Allopurinol enhanced adenine nucleotide repletion after myocardial ischemia in the isolated rat heart.

Allopurinol, a competitive inhibitor of xanthine oxidase, has been shown to have a protective effect on ischemic myocardium, but its mechanism of action remains controversial. We used an isolated rat heart preparation to test the hypothesis that allopurinol could restore adenosine triphosphate (ATP) levels and improve the recovery of left ventricular function after global myocardial ischemia. Hearts were equilibrated for 30 min, subjected to 10 min of global, normothermic (37 degrees C) ischemia, and reperfused for 15, 30, and 60 min. Hearts treated with allopurinol (100 microM) exhibited greater ATP levels and improved function during reperfusion than did untreated control hearts. Hearts treated with hypoxanthine (100 microM), the substrate for xanthine oxidase, also showed increased ATP and functional recovery compared with controls. These results suggest that allopurinol may protect the globally ischemic myocardium by enhancing the salvage of hypoxanthine for reincorporation into adenine nucleotides.     

Oncogenic Wnt3a is a promising sensitive biomarker for monitoring hepatocarcinogenesis

Background: The effective treatment for hepatocellular carcinoma(HCC) depends on early diagnosis. Previously, the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/β-catenin pathway was found in HCC cells and could be released into the circulation. In this study, we used rat model of hepatocarcinogenesis to dynamically investigate the alteration of oncogenic Wnt3a and to explore its early monitor value for HCC. Methods: Sprague-Dawley rats(SD) were fed with diet 2-fluorenylac...     

Wnt-1在大鼠脑缺血再灌注海马组织内源性神经干细胞早期增殖分化中的作用

目的:检测wnt-1在大鼠脑缺血再灌注海马组织神经干细胞早期增殖分化中的表达及其变化,探讨影响神经干细胞早期增殖分化的分子调控机制。方法:实验于2005-08/2006-08在沈阳医学院完成。选择健康雄性Wistar大鼠30只,随机分为正常组,缺血再灌注3,7,14,21d组,每组6只。缺血再灌注各组采用颈动脉负压分流法制作大鼠脑缺血再灌注模型。正常组不作任何手术处理。用免疫组织化学SP法及显微图像分析检测海马神经干细胞中BrdU,Wnt-1的表达。结果:30只大鼠均进入结果分析。①缺血再灌注各组大鼠海马均可见BrdU阳性细胞。阳性细胞呈棕黄色,形态多样,呈圆形、椭圆形或梭形。脑缺血再灌注第3天缺血海马神经元BrdU阳性细胞明显增多,BrdU阳性细胞百分率为(56.78±2.37)%,第7天达高峰,BrdU阳性细胞百分率为(69.99±6.01)%,第14,21天逐渐减少,分别为(49.35±5.57)%,(38.33±7.89)%。缺血再灌注各组与正常组[(4.89±5.60)%]比较,差异有显著性意义(P<0.05)。②缺血再灌注各组大鼠均有wnt-1表达,海马颗粒层细胞质呈棕黄色颗粒,不着色为阴性。脑缺血再灌注第3天Wnt-1反应产物有所增多,海马组织Wnt-1表达的平均灰度值为103.67±5.49。第7天表达最强,平均灰度值为75.34±6.75,以后表达逐渐减少。缺血再灌注各组与正常组(132.47±2.96)比较,差异有显著性意义(P<0.05)。结论:Wnt-1时间依赖性表达与神经干细胞增殖分化进程相吻合,说明其在神经干细胞早期增殖分化中起重要调控作用。     

面神经损伤后面神经核中黏附分子CD44表达与穴位电针刺激的影响

目的:观察穴位电针在面神经损伤后面神经再生中的作用及对黏附分子CD44表达的影响。方法:实验于2005-09/2006-02在泸州医学院神经生物学实验室完成。①实验材料:普通级6～8个月龄新西兰家兔36只,体质量2～2.75kg,雌雄不拘。②实验方法:采用随机数字法取兔32只,压榨损伤右侧面神经上颊支制备面神经损伤模型。③实验分组:随机分为手术对照组16只,不作穴位电针刺激,自然恢复;针刺组16只术后立即行翳风、颧髎、颊车、地仓、阳白、四白及合谷穴位电针治疗,1次/d,30min/次;另取4只家兔做正常对照组。④实验评估:于术后1,4,7,14d每组分别取4只兔麻醉后,经心灌注处死动物,苏木精-伊红染色观察面神经核的改变,免疫组织化学观察CD44的表达。结果:36只兔全部进入结果分析。①手术对照组和针刺组兔面神经核运动神经元的形态学改变:术后1d,两组细胞形态正常;术后4d,两组细胞肿胀、胞浆空泡化、染色质溶解、核仁偏移、尼氏小体消失;术后7d,手术对照组有明显神经元的死亡,针刺组仅有神经元变性表现,并出现核仁回归、尼氏小体重现;术后14d,手术对照组神经元的坏死更为明显,针刺组神经元肿胀及变性程度有明显改善。②各组CD44标记阳性面神经核运动神经元数目:正常组,面神经核中有CD44表达。术后1d,针刺组和手术对照组CD44有明显增加;术后4d,针刺组CD44阳性细胞数较手术对照组显著性增加(P<0.01);术后7d,手术对照组的CD44阳性细胞数目较针刺组增加(P<0.05)。术后14d,两组比较无差别,阳性细胞免疫染色着色不一。结论:穴位电刺激能促进黏附分子CD44在损伤面神经核的表达。     

Genetic variation in lipid desaturases and its impact on the development of human disease

Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.     

Programmed cell death in periodontitis: recent advances and future perspectives

Periodontitis is a highly prevalent infectious disease, characterized by destruction of the periodontium, and is the main cause of tooth loss. Periodontitis is initiated by periodontal pathogens, while other risk factors including smoking, stress, and systemic diseases aggravate its progression. Periodontitis affects many people worldwide, but the molecular mechanisms by which pathogens and risk factors destroy the periodontium are unclear. Programmed cell death (PCD), different from necrosis, is an active cell death mediated by a cascade of gene expression events and can be mainly classified into apoptosis, autophagy, necroptosis, and pyroptosis. Although PCD is involved in many inflammatory diseases, its correlation with periodontitis is unclear. After reviewing the relevant published articles, we found that apoptosis has indeed been reported to play a role in periodontitis. However, the role of autophagy in periodontitis needs further verification. Additionally, implication of necroptosis or pyroptosis in periodontitis remains unknown. Therefore, we recommend future studies, which will unravel the pivotal role of PCD in periodontitis, allowing us to prevent, diagnose, and treat the disease, as well as predict its outcomes.