In Central Obesity,Weight Loss Restores Platelet Sensitivity to Nitric Oxide and Prostacyclin

Central obesity shows impaired platelet responses to the antiaggregating effects of nitric oxide (NO), prostacyclin, and their effectors—guanosine 3′,5′‐cyclic monophosphate (cGMP) and adenosine 3′,5′‐cyclic monophosphate (cAMP). The influence of weight loss on these alterations is not known. To evaluate whether a diet‐induced body‐weight reduction restores platelet sensitivity to the physiological antiaggregating agents and reduces platelet activation in subjects affected by central obesity, we studied 20 centrally obese subjects before and after a 6‐month diet intervention aiming at reducing body weight by 10%, by measuring (i) insulin sensitivity (homeostasis model assessment of insulin resistance (HOMA_IR)); (ii) plasma lipids; (iii) circulating markers of inflammation of adipose tissue and endothelial dysfunction, and of platelet activation (i.e., soluble CD‐40 ligand (sCD‐40L) and soluble P‐selectin (sP‐selectin)); (iv) ability of the NO donor sodium nitroprusside (SNP), the prostacyclin analog Iloprost and the cyclic nucleotide analogs 8‐bromoguanosine 3′,5′‐cyclic monophosphate (8‐Br‐cGMP) and 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐Br‐cAMP) to reduce platelet aggregation in response to adenosine‐5‐diphosphate (ADP); and (v) ability of SNP and Iloprost to increase cGMP and cAMP. The 10 subjects who reached the body‐weight target showed significant reductions of insulin resistance, adipose tissue, endothelial dysfunction, and platelet activation, and a significant increase of the ability of SNP, Iloprost, 8‐Br‐cGMP, and 8‐Br‐cAMP to reduce ADP‐induced platelet aggregation and of the ability of SNP and Iloprost to increase cyclic nucleotide concentrations. No change was observed in the 10 subjects who did not reach the body‐weight target. Changes of platelet function correlated with changes of HOMA_IR. Thus, in central obesity, diet‐induced weight loss reduces platelet activation and restores the sensitivity to the physiological antiaggregating agents, with a correlation with improvements in insulin sensitivity.     

阿托伐他汀改善冠心病患者血管内皮功能的临床研究

目的:观察短期阿托伐他汀治疗对高胆固醇血症的冠心病患者血管内皮功能的影响。方法:78例高胆固醇血症患者每日口服阿托伐他汀共8周,服药前后测量患者血清的总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和氧化低密度脂蛋白(ox-LDL)以及NO值,并用彩色多普勒超声测定反应性充血时肱动脉内径的变化。结果:高胆固醇血症患者经阿托伐他汀8周治疗后,血清的TC、TG、LDL-C和ox-LDL明显下降,血清的HDL-C以及NO值明显增加,反应性充血时肱动脉内径扩张程度明显增加,这些与治疗前相比有明显差异。结论:阿托伐他汀治疗能使高胆固醇血症的冠心病患者血脂改变,NO值增加,血管内皮功能改善。     

乳腺生物反应器表达的重组人乳清白蛋白的高效分离纯化

利用乳腺生物反应器高效地表达重组人乳清白蛋白,但是目标产物分离纯化的难度较大。通过分子模拟计算比较待分离原料中主要蛋白组分的物化性质,包括表面电势和表面疏水性,在此基础上设计了高分辨率、快速的分离纯化工艺。通过硫酸铵沉淀的正交试验条件优化,有效地去除了干扰层析精制过程的IgG杂质,提高了后续疏水层析的稳定性,从而成功地分离开目标蛋白及与其同源的牛乳清白蛋白杂质,得到纯度>95%的rHLA纯品,工艺回收率48.6%。乳糖合成活性和圆二色谱检测结果表明,纯化rHLA具有调节β-1,4-半乳糖苷转移酶活性和天然的空间结构。     

派伦螨属四已知种雄螨及若螨描述(蜱螨亚纲:中气门目:派盾螨科)

本文描述拟双毛派伦螨Parholaspulus paradichaetes Petrova,1967雄螨及前若螨,阿氏派伦螨 P.alstoni Evans,1956后若螨及前若螨,微小派伦螨 P.minutus Petrova,1967和东方派伦螨 P.orientalis Petrova,1967后若螨.     

The link between the PDL1 costimulatory pathway and Th17 in fetomaternal tolerance

Fetomaternal tolerance has been shown to depend both on regulatory T cells (Tregs) and negative signals from the PD1-PDL1 costimulatory pathway. More recently, IL-17-producing T cells (Th17) have been recognized as a barrier in inducing tolerance in transplantation. In this study, we investigate the mechanisms of PDL1-mediated regulation of fetomaternal tolerance using an alloantigen-specific CD4(+) TCR transgenic mouse model system (ABM-tg mouse). PDL1 blockade led to an increase in embryo resorption and a reduction in litter size. This was associated with a decrease in Tregs, leading to a lower Treg/effector T cell ratio. Moreover, PDL1 blockade inhibited Ag-specific alloreactive T cell apoptosis and induced apoptosis of Tregs and a shift toward higher frequency of Th17 cells, breaking fetomaternal tolerance. These Th17 cells arose predominantly from CD4(+)Foxp3(-) cells, rather than from conversion of Tregs. Locally in the placenta, similar decrease in regulatory and apoptotic markers was observed by real-time PCR. Neutralization of IL-17 abrogated the anti-PDL1 effect on fetal survival rate and restored Treg numbers. Finally, the adoptive transfer of Tregs was also able to improve fetal survival in the setting of PDL1 blockade. This is to our knowledge the first report using an alloantigen-specific model that establishes a link between PDL1, Th17 cells, and fetomaternal tolerance.     

Markers of stemness in equine mesenchymal stem cells: a plea for uniformity

Mesenchymal stromal cells (MSC) are a very promising subpopulation of adult stem cells for cell-based regenerative therapies in veterinary medicine. Despite major progress in the knowledge on adult stem cells during recent years, a proper identification of MSC remains a challenge. In human medicine, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) recently proposed three criteria to define MSC. Firstly, cells must be plastic-adherent when maintained under standard culture conditions. Secondly, MSC must express CD73, CD90 and CD105, and lack expression of CD34, CD45, CD14 or CD11b, CD79α or CD19 and MHC class II antigens. Thirdly, MSC must be able to differentiate into osteoblasts, adipocytes and chondroblasts in vitro. Successful isolation and differentiation of equine MSC from different sources such as bone marrow, fat tissue, umbilical cord blood, Wharton's Jelly or peripheral blood has been widely reported. However, their unequivocal immunophenotyping is hampered by the lack of a single specific marker and the limited availability of monoclonal anti-horse antibodies, which are two major factors complicating successful research on equine MSC. Detection of gene expression on mRNA level is hereby a valuable alternative, although the need still exists to test several antibody clones in search for cross-reactivity. To date, commercial antibodies recognizing equine epitopes are only available for CD13, CD44 and MHC-II. Moreover, as the expression of certain adult stem cell markers may differ between species, it is mandatory to define a set of CD markers which can be uniformly applied for the identification of equine MSC.     

Associations of Whole Blood n-3 and n-6 Polyunsaturated Fatty Acids with Blood Pressure in Children and Adolescents – Results from the IDEFICS/I.Family Cohort

BackgroundPolyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents.MethodsIn a subsample of 1267 children aged 2–9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status.ResultsThe baseline level of arachidonic acid was positively associated with subsequent systolic BP (β = 0.08, P = 0.002) and diastolic BP (β = 0.07, P<0.001). In thin/normal weight children, baseline alpha-linolenic (β = -1.13, P = 0.003) and eicosapentaenoic acid (β = -0.85, P = 0.003) levels were inversely related to baseline and also to subsequent systolic BP and alpha-linolenic acid to subsequent diastolic BP. In overweight/obese children, baseline eicosapentaenoic acid level was positively associated with baseline diastolic BP (β = 0.54, P = 0.005).ConclusionsLow blood arachidonic acid levels in the whole sample and high n-3 PUFA levels in thin/normal weight children are associated with lower and therefore healthier BP. The beneficial effects of high n-3 PUFA on BP were not observed in overweight/obese children, suggesting that they may have been overlaid by the unfavorable effects of excess weight.     

干旱胁迫条件下AMF促进小马鞍羊蹄甲幼苗生长的机理研究

采用温室水分控制试验,在干旱胁迫条件下,定量化研究优势丛枝菌根真菌(AMF)影响优势乡土植物小马鞍羊蹄甲(Bauhinia faberi var.microphylla)幼苗生长的机理,主要通过研究干旱胁迫条件下摩西球囊霉菌(Funneliformis mosseae)与小马鞍羊蹄甲的共生关系,阐明AMF在植物生长初期的作用。结果表明,干旱胁迫条件下,摩西球囊霉菌能够很好地侵染幼苗,侵染率高达89%—97%,并且不受水分条件影响。接种的幼苗最大光合速率、水分利用效率随着干旱胁迫程度从重度到轻度(水分从低到高)逐渐增大,相反地,叶片脯氨酸含量逐渐减小。接种显著地促进幼苗株高、叶片数、叶面积、根长、根面积等生长指标,提高幼苗各部分生物量、地上地下磷(P)含量。当含水量为60%田间持水量时,AMF促进小马鞍羊蹄甲幼苗吸收P的效果最好。接种还显著影响幼苗的生物量分配,在重度干旱胁迫时影响P分配,水分条件也显著影响幼苗的生物量分配。此外,接种和水分的交互作用对叶生物量、总生物量、生长指标以及地上部氮(N)总量影响显著。结果表明干旱胁迫条件下菌根效应显著,并在干旱条件下显著促进了小马鞍羊蹄甲幼苗的生长,这为进一步干旱河谷植被恢复提供了理论依据。