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61.
In search of potent acetyl cholinesterase inhibitors with low hepatotoxicity for the treatment of Alzheimer’s disease, introduction of a chloro substitution to tacrine and some of its analogs has proven to be beneficial in maintaining or potentiating the cholinesterase inhibitory activity. Furthermore, it was found to be able to reduce the hepatotoxicity of the synthesized compounds, which is the main target of the study. Accordingly, a series of new 4-(chlorophenyl)tetrahydroquinoline derivatives, was synthesized and characterized. The synthesized compounds were evaluated for their in vitro and in vivo anti-cholinesterase activity using tacrine as a reference standard. Furthermore, they were investigated for their hepatotoxicity compared to tacrine. The obtained biological results revealed that all synthesized compounds displayed equivalent or significantly higher anti-cholinesterase activity and lower hepatotoxicity in comparison to tacrine. In addition, in silico drug-likeness of the synthesized compounds were predicted and their practical logP were assessed indicating that all synthesized compounds can be considered as promising hits/leads. Furthermore, docking study of the compound showing the highest in vitro anticholinesterase activity was performed and its binding mode was compared to that of tacrine. 相似文献
62.
Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l-glutamate-stimulated PC12 and Aβ25-35-stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-β peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Aβ1-42 deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six β-carboline alkaloids (1–6), seven canthin-6-one alkaloids (7–13), and five quassinoids (14–18). Among them, four β-carbolines (1–3, and 6) and six canthin-6-ones (7–11, and 13) exhibited potential neuroprotective activities in vitro. Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE). 相似文献
63.
THOMAS G. T. JAENSON 《Medical and veterinary entomology》1988,2(2):177-187
1. Blood-seeking diel activity cycles of mosquitoes are described from 24 h landing catches on human bait in a field and a forest habitat during June-August in central Sweden. 2. Daytime activity in the field was low or absent, whilst in the forest activity was relatively even throughout the diel. 3. In both habitats, activity peaks generally occurred about sunset and sunrise and were more distinct in the field than in the forest. 4. Data from this and other studies show that, in general, Aedes cinereus Meigen feeds at night in field-type habitats and Ae.communis (DeGeer) during the diurnal-crepuscular period in forest and woodland habitats. 5. Although abundant in the study area, Anopheles maculipennis Meigen sensu lato, Culex pipiens L., Cx torrentium Martini and Culiseta morsitans (Theobald) were not caught on the human bait. This is because, in central Sweden, An.maculipennis s.l. is mainly feeding in animal sheds whereas the others are ornithophagous. 6. Ae.geniculatus (Olivier) was recorded from central Sweden for the first time. 7. Blood feeding success (proportion of mosquitoes that managed to obtain blood from the human bait) was significantly greater in Ae.cinereus (14.9%) than in Ae.punctor (Kirby), Ae.communis and Ae.annulipes (Meigen) (2.8-0.7%). 8. The data are interpreted in relation to the transmission of Ockelbo disease (caused by Sindbis virus) and tularaemia in Sweden. 相似文献
64.
In this paper we consider a cell population such as bacteria consisting of two types of cells, mutant and nonmutant. Under the mutation and homogeneous pure birth processes, this paper derives a maximum likelihood estimation procedure for estimating mutation rate and birth rate. The method is applied to Newcombe's data; further some Monte Carlo studies are generated. The numerical results indicate that the method is quite efficient for estimating genetic parameters in cell populations. 相似文献
65.
Richard E. Litz 《Journal of nematology》1986,18(1):18-22
In vitro procedures are playing a major role in plant breeding. Embryo rescue, either through the culture of excised embryos derived from incompatible crosses or by means of ovule culture, has been a standard procedure for the introgression of genes conferring disease resistance into economically important plants. Somatic hybridization (i.e., protoplast fusion) has also been demonstrated to have some potential in obtaining hybrids that result from very wide interspecific and intergeneric crosses. Wide crosses have also been achieved by means of in vitro pollination of excised ovaries or ovules. Tissue culture-induced variability in regenerated plant (i.e., somaclonal variation) appears to be an effective way of obtaining undirected genetic change that can enhance disease resistance and yield and alter the growth habit of crops that are normally propagated vegetatively (e.g., potato) or by seed (e.g., tomato). In the near future, the isolation and sequencing of genes that confer resistance to specific plant pathogens will be possible, and transfer of this information between species will become a reality. 相似文献
66.
The uptake of two different preparations of99mTechnetium-methylene diphosphonate in fetal rat calvaria is compared. The localization of99mTc after administration of99mTc(Sn)-MDP and99mTc-MDP showed equal distribution in autoradiography. 相似文献
67.
Linda Partridge 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1537):147-154
Human life expectancy in developed countries has increased steadily for over 150 years, through improvements in public health and lifestyle. More people are hence living long enough to suffer age-related loss of function and disease, and there is a need to improve the health of older people. Ageing is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. This view has been reinforced by the realization that ageing is a disadvantageous trait that evolves as a side effect of mutation accumulation or a benefit to the young, because of the decline in the force of natural selection at later ages. However, important recent discoveries are that mutations in single genes can extend lifespan of laboratory model organisms and that the mechanisms involved are conserved across large evolutionary distances, including to mammals. These mutations keep the animals functional and pathology-free to later ages, and they can protect against specific ageing-related diseases, including neurodegenerative disease and cancer. Preliminary indications suggest that these new findings from the laboratory may well also apply to humans. Translating these discoveries into medical treatments poses new challenges, including changing clinical thinking towards broad-spectrum, preventative medicine and finding novel routes to drug development. 相似文献
68.
BackgroundComparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden – incidence, prevalence, mortality, disability-adjusted life years (DALYs) – and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD).MethodsThe general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors.ResultsIn 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908–217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061–49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2–29.8) of total deaths and 17.0% (95% UI: 15.0–19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1–37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24th based on ASIR and ASDR, respectively.ConclusionThe incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge. 相似文献
69.
Santiago F. Elena Fernando González-Candelas Andrés Moya 《Journal of molecular evolution》1992,35(3):223-229
Summary We have carried out a phylogenetic study of the evolution of the VP1 gene sequence from different serological types and subtypes of foot-and-mouth disease virus (FMDV). The maximum-likelihood method developed by Hasegawa and co-workers (Hasegawa et al. 1985) for the estimation of evolutionary parameters and branching dates has been used to decide between alternative models of evolution: constant versus variable rates. The results obtained indicate that a constant rate model, i.e., a molecular clock, seems to be the most plausible one. However, additional information suggests the possibility that the appearance of serotype CS has been accompanied by an episode of rapid evolution (Villaverde et al. 1991). We discuss the possibility that this evolution of RNA viruses was due to episodic positive Darwinian selection, which would have helped the new variant to escape the immunogenic pressure from the hosts.
Offprint requests to: A. Moya 相似文献
70.
1. Metabolism is the fundamental process that powers life. Understanding what drives metabolism is therefore critical to our understanding of the ecology and behaviour of organisms in nature. 2. Metabolic rate generally scales with body size according to a power law. However, considerable unexplained variation in metabolic rate remains after accounting for body mass with scaling functions. 3. We measured resting metabolic rates (oxygen consumption) of 227 field‐caught wolf spiders. Then, we tested for effects of body mass, species, and body condition on metabolic rate. 4. Metabolic rate scales with body mass to the 0.85 power in these wolf spiders, and there are metabolic rate differences between species. After accounting for these factors, residual variation in metabolic rate is related to spider body condition (abdomen:cephalothorax ratio). Spiders with better body condition consume more oxygen. 5. These results indicate that recent foraging history is an important determinant of metabolic rate, suggesting that although body mass and taxonomic identity are important, other factors can provide helpful insights into metabolic rate variation in ecological communities. 相似文献