Caloric restriction alters galanin and its receptor in hypothalamus of wistar rats

Caloric restriction (CR) reverses obesity and insulin resistance, yet the detailed mechanism underlying its beneficial effects is poorly understood. The galanin system is closely associated with energy metabolism. It is yet unclear whether this effect of CR is operating through the regulation of the galanin system. To test this effect, we subjected rats to either 60% or 40% calorie restriction for one week. After the one-week's experiment, galanin and many genes associated with the function of metabolism were examined. The present findings showed that 7 days of 60% or 40% calorie restriction lowered body weight and plasma glucose concentration in rats, suggesting that rats under CR have improved weight loss and systemic glucose metabolism. Besides, the lower plasma glucose was associated with an increase in muscle glucose uptake resulting from elevations of both glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in skeletal muscles. Moreover, the levels of galanin and its receptors (GALR1-3) mRNA markedly increased in the hypothalamus of CR rats. Taken together, these results supported that non-pharmacological activation of the galanin/GALR signaling with CR regimen led to activation of the PGC-1α/GLUT4 axis in skeletal muscles which can enhance energy metabolism. The current findings provide additional evidence that galanin is a critical factor for CR-induced weight loss and metabolic changes. CR regimen may be recognized as a non-pharmacological intervention that could prevent obesity and its associated metabolic disorders.     

Translating depression biomarkers for improved targeted therapies

Mood disorders are among the most common medical conditions and cause amongst the greatest disease burden. Currently approved antidepressants target monoamine pathways; these medicines take many weeks to relieve symptoms, and most patients do not have sustained responses. This review will highlight recent advances in translational science identifying dysfunctional biochemical processes and neuronal circuits associated with mood disorders. We will also summarize strategies for targeting these pathways and for enhancing synaptic plasticity to develop most effective and rapidly acting antidepressant therapies.     

藏药翁布总苷对大鼠佐剂性关节炎的治疗作用

目的：研究翁布总苷对佐剂性关节炎（AA）大鼠的治疗作用及部分机制。方法：用弗氏完全佐剂（FCA）诱导大鼠AA模型。足容积法测量继发侧足肿胀度,进行关节炎评分,测定AA大鼠血清中超氧化物歧化酶（SOD）和一氧化氮（NO）的水平,酶联免疫吸附测定法（ELISA）测定脂多糖（LPS）诱导的滑膜腔单核巨噬细胞（AM）产生IL-1、TNF-α和PGE2的水平。结果：致炎后第12天,大鼠继发性关节炎出现,同时灌胃给予不同剂量的翁布总苷及吲哚美辛,连续两周。从第24天起,翁布总苷（1.0、1.5 g/kg）对AA大鼠继发性炎症反应（继发性足肿胀、多发性关节炎）有明显的治疗作用。翁布总苷（1.0、1.5 g/kg）可不同程度纠正AA大鼠血清中低下的SOD水平,降低AA大鼠血清中NO水平,同时降低AA大鼠滑膜腔单核巨噬细胞产生过高的白介素（IL-1）、肿瘤坏死因子（TNF-α）、前列腺素E2（PEG2）。结论：翁布总苷对AA大鼠继发性炎症有治疗作用,其作用机制可能与维持细胞因子网络平衡,减少炎症介质的释放和提高机体抗氧化能力有关。     

重组腺病毒介导TIMP1基因对类风湿关节炎大鼠滑膜新生血管的影响

背景：滑膜血管翳形成后可分泌一系列酶如基质金属蛋白酶等,可促进血管新生和炎症反应,形成软骨和骨的破坏。 目的：研究重组腺病毒介导的基质金属蛋白酶组织抑制因子1(TIMP1)基因对类风湿关节炎模型大鼠关节炎症及滑膜血管新生的影响。 设计、时间及地点：基因治疗动物体内实验,于2005-07/2007-06在扬州大学完成。 材料：HEK-293A细胞系购于中科院上海细胞生物研究所细胞库,ECV-304细胞为自备,带有绿色荧光蛋白(GFP)基因或/和基质金属蛋白酶组织抑制因子1基因的重组腺病毒(rAD-GFP-TIMP1及rAD-GFP)的病毒贮存液由南京师范大学分子医学实验室惠赠。清洁级4~6周龄SD大鼠40只。 方法：将rAD-GFP-TIMP1和rAD-GFP扩增、纯化,用紫外分光光度法检测重组腺病毒的颗粒数。用rAD-GFP-TIMP1感染ECV-304细胞检测病毒活力。30只大鼠注射Ⅱ型胶原建立类风湿关节炎大鼠模型,分为：①模型组注射PBS。②模型+ rAD-GFP-TIMP1组注射rAD-GFP-TIMP1。③模型+RAD-GFP组注射rAD-GFP,均为膝关节腔内注射;10只大鼠注射生理盐水造模做对照组。1次/周,4周。 主要观察指标：①rAD-GFP-TIMP1及rAD-GFP在HEK-293A细胞中扩增、纯化后病毒的颗粒数及GFP蛋白表达。②各组大鼠每周进行1次关节炎指数评分。③于造模第4周处死大鼠取膝关节行滑膜病理免疫组织化学染色及微血管密度检测。④取血清采用Western Blot检测大鼠体内基质金属蛋白酶组织抑制因子1、血管内皮生长因子、基质金属蛋白酶1,2,3,9的表达。 结果：①纯化后的rAD-GFP-TIMP1和rAD-GFP滴度分别为：5.7×1012,4.8×1012 pfu/mL;A260 nm/A280 nm均> 1.3;用rAD-GFP-TIMP1感染ECV-304细胞获得成功提示病毒活力正常。②感染rAD-GFP-TIMP1的关节炎大鼠血清中基质金属蛋 白酶组织抑制因子1获得了高表达,rAD-GFP-TIMP1治疗组大鼠血清中基质金属蛋白酶组织抑制因子1的相对含量明显高于模型组和rAD-GFP治疗组。③rAD-GFP-TIMP1治疗组的关节炎指数评分明显低于模型组。④感染rAD-GFP-TIMP1可使滑膜新生血管数目明显减少,同时能抑制基质金属蛋白酶1,3,9的表达,而对血管内皮生长因子和基质金属蛋白酶2的抑制作用不明显。 结论：①感染rAD-GFP-TIMP1的大鼠体内基质金属蛋白酶组织抑制因子1基因获得了有效的表达。②感染rAD-GFP-TIMP1能明显降低模型大鼠的关节炎指数评分。③血管内皮生长因子,基质金属蛋白酶1,2,3,9共同参与促进关节炎大鼠滑膜血管新生的形成和发展,rAD-GFP-TIMP1可能通过抑制基质金属蛋白酶1,3,9的表达而发挥抗血管新生的作用。     

Twist、Snail蛋白在喉鳞状细胞癌中的表达及其临床意义

目的 探讨Twist、Snail蛋白在喉鳞状细胞癌（喉鳞癌）组织中的表达及其临床意义.方法 应用免疫组织化学法检测60例喉鳞癌组织、30例癌旁组织中Twist、Snail蛋白的表达情况.结果 喉鳞癌组织中Twist的阳性表达为68.3％（41/60）,Snail的阳性表达为71.7％ （43/60）,均显著高于癌旁组织中的表达率;在喉鳞癌组织中Twist、Snail蛋白的表达之间存在显著正相关,相关系数（r）为0.529（P ＜0.01）.结论 喉鳞癌组织中存在Twist、Snail蛋白的高表达,两者的联合表达能增加肿瘤细胞侵袭力,促进喉鳞癌的浸润、转移.     

Links Between Infectious Diseases and Cardiovascular Disease: A Growing Body of Evidence

It is widely acknowledged that a systemic inflammatory process is involved in atherogenesis leading to subsequent cardiovascular disease (CVD). Several types of microbes have been implicated as possible causative agents in acquired CVD. This article reviews current and emerging links established between specific microorganisms and cardiac vessel and other vascular damage. Studies are reviewed that have investigated a possible role for antibiotics in treatment and prevention; other potential primary and secondary preventive measures are then explored. Nurse practitioners have an important role in recognizing and effectively managing the multiple complex processes involved in the development of CVD.