in peritoneal dialysis: A European experience显示文摘 | Norbert L WimVB Mieke VL | 1998 | Kidney Int1998，54，： | 1 |
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| 11 | Transcending the gender dichotomy in educational gender gap research: The association between gender identify and academic self-efficacy显示文摘 | Wendelien V Hans V Mieke V H | 2014 | Contemporary Educational Psychology2014，39，4： | 1 |
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