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91.
Nadezhda Tikhmyanova Nicholas Paparoidamis James Romero-Masters Xin Feng Farheen Sultana Mohammed Poli Adi Narayana Reddy Shannon C. Kenney Paul M. Lieberman Joseph M. Salvino 《Bioorganic & medicinal chemistry letters》2019,29(16):2259-2264
Epstein-Barr virus (EBV) is a human herpesvirus that infects over 90% of the world's population that persists as a latent infection in various lymphoid and epithelial malignancies. The total number of EBV associated malignancies is estimated to exceed 200,000 new cancers per year. Current chemotherapeutic treatments of EBV-positive cancers include broad-spectrum cytotoxic drugs that ignore the EBV positive status of tumors and have limited safety and selectivity. In an effort to develop new and more efficacious molecules for inducing EBV reactivation, we have developed high-throughput screening assays to identify a class of small molecules (referred to as the C60 series) that efficiently activate the EBV lytic cycle in multiple latency types, including lymphoblastoid and nasopharyngeal carcinoma cell lines. In this paper we report our preliminary structure activity relationship studies and demonstrate reactivation of EBV in the SNU719 gastric carcinoma mouse model and the AGS-Akata gastric carcinoma mouse model. 相似文献
92.
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
93.
Anti-cholinesterase hybrids as multi-target-directed ligands against Alzheimer’s disease (1998–2018)
Alzheimer’s disease (AD) is a genetically complex, progressive and irreversible neurodegenerative disorder of the brain which involves multiple associated etiological targets. The complex pathogenesis of AD gave rise to multi-target-directed ligands (MTDLs) principle to combat this dreaded disease. Within this approach, the design and synthesis of hybrids prevailed greatly because of their capability to simultaneously target the intertwined pathogenesis components of the disease. The hybrids include pharmacophoric hybridization of two or more established chemical scaffolds endowed with the desired pharmacological properties into a single moiety. In AD, the primary foundation of medication therapy and drug design strategies includes the inhibition of cholinesterase (ChE) enzymes. Hence the development of ChE inhibition based hybrids is the central choice of AD medicinal chemistry research. To illustrate the progress of ChE inhibition based hybrids and novel targets, we reviewed the medicinal chemistry and pharmacological properties of the multi-target molecules published since 1998-December 2018. We hope that this article will allow the readers to easily follow the evolution of this prominent medicinal chemistry approach to develop a more efficient inhibitor. 相似文献
94.
Saranna Fanning Aftabul Haque Thibaut Imberdis Valeriya Baru M. Inmaculada Barrasa Silke Nuber Daniel Termine Nagendran Ramalingam Gary P.H. Ho Tallie Noble Jackson Sandoe Yali Lou Dirk Landgraf Yelena Freyzon Gregory Newby Frank Soldner Elizabeth Terry-Kantor Tae-Eun Kim Dennis Selkoe 《Molecular cell》2019,73(5):1001-1014.e8
95.
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
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99.
《Journal of Asia》2022,25(4):101972
The maize spotted stem borer Chilo partellus Swinhoe 1885 (Lepidoptera: Crambidae) was recorded for the first time in Turkey in 2014. This pest is described as invasive, especially in the current climate change dispensation. It is important to investigate the population dynamics of C. partellus for better management practices. We studied the species abundance distribution (SAD) models and some biodiversity indices of three major stem bores, C. partellus, Ostrinia nubilalis and Sesamia nonagrioides as these are the most common and major stem borers of maize in the Mediterranean Region. With the help of light traps, weekly catches of the three major maize stem borers were collected during two maize growing seasons (first cropping and second cropping seasons) in 2018 and 2019. The results showed that C. partellus emerged earlier (April-May) and was very dominant throughout the first cropping season of maize. Ostrinia nubilalis and S. nonagrioides emerged late in June-July, and its population remained low throughout the first cropping season. The population structure of all three stem borers was similar throughout the second cropping season of maize. The relative abundance (RA) of C. partellus was significantly higher than that of O. nubilalis and S. nonagrioides in the first cropping (p <.0001) when compared to the second cropping season (p >.05) for both years. In the first cropping season for both years, no SAD model fitted the observed species distribution, although Fisher’s log series was relatively similar. In the second cropping for both years, the geometric series distribution model fitted the observed SAD. The Berger-Parker dominance index was greater for the first cropping season than that of the second, whereas the opposite was true for the Simpson’s evenness and evenness of Pielou. High RA of C. partellus and the geometric series distribution observed in the second cropping are indicative of a possible dominant status of the C. partellus in the Mediterranean Region of Turkey. Our findings indicated that seasonality is a fundamental driving factor influencing the distribution of the three major stem borers of maize in the Mediterranean Region. In addition, the long and warmer winters could be the reason for the dominance of C. partellus as indicated by the diversity indices. 相似文献
100.
The Static Optimization (SO) solver in OpenSim estimates muscle activations and forces that only equilibrate applied moments. In this study, SO was enhanced through an open-access MATLAB interface, where calculated muscle activations can additionally satisfy crucial mechanical stability requirements. This Stability-Constrained SO (SCSO) is applicable to many OpenSim models and can potentially produce more biofidelic results than SO alone, especially when antagonistic muscle co-contraction is required to stabilize body joints. This hypothesis was tested using existing models and experimental data in the literature. Muscle activations were calculated by SO and SCSO for a spine model during two series of static trials (i.e. simulation 1 and 2), and also for a lower limb model (supplementary material 2). In simulation 1, symmetric and asymmetric flexion postures were compared, while in simulation 2, various external load heights were compared, where increases in load height did not change the external lumbar flexion moment, but necessitated higher EMG activations. During the tasks in simulation 1, the predicted muscle activations by SCSO demonstrated less average deviation from the EMG data (6.8% −7.5%) compared to those from SO (10.2%). In simulation 2, SO predicts constant muscle activations and forces, while SCSO predicts increases in the average activations of back and abdominal muscles that better match experimental data. Although the SCSO results are sensitive to some parameters (e.g. musculotendon stiffness), when considering the strategy of the central nervous system in distributing muscle forces and in activating antagonistic muscles, the assigned activations by SCSO are more biofidelic than SO. 相似文献