Water-soluble ferulic acid derivatives improve amyloid-β-induced neuronal cell death and dysmnesia through inhibition of amyloid-β aggregation

Ferulic acid (FA) has been reported to exhibit protective effects against amyloid-β (Aβ)-induced neurodegeneration in vitro and in vivo. Recently, we developed two water-soluble FA derivatives: 1-feruloyl glycerol and 1-feruloyl diglycerol. In this study, we examined the neuroprotective effects of these water-soluble FA derivatives on Aβ-induced neurodegeneration both in vitro and in vivo. FA and water-soluble FA derivatives inhibited Aβ aggregation and destabilized pre-aggregated Aβ to a similar extent. Furthermore, water-soluble FA derivatives, as well as FA, inhibited Aβ-induced neuronal cell death in cultured neuronal cells. In in vivo experiments, oral administration of water-soluble FA derivatives to mice improved Aβ-induced dysmnesia assessed by contextual fear conditioning test and protected hippocampal neurons against Aβ-induced neurotoxicity. This study provides useful evidence suggesting that water-soluble FA derivatives are expected to be effective neuroprotective agents.     

Expression of recombinant organophosphorus hydrolase in the original producer of the enzyme,Sphingobium fuliginis ATCC 27551

The plasmid encoding His-tagged organophosphorus hydrolase (OPH) cloned from Sphingobium fuliginis was modified to be transferred back to this bacterium. The replication function of S. amiense plasmid was inserted at downstream of OPH gene, and S. fuliginis was transformed with this plasmid. The transformant produced larger amount of active OPH with His-tag than E. coli.     

Discovery of 3-benzyl-1,3-benzoxazine-2,4-dione analogues as allosteric mitogen-activated kinase kinase (MEK) inhibitors and anti-enterovirus 71 (EV71) agents

Enterovirus 71 (EV71) is a kind of RNA virus and one of the two causes of Hand, foot and mouth disease (HFMD). Inhibitors that target key components of Ras/Raf/MEK/ERK pathway in host cells could impair replication of EV71. A series of 3-benzyl-1,3-benzoxazine-2,4-diones were designed from a specific MEK inhibitor G8935, by replacing the double bond between C3 and C4 within the coumarin scaffold with amide bond. One compound (9f) showed submicromolar inhibitory activity among the 12 derivatives. Further optimization on 9f led to two active compounds (9k and 9m) with nanomolar bioactivities (55 nM and 60 nM). The results of enzymatic assays also demonstrated that this series of compounds were allosteric inhibitors of unphosphorylated MEK1. The binding mode of compound 9k was predicted by molecular dynamic simulation and the key interactions were same as published MEK1/2 allosteric inhibitors. In the cell-based assays, compounds 9k and 9m could effectively suppress the ERK1/2 pathway, expression of EV71 VP1, and EV71 induced cytopathic effect (CPE) in rhabdomyosarcoma (RD) cells.     

不同抗生素对金发草愈伤组织生长分化的影响

该研究以金发草愈伤组织为材料,通过分析比较不同抗生素种类(卡那霉素、潮霉素、头孢噻呋钠和氨苄青霉素)和浓度对金发草愈伤组织生长分化的影响,来确定适用于金发草遗传转化体系中的抗性筛选剂和抑菌剂。结果表明：(1)金发草愈伤组织对卡那霉素很敏感,且其分化率随着卡那霉素浓度的增加显著减少( P＝0.01)。当卡那霉素浓度为10 mg·L-1时,金发草愈伤组织的生长分化受到明显抑制,且有大量的白化苗形成,但分化率仍有36.56％;当卡那霉素浓度为15 mg·L-1时,金发草愈伤组织的分化率为11.94％,只有很少部分的愈伤分化出绿色的丛生苗;当卡那霉素浓度为20 mg·L-1时,金发草愈伤组织基本褐化死亡,分化率仅为2.26％。因此,浓度为15 mg·L-1的卡那霉素适合作为金发草遗传转化体系中的抗性筛选剂。(2)金发草愈伤组织对潮霉素的敏感性要比卡那霉素弱,且潮霉素对金发草愈伤组织分化率的影响小,但毒害作用大。因此,潮霉素不适合作为金发草遗传转化体系中的抗性筛选剂。(3)300 mg·L-1的头孢霉素和氨苄青霉素对金发草愈伤组织生长分化影响很小且能有效抑制杂菌的生长,较高浓度的氨苄青霉素对金发草愈伤组织的抑制作用不太明显。因此,300 mg·L-1的头孢霉素和较高浓度的氨苄青霉素均可作为金发草遗传转化体系中的抑菌剂。该研究确定了适用于农杆菌介导的金发草遗传转化体系中的抗性筛选剂和抑菌剂,为金发草的遗传改良及功能性基因的研究奠定了基础。     

Naturally occurring biflavonoids with amyloid β aggregation inhibitory activity for development of anti-Alzheimer agents

Amyloid β (Aβ) aggregation plays an essential role in promoting the progression of Alzheimer’s disease (AD). Therefore, the inhibition of Aβ aggregation is a potential therapeutic approach for AD. Herein, twenty-seven biflavonoids with different inter-flavonyl linkages and methoxy substitution patterns were isolated from several plants, and their Aβ₄₀ aggregation inhibitory activity was evaluated by the thioflavin-T fluorescence assay. Amentoflavone (1) and its monomethoxy derivatives (2, 3, and 5) exhibited the most potent inhibitory activity, with IC₅₀ values of approximately 5 μM. It was clarified that increasing the number of methoxy substituents on the biflavonoid structures attenuated the inhibitory activity. Moreover, the linkage and the methoxy substitution pattern had a marked influence on the inhibitory activity. Our investigation strongly supports that biflavonoids can be considered a new type of anti-Alzheimer agents that may be successfully developed for AD patients.     

靶向炎性细胞因子的生物制剂及其临床应用

细胞因子可介导许多生物学过程并受到机体的严格调节,其调节的失控可引发一系列疾病如自身免疫炎症和肿瘤。在过去的十几年中,一些能够有效调节细胞因子生物学作用的生物制剂如重组抗炎细胞因子、细胞因子受体以及中和性抗体等被广泛应用到由细胞因子失调引起的相关疾病的治疗。尤其是近年来,一些具有创新性的靶向细胞因子的新型生物制剂在不断涌现。文中对近年来国际上靶向炎症细胞因子(TNF-α、IL-1β、IL-6、IL-17)的生物制剂的研发和临床应用的相关进展进行了综述,指出其副作用和应用风险,并结合其他学者和自己的研究工作提出减少副作用和风险的途径和方法。利用现代生物技术提高抗细胞因子生物制剂针对炎症或肿瘤组织的特异性,是靶向炎性细胞因子生物制剂未来的重要发展方向。     

Effect of the Photodynamic Therapy Applications with Potent Microalgae Constituents on Several Types of Tumor

Background

In recent years, microalgae (MA) have attracted much interest considering their possible therapeutic application. They contain active natural compounds or derivatives (extracts, pure or chemically modified compounds) that have increasing applications in the pharmaceutical industry.

4种种子处理剂对菜心安全性及保护作用评价

为评价4种种子处理剂对菜心种子的安全性以及对黄曲条跳甲Phyllotreta striolata (Fabricius)的防治效果和保苗作用,本研究开展了室内、田间安全性试验以及田间保护试验。室内安全性试验结果显示,40%溴酰·噻虫嗪种子处理悬浮剂、600 g/L吡虫啉悬浮种衣剂、18%噻虫胺种子处理悬浮剂、54%吡虫·氟虫腈悬浮种衣剂用量分别低于5 120、9 600、2 880、7 040 g(a.i.)/100 kg种子时,对菜心种子发芽和生长无影响。田间安全性及保护作用结果显示,40%溴酰·噻虫嗪种子处理悬浮剂和54%吡虫·氟虫腈悬浮种衣剂保护作用显著,菜心出苗后25 d的株高和鲜重与对照组相比均有增加,且差异显著。结果表明40%溴酰·噻虫嗪种子处理悬浮剂和54%吡虫·氟虫腈悬浮种衣剂对菜心种子具有较好的安全性,且对菜心苗期有良好的保护作用。     

Does experimental evolution produce better biological control agents? A critical review of the evidence

Biological control of crop pests is considered a good alternative or complement to the use of pesticides. However, legislation restricts the importation of natural enemies of pests. A potential way to circumvent this limitation is by using experimental evolution and/or artificial selection to improve native biological control agents. Here, we review studies that have used these methodologies and evaluate their success. Experimental evolution or artificial selection has been used on a wide range of traits, with most focusing on improving the performance of natural enemies in ecologically relevant environments, such as in the presence of pesticides or at different temperatures. Although most studies were poorly replicated, the selected traits generally improved following the selection process. However, correlated responses (often in the form of trade‐offs) with other traits of interest were common. We suggest that the selection procedure can be improved by increasing replication and performing experimental evolution under more semi‐natural environments, to ensure that the most useful traits are being selected.