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101.
Hongyan Liu Xiaoming Qiang Qing Song Wei Li Yuxi He Chanyuan Ye Zhenghuai Tan Yong Deng 《Bioorganic & medicinal chemistry》2019,27(6):991-1001
A series of 4′-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (65.03% at 25.0?μM). Moreover, this representative compound also exhibited good antioxidant activity, biometal chelating ability and anti-neuroinflammatory activity in vitro. Furthermore, compound 8n displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 8n as promising candidate for further development of multi-functional drugs against AD. 相似文献
102.
《Chronobiology international》2013,30(3):328-336
We studied the sleep/wake patterns and circadian typology of Japanese preschool children living in the Tokyo metropolitan area (193 boys and 190 girls, 4–6 years of age) from June to July 2012 based on a standardized parental self-reporting questionnaire. Our major findings are as follows: (1) sleep/wake timing was delayed, and the duration of nocturnal sleep (sleep period as well as time in bed) increased from that on scheduled days (weekdays) to that on free days (weekends) for all ages. (2) The duration of daily sleep (24?h), including daytime nap, was longer for 4-year-old children compared with that in 5- to 6-year-old children, but not significantly different between scheduled and free days within each age group. (3) The distribution of chronotypes was 36.3% for morning (M)-type, 48.8% for neither (N)-type and 11.2% for evening (E)-type, and this distribution was independent of sex or age. (4) Sleep/wake timing delays were observed from M-type and N-type to E-type during scheduled and free days. (5) The duration of nocturnal sleep decreased but increased for 24-h sleep time from M-type and N-type to E-type on scheduled days. (6) Sleep durations did not differ among chronotypes on free days. (7) Chronotypes were associated with parents’ diurnal preferences, mealtimes and attendance at kindergartens or childcare centers but not with sex, age, season of birth, exposure to multimedia or exposure to morning sunlight in their bedrooms. When these results were compared with those for older children and adolescents, similar sleep/wake patterns and circadian typology were observed, although to a lesser degree, in children as young as 4–6 years of age. Napping may compensate, in part, for an accumulated weekday sleep deficit. The distribution of chronotypes was associated with differences in sleep/wake timing and duration and was influenced by the parents’ diurnal preferences and lifestyles. Further research on preschool children is required to investigate whether circadian typology affects their behavioral, emotional and cognitive development. 相似文献
103.
不同温度条件下香水文心兰花香气的成分分析及感官评定 总被引:1,自引:0,他引:1
Flower aromatic components and their relative contents of Oncidium Sharry Baby ‘Sweet Fragrance ’ at full flowering stage under conditions of 10 ℃, 20 ℃ and 30 ℃ were analyzed by solid phase micro-extr... 相似文献
104.
目的:基于前期茵陈蒿汤类方抗肝硬化的方证病理基础结果,围绕“方-证相关”的学术内涵,提出了“方证相关时,方剂对机体基因的调控遵循‘无差错修复’原则”的假说;并探讨茵陈蒿汤对DMN诱导大鼠肝纤维化形成阶段肝组织库普弗细胞(Kupffer Cells,KCs)相关基因表达及对丝裂原活化蛋白激酶(MAPK)通路的影响。方法:采用wistar大鼠,于每周前3天连续腹腔注射0.5%二甲基亚硝胺(Dimethylnitrosamine,DMN)制备大鼠肝纤维化模型,2周末取模型组6只做动态观察。第3周初开始,在持续造模的同时给予茵陈蒿汤干预治疗到4周末,正常组与模型对照组给予等量生理盐水。4周末在3%戊巴比妥钠腹腔注射麻醉情况下,杀鼠取材,检测肝功能、肝组织病理、肝组织羟脯氨酸含量、胶原半定量,并采用基因芯片检测分析茵陈蒿汤对模型大鼠肝组织基因表达谱的影响。结果:与正常组比较,造模4周大鼠血清肝功能水平明显升高(P<0.01);病理观察肝组织炎细胞显著浸润,胶原显著沉积(P<0.01),肝组织白介素1(IL-1 b)、Cd68、肿瘤坏死因子受体超家族成员14(Tnfrsf14)、肿瘤坏死因子受体超家族成员9(Tnfrsf9)、TNF受体超家族成员6(Fas)、Cd14、结缔组织生长因子(Ctgf)、Ⅰ型胶原α2(Col1 a2)、胰岛素样生长因子结合蛋白(Igfals)、胰岛素样生长因子1(Igf1)、胰岛素样生长因子结合蛋白1(Igfbp1)、基质金属蛋白酶12(Mmp12)、基质金属蛋白酶2(Mmp2)、基质金属蛋白酶23(Mmp23)、趋化因子配体21(Ccl21)、蛋白激酶Cβ(Prkcb)基因表达明显上调,MAPK通路被激活。经2周治疗后茵陈蒿汤能显著降低DMN诱导的大鼠血清肝功能水平,抑制组织炎细胞的浸润与坏死,胶原沉积,并下调了肝组织IL-1 b、Cd68、Tnfrsf14、Tn-frsf9、Fas、Cd14、Ctgf、Col1 a2、Igfals、Igf1、Igfbp1、Mmp12、Mmp2、Mmp23、Ccl21、Prkcb 基因的表达,抑制了MAPK通路的活化。通过全基因芯片的分析,在茵陈蒿汤干预治疗后基因表达得到了不同程度的修复。结论:验证了“方证相关时,方剂对机体基因的调控遵循‘无差错修复’原则”的假说;茵陈蒿汤显著抑制DMN 诱导肝纤维化形成,其机制可能是调控了KCs,抑制相关炎症因子的释放,同时可能参与调控MAPK通路,从而达到抗肝纤维化的作用。 相似文献
105.
106.
Parkinson’s disease is characterised by the death of the nigrostriatal neurons and depletion of striatal dopamine. The standard symptomatic therapy consists of dopamine replacement with l-dopa, the metabolic precursor of dopamine, which represents the most effective treatment. Since monoamine oxidase (MAO) B is a key dopamine metabolising enzyme in the brain, MAO-B inhibitors are often used as adjuvants to l-dopa. In addition to the symptomatic benefits offered by MAO-B inhibitors, these drugs may also possess neuroprotective properties and possibly delay the progression of Parkinson’s disease. Based on the therapeutic use of MAO-B inhibitors, the present study evaluates a series of mono- and disubstituted derivatives of 4(3H)-quinazolinone as potential inhibitors of recombinant human MAO-A and MAO-B. Twelve C6-monosubstituted and nine N3/C6-disubstituted 4(3H)-quinazolinone derivatives were synthesised, which led to the discovery of novel quinazolinone derivatives with micromolar and submicromolar activities as inhibitors of MAO-B. The most potent mono- and disubstituted derivatives exhibited IC50 values of 6.35 μM (7f) and 0.685 μM (8b), respectively. This study identifies suitable substitution patterns for the design of 4(3H)-quinazolinone derivatives as MAO-B inhibitors. 相似文献
107.
目的 使用剖宫产净化方法建立无菌APPswe/PS1ΔE9(PAP)双转基因小鼠模型并对动物脑内斑块沉积情况进行初步观察,为研究肠道菌群与阿尔茨海默症关系提供新的动物模型。方法 选择阳性PAP雄性杂合子鼠与经产的C57野生型雌鼠1∶2进行交配。怀孕母鼠在超净工作台内行剖宫产手术,用无菌ICR小鼠代乳。术后每个月进行无菌状态检测;PCR方法检测剖宫产所得PAP仔鼠的基因型;免疫组化方法定量检测9月龄PAP小鼠脑内斑块变化情况。结果 实施剖宫产手术12例,获仔鼠66只,剖宫产存活率及离乳存活率分别为95.45%(63/66)和95.24%(60/63),净化后按国标检测无菌状态均为合格。免疫组化结果显示9月龄无菌PAP小鼠海马内斑块较同月龄SPF级动物减少。结论 通过剖宫产净化技术去除了PAP小鼠携带的菌群,9月龄无菌PAP小鼠脑内斑块减少。 相似文献
108.
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110.
In Bazhong City, Sichuan Province, China, top dieback symptoms were found on many pine trees (Pinus thunbergii Parl). The tips of old needles first turned grayish-green and then developed into brown bands in the field. Phylogenetic analysis of concatenated ITS and EF1-α indicated the pathogen of this dieback disease as Diplodia neojuniperi. Additionally, effects of temperature, pH and medium on the mycelial growth were also characterized. The most favorable temperature and pH level for mycelial growth are 25°C and 8, respectively. The optimal medium for mycelial growth is PDA medium. To our knowledge, this is the first report of D. neojuniperi causes Diplodia top dieback on Pinus thunbergii. Our results provide fundamental information for monitoring and preventing such disease in the future. 相似文献