Evaluation of the In vitro cytotoxic activity of caffeic acid derivatives and liposomal formulation against pancreatic cancer cell lines

Pancreatic cancer belongs to the most aggressive group of cancers, with very poor prognosis. Therefore, there is an important need to find more potent drugs that could deliver an improved therapeutic approach. In the current study we searched for selective and effective caffeic acid derivatives. For this purpose, we analyzed twelve compounds and evaluated their in vitro cytotoxic activity against two human pancreatic cancer cell lines, along with a control, normal fibroblast cell line, by the classic MTT assay. Six out of twelve tested caffeic acid derivatives showed a desirable effect. To improve the therapeutic efficacy of such active compounds, we developed a formulation where caffeic acid derivative (7) was encapsulated into liposomes composed of soybean phosphatidylcholine and DSPE-PEG2000. Subsequently, we analyzed the properties of this formulation in terms of basic physical parameters (such as size, zeta potential, stability at 4 °C and morphology), hemolytic and cytotoxic activity and cellular uptake. Overall, the liposomal formulation was found to be stable, non-hemolytic and had activity against pancreatic cancer cells (IC50 19.44 µM and 24.3 µM, towards AsPC1 and BxPC3 cells, respectively) with less toxicity against normal fibroblasts. This could represent a promising alternative to currently available treatment options

Azacarbazole n-3 and n-6 polyunsaturated fatty acids ethyl esters nanoemulsion with enhanced efficacy against Plasmodium falciparum

Alternative therapies are necessary for the treatment of malaria due to emerging drug resistance. However, many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery systems, which seriously limits their activity. To address this problem, we synthesized a series of azacarbazoles that were evaluated for antimalarial activity against D10 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains of P. falciparum. The most active compound, 9H-3-azacarbazole (3), was encapsulated in a novel o/w nanoemulsion consisting of ethyl esters of polyunsaturated fatty acids n-3 and n-6 obtained from flax oil as the oil phase, Smix (Tween 80 and Transcutol HP) and water. This formulation was further analyzed using transmission electron microscopy, dynamic light scattering and in vitro and in vivo studies. It was shown that droplets of the 3-loaded nanosystem were spherical, with satisfactory stability, without cytotoxicity towards fibroblasts and intestinal cell lines at concentrations corresponding to twice the IC50 for P. falciparum. Moreover, the nanoemulsion with this type of oil phase was internalized by Caco-2 cells. Additionally, pharmacokinetics demonstrated rapid absorption of compound 3 (tmax = 5.0 min) after intragastric administration of 3-encapsulated nanoemulsion at a dose of 0.02 mg/kg in mice, with penetration of compound 3 to deep compartments. The 3-encapsulated nanoemulsion was found to be 2.8 and 4.2 times more effective in inhibiting the D10 and W2 strains of the parasite, respectively, compared to non-encapsulated 3. Our findings support a role for novel o/w nanoemulsions as delivery vehicles for antimalarial drugs

Impact of N-alkylamino substituents on serotonin receptor (5-HTR) affinity and phosphodiesterase 10A (PDE10A) inhibition of isoindole-1,3-dione derivatives

In this study, a series of compounds derived from 4-methoxy-1H-isoindole-1,3(2H)-dione, potential ligands of phosphodiesterase 10A and serotonin receptors, were investigated as potential antipsychotics. A library of 4-methoxy-1H-isoindole-1,3(2H)-dione derivatives with various amine moieties was synthesized and examined for their phosphodiesterase 10A (PDE10A)-inhibiting properties and their 5-HT1A and 5-HT7 receptor affinities. Based on in vitro studies, the most potent compound, 18 (2-[4-(1H-benzimidazol-2-yl)butyl]-4-methoxy-1H-isoindole-1,3(2H)-dione), was selected and its safety in vitro was evaluated. In order to explain the binding mode of compound 18 in the active site of the PDE10A enzyme and describe the molecular interactions responsible for its inhibition, computer-aided docking studies were performed. The potential antipsychotic properties of compound 18 in a behavioral model of schizophrenia were also investigated

Effects of Energy Crop Monocultures and Sewage Sludge Fertiliser on Soils and Earthworm Community Attributes

Biomass is one of the most significant renewable energy sources. Doubts arise from large-area plantations of energy monocultures, which can lead to the depletion of, and a decrease in, soil biodiversity. Community association analyses of Lumbricidae may help to indicate environmental change. Therefore, the study objectives were to determine the qualitative and quantitative diversity of Lumbricids in plantations of energy crops—basket willow (Salix viminalis L.), foxglove tree (Paulownia tomentosa Steud.), and black locust (Robinia pseudoacacia L.)—by investigating the following cultivation treatments: SV and SVSS—S. viminalis without (w/o) and with the addition of sewage sludge to the soil (+SS); PT and PTSS—P. tomentosa w/o and + SS; RP and RPSS—R. pseudoacacia w/o and +SS; and MW—meadow community. A significantly higher density (p < 0.05) and biomass (p < 0.05) of earthworms were found in the SV and SVSS plantations than in other sites. The application of sewage sludge contributed to a significant increase in the mean number and biomass of all Lumbricids within cultivations of S. viminalis and R. pseudoacacia, which were significantly higher than those in the control site. This work suggests that woody energy crop production with an appropriate selection of plants and fertilisation can be a favourable habitat for the development of earthworm populations

Aneks 2 (2016). A synchronous data related to the process of ageing of scientific literature in random sample of publications

A number of citations of scientific publications which were published in 2015 and earlier. The citations were observed and counted within an empirical study conducted on the basis of the periodicals listed in Appendix 1 (2016)

Aneks 3 (2016). Citations distribution observed in an empirical study of Polish scientific literature

A graphic representation of a citations distribution observed within the frame of an empirical study which was conducted on the basis of periodicals listed in Appendix 1 (2016

Social Activity of Outstanding Youths: SAPERE AUSO Scholarship Recipients

In this article, the authors analyze the pro-societal activities of students who were awarded the SAPERE AUSO scholarship, which is given to students in Warsaw, Poland. The aim of this study was to investigate the scope of social activities undertaken by scholarship beneficiaries of the SAPERE AUSO Warsaw scholarship program. The analysis revealed that these students were socially active at school, in their local community and across the country. The research also showed that the students were willing to share their talents, trying to find a use for them in society. Another group of students was those with social skills: increased empathy, an aptitude for organizing work and events, and leadership skills. Such young people are socially active regardless of their educational achievements. This is particularly important for educators and local governments, as it guides thinking about the education of gifted students, not only in the context of academic achievement, but also social achievement