Enterohemorrhagic E.coli effector NleL disrupts host NF-κB signaling by targeting multiple host proteins

Dear Editor,Enterohemorrhagic Escherichia coli(EHEC)0157:H7,a major diarrheagenic pathogen,can cause bloody diarrhea,hemorrhagic colitis,and>90%of hemolytic uremic syndrome in humans(Mead and Griffin,1998).Many previous studies have demonstrated that 0157:H7 could disrupt host ubiquitin(Ub)system by delivering virulence effectors into host cells with the type III secretion system(T3SS).NleL(also named EspX7)emerged as one of such effectors,whose E3-like activity was first identified in vitro in 2011(Lin et al.,2011).

HDL quality features revealed by proteome–lipidome connectivity are associated with atherosclerotic disease

Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.

Dysfunction of PLA2G6 and CYP2C44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma

很少长期的发炎怎么贡献 hepatocellular 癌(HCC ) 的前进被知道，特别癌症的开始。揭开从长期的发炎的批评转变到在网络水平的 HCC 和分子的机制，我们用我们的动态网络 biomarker (DNB ) 分析了土拨鼠肝炎 virus/c-myc 鼠标和匹配年龄的 wt-C57BL/6 鼠标的时间系列 proteomic 数据模型。DNB 分析显示在转基因的老鼠的出生以后的第 5 月是癌症开始的批评时期，就在批评转变前，它与临床的症状一致。同时，联系 DNB 的网络在批评转变前后显示出蛋白质表示和 coexpression 层次的激烈的倒置。DNB， PLA2G6 和 CYP2C44 的二个成员，与他们的联系差别一起表示了蛋白质，被发现导致 arachidonic 酸新陈代谢的机能障碍，进一步通过短暂受体潜力隧道的煽动性的调停人规定激活煽动性的回答，并且最后导致肝 detoxification 和恶意的转变的缺陷到癌症。作为一个 c-Myc 目标， PLA2G6 断然在表示与 c-Myc 相关，显示出从减少到在 carcinogenesis 期间增加的一个趋势，与在批评转变的最小的点或付小费给的点。相应 PLA2G6 和 c-Myc 的如此的趋势也在人的 hepatocarcinogenesis 期间被观察，与在高级 dysplastic 小瘤(就在 carcinogenesis 前的一个阶段) 的最小的点。我们的学习暗示 PLA2G6 可能在 hepatocarcinogenesis 期间作为象著名 c-Myc 一样的 oncogene 工作，当 PLA2G6 和 c-Myc 的 downregulation 能是显示逼近的 carcinogenesis 的一个警告信号时。