Potential antimutagenic activity of berberine, a constituent of Mahonia aquifolium

BACKGROUND: As part of a study aimed at developing new pharmaceutical products from natural resources, the purpose of this research was twofold: (1) to fractionate crude extracts from the bark of Mahonia aquifolium and (2) to evaluate the strength of the antimutagenic activity of the separate components against one of the common direct-acting chemical mutagens. METHODS: The antimutagenic potency was evaluated against acridine orange (AO) by using Euglena gracilis as an eukaryotic test model, based on the ability of the test compound/fraction to prevent the mutagen-induced damage of chloroplast DNA. RESULTS: It was found that the antimutagenicity of the crude Mahonia extract resides in both bis-benzylisoquinoline (BBI) and protoberberine alkaloid fractions but only the protoberberine derivatives, jatrorrhizine and berberine, showed significant concentration-dependent inhibitory effect against the AO-induced chloroplast mutagenesis of E. gracilis. Especially berberine elicited, at a very low dose, remarkable suppression of the AO-induced mutagenicity, its antimutagenic potency being almost three orders of magnitude higher when compared to its close analogue, jatrorrhizine. Possible mechanisms of the antimutagenic action are discussed in terms of recent literature data. While the potent antimutagenic activity of the protoberberines most likely results from the inhibition of DNA topoisomerase I, the actual mechanism(s) for the BBI alkaloids is hard to be identified. CONCLUSIONS: Taken together, the results indicate that berberine possesses promising antimutagenic/anticarcinogenic potential that is worth to be investigated further

Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.

STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression

An algorithmic approach for the analysis of finite-source M/GI/1 retrial queueing systems with collisions and server subject to breakdowns and repairs

In this paper retrial queuing systems with a finite number of sources and collisions of the customers is considered, where the server is subjects to random breakdowns and repairs depending on whether it is idle or busy. The novelty of this system comparing to the previous ones is that the service time is assumed to follow a general distribution while the source times, retrial times, servers lifetime and repair time are supposed to be exponentially distributed. A new numerical algorithm for finding the joint probability distribution of the number of customers in the system and the server’s state is proposed. Several numerical examples and Figures show the effect of different input parameters on the main steady state performance measures, such as mean response and waiting time of the customers, probability of collision and retrials

A survey of recent results in finite-source retrial queues with collisions

The aim of the present paper is to give a review of recent results on single server finite-source retrial queuing systems with collision of the customers. There are investigations when the server is reliable and there are models when the server is subject to random breakdowns and repairs depending on whether it is idle or busy. Tool supported, numerical, simulation and asymptotic methods are considered under the condition of unlimited growing number of sources. Several cases and examples are treated and the results of different approaches are compared to each other showing the advantages and disadvantages of the given method. In general we could prove that the steady-state distribution of the number of customers in the service facility can be approximated by a normal distribution with given mean and variance. Using asymptotic methods under certain conditions in steady-state the distribution of the sojourn time in the orbit and in the system can be approximated by a generalized exponential one. Furthermore, it is proved that the distribution of the number of retrials until the successful service in the limit is geometrically distributed. By the help of stochastic simulation several systems are analyzed showing directions for further analytic investigations. Tables and Figures are collected to illustrate some special features of these systems

Mining of microsatellites using next generation sequencing of seabuckthorn (Hippophae rhamnoides L.) transcriptome

Gene based microsatellite markers are becoming more popular as compared to traditional random genomic microsatellite markers due to rapid and inexpensive method of isolation and their cross species portability. The present study documents occurrence of microsatellites in the transcriptome of seabuckthorn, a plant with immense medicinal, nutritional and ecological value. De novo assembly of over 80 million high quality short reads generated by high throughput next generation sequencing yielded 88297 putative unigenes. Of these, 7.69 % unigenes harbored microsatellite repeats with an average of one microsatellite per 6.704 Kb transcriptome. Dinucleotide repeats were most abundant followed by trinucleotide repeats. Microsatellites were densely populated in coding regions followed by 3′ and 5′ untranslated regions. AG and AAG type repeats were most frequently represented. Of the microsatellite positive unigenes, 48.81 % could be assigned gene ontology (GO) terms in order to assess associations between microsatellite containing unigenes and biological role of known genes. Utility of unigene specific microsatellites was assessed on the basis of polymorphism(s) detected in 18 seabuckthorn collections from Leh (India) using a set of randomly selected 25 unigene specific microsatellites. The findings presented here are likely to find immense use in future breeding and molecular biology research projects in seabuckthorn aiming at its overall development as a crop. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12298-013-0210-6) contains supplementary material, which is available to authorized users

Nesfatin-1 exerts long-term effect on food intake and body temperature

Objective:To determine whether the anorexigenic peptide, nesfatin-1 affects energy expenditure, and to follow the time course of its effects.Design:Food intake duration, core body temperature, locomotor activity and heart rate of rats were measured by telemetry for 48 h after a single intracerebroventricular injection of 25 or 100 pmol nesfatin-1 applied in the dark or the light phase of the day. Body weight, food and water intake changes were measured daily. Furthermore, cold-responsive nesfatin-1/NUCB2 neurons were mapped in the brain.Results:Nesfatin-1 reduced duration of nocturnal food intake for 2 days independently of circadian time injected, and raised body temperature immediately, or with little delay depending on the dose and circadian time applied. The body temperature remained higher during the next light phases of the 48 h observation period, and the circadian curve of temperature flattened. After light phase application, the heart rate was elevated transiently. Locomotion did not change. Daily food and water intake, as well as body weight measurements point to a potential decrease in all parameters on the first day and some degree of compensation on the second day. Cold-activated (Fos positive) nesfatin-1/NUCB2 neurones have been revealed in several brain nuclei involved in cold adaptation. Nesfatin-1 co-localised with prepro-thyrotropin-releasing hormone in cold responsive neurones of the hypothalamic paraventricular nucleus, and in neurones of the nucleus raphe pallidus and obscurus that are premotor neurones regulating brown adipose tissue thermogenesis and skin blood flow.Conclusion:Nesfatin-1 has a remarkably prolonged effect on food intake and body temperature. Time course of nesfatin-1's effects may be varied depending on the time applied. Many of the nesfatin-1/NUCB2 neurones are cold sensitive, and are positioned in key centres of thermoregulation. Nesfatin-1 regulates energy expenditure a far more potent way than it was recognised before making it a preferable candidate anti-obesity drug.International Journal of Obesity advance online publication, 31 January 2012; doi:10.1038/ijo.2012.2