左旋多巴甲酯对斜视性弱视猫模型的作用

目的观察左旋多巴甲酯对斜视性弱视猫视皮质c-fos基因表达的影响,探讨盐酸左旋多巴甲酯对弱视的治疗作用及其作用机制。方法正常幼猫30只随机分成6组:左旋多巴甲酯低剂量、中剂量和高剂量组、模型对照组、阳性对照组及正常对照组,每组5只,于4wk时行眼外直肌切除术造成人工斜视(正常对照组除外),经图形视觉诱发电位(P-VEP)确定形成弱视后,灌胃给予左旋多巴甲酯20,40,80mg·kg-1,阳性对照组给予左旋多巴40mg·kg-1,正常对照组及模型组均给予等量生理盐水。观察P-VEP的变化并采用原位杂交技术检测各组猫视皮质的c-fosmRNA表达情况。结果左旋多巴甲酯明显的缩短猫斜视性弱视眼的P100波峰潜时及提高P100波幅值。斜视猫视皮质的阳性染色细胞较正常猫减少,差异有显著性(P<0.01),用药后各组阳性染色细胞较模型对照组明显增加(P<0.01)。结论左旋多巴甲酯明显地改善斜视性弱视猫模型弱视眼的传导和感觉功能,其机制可能与左旋多巴甲酯进入脑内的量增加及介导视皮质c-fos mRNA的表达调控有关。     

The effect of early auditory deprivation on the age-dependent expression pattern of NR2B mRNA in rat auditory cortex

NMDA receptors have been well shown to be involved in neuronal plasticity. In order to understand the role of NR2B subtype NMDA receptors in auditory function development, the present study investigated the effect of early auditory deprivation on the expression of NR2B mRNA in rat auditory cortex (AC) during postnatal development. For normal rats, the NR2B mRNA expression was highest at birth (postnatal day 1 [P1]) and declined rapidly to low level during adulthood. However, during the critical period of rat auditory development (two to three weeks after birth), there was a transient NR2B expression peak on postnatal day 21 (P21). For the auditory-deprived rats, the general declining trend of NR2B mRNA expression from birth to adult was similar to that observed in the normal group, whereas the expression level from P15 to P27 was significantly lower than normal and the transient peak on P21 disappeared. In both groups, the distribution pattern of NR2B mRNA-positive neurons was also examined in various layers and dorsal, medial and ventral subdistricts of AC. There is no significant effect on the spatial expression of the NR2B mRNA in the AC between normal and deprived group. Our results indicated that the early auditory deprivation decreased the expression levels of NR2B mRNA in AC during the critical period of rat auditory development, suggesting that NR2B plays an important role in the developmental plasticity of auditory function in rats.     

Alterations in BDNF and trkB mRNAs following acute or sensitizing cocaine treatments and withdrawal

In the present study, we used in situ hybridization to examine the influence of acute or repeated cocaine administrations and withdrawal from repeated cocaine treatment on the level of brain-derived neurotrophic factor (BDNF) and its receptor trkB mRNAs in rat brain. Cocaine (10 mg/kg i.p.) injected acutely produced locomotor hyperactivation, while repeated (single injection for 5 days) administrations of cocaine (10 mg/kg) induced a two-fold increases in the locomotor activity in rats in response to a challenge cocaine dose (10 mg/kg) on day 10, as compared to the saline-treated animals (sensitization). Cocaine treatments induced a brain-region-specific decrease in the levels of trkB mRNA. On the other hand, BDNF mRNA in the rat hippocampus was increased only in the group of rats subjected to cocaine withdrawal. Animals under cocaine withdrawal demonstrated a significant increase in the immobility time measured by the use of modified forced swimming test. Therefore, the increases in the levels of BDNF mRNA in the rat hippocampus seem to be correlated with "depressive-like" behavioral effects during withdrawal from repeated cocaine treatment. In the shell (but not in the core) of the nucleus accumbens, the levels of BDNF mRNA were significantly increased following acute and repeated cocaine treatment as well as during cocaine withdrawal, which indicates that the alterations in the neurotrophin level in the brain region important for the expression of cocaine-induced sensitization involve other mechanisms.     

Quantitative detection of metastasis-associated 1 mRNA and protein expression in breast cancer

Objective Understanding the mechanism of breast cancer metastasis will benefit those patients in need of aggressive treatment and avoid side effects caused by chemotherapy over treatment.Recently,a pot...     

Foxp3 mRNA在肝癌外周血中的表达及肝动脉化疗栓塞对其表达的影响

目的 探讨肝癌患者外周血单核细胞中叉头状螺旋转录因子(Foxp3)mRNA表达量的变化.方法 分别收集30例肝癌患者肝动脉化疗栓塞(TACE)化疗前、化疗后1周外周血标本和14例健康人群及14例慢性乙肝患者的外周血标本,以GADPH为内参采用RT-PCR方法对外周血单核细胞Foxp3 mRNA表达水平进行检测.结果 Foxp3 mRNA表达水平在健康对照组、慢性乙肝组及肝癌TACE术前组间比较,差异有统计学意义(P＜0.01);健康对照组Foxp3 mRNA表达水平明显低于慢性乙肝组及肝癌TACE术前组,差异有统计学意义(P＜0.01),慢性乙肝组Foxp3 mRNA表达水平明显低于肝癌TACE术前组,差异有统计学意义(P＜0.01),肝癌TACE术后组中Foxp3 mRNA表达水平明显低于肝癌TACE术前组,两者比较差异有统计学意义(t=48.3,P＜0.01).结论 肝癌患者外周血单核细胞Foxp3 mRNA表达明显高于慢性乙肝组及健康对照组,说明Foxp3 mRNA表达的变化与肝癌的发生及发展有关.肝癌患者行TACE化疗后Foxp3 mRNA表达量明显下降,说明TACE可影响肝癌患者机体的免疫功能.     

瘢痕疙瘩成纤维细胞中有关传导分子mRNA水平的实验研究

目的比较转化生长因子βSmad蛋白（TGF-β／Smads）信号传导通路中有关传导分子mRNA在瘢痕疙瘩成纤维细胞中的表达。方法切取确诊为瘢痕疙瘩患者的部分瘢痕疙瘩组织,正常者的皮肤作为对照组;细胞总RNA提取;反转录-聚合酶链反应（RT—PCR）检测TIEG、Smad2、Smad7mRNA的表达。结果瘢痕疙瘩中成纤维细胞TIEG、Smad2 mRNA表达远高于正常皮肤,Smad7 mRNA表达低于正常皮肤（P〈0．05）。结论瘢痕疙瘩中的成纤维细胞表达TIEG增高,使表达Smad2增强,Smad7减弱,促使瘢痕生成。     

黄芪多糖对2型糖尿病大鼠HPA轴及海马糖皮质激素受体水平的调节作用

目的：观察黄芪多糖（APS）对2型糖尿病大鼠HPA轴及海马组织中糖皮质激素受体水平的调节作用。方法：30只SD大鼠随机分为正常对照组、DM模型组、APS干预组组,采用小剂量链脲佐茵素加高脂饮食饲养的方法建立2型糖尿病肥胖大鼠模型。成模4周后,断头处死所有大鼠,检测各组大鼠血CRH、ACTH、CorT的含量,以及海马组织中糖皮质激素受体（GR）mRNA的表达。结果：DM模型组血ACTH、CorT含量较正常组显著升高,与模型组大鼠相比,APS干预组大鼠血ACTH、CorT含量显著降低（P〈0．05）;DM模型组海马GRmRNA含量较正常组极显著降低,与模型组大鼠相比,APS干预组大鼠海马GRmRNA含量明显上调（P〈0．01）。结论：APS保护高糖环境下的海马组织,改善HPA轴功能。对糖尿病以及合并症起到治疗作用。     

Inhibition of immunological function mediated DNA damage of alveolar macrophages caused by cigarette smoke in mice

Exposure to cigarette smoke impairs the pulmonary immune system, including alveolar macrophage function, although the mechanisms by which this occurs are not fully elucidated. This study investigates the effect of cigarette smoke exposure on the antigen-presenting activity of alveolar macrophages, which is required for antigen-specific response to T cells. C57BL/6 mice were exposed to cigarette smoke for 10 days using a Hamburg II smoking machine, and alveolar macrophages were obtained by bronchoalveolar lavage. The antigen-presenting activity of alveolar macrophages was significantly inhibited in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. Major histocompatibility complex class II cell surface molecule–positive cells, B7-1 molecule–positive cells, and interleukin-1β messenger RNA gene expression in alveolar macrophages were significantly decreased in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. In contrast, DNA damage and generation of superoxide and hydrogen peroxide in alveolar macrophages were significantly increased by cigarette smoke exposure. These results suggest that inhibition of the antigen-presenting activity of alveolar macrophages may result from decreased expression of major histocompatibility complex class II and B7-1 molecules and interleukin-1β messenger RNA gene expression following cigarette smoke exposure. Furthermore, inhibition of antigen presentation in alveolar macrophage may result from DNA damage induced by excessive amounts of reactive oxygen species being generated by alveolar macrophages following cigarette smoke exposure. These findings suggest that cigarette smoke impairs the immunological function of alveolar macrophages and, as a result, increases the risk for pulmonary infection.     

Use of mTOR inhibitors in the treatment of malignancies

Introduction: mTOR and its effectors are central regulators of cellular metabolism in malignant cells and control mRNA translation that ultimately leads to generation of mitogenic proteins. Efforts to target this pathway have been ongoing for over a decade and have had a substantial impact in the management of certain patients with solid tumors. Although activity of mTOR inhibitors has been established in several trials, inability to predict responses remains a limiting factor for the successful incorporation of these agents in the treatment of a variety of malignancies.

Areas covered: Recent clinical findings are discussed and studies focused on advanced phase development of mTOR inhibitors are summarized. The emergence of precision medicine approaches and the effects that such approaches may have on prospective selection of patients for treatment with mTOR inhibitors are discussed. Also, potential approaches and future prospects to improve responses to mTOR inhibitors by modulating other parallel mitogenic pathways essential for malignant cell proliferation are discussed.

Expert opinion: Selective targeting of the mTOR pathway offers significant clinical advantage in subsets of patients with diverse malignancies. Approaches to enhance responses by concomitant targeting of resistance pathways and/or predict responses via identification of molecular markers should substantially impact this area in the near and distant future.