Ultrastructural immunogold labelling of human langerhans cells enriched epidermal cell suspension

Summary Colloidal gold particles are well suited as markers in electron microscopy. Indirect immunogold staining was used to identify cell membrane antigens defined by monoclonal antibodies OKT6 and BL6 on human Langerhans cells (LC) in suspensions. Isolated epidermal cells were obtained by skin trypsinization and enriched or depleted in OKT6 positive on BL6 positive LC using the panning method: incubation of OKT6 or BL6 preincubated cells on immunoglobulin coated dishes. Indirect immunogold staining was then performed after prefixation in 2% paraformaldehyde. In LC enriched suspensions, only LC exhibited a specific membrane labelling with OKT6 or BL6 recognized by the presence of small evently distributed gold granules. Neither Birbeck granules, nor other cytoplasmic organelles, were labelled. No other epidermal cells were found positive. In LC depleted suspensions, no labelling was observed. Immunogold labelling on LC enriched suspensions after panning is now in progress for the qualitative evaluation and the quantitative analysis of cell surface constituants and antigens expressed by human dendritic epidermal cells.Presented at the Society for Investigative Dermatology and the European Society for Dermatological Research (Joint International Meeting Washington, April 27, May 1, 1983)     

富氧对海拔3700m高原人体运动心力储备的影响

目的　探讨富氧对高原人体运动心力储备方面的影响。方法　对海拔 3 70 0m高原的 1 2名健康青年富氧 (氧浓度为 2 4%～ 2 5 %)前后分别进行踏阶运动 ,采用心力监护仪采集和记录心动周期和心力信息 ,把完成规定运动量运动后第一心音 (S1 )幅值对安静时S1 幅值增加的相应倍数评估心肌收缩能力储备指数 (CCRI) ;利用舒张期和收缩期时限数据计算舒张期 /收缩期比值 (D/S比 )。结果　运动后较安静时HR ,D/S ,S1 幅值均增高 ,有非常显著性差异 (P <0 .0 1 ) ;富氧运动较未富氧运动CCRI,D/S ,S1 幅值增高 ,有显著性差异 (P <0 .0 5 ) ,HR无统计学意义 (P >0 .0 5 )。结论　高原低氧环境下心脏储备主要是心肌收缩能力储备而不是心率储备。富氧对增强机体心力储备具有重要作用     

富氧对缺氧大鼠心肌琥珀酸脱氢酶及超微结构的影响

目的：探讨富氧对缺氧大鼠心肌损伤的保护作用及机理。方法：雄性Wistar大鼠32只随机分为平原对照组、低氧组、富氧组，低氧组在模拟海拔5400m低压舱内24h，富氧组在模拟5400m的低压舱内12h，然后富氧（27．0％的氧混合气）12h，观察心肌琥珀酸脱氢酶（SDH）及超微结构的改变。结果：低氧组心肌细胞灶性变性坏死，肌丝溶解凝固，间质水肿液和纤维素样渗出。富氧组心肌无明显病变，仅滑面内质网轻度扩张。富氧组SDH活性明显高于低氧组。结论：低氧导致心肌SDH活性及超微结构的改变，富氧对心肌有保护作用。     

海拔5380m富氧室对士兵力竭运动后心肌酶活性的影响

目的 :研究富氧室对高原人体运动血中心肌酶活性的影响。方法 :在海拔 53 80m将室内氧浓度提高到 2 7% ,检测 10名青年安静时、进入富氧室前后力竭运动后的天冬氨酸基转移酶 (AST)、乳酸脱氢酶 (LDH)、α -羟丁酸脱氢酶 (α -HBDH)、肌酸肌酶 (CK)及其同工酶 (CK -MB)的含量或活性。结果 :力竭运动后较安静时AST、LDH、α -HBDH、CK及CK -MB活性均升高(P <0 .0 1或P <0 .0 5)。富氧及力竭运动后较未富氧力竭运动后AST、LDH、CK -MB降低 (P <0 .0 1或 <0 .0 5) ,α -HBDH、CK无统计学差异 (P >0 .0 5)。结论 :富氧能减少高原运动时心肌酶的释放 ,增强氧合功能 ,是一种较为理想的高原供氧途径     

帕金森病和抑郁症转录组生物信息学分析

目的抑郁症状(MDD)是帕金森病(PD)常见的非运动症状,探讨帕金森病和抑郁症可能具有的共同致病机制。方法通过文本挖掘及转录组数据分析帕金森病与抑郁症共同的致病机制。结果文本挖掘发现63. 8%的MDD基因和32%的PD基因为共有基因及438个共有的生物学过程;转录组筛选出有统计学意义的10个共同差异基因:I类肌球蛋白(MYO1F)、活化免疫球蛋白样受体(LILRA2)、垂体腺苷酸环化酶激活多肽(ADCYAP1)、骨骼肌肌球蛋白轻链激酶(MYLK2)、钙结合蛋白2(CLSTN2)、钙调蛋白依赖性蛋白激酶4(CAMK4)、前蛋白转化酶枯草杆菌蛋白酶1 (PCSK1)、瞬时受体电位阳离子通道5(TRPC5)、钠离子葡萄糖联合转运子(SLC5A1)、酪氨酸酶相关蛋白1 (TYPR1)(P 0. 01);基因功能富集分析发现PD和MDD具有相同的14个生物学过程,6个细胞组成,10个分子功能,并且有3个相同的京都基因与基因组百科全书(KEGG)信号通路(P 0. 05);通过蛋白质网络构建,筛选出4个共同的关键基因(MYO1F、CAMK4、PCSK1、TRPC5);通过对蛋白质网络模块分析后发现关键模块具有共同的生物学过程。结论帕金森病和抑郁症具有共同的致病基因及通路,这为帕金森病和抑郁症伴存现象提供了理论基础。     

Mid‐life environmental enrichment increases synaptic density in CA1 in a mouse model of Aβ‐associated pathology and positively influences synaptic and cognitive health in healthy ageing

Early‐life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later‐life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later‐life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APP_SWE/PS1_dE9) from 6 months of age. After 6 months of housing in standard laboratory cages, APP_SWE/PS1_dE9 (n = 27) and healthy wildtype (n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to Aβ plaque pathology in the neocortex or hippocampus of APP_SWE/PS1_dE9 mice. However, a significant increase in synaptophysin immunolabeled puncta in the hippocampal subregion, CA1, in APP_SWE/PS1_dE9 mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APP_SWE/PS1_dE9 mice exposed to EE, however, no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later‐life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with Aβ deposition.     

基于网络药理学探讨小青龙汤治疗慢性阻塞性肺疾病的作用机制

目的：利用网络药理学分析小青龙汤治疗慢性阻塞性肺疾病（COPD）的作用机制。方法：在中药系统药理学数据库与分析平台（TCMSP）检索小青龙汤药物活性成分和靶点,绘制中药-化合物-靶基因网络,筛选关键化合物;利用GeneCards和人类孟德尔遗传数据库（OMIM）搜索COPD疾病基因;绘制韦恩图并获取药物-疾病共同基因;利用小青龙汤-慢阻肺药物疾病共同基因绘制蛋白质-蛋白质相互作用（PPI）网络,根据网络关系选择核心基因;对核心基因分别进行基因本体（GO）功能注释和富集分析和京都基因和基因组百科全书（KEGG）通路富集分析。结果：挖掘得到小青龙汤中药活性成分137个,潜在作用靶点188个,慢性阻塞性肺疾病相关靶点6 949个,小青龙汤-COPD共同靶点160个,主要富集于92个生物过程和49条信号通路上。结论：小青龙汤中多个药物含有山柰酚、槲皮素、（+）-儿茶素、豆甾醇、β-谷固醇等成分,可作用于AKT1、IL6、MAPK1、PTGS2、TP53等核心基因,调控氧化应激反应、血小板α-颗粒等生物过程,参与HIF-1、PI3K-AKT信号通路的调节,干预氧化应激反应和炎症反应等过程,产生抑制炎症反应、抗氧化应激的作用,进而通过上述过程参与COPD的炎症反应与氧化应激过程。     

Enriched environment promotes adult neural progenitor cell mobilization in mouse demyelination models

Since the discovery of adult neural stem cells, mobilization of endogenous stem cells from the subventricular zone (SVZ) emerges as a promising strategy to promote brain repair. Here, we examined the effect of environment enrichment on SVZ cell mobilization in demyelinating pathologies. We showed that enriched housing conditions reduced functional impairment in experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. Furthermore, both in a focal demyelination model (lysolecithin injection) and in the inflammatory EAE model, SVZ mitotic activity and the number of SVZ-derived cells in demyelinated areas were significantly increased by environment enrichment. Enriched housing conditions also promoted the oligodendrocyte fate of SVZ-recruited cells in the EAE lesions. Altogether our results show that environment enrichment provides beneficial conditions to promote the mobilization of neural progenitors into demyelinating lesions and to favour functional recovery.     

Environmental enrichment improves cognitive deficits in Spontaneously Hypertensive Rats (SHR): Relevance for Attention Deficit/Hyperactivity Disorder (ADHD)

The interaction between genes and environment seems to be relevant for the development of Attention Deficit/Hyperactivity Disorder (ADHD), one of the most prevalent childhood psychiatric diseases. The occurrence of ADHD is typically associated with poor academic performance, probably reflecting learning difficulties and/or cognitive impulsiveness. The inbred Spontaneously Hypertensive Rats (SHR) strain has often been considered as an animal model of ADHD, since they ‘naturally’ display the main ADHD symptomatology. Although pharmacological agents improve SHR's cognitive deficits, little is known about the involvement of environmental factors in SHR disabilities and to what extent ‘protective’ non-pharmacological factors may be considered as strategy for ADHD prevention. Here we investigated whether the rearing environment during neurodevelopment may counteract later cognitive deficits presented by adult SHR. Wistar (WIS) rats were also used to investigate whether the putative effects of environmental enrichment depend on a specific genetic background. The animals were reared in enriched environment (EE) or standard environment (SE) from the post-natal day 21 until 3 months of age (adulthood) and tested for cognitive and non-cognitive phenotypes. EE improved SHR's performance in open field habituation, water maze spatial reference, social and object recognition tasks, while non-cognitive traits, such as nociception and hypertension, were not affected by EE. Response of WIS rats was generally not affected by the present EE. These results show that the general low cognitive performance presented by SHR rats strongly depends on the rearing environment and they may suggest modifications of the familial environment as a putative preventive strategy to cope with ADHD.     

17β-estradiol and enriched environment accelerate cognitive recovery after focal brain ischemia

Cognitive impairments, including spatial memory and learning deficiencies, are common after ischemic stroke. Estrogen substitution improves cognitive functions in post-menopausal women and ovariectomized rodents, partially through induction of neuroplasticity in the hippocampal formation. Post-ischemic housing of male rats in an enriched environment (EE) improves functional outcome, without changing infarct volume. We hypothesized that 17β-estradiol combined with an EE would accelerate cognitive recovery after focal brain ischemia in ovariectomized rats and that recovery would be related to altered expression of nerve growth factor-induced gene (NGFI)-A in the hippocampus. 17β-estradiol or placebo pellets were implanted 6 h after transient middle cerebral artery occlusion. Two days later, rats were placed in an EE or a deprived environment (DE) for 6 weeks. At 5 weeks after middle cerebral artery occlusion, 17β-estradiol-treated rats housed in an EE showed improvements in cognitive function (i.e. shorter latency and path in the Morris water maze task) compared with placebo-treated animals housed in an EE. Furthermore, beneficial effects on latency and path were observed when comparing EE-housed vs. DE-housed 17β-estradiol-treated rats. When comparing 17β-estradiol-treated EE-housed rats vs. placebo-treated DE-housed rats, pronounced effects on latency and path were observed. Infarct volumes did not differ between groups. 17β-estradiol-treated EE-housed rats had significantly higher NGFI-A mRNA expression bilaterally in the cornu ammonis 1 region and in the ipsilateral dentate gyrus of the hippocampus, compared with placebo-treated EE-housed rats. In conclusion, 17β-estradiol treatment combined with an EE improved recovery of cognitive function after experimental brain ischemia, putatively through the upregulation of NGFI-A in hippocampal subregions.