慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象的尿代谢组研究

目的：探索慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿代谢差异指标,为中医舌象生物学物质基础微观辨证提供证据。方法：采用气相色谱／质谱联用（GC／MS ）技术方法获取慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿液样本代谢指纹谱,用无监督的学习模式进行多变量统计分析,观察不同组别的人群之间是否存在“自然”的分类结构。利用有监督的学习模式进行数据分类模型的建立和检验,寻找造成样本聚集和离散的主要差异变量。利用商业化的代谢物谱库以及标准品数据库,进行物质鉴定。结果：慢性乙型肝炎舌红苔黄和舌淡苔白者在有监督的学习模式下具有良好的分开趋势,慢乙肝不同舌象者较健康者的差异代谢物谱主要与能量代谢、氨基酸代谢、核苷酸代谢以及肠道菌群代谢相关。结论：舌象是机体变化的重要窗口,不同舌象的外在表观潜在体内的代谢差异。     

The alteration in the architecture of a T‐DNA insertion rice mutant osmtd1 is caused by up‐regulation of MicroRNA156f

Plant architecture is an important factor for crop production. Some members of microRNA156 (miR156) and their target genes SQUAMOSA Promoter‐Binding Protein‐Like (SPL) were identified to play essential roles in the establishment of plant architecture. However, the roles and regulation of miR156 is not well understood yet. Here, we identified a T‐DNA insertion mutant Osmtd1 (Oryza sativa multi‐tillering and dwarf mutant). Osmtd1 produced more tillers and displayed short stature phenotype. We determined that the dramatic morphological changes were caused by a single T‐DNA insertion in Osmtd1. Further analysis revealed that the T‐DNA insertion was located in the gene Os08g34258 encoding a putative inhibitor I family protein. Os08g34258 was knocked out and OsmiR156f was significantly upregulated in Osmtd1. Overexpression of Os08g34258 in Osmtd1 complemented the defects of the mutant architecture, while overexpression of OsmiR156f in wild‐type rice phenocopied Osmtd1. We showed that the expression of OsSPL3, OsSPL12, and OsSPL14 were significantly downregulated in Osmtd1 or OsmiR156f overexpressed lines, indicating that OsSPL3, OsSPL12, and OsSPL14 were possibly direct target genes of OsmiR156f. Our results suggested that OsmiR156f controlled plant architecture by mediating plant stature and tiller outgrowth and may be regulated by an unknown protease inhibitor I family protein.     

ABORTED GAMETOPHYTE 1 is required for gametogenesis in Arabidopsis

In flowering plants, the male and female gametogenesis is a crucial step of sexual reproduction. Although many genes have been identi fied as being involved in the gametogenesis process, the genetic mechanisms underlying gametogenesis remains poorly understood. We reported here characterization of the gene, ABORTED GAMETOPHYTE 1(AOG1) that is newly identi fied as essential for gametogenesis in Arabidopsis thaliana. AOG1 is expressed predominantly in reproductive tissues including the developing pollen grains and ovules. The AOG1 protein shares no signi ficant amino acid sequence similarity with other documented proteins and is located mainly in nuclei of the cells. Mutation in AOG1 caused degeneration of pollen at the uninucleate microspore stage and severe defect in embryo sacs, leading to a signi ficant reduction in male and female fertility.Furthermore, the molecular analyses showed that the aog1 mutant signi ficantly affected the expression of several genes, which are required for gametogenesis. Our results suggest that AOG1 plays important roles in gameto genesis at the stage prior to pollen mitosis I(PMI)in Arabidopsis, possibly through collaboration with other genes.     

Arabidopsis SMALL ORGAN 4, a homolog of yeast NOP53, regulates cell proliferation rate during organ growth

Cell proliferation is a fundamental event essential for plant organogenesis and contributes greatly to the final organ size. Although the control of cell proliferation in plants has been extensively studied, how the plant sets the cell number required for a single organ is largely elusive. Here, we describe the Arabidopsis SMALL ORGAN 4 (SMO4) that functions in the regulation of cell proliferation rate and thus final organ size. The smo4 mutant exhibits a reduced size of organs due to the decreased cell number, and further analysis reveals that such phenotype results from a retardation of the cell cycle progression during organ development. SMO4 encodes a homolog of NUCLEOLAR PROTEIN 53 (NOP53) in Saccharomyces cerevisiae and is expressed primarily in tissues undergoing cell proliferation. Nevertheless, further complementation tests show that SMO4 could not rescue the lethal defect of NOP53 mutant of S. cerevisiae. These results define SMO4 as an important regulator of cell proliferation during organ growth and suggest that SMO4 might have been evolutionarily divergent from NOP53.     

PNPLA3在实验性非酒精性脂肪性肝病中的表达及其CpG岛甲基化状态的研究

目的:探讨PNPLA3在非酒精性脂肪性肝病中的表达水平及其Cp G岛甲基化状态,探讨PNPLA3在NAFLD发生、发展中的作用。方法:1.采用10μg/m L的油酸作用于人正常肝细胞株L02建立脂肪肝细胞模型,72 h后经油红O染色,观察正常组、脂肪肝模型组及给药组细胞内脂滴形成情况,并用荧光定量PCR检测PNPLA3在三组肝细胞中的表达情况。2.采用专用DNA提取试剂盒分别提取正常组、脂肪肝模型组、给药组细胞中DNA,经亚硫酸转化后行PCR扩增目的基因,并用焦磷酸测序方法检测不同组PNPLA3 Cp G岛中甲基化水平,探讨其在非酒精性脂肪肝中的作用。结果:1、脂肪肝模型组肝细胞PNPLA3 m RNA的表达高于正常组,经姜黄素给药后,其表达降低,差异均有统计学意义(P0.05)。2、在PNPLA3启动子区6个检测位点中,脂肪肝组位点2甲基化水平高于正常组,姜黄素给药后甲基化水平降低,差异均有统计学意义(P0.05),在其余各检测位点中甲基化水平无差异。结论:1、油红O染色后,脂肪肝模型组细胞内发现有大量红色脂滴积聚,而正常组基本上未见脂滴,姜黄素给药组脂滴较模型组减少,表明用10μg/m L的油酸诱导能成功建立体外肝细胞模型。2、PNPLA3 m RNA在肝细胞中高表达及其启动子区甲基化状态异常参与非酒精性脂肪肝发病。3、抑制肝脏PNPLA3活性或降低肝细胞PNPLA3 m RNA的表达水平可能是今后治疗非酒精性脂肪性肝病(NAFLD)的一个新的治疗方法。     

ST 段抬高心肌梗死靶血管长病变急诊介入治疗的安全性及疗效分析

目的:探讨ST段抬高急性心肌梗死(ST-elevation myocardial infarction,STEMI)患者靶血管长病变(病变>25 mm)急诊经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗的临床疗效及安全性。方法:回顾性收集2009年1月-2010年6月因STEMI就诊于沈阳军区总医院并急诊行PCI处理的患者442例,以靶病变长度分为两组,即≤25 mm为短病变组(n=235)和>25mm为长病变组(n=207),均急诊行PCI治疗,分析和比较两组患者术前的基线资料、术中资料及并发症的发生情况、辅助措施(临时起搏、IABP、血栓抽吸装置)应用情况,术后30天、2年电话或临床随访,记录主要不良心血管事件(major adverse cardiac events,MACE)的发生情况。结果:与短病变组比较,长病变组吸烟者更多(81.6%vs 62.6%,P=0.000);以三支病变偏多(34.8%vs 24.7%,P=0.037);多枚支架使用率更高(1.47±0.63 vs 1.04±0.28,P=0.000),平均支架总长度显著增加(29.80±7.02 mm vs 22.95±5.58mm,P=0.000),手术成功率、术中并发症及辅助措施应用情况比较差异无统计学意义(P>0.05),30天及2年随访MACE的发生率比较差异无统计学意义(P>0.05)。结论:与急诊PCI治疗的STEMI短病变患者对比,长病变患者虽然病变复杂,多枚支架使用率高,平均支架总长度增加,但术中并发症、30天、2年内MACE与短病变患者相当,提示在以药物洗脱支架为主的介入治疗时代,急诊PCI处理STEMI靶血管长病变具有良好的疗效及安全性。     

Global Establishment Risk of Economically Important Fruit Fly Species (Tephritidae)

The global invasion of Tephritidae (fruit flies) attracts a great deal of attention in the field of plant quarantine and invasion biology because of their economic importance. Predicting which one in hundreds of potential invasive fruit fly species is most likely to establish in a region presents a significant challenge, but can be facilitated using a self organising map (SOM), which is able to analyse species associations to rank large numbers of species simultaneously with an index of establishment. A global presence/absence dataset including 180 economically significant fruit fly species in 118 countries was analysed using a SOM. We compare and contrast ranked lists from six countries selected from each continent, and also show that those countries geographically close were clustered together by the SOM analysis because they have similar fruit fly assemblages. These closely clustered countries therefore represent greater threats to each other as sources of invasive fruit fly species. Finally, we indicate how this SOM method could be utilized as an initial screen to support prioritizing fruit fly species for further research into their potential to invade a region.     

Splenocytes Seed Bone Marrow of Myeloablated Mice: Implication for Atherosclerosis

Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease.     

The Novel Analogue of Hirsutine as an Anti-Hypertension and Vasodilatary Agent Both In Vitro and In Vivo

In this paper, an analogue of hirsutine (compound 1) has been synthesized and evaluated as an anti-hypertension agent, which exhibits extraordinary effects on the contractile response of thoracic aorta rings from male SD rats in vitro (IC₅₀ = 1.129×10^-9±0.5025) and the abilities of reducing the systolic blood pressure (SBP) and heart rate (HR) of SHR in vivo. The mechanism investigation reveals that the vasodilatation induced by compound 1 is mediated by both endothelium-dependent and -independent manners. The relaxation in endothelium-intact aortic rings induced by compound 1 can be inhibited by L-NAME (1×10^-6 mol•L^-1) and ODQ (1×10^-6 mol•L^-1). Moreover, compound 1 can also block Ca²⁺ influx through L-type Ca²⁺ channels and inhibit intracellular Ca²⁺ release while no effect on K⁺ channel has been observed. All these data demonstrated that the NO/cyclic GMP pathway can be involved in endothelium-dependent manner induced by compound 1. Meanwhile the mechanism on the vasodilatation of compound 1 probably also related to blockade of Ca²⁺ influx through L-type Ca²⁺ channels and inhibition of intracellular Ca²⁺ release may have no relationship with K⁺ channels.