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.     

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。     

Treatments and compositions targeting α-synuclein: a patent review (2010-2016)

Introduction: Abnormal deposition of α-synuclein (ASN) is a hallmark and possible central mechanism of Parkinson’s disease and other synucleinopathies. Their therapy is currently hampered by the lack of early, screening-compatible diagnostic methods and efficient treatments.

Areas covered: Patent applications related to synucleinopathies obtained from Patentscope and Espacenet databases are described against the background of current knowledge regarding the regulatory mechanisms of ASN behavior including alternative splicing, post-translational modifications, molecular interactions, aggregation, degradation, and changes in localization.

Expert opinion: As the central pathological feature and possibly one of root causes in a number of neurodegenerative diseases, deregulation of ASN is a potentially optimal diagnostic and therapeutic target. Changes in total ASN may have diagnostic value, especially if non-invasive /peripheral tissue tests can be developed. Targeting the whole ASN pool for therapeutic purposes may be problematic, however. ASN mutations, truncation, and post-translational modifications have great potential value; therapeutic approaches selective towards aggregated or aggregation-prone ASN forms may lead to more successful and safe treatments. Numerous ASN interactions with signaling pathways, protein degradation and stress mechanisms widen its potential therapeutic significance dramatically. However, significant improvement in the basic knowledge on ASN is necessary to fully exploit these opportunities.     

灵芝孢子粉对急性肝衰竭模型大鼠血清TNF—α及HGF的影响

目的：通过观察灵芝孢子粉对急性肝衰竭模型大鼠肿瘤坏死因子（TNF—α）、肝细胞生长因子（HGF）、及肠道双歧杆菌的调整作用,从微生态学的角度来评价灵芝孢子粉对肝衰竭造成损伤的肝细胞再生过程中细胞因子的影响。方法：本实验采用D-氨基半乳糖（D—Gal）制备急性肝衰竭大鼠模型．分3组：健康对照组,自然恢复组,灵芝孢子粉组。实验第14天处死实验动物,检测肠道菌群、血清ALT、血清TNF—α、HGF的变化。结果：灵芝孢子粉能调整肠道菌群失调,降低THF—α含量．提高血清HGF含量。从而有效地改善肝功能。各项指标与对照组相比差异显著（P〈0．01）。结论：灵芝孢子粉具有扶植双歧杆菌及抑制肝大肠杆菌过度生长的作用,同时具有保护肝脏细胞的功能,促进HGF的分泌,降低THF—α、促进肝细胞再生。     

PAK1、HIF-1α在结肠癌组织中侵袭、转移中的表达研究

目的 探讨PAK1(p-21活化激酶1)、缺氧诱导因子1α (HIF-1α)在结肠癌组织中侵袭、转移中的表达.方法 分别采用免疫组化法和荧光原位杂交检测41例结肠癌组织和癌旁正常组织中的HIF-1α、PAK1表达,并分析HIF-1α、PAK1与临床病理的关系.结果 本组研究中,结肠癌组织HIF-1α mRNA、PAK1 mRNA阳性表达率和HIF-1α蛋白、PAK1蛋白阳性表达率均显著高于癌旁正常组织(P＜0.05).从蛋白水平上讲,HIF-1α、PAK1在淋巴结转移、TNM分期为Ⅲ～Ⅵ期和Dukes分期为C、D期中阳性表达率显著高于无淋巴结转移、TNM分期为Ⅰ～Ⅱ期、Dukes分期为A、B期患者,差异具有统计学意义(P＜0.05).Spearman等级相关性分析显示,在蛋白水平,HIF-1α、PAK1在结直肠癌表达中呈正相关关系.结论 HIF-1α、PAK1可能参与结肠转侵袭和转移中.     

不同产地槐米炮制前后主成分的含量变化对α－葡萄糖苷酶活性抑制的影响

目的：比较研究10批不同产地槐米炒制前后对槐米中芦丁,槲皮素的含量变化及其对α－糖苷酶活性抑制作用的影响。方法对10批不同产地的槐米药材分别进行炒制,采用高效液相色谱法分别测定各槐米药材提取液中芦丁和槲皮素含量;以对硝基苯酚－β－1,4－葡萄糖苷（ pNPG）为底物,阿卡波糖为阳性对照,测定各槐米药材提取液对α－葡萄糖苷酶活性抑制率,比较了芦丁和槲皮素含量变化对α－葡萄糖苷酶的抑制活性的影响。结果经过炒制后,10批槐米炒制品中的芦丁含量均有所降低,而槲皮素含量则明显升高;槐米炒制品对α－糖苷酶活性抑制作用均优于生品。结论不同产地槐米炮制后,由于槲皮素含量的普遍升高,导致了槐米炒制品对α－葡萄糖苷酶活性抑制作用升高,表明槲皮素在对α－糖苷酶抑制活性起着重要作用。在治疗糖尿病疾病时选用炒制槐米更为合理。     

密蒙花总黄酮对去势雄鼠干眼症模型角膜和泪腺组织中TNF-α,IL-1β表达的影响

目的:探讨密蒙花总黄酮对去势雄鼠干眼症动物模型角膜及泪腺组织炎症因子表达的影响与组织损伤的关系。方法:选取150只健康1月龄Wistar雄性大鼠随机分为5组(正常组、假手术组、手术对照组、雄激素治疗组、密蒙花总黄酮治疗组,分别用A,B,C,D,E组表示),每组30只。将C,D,E三组实验鼠切除双侧睾丸及附睾;B组只切开阴囊,不切除睾丸,作为假手术对照组,A组不作处理。自造模后1wk,待伤口基本愈合开始用药。A,B,C组以生理盐水灌胃,1次/d;D组用丙酸睾酮注射液大腿肌肉注射,3d1次;E组以密蒙花提取物生理盐水混悬液灌胃,1次/d。各组实验动物分别于用药1,3,5mo后随机取10只,行SchirmerⅠ试验、泪膜破裂时间(break-up time,BUT)及角膜荧光素染色检查并处死各组动物,取双眼泪腺、角膜组织采用免疫组织化学方法观察各组角膜和泪腺组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),白细胞介素1β(interleukin 1β,IL-1β)蛋白的表达。结果:A与B组泪腺、角膜上皮细胞中TNF-α,IL-1β阳性表达均不明显;C组泪腺、角膜上皮细胞中TNF-α,IL-1β阳性表达的细胞数明显高于D,E组(P<0.05);D,E各组间差异不显著(P>0.05)。结论:去势雄鼠干眼症角膜和泪腺组织局部炎症反应可能是角膜损伤和泪腺分泌功能丧失的原因之一,TNF-α,IL-1β表达增加与其炎症反应有关。密蒙花总黄酮能够下调去势雄鼠角膜和泪腺局部TNF-α,IL-1β蛋白的表达,可能是其治疗干眼症的关键机制之一。     

卤虫卵油脂肪酸组成分析及α-亚麻酸含量测定

目的采用毛细管气相色谱法分析卤虫卵油的脂肪酸主要组成并建立测定卤虫卵油中α-亚麻酸含量的方法。方法采用DB-WAX毛细管柱;程序升温:起始温度150℃,升温速率3℃.min-1,结束温度240℃,保持10 min;氢焰离子化检测器温度250℃。结果卤虫卵油中不饱和脂肪酸占总脂肪酸质量分数超过70%,其中油酸、α-亚麻酸质量分数分别为26.9%、27.7%。α-亚麻酸甲酯质量在0.719～3.60μg内线性关系良好(r=0.999 8,n=5),平均回收率为101.6%,RSD=2.3%。结论毛细管气相色谱法可作为卤虫卵油α-亚麻酸的含量测定方法。