Metabolic syndrome and endothelial fibrinolytic capacity in obese adults

The metabolic syndrome (MetS) often accompanies obesity and contributes to the increased risk of atherothrombotic events with increased body fatness. Indeed, the risks for coronary artery disease and acute vascular events are greater with obesity combined with MetS compared with obesity alone. Endothelial release of tissue-type plasminogen activator (t-PA) is a key defense mechanism against thrombosis and has been shown to be impaired with obesity. The aim of the present study was to determine whether the presence of MetS exacerbates endothelial fibrinolytic dysfunction in obese adults. Net endothelial release of t-PA was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside in 47 sedentary adults: 15 normal weight (age 57 +/- 2 yr; body mass index 22.9 +/- 0.5 kg/m(2)), 14 obese but otherwise healthy (55 +/- 1 yr; 29.4 +/- 0.3 kg/m(2)), and 18 obese with MetS (55 +/- 2 yr; 32.3 +/- 1 kg/m(2)). MetS was established according to National Cholesterol Education Program ATP III criteria. Net release of t-PA antigen to bradykinin was approximately 50% lower (P < 0.01) in the obese (from 2.5 +/- 1.9 to 37.1 +/- 5.3 ng.100 ml tissue(-1).min(-1)) and obese with MetS (from 0.4 +/- 0.8 to 32.5 +/- 3.8 ng.100 ml tissue(-1).min(-1)) compared with normal-weight (from 0.9 +/- 1.0 to 74.3 +/- 8.1 ng.100 ml tissue(-1).min(-1)) subjects. However, there were no significant differences in the capacity of the endothelium to release t-PA in the obese and obese with MetS adults. These results indicate that the presence of the MetS does not worsen the obesity-related endothelial fibrinolytic dysfunction.     

关于神经病学PBL教学中心理因素的思考

神经病学是涉及多个基础学科的临床专门学科,其内容复杂抽象,令学生望而生畏。PBL是学生自主学习建构知识和教师引导的教学模式,有利于学生克服畏难情绪,提高学习效率。根据我们的实践体会,教师与学生的心理是影响PBL教学效果的重要因素。只有把握好教学过程中的心理因素,才能使PBL的优势真正得以体现。     

Wistar大鼠幼年期丰富环境刺激对其社会竞争行为的影响

目的：探讨大鼠幼年期丰富环境经历对其成年后焦虑样行为和社会竞争行为的影响。方法：幼年期Wistar大鼠（生后21天）分为标准饲养组（对照组）和丰富环境刺激（EE）组。对照组为持续在标准实验室饲养条件下饲养;丰富环境组为生后21天至行为学检查时持续在丰富环境下饲养。在生后70天进行行为学检测：采用高架十字迷宫方法测试焦虑样行为;采用社会优势管道试验观察社会竞争性行为。结果：高架十字迷宫实验结果显示,与对照组相比,丰富环境组在开放臂的时间和次数显著增加;优势管道实验结果显示丰富环境刺激组大鼠的社会竞争力明显下降。结论：大鼠幼年期丰富环境刺激可改善大鼠的焦虑样情绪,但导致大鼠社会竞争力下降。     

液质连用分析重组胰高血糖素样肽-1受体激动剂肽图

目的：建立高效液相系统肽图分析法,用于重组胰高血糖素样肽-1受体激动剂（rExendin-4）的质量控制。方法：应用高效液相系统摸索最佳胰蛋白酶切和色谱条件,并采用液质联用系统分析肽段的精确相对分子量和氨基酸序列。结果：根据酶切条件摸索,确定酶切条件为：rExendin-4原液与胰蛋白酶按照质量比为100：1混匀,37℃酶切4小时,根据肽段的色谱保留时间、相对分子质量及对其碰撞诱导解离质谱的解析结果,归属出肽图中各肽段所在的色谱峰,与理论值完全一致。结论：本法精确度高、重复性好、自动化程度高,能够用于rExendin-4原液肽图分析。     

不同粘度对比剂对冠状动脉造影患者肾功能的影响

目的：对比剂肾病（CIN）是介入治疗中常见并发症之一。由于对比剂肾病发病机制复杂,其确切的机制尚不明确,有研究认为应用渗透压相似的对比剂,高粘度组对比剂引起CIN的几率明显高于低粘度组。本研究探讨接受不同粘度对比剂冠状动脉造影检查的患者术后引起肾功能损害的差异及其可能的机制。方法：80例接受冠状动脉造影检查的患者随机分为两组。分别为20℃碘海醇组、37℃碘海醇组,每组各40例。分别于冠脉造影前8h、冠脉造影后48h采集同一患者肘正中静脉血进行血清肌酐（Scr）、血清胱抑素C（CysC）检测,并对数据进行统计学分析。结果：两组患者组间比较基本资料无明显差异,两组患者术后Ser、CysC较术前均升高,差异均有统计学意义（P〈0．05）;20℃碘海醇组术后Scr较37℃碘海醇组升高不明显,差异无统计学意义（P〉0．05）;20℃碘海醇组术后CysC较37℃碘海醇组升高明显,差异有统计学意义（P〈0．05）。结论：冠脉造影检查时．对比剂对患者的肾功能有损害;选择低粘度对比剂可能减少其对冠状动脉造影患者的肾功能的不良影响;其作用机制可能与对比剂改变血液粘滞性,从而影响肾血流有关。     

Toll‐like receptor 9 protects non‐immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2

Toll‐like receptor 9 (TLR9) has a key role in the recognition of pathogen DNA in the context of infection and cellular DNA that is released from damaged cells. Pro‐inflammatory TLR9 signalling pathways in immune cells have been well investigated, but we have recently discovered an alternative pathway in which TLR9 temporarily reduces energy substrates to induce cellular protection from stress in cardiomyocytes and neurons. However, the mechanism by which TLR9 stimulation reduces energy substrates remained unknown. Here, we identify the calcium‐transporting ATPase, SERCA2 (also known as Atp2a2), as a key molecule for the alternative TLR9 signalling pathway. TLR9 stimulation reduces SERCA2 activity, modulating Ca²⁺ handling between the SR/ER and mitochondria, which leads to a decrease in mitochondrial ATP levels and the activation of cellular protective machinery. These findings reveal how distinct innate responses can be elicited in immune and non‐immune cells—including cardiomyocytes—using the same ligand‐receptor system.     

Identification of candidate biomarker proteins released by human endometrial and cervical cancer cells using two-dimensional liquid chromatography/tandem mass spectrometry

Candidate biomarker proteins, including chaperonin 10 and pyruvate kinase, previously discovered and identified using mass-tagging reagents with multidimensional liquid chromatography and tandem mass spectrometry (DeSouza, L.; et al. J. Proteome Res. 2005, 4, 377-386) have been identified in serum-free media of cultured endometrial cancer (KLE and HEC-1-A) and cervical cancer (HeLa) cells. These and other cancer-associated proteins were released by the cultured cells within 24 h of growth. A total of 203 proteins from the KLE cells, 86 from HEC-1-A, and 161 from HeLa are reported.     

A protocol for the delimitation of areas of endemism and the historical regionalization of the Brazilian Atlantic Rain Forest using harvestmen distribution data

The concept of areas of endemism (AoEs) has rarely been discussed in the literature, even though the use of methods to ascertain them has recently increased. We introduce a grid‐based protocol for delimiting AoEs using alternative criteria for the recognition of AoEs that are empirically tested with harvestmen species distributions in the Atlantic Rain Forest. Our data, comprising 778 records of 123 species, were analysed using parsimony analysis of endemicity and endemicity analysis on four different grids (two cell sizes and two cell placements). Additionally, we employed six qualitative combined criteria for the delimitation of AoEs and applied them to the results of the numerical analyses in a new protocol to objectively delimit AoEs. Twelve AoEs (the most detailed delimitation of the Atlantic Rain Forest so far) were delimited, partially corroborating the main divisions previously established in the literature. The results obtained with the grid‐based methods were contradictory and were plagued by artefacts, probably due to the existence of different endemism patterns in one cell or to a biogeographical barrier set obliquely to latitudinal and longitudinal axes, for example. Consequently, the congruence patterns found by them should not be considered alone; qualitative characteristics of species and clade distributions and abiotic factors should be evaluated together. Mountain slopes are the main regions of endemism, and large river valleys are the main divisions. Refuges, marine transgressions and tectonic activity seem to have played an important role in the evolution of the Atlantic Rain Forest.     

C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity

The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer (NK) cells and granulocytes. The latter and most prevalent blood cell population contributes to phagocytosis, but is not effective in inducing ADCC. Here, we report that targeted delivery of the tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL. Upon CLL1-selective binding of this fusion protein, granulocytes acquire additional TRAIL-mediated cytotoxic activity that, importantly, potentiates antibody-mediated cytotoxicity of clinically used therapeutic antibodies (e.g., rituximab, cetuximab). Thus, CLL1:TRAIL could be used as an adjuvant to optimize the clinical potential of anticancer antibody therapy by augmenting tumoricidal activity of granulocytes.     

非酒精性脂肪肝病大鼠肝脏SOCS-3的表达与吡格列酮干预研究

目的：探讨SOCS-3在非酒精性脂肪肝病（NAFLD）发病中的作用以及吡格列酮的干预作用。方法：29只雄性SD大鼠随机分为正常对照组（8只）,高脂饮食组（21只）。饲养8周后,从高质饮食组随机抽取5只大鼠证实造模成功后,将该组余下的16只大鼠继续以高脂饲料喂养,并随机分为NAFLD对照组（8只）;吡格酮干预组（8只）,予以吡格列酮3mg·kg^-1·d^-1灌胃。16周末,处死所有大鼠,检测血糖、血胰岛素、血脂、肝脏SOCS-3mRNA和SREBP-lcmRNA表达及肝脏病理学。结果：与正常对照组相比,NAFLD组血糖、血胰岛素、血脂、肝脏脂肪变水平及肝组织SOCS-3mRNA、SREBPlCmRNA表达显著上调。吡格列酮干预组sOCS．3mRNA、SREBP-1cmRNA表达较NAFLD组下调,且血糖、血胰岛素、血脂、肝脏脂肪变水平下降。SOCS-3mRNA表达水平与胰岛素抵抗指数、SREBP．1cmRNA表达水平、肝脂肪变成显著正相关。结论：SOCS-3可能通过胰岛素抵抗及上调肝组织SREBP-lcmRNA表达参与NAFLD发病,吡格列酮能抑制肝脏SOCS-3的表达,对NAFLD有一定治疗作用。