Inflammation in atherosclerosis

Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies. Identifying the triggers for inflammation and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.     

Creatine accelerates the circadian clock in a unicellular alga

The circadian clock is considered to be a universal feature of eucaryotic organisms, controlling the occurrence and rates of many different aspects of life, ranging from single enzymatic reactions and metabolism to complex behaviours such as activity and rest. Although the nature of the underlying cellular/biochemical oscillator is still unknown, many substances are known to influence either phase or period of circadian rhythms in different organisms. These include D2O, electrolytes and ion channel inhibitors, small organic molecules such as alcohols and aldehydes, inhibitors of protein synthesis and amino-acid analogues. Certain transmitter and neurochemical drugs also influence the circadian clock in higher animals. We report here that the period of free-running circadian rhythms in the unicellular marine alga Gonyaulax polyedra is shortened by extracts from mammalian cells. The effect is dose-dependent, accelerating the circadian clock by as much as 4 hours per day. The substance responsible for this effect has been isolated from bovine muscle and identified as creatine. Authentic creatine has identical biological effects at micromolar concentrations and is known in animal systems for its involvement in cellular energy metabolism. A period shortening substance with similar chemical properties is also present in extracts of Gonyaulax itself.     

Myocardial gene therapy.

Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.     

肌钙蛋白I对小儿心肌炎诊断及与酶学对比研究

目的 评估血清心肌肌钙蛋白I (cTnI) 对小儿心肌炎的诊断价值,并与肌酸激酶(CK)及其同功酶MB(CK-MB)进行对比研究.方法 全自动生化分析仪对cTnI,CK及CK-MB进行定量检测.结果 1)心肌炎组cTnI,CK及CK-MB均明显高于正常对照组(P<0.001).cTnI升高38例,占76%;CK升高21例,占42%;CK-MB升高25例,占50%.cTnI与CK,CK-MB呈正相关关系.2)治疗2周后,cTnI与对照组比较有显著性差异(P<0.001),CK及CK-MB与对照组无显著性差异(P>0.05).3)心肌炎组22例ST-T改变患儿测cTnI升高20例(91%),CK升高8例(37%),CK-MB升高6例(27%).结论 cTnI及CK,CK-MB对小儿心肌炎的诊断均较敏感,其中cTnT对心肌损害的敏感性及特异性均高于CK和CK-MB.cTnI诊断时间窗宽于CK,CK-MB,特异性也高于心肌酶学检查.     

Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing

Ataxia-telangiectasia (A-T) results from the loss of ataxia-telangiectasia mutated (Atm) function and is characterized by accelerated telomere loss, genomic instability, progressive neurological degeneration, premature ageing and increased neoplasia incidence. Here we evaluate the functional interaction of Atm and telomeres in vivo. We examined the impact of Atm deficiency as a function of progressive telomere attrition at both the cellular and whole-organism level in mice doubly null for Atm and the telomerase RNA component (Terc). These compound mutants showed increased telomere erosion and genomic instability, yet they experienced a substantial elimination of T-cell lymphomas associated with Atm deficiency. A generalized proliferation defect was evident in all cell types and tissues examined, and this defect extended to tissue stem/progenitor cell compartments, thereby providing a basis for progressive multi-organ system compromise, accelerated ageing and premature death. We show that Atm deficiency and telomere dysfunction act together to impair cellular and whole-organism viability, thus supporting the view that aspects of A-T pathophysiology are linked to the functional state of telomeres and its adverse effects on stem/progenitor cell reserves.     

Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis

Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types. Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A. Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected. However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression.     

Global warming accelerates the upfreezing of permafrost in arid middle Tianshan Mountains

Upfreezing is an important geomorphic process in the periglacial environment. It is a product of cold climate and thus an important part of the cryospheric processes. Based on the long-term positioning observations in the source area of the Urumqi River, this article represents an in-depth discussion of the characteristics of sorted circles and upfreezing mechanisms in the Tianshan Mountains. In the source area of the Urumqi River, the intensity of upfreezing is the highest within the top 25 cm near the surface, while targets with a diameter of 3 cm are least affected by upfreezing. There is no distinct difference between the centre with fine grains and the margin with coarse debris within the same sorted circle in terms of the intensity of upfreezing. The correlation analysis demonstrates that temperature plays an important role in upfreezing and the development of sorted circles. A long-time positioning observation of sorted circles reveals that periglacial landforms are sensitive to regional climate change and respond quickly to the temperature increase of the recent two decades. Enhanced upfreezing was found to be due to increased soil moisture content.     

大鼠心肌肥厚中PTEN,p-PI_3K蛋白表达对心肌纤维化的影响

对健康成年SD大鼠采用皮下注射异丙肾上腺素造成心肌肥厚模型;取心肌组织,常规石蜡切片,Masson染色,观察心肌组织的成纤维细胞变化;免疫荧光染色检测PTEN和p-PI3K的表达及分布.结果与对照组相比,实验组细胞间纤维细胞增多;免疫荧光检测PTEN和p-PI3K的阳性表达明显增高.表明PTEN和p-PI3K蛋白表达增高可能在心肌纤维化的发生和发展过程中起重要作用.     

细胞凋亡与心肌缺血再灌注损伤研究

近年来的研究表明,细胞凋亡(apoptosis)与心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)有着密切关系.全面了解有关研究进展,进一步开展相关的研究,将会为心肌缺血再灌注损伤的防治提供更多的途径.为此,文章从细胞凋亡的基本知识、心肌缺血再灌注与细胞凋亡的关系、药物干扰作用及研究方法等方面进行了阐述.     

心肌缺血性损伤与硫氧还蛋白系统

心肌缺血时氧化应激对心肌细胞的影响包括对心肌细胞的损伤和对心肌细胞的保护.心肌细胞存活与死亡有赖于细胞的氧化还原状态,通过改变细胞内的氧化还原状态可干预氧化应激.Trx系统对机体内氧化还原调节及其重要,通过抗氧化和氧化还原调节作用,在基因表达、信号转导、细胞生长、细胞凋亡等方面起着重要作用.Trx系统自身也受到氧化还原调节.     

An arbuscular mycorrhizal fungus accelerates decomposition and acquires nitrogen directly from organic material

Arbuscular mycorrhizal fungi (order Glomales), which form mycorrhizal symbioses with two out of three of all plant species, are believed to be obligate biotrophs that are wholly dependent on the plant partner for their carbon supply. It is thought that they possess no degradative capability and that they are unable to decompose complex organic molecules, the form in which most soil nutrients occur. Earlier suggestions that they could exist saprotrophically were based on observation of hyphal proliferation on organic materials. In contrast, other mycorrhizal types have been shown to acquire nitrogen directly from organic sources. Here we show that the arbuscular mycorrhizal symbiosis can both enhance decomposition of and increase nitrogen capture from complex organic material (grass leaves) in soil. Hyphal growth of the fungal partner was increased in the presence of the organic material, independently of the host plant.     

经PCI治疗ST段抬高心梗患者QRS宽度与心肌呈色分级关联

目的评价经皮冠状动脉介入(PCI)治疗ST段抬高型心肌梗死(STEMI)患者QRS宽度与心肌呈色分级(MBG)的关系。方法对100例12 h内就诊的STEMI患者进行术前和术后心电图分析,根据MBG分为2个研究组:A组(MBG 0-1)(n=40)和B组(MBG 2～3)(n=60)。结果 2组患者基线特征相似。在血管成形术后即刻心电图(95.56±15.63vs 80.87±12.80 ms,P <0.001)和60 min心电图(96.95±16.24 vs 78.82±12.08 ms,P <0.001)检测中,A组QRS持续时间均比B组长。2组血管成形术后即刻(10.99±10.05 vs 6.64±10.61 ms,P <0.00)和60 min心电图(13.03±11.64 vs7.95±11.11 ms,P <0.001)QRS宽度差别有显著性差异。ROC曲线分析显示血管成形术后60 min QRS变窄可预测心肌再灌注。结论 STEMI患者血管成形术后QRS宽度变窄与心肌再灌注密切相关。