Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

鼻咽癌组织中Survivin蛋白和HIF-1α表达水平及临床意义

目的 探讨鼻咽癌组织中Survivin蛋白和缺氧诱导因子-1α(HIF-1 α)表达水平及临床意义.方法 选取2010年12月-2015年12月经病理切片确诊为鼻咽癌的患者72例;同时选取24例慢性鼻咽炎组织标本进行对照.应用免疫组织化学检测Survivin蛋白和HIF-1α的表达情况,并分析其表达水平的临床意义.结果 鼻咽癌组织中Survivin蛋白和HIF-1α阳性表达率均高于慢性鼻咽炎组织(P＜ 0.001).Ⅲ+Ⅳ期鼻咽癌组织Survivin蛋白和HIF-1α的阳性表达率、中等及以上阳性表达率均高于Ⅰ+Ⅱ期鼻咽癌组织(P ＜0.001);有淋巴结转移的患者Survivin蛋白和HIF-1α的阳性表达率均高于无淋巴结转移的患者(P＜0.05和P＜0.001).结论 Survivin和HIF-1α表达在鼻咽癌组织中具有较高的表达,两者在鼻咽癌的分期,进展过程中起到了重要的作用.     

电针对胶原诱导性关节炎大鼠外周血与关节液中TNF-α、VEGF的影响

目的观察CIA大鼠造模成功后外周血和关节液中TNF-α、VEGF的改变,并且观测电针治疗后这些指标的变化。方法取样后测定CIA大鼠外周血和关节液中TNF-α、VEGF的含量,并与正常的大鼠样本进行比较;对CIA大鼠按疗程进行治疗,测定治疗后的这些指标,对指标进行治疗前后比较、与模型组比较。结果 CIA大鼠外周血和关节液中TNF-α、VEGF的含量高于正常组（P〈0.05）;电针治疗后这些指标有了显著改善（P〈0.05）,与模型组比较差异有统计学意义（P〈0.05）。结论电针能有效降低CIA大鼠外周血和关节液中TNF-α、VEGF的含量,这些致炎性因子的降低对阻止CIA大鼠关节滑膜细胞浸润、破骨细胞激活,抑制病变发展有非常重要的意义。     

聚乙二醇1000维生素E琥珀酸酯在纳米制剂中的应用进展

目的综述聚乙二醇1000维生素E琥珀酸酯(D-α-tocopherol polyethylene glycol 1000 succi-nate,TPGS)在各种纳米制剂中的最新进展。方法查阅国内外相关文献共48篇,对这些文献进行分析、概括和总结。结果 TPGS能够提高药物包封率和细胞吸收,改善药物释放,提高药物生物利用度,并能协同起抗癌疗效。广泛应用于聚合物纳米粒、聚合物胶束、纳米脂质体、纳米药物等纳米给药系统中。结论 TPGS在纳米制剂中有着良好应用前景。     

胱抑素C/肌酐比值在糖尿病肾病监测中的应用

目的建立胱抑素C/肌酐比值的参考值范围以及在糖尿病肾病监测中的应用。方法检测120例健康人员和65例糖尿病患者的尿胱抑素C、肌酐、微量白蛋白、α1-微球蛋白等指标,按α1-MG的检测结果将糖尿病患者分为正常、升高两组,胱抑素C/肌酐比值参考值范围按CLSI C28-A2进行统计处理。结果胱抑素C/肌酐比值参考值范围为0.7~8.5 mg·mol-1CR,胱抑素C/肌酐比值在肾小管功能受损组显著升高(P<0.01)。结论胱抑素C/肌酐比值有较高的灵敏度和特异性,是糖尿病肾病时肾小管功能障碍的敏感指标。     

The possible mechanisms of protocatechuic acid-induced central analgesia

It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT_2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300?mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300?mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5?mg/kg, i.p.), serotonin 5-HT_2A/2C receptor antagonist ketanserin (1?mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1?mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5?mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300?mg/kg in tail-immersion test, at the doses of 150 and 300?mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies.     

Polymer hydration and stiffness at biointerfaces and related cellular processes

The direct and indirect (by changing mechanical properties) effects of hydration at interfaces on cellular processes and tissue diseases are reviewed. The essential effect of substrate stiffness on cellular processes was demonstrated in the last decade. The combined effect of surface stiffness and hydration at interfaces has garnered much less attention, though hydration and dehydration play important roles in biological processes. This review focuses on the studies that demonstrate how hydration affects biological processes at interfaces. Elevated sodium and dehydration stimulate inflammatory signaling in endothelial cells and promote atherosclerosis. Various types of implant and blood contacting device coatings with varied surface stiffness and hydration have been reported. Effect of hydration on polymer modulus of elasticity and viscoelasticity was discussed taking into account cells adhesion, migration, proliferation, differentiation on surfaces with various degree of hydration. Future directions of research were considered, including the use of nanotechnology to regulate the hydration degree.     

1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐对大鼠心脏α_1受体的影响

DDPH 3 mg/kg对毁脊髓大鼠有拮抗甲氧胺升高左心室压力及室内压最大变化速率(±dP/dt_(max))、左室舒张末期压、血压和心率的作用;在大鼠离体工作心脏上,有普萘洛尔存在时,DDPH 1～10μmol/L有阻断苯福林升高左心室压力及dP/dt_(max)、主动脉流量和心率的作用;DDPH60μmol/L灌流大鼠在体心肺,有取消甲氧明提高左心室压力和心输出量的作用。DDPH尚可显著减慢大鼠工作心脏和在体心肺装置的心率。上述结果提示DDPH对血管平滑肌及心肌的α_1受体有阻断作用。