Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.     

Design,in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas ( 1 – 16 ) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives ( 17 – 32 ). All compounds were evaluated with several in vitro antioxidant and enzyme inhibition activities. Compound 30 was the most active compound against AChE, with a value of IC₅₀=8.09±0.58 μM. On the other hand, all compounds were tested in silico absorption, distribution, metabolism, and excretion (ADME) assays to better understand their bioavailability. These physicochemical properties, pharmacokinetics, and drug-likeness of all compounds were calculated using SwissADME. Furthermore, according to molecular docking analyses compound 30 exhibited significant binding affinities for all enzymes. Based on our overall observations, compound 30 could be recommended as a potential lead for the therapuetic of Alzheimer's.     

A unified framework for diversity gradients: the adaptive trait continuum

Aim Adaptive trait continua are axes of covariation observed in multivariate trait data for a given taxonomic group. These continua quantify and summarize life‐history variation at the inter‐specific level in multi‐specific assemblages. Here we examine whether trait continua can provide a useful framework to link life‐history variation with demographic and evolutionary processes in species richness gradients. Taking an altitudinal species richness gradient for Mediterranean butterflies as a study case, we examined a suite of traits (larval diet breadth, adult phenology, dispersal capacity and wing length) and species‐specific habitat measures (temperature and aridity breadth). We tested whether traits and species‐specific habitat measures tend to co‐vary, whether they are phylogenetically conserved, and whether they are able to explain species distributions and spatial genetic variation in a large number of butterfly assemblages. Location Catalonia, Spain. Methods We formulated predictions associated with species richness gradients and adaptive trait continua. We applied principal components analyses (PCAs), structural equation modelling and phylogenetic generalized least squares models. Results We found that traits and species‐specific habitat measures covaried along a main PCA axis, ranging from multivoltine trophic generalists with high dispersal capacity to univoltine (i.e. one generation per year), trophic specialist species with low dispersal capacity. This trait continuum was closely associated with the observed distributions along the altitudinal gradient and predicted inter‐specific differences in patterns of spatial genetic variability (F_ST and genetic distances), population responses to the impacts of global change and local turnover dynamics. Main conclusions The adaptive trait continuum of Mediterranean butterflies provides an integrative and mechanistic framework to: (1) analyse geographical gradients in species richness, (2) explain inter‐specific differences in population abundances, spatial distributions and demographic trends, (3) explain inter‐specific differences in patterns of genetic variation (F_ST and genetic distances), and (4) study specialist–generalist life‐history transitions frequently involved in butterfly diversification processes.     

Biogeography,ecology and conservation of Erebia oeme (Hübner) in the Carpathians (Lepidoptera: Nymphalidae: Satyrinae)

The European endemic Erebia oeme (Hübner [1804]) (Lepidoptera: Nymphalidae: Satyrinae) is discovered in the Carpathian Chain, from where it was considered to be absent. The single population found is situated in the southern part of the Romanian Carpathians (Retezat Mountains), where it flies sympatrically and synchronically with Erebia medusa ([Denis & Schiffermüller] 1775). The similar external morphology of these two species probably caused E. oeme to be overlooked in the Carpathians, leading to an unexpected information gap in the otherwise thoroughly studied European continent. The morphology of the Romanian specimens is compared to populations from the rest of the species’ range and to E. medusa. In addition, we tested DNA barcoding as a method to discriminate between these species and confirmed that it represents an effective identification tool for the taxa involved. The habitat of E. oeme, adults of both sexes and their genitalia are illustrated in comparison with E. medusa. Based on the study of several collections, we show that E. oeme is likely to be extremely local in the Carpathians and provide arguments to consider the species as vulnerable in Romania.     

Dispersal,fragmentation, and isolation shape the phylogeography of the European lineages of Polyommatus (Agrodiaetus) ripartii (Lepidoptera: Lycaenidae)

Polyommatus ripartii is a biogeographically and taxonomically poorly understood species of butterfly with a scattered distribution in Europe. Recently, it has been shown that this species includes several European endemic and localized taxa (galloi, exuberans, agenjoi) that were previously considered species and even protected, a result that poses further questions about the processes that led to its current distribution. We analysed mitochondrial DNA and the morphology of P. ripartii specimens to study the phylogeography of European populations. Three genetically differentiated but apparently synmorphic lineages occur in Europe that could be considered evolutionarily significant units for conservation. Their strongly fragmented and counterintuitive distribution seems to be the result of multiple range expansions and contractions along Pleistocene climatic oscillations. Remarkably, based on the 79 specimens studied, these genetic lineages do not seem to extensively coexist in the distributional mosaic, a phenomenon most evident in the Iberian Peninsula. One of the important gaps in the European distribution of P. ripartii is reduced by the discovery of new Croatian populations, which also facilitate a better understanding of the biogeography of the species. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 817‐829.     

A stereological study of the effects of mercury inhalation on the cerebellum

Mercury in the environment that arises from organic and inorganic sources can cause irreversible damage to the nervous system. Toxicity may be direct or may arise from interactions with other metals in the environment. We evaluated the possible effects of mercury vapor on rat cerebellum. Twelve adult female rats were divided into control and experimental groups. The rats in the experimental group were exposed to mercury vapor for 9 h/day for 45 days. Cerebellar tissue samples were evaluated using stereology and for histopathology. The total number of Purkinje cells was estimated using a physical disector method. We found that in the experimental group, overall volume decreased and the number of Purkinje cells was reduced. We also found cellular damage including pycnotic nuclei, eosinophilic cytoplasm and vacuolization; these features were absent in the control group. We found that chronic exposure to inorganic mercury vapor is toxic to the cerebellum.     

Healing-promoting effect of bombesin treatment on chronic gastric ulcer in rats

To evaluate whether bombesin treatment has a facilitatory effect on the healing of chronic gastric ulcer, following the induction of ulcer by serosal application of acetic acid, rats were given bombesin (30 microg/kg/day; subcutaneously) or vehicle three times a day for 7, 14 or 21 days until they were decapitated. Neither food intake nor gastric emptying rate in either vehicle-treated or bombesin-treated groups was not statistically different from control rats. Similarly, ulcer indices and gastric myeloperoxidase (MPO) activities at the first and second weeks of injury were not different among the groups. However, in the 3-week ulcer group, bombesin treatment reduced tissue MPO level significantly back to control levels. Moreover, the analysis of the surface epithelium by scanning electron and light microscopy demonstrated a significant reduction in the severity of ulcers by bombesin treatment. Pretreatment with CCK antagonists (L-364,718 or L365,260; 25 micromol/kg/day) before bombesin treatment showed that neither of the CCK antagonists had a significant effect on the bombesin-mediated healing process, suggesting that CCK receptors are not involved in the action of bombesin. In accordance with the previous studies that show its acute gastroprotective effects, bombesin is also effective in promoting the healing process of chronic gastric ulcer in rats.     

Quantification of mesna and total mesna in kidney tissue by high-performance liquid chromatography with electrochemical detection

A sensitive and selective assay for the determination of mesna and total mesna in tissue was developed and validated. After a simple homogenization, extraction and deproteinization step, mesna could be measured immediately by HPLC with an electrochemical detector provided with a sensitive wall-jet gold electrode. Total mesna (i.e., free mesna and mesna present in mesna disulfides and mixed mesna disulfides) could be measured after pre-column reduction with sodium borohydride to free mesna. The lower limit of quantification of mesna and total mesna was for both compounds 10 nmol/g. The assays for mesna and total mesna in tissue were linear over the ranges of 10-3000 and 10-10000 nmol/g, respectively. The within-day and between-day precisions of both methods were better than 9%. The within-day and between-day accuracy of the mesna assay ranged from 103.7 to 113.6%, whereas the accuracies of the total mesna assay ranged from 97.8 to 106.7%. Mesna in an EDTA containing tissue homogenate or in deproteinized tissue homogenate stored at -80 degrees C was stable for at least 12 weeks. Total mesna was stable under all conditions measured. The developed assays will be applied for the determination of the distribution of mesna and total mesna in tissues of the rat after administration of mesna or BNP7787.     

Does the platelet-activating factor affect the antioxidant defense system?

The platelet-activating factor (PAF) is an inflammatory mediator and it may exert some of its effects by reactive oxygen species (ROS). We investigated the effects of PAF and hyperbaric oxygenation (HBO) on copper (Cu) and zinc (Zn) levels in plasma and the intracellular antioxidant enzyme activities of rats. PAF administration caused a decrease in erythrocyte catalase (CAT) and glutathione peroxidase (GPx) activities and in the plasma zinc level. Following PAF administration, exposure to HBO also caused a decrease in erythrocyte GPx activity. These results support the hypothesis that PAF may produce free oxygen radicals and HBO enhances this effect. The enzyme activities of the antioxidant defense system were found to be affected by these oxidative processes. This is likely to be the result of excessive production of ROS or overutilization and/or inhibition of the antioxidant enzymes.