线粒体质量控制在外源化学物引起坏死性凋亡中的作用

坏死性凋亡是一种可调控的、半胱氨酸天冬氨酸蛋白酶(Cysteine aspartic acid specific protease,Caspase)非依赖的程序性细胞死亡,相较于细胞凋亡,其主要特点是没有核固缩和气球样变,而出现的是线粒体肿胀和三磷酸腺苷(Adenosine triphosphate,ATP)耗竭、胞质肿胀和空泡形成,其最终引起质膜破裂和通透性改变,释放损伤相关分子,如白细胞介素1α、高国家自然科学基金(81573181,81472997);;福建省自然科学基金(2015J01344

蛋白磷酸酶2A调控细胞周期发挥抗肿瘤作用的研究进展

蛋白磷酸酶2A(PP2A)是真核细胞内广泛表达的丝氨酸/苏氨酸蛋白磷酸酶家族的主要成员,参与细胞周期、增殖分化及凋亡等过程中信号通路的去磷酸化调控。研究表明,PP2A不同亚基表达调控与人群肿瘤风险存在关联性;PP2A与细胞周期相关激酶相互作用,二者调控平衡的研究有助于致癌机制的探讨和靶向PP2A抗肿瘤作用的探索。本文对PP2A调控细胞周期的研究进行综述,着重阐述PP2A-B亚基经由细胞周期因子依赖性激酶1(CDK1)调控细胞周期发挥抑癌作用的机制,为肿瘤的化学预防和靶向干预提供理论依据。国家自然科学基金(81172705,81472997,81573181);; 973计划前期研究专项(2014CB560710);; 福建省自然科学基金项目(2014J 01372,2015J01344);; 厦门大学山海基金项目(2013SH007

蛋白磷酸酶2A在线粒体质量控制中的作用研究进展

蛋白磷酸酶2A(PP2A)是真核细胞内广泛表达的丝/苏氨酸蛋白磷酸酶家族成员之一,通过去磷酸化作用参与外源物诱导细胞毒性损伤和致癌过程中关键调控蛋白的可逆磷酸化,进而抑制绝大多数丝/苏氨酸激酶的活性。近年来,PP2A在线粒体质量控制(MQC)中的作用逐渐被认识,广泛参与线粒体生物发生、线粒体动态、线粒体氧化还原平衡和线粒体自噬等重要生物学过程,对拓展MQC相关蛋白翻译后修饰在以线粒体为核心枢纽的信号流中的研究具有重要意义。本文重点阐述PP2A介导的去磷酸化机制在MQC调控中的作用,为从翻译后修饰层面阐明外源物诱导线粒体关联性损伤和致癌作用或肿瘤相关疾病的分子机制、以及为人群暴露和危害标志物的筛查和靶向干预提供依据。国家自然科学基金(81573181,81773465,81874272

外源物诱导肝脏局部先天免疫反应的线粒体调控机制

肝脏作为体内代谢外源因素暴露最重要的器官之一,具有独特的血窦结构和丰富的免疫细胞亚群,构成了肝脏局部免疫微环境。其中,肝脏的先天免疫细胞既可通过清除病原体、抗原提呈作用参与宿主防御,还通过与肝实质细胞的相互作用参与外源因素介导的急性免疫反应、肝细胞毒性转归、慢性肝损伤以及肝致癌作用。线粒体作为细胞应激的关键靶细胞器,是整合肝脏局部免疫信号的分子互作平台,既通过线粒体质量控制精细调控细胞内的分子事件,也通过线粒体损伤相关分子模式介导不同细胞间通讯和交互作用调控免疫微环境的稳态。本文通过对参与肝脏局部免疫反应的先天免疫细胞亚群组成及其介导免疫反应级联的综述,阐述不同外源物诱导肝脏局部免疫的线粒体相关调控机制,为探讨经由肝脏局部免疫反应生物标志筛查和靶向干预以预防和控制肝脏损伤提供线索

Mechanisms and Prevention of Skin Photoaging

皮肤老化是一个复杂、多因素所致的过程,其结果是皮肤弹性和功能发生改变。引起皮肤老化的原因包括内源性(如年龄等)和外源性(如紫外线等)因素,后者所致的皮肤老化即皮肤光老化。本文以国外文献为基础,着重介绍皮肤光老化的发生机制,描述与之相关的主要信号通路,总结皮肤光老化的预防措施,以指导进一步的研究。Skin aging is a very complicated process with many factors involved, which will lead to changes in skin elasticity and functions.Skin aging can be triggered by both intrinsic(e.g., age) and extrinsic(e.g., ultraviolet light) factors.The latter is also called skin photoaging.This paper reviewed the mechanisms of photoaging and related prevention approaches based on international literature.It also described the major signaling pathways involved in the process of photoaging so as to inform further studies.国家自然科学基金青年项目(编号:81101562); 广东省科技计划项目(编号:2012B060300005); 广东省自然科学基金面上项目(编号:S2012010009633

细胞外囊泡参与调控外源因素诱导的肝毒性损伤的研究进展

肝脏是机体代谢外源因素的主要功能性器官，其具有独特的血窦结构和丰富的细胞组成，而细胞的功能改变是造成肝毒性损伤的主要原因。细胞外囊泡（extracellular vesicles, EVs）是由脂质双分子层所形成的纳米级球形囊泡，源自于各细胞亚群，用于负载特定的内容物，并可作为载体介导相邻或远处细胞间的信息交流。该文综述了外源因素暴露下EVs介导肝毒性损伤进程中各细胞的信息传递，并探讨靶向干预EVs的具体途径，为预防和控制肝毒性损伤提供线索以及潜在的应用价值。国家重点研发计划(2017YFA0205201)国家自然科学基金(81422023,51273165,U1705281,U1505221)教育部新世纪优秀人才支持计划(ncet-13-0502

Research on construction and application of medical decision support system

目的:针对医院决策手段不丰富的现状,构建一套智能辅助决策系统为医院管理决策提供支持。方法:基于医院现有医疗数据,利用数据仓库、数据挖掘、联机分析处理等技术进行数据分析,构建智能知识库,将数据转化为用于辅助的知识决策,形成一体化的智能决策平台。结果:该决策支持系统能够帮助医院决策者更有效作出决策,提高了决策者的工作效率。结论:该决策系统具有较好的应用前景,适合在各医院推广应用。Objective To develop an intelligent decision support system for hospital decision-making.Methods Based on the existing medical data in the hospital, such technologies as data warehouse, data mining and online analytical processing were used for analyzing data and constructing intelligent knowledge base and integrated intelligent decision-making platform.Results The system might help the hospital administrator in decision making.Conclusion The decision support system is worthy popularizing in the hospital.南京军区重点项目(11Z023); 漳州市自然科学基金项目(Z2011009

澄江学派传人黄宗勖先生针灸学术特色

黄宗勖师从澄江针灸学派创始人承淡安先生,是福建针灸名家。通过收集整理黄宗勖先生的论文和医案,发现其针灸学术特色主要表现为:重视经络,辨证论治;重视得气,善用补泻;重视调理脾胃,针药结合,治各科疑难杂症;擅用外治法,且善用透穴;重视养生保健,善出食疗奇方

Research of 120 pre-hospital emergency system based on wireless 3G network

目的:针对国内院前急救的发展现状和不足,提出一种基于无线3g网络的120院前急救系统的解决方法。方法:利用无线3g网络通信技术,建立救护车、接诊医院与远端专家之间的信息通路,实现实时音视频和生命体征信息的传输。结果:该系统实现了远程救护指导、抢救方案的提前制订及接诊的准备,从而缩短了患者的救治时延,提高了患者的救治率,减少了医疗纠纷。结论:基于无线3g网络的120院前急救系统是可行的,并将在提高院前急救和转运水平、提高患者的救治率、节约急救资源、减少医疗纠纷等方面发挥更积极的作用。Objective To analyze the current development situation and the deficiency of pre-hospital emergency treatment in China, and to propose a solution for 120 pre-hospital emergency system based on wireless 3G network.Methods Using wireless 3G network communication technology, a remote access of information between ambulance, the admission hospital and remote experts was established, and the real-time transmission of information on audio, video and vital signs was implemented.Results The functions including the guidance of remote ambulance, the early formulation of rescue program and the preparation of clinical reception were implemented by this system, which could reduce the delay time before treatment of patient, improve the patient's treatment rate and reduce medical disputes.Conclusion It is feasible to use a 120 pre-hospital emergency system based on the wireless 3G network.It can greatly shorten the delay before patient treatment, improve the patient treatment rate and reduce medical disputes.南京军区重点项目(11Z023); 漳州市自然科学基金项目(Z2011009

Pregnane X receptor involves in the effect of aflatoxin B1 on necroptosis in human normal L02 liver cells

目的初步探讨孕烷X受体(PXr)对黄曲霉毒素b1(Afb1)诱导肝细胞dnA损伤和坏死性凋亡的影响。方法采用已构建的PXr高表达l02-PXr和空白载体对照l02-P b细胞;实时荧光定量PCr(Q rT-PCr)检测细胞nr1I2和CyP3A4 M rnA水平改变;蛋白免疫印迹(WESTErn blOTTIng)检测细胞内PXr和坏死性凋亡下游效应自噬分子lC3-Ⅰ和lC3-Ⅱ蛋白相对表达含量;双核微核试验(CbMn)检测细胞遗传损伤情况;采用噻唑蓝(MTT)法测定Afb1对细胞活性抑制影响;利用坏死性凋亡抑制剂nEC-1构建坏死性凋亡抑制的细胞模型,验证Afb1诱导的坏死性凋亡的效应。结果与l02-P b细胞相比,l02-PXr细胞nr1I2 M rnA和PXr蛋白显著上调(均P<0.001)。Afb1显著地诱导l02-P b和l02-PXr细胞中CyP3A4 M rnA上调(均P<0.05),在l02-PXr细胞中的效应更为明显。与对照组相比,Afb1在5~30μMOl/l呈剂量反应关系诱导l02-P b和l02-PXr细胞的微核率增高(均P<0.05),l02-PXr细胞更为明显;同时,Afb1明显地诱导两株细胞的核芽率和核桥率,但随Afb1剂量增高都有下降趋势。细胞活性随Afb1浓度(1.875~120μMOl/l)增加呈剂量反应关系抑制(均P<0.05);且相对于l02-P b细胞,l02-PXr细胞对Afb1处理48 H诱导的细胞活性抑制作用更为敏感(P<0.05)。nEC-1可显著性抑制Afb1诱导的l02-PXr细胞活性抑制率(P<0.05),然而却不能降低Afb1诱导l02-P b细胞活性抑制率。此外,Afb1显著性诱导l02-P b和l02-PXr坏死性凋亡下游lC3-Ⅱ的上调(均P<0.05);且与l02-P b细胞相比,nEC-1对Afb1诱导的l02-PXr细胞活性抑制和lC3-Ⅱ上调的抑制效果更为明显(P<0.05)。结论 PXr参与Afb1诱导人肝细胞dnA损伤介导的坏死性凋亡,与PXr促进Afb1诱导CyP3A4基因上调有关。Objective To investigate the effects of pregnane X receptor(PXR) over expression on aflatoxin B1(AFB1)-induced DNA damage and necroptosis in human normal liver L02 cells.Methods The established cells models of stable transfection of over expression PXR(L02-PXR) and null vector p Babe-puro(L02-p B) were used.The background levels of NR1I2 m RNA and PXR protein, and the expression of AFB1-induced CYP3A4 m RNA and LC3-I / LC-3II protein were determined by the real time PCR(q RT-PCR) and Western blotting, respectively.The cytokinesis-block micronucleus(CBMN)assay was adopted to evaluate the genotoxicity.The cell viability inhibition rate was determined by MTT assay, after treatment with different doses of AFB1.The inhibition models of necroptosis were established by treatment with necroptosis inhibitor Nec-1.Results The expression of NR1I2 m RNA and PXR protein in L02-PXR cells were higher than that in L02-p B cells(all P<0.001).The level of CYP3A4 m RNA was significantly up regulated in L02-p B and L02-PXR cells by treatment with AFB1(all P<0.05).Compared with control group(Ctrl), MN frequencies in L02-p B and L02-PXR cells were significantly increased by treatment with AFB1 in a dose-dependent manner(all P <0.05), especially, in L02-PXR cells.Meanwhile, NBD and NBP frequencies were significantly increased by treatment with AFB1.However, AFB1 with a higher dose induced downward trends in frequencies of NBD and NBP.Moreover, the inhibition rate of cell viability was increased after treatment with AFB1(1.875~120 μmol / L) in a dose-dependent manner(all P <0.05); specifically, the inhibitory effects of AFB1-treatment after 48 h were significantly stronger in L02-PXR cells than in L02-p B cells(P <0.05).Interestingly, necroptosis inhibitor Nec-1 could inhibit AFB1-induced cell death in L02-PXR cells(P<0.05).On the contrary, Nec-1 could not prevent L02-p B cells from death by treatment with AFB1.In addition, the expression of necroptotic LC3-II, a classical marker of autophagy, was significantly increased by treatment with AFB1 in two cell lines(all P <0.05).Notably, pre-treatment with Nec-1 was able to block the inducement of necroptotic LC3-II in a more efficiently way in L02-PXR cells than in L02-p B cells(P <0.05).Conclusion PXR involved in the effect of AFB1 on necroptosis by DNA damage mediation in human liver cells;specifically, the up regulation of CYP3A4 gene may relate to the AFB1-induced DNA damage.国家自然科学基金(81172705;81072334); 广东省自然科学基金(S2011020002769); 福建省自然科学基金(2014J01372