Insulin-Like Growth Factor-2 Is Induced Following 5-Aminolevulinic Acid-Mediated Photodynamic Therapy in SW620 Human Colon Cancer Cell Line

The IGF system is a family of polypeptide growth factors, which plays a significant role in the development and growth of many cells. Dysregulation of insulin-like growth factors and their pathway components has been connected with essential tumor properties, such as tumor cell proliferation, antiapoptotic properties, invasive behavior and chemotherapy resistance. However, the effects of photodynamic therapy (PDT), one of the cancer treatment methods for the regulation of the IGF signaling pathway, are still unclear. The aim of this study was to investigate the expression of IGF-2 after 5-aminolevulinic acid (5-ALA)-mediated-PDT in SW620 human colorectal cancer cells with evaluation of cell proliferation and apoptosis and to determine the effects of PDT on the IGF-2 receptor (IGF-2R), IGF-2 binding protein-1 (IGF-2BP-1) and the proapoptotic protein, BAX. Cells were treated with 5-aminolevulinic acid and its methyl ester. Changes of the expression and concentration of IGF-2 before and after treatment were assayed by immunocytochemistry, Western blot and ELISA. We found that IGF-2 was significantly overexpressed in the SW620 cell line, while its receptor and binding protein-1 were not significantly changed. Within this study, we would like to suggest that IGF-2 contributes to the effects of PDT and that its expression will influence post-PDT efficacy.     

Apoptosis Signaling Is Altered in CD4(+)CD25(+)FoxP3(+) T Regulatory Lymphocytes in Pre-Eclampsia

The aim of our study was to estimate the surface expressions of CD95 (APO-1/Fas) antigen and the intracellular expressions of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in CD4(+)CD25(+)FoxP3(+) T regulatory lymphocytes (Tregs) as well as the percentage of CD8(+)CD28(+) T cytotoxic cells in peripheral blood of patients with pre-eclampsia in comparison with healthy pregnant women in the third trimester of physiological pregnancy. Twenty-four women with pre-eclampsia and 20 normal third trimester pregnant women were included in the study. The lymphocytes were isolated from peripheral blood samples and labeled with monoclonal antibodies. The expressions of surface antigens and intracellular proteins were estimated using flow cytometry. The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in peripheral blood of patients with pre-eclampsia when compared to normal third trimester pregnant women. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells that express Bcl-2 protein were significantly lower in peripheral blood of patients with pre-eclampsia when compared to healthy pregnant women, whereas the percentages of CD4(+)CD25(+)FoxP3(+) Treg cells with the expressions of Bax protein did not differ in both groups. Moreover, the mean fluorescence intensity (MFI) of Bcl-2 protein in CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower and MFI of Bax protein significantly higher in pre-eclampsia when compared to the control group. The percentage of CD8(+)CD28(+) T cells did not differ in both studied groups but MFI of CD28 antigen on T CD8(+) cells was significantly higher in pre-eclampsia when compared to the control group. The obtained results suggest that the deficit of CD4(+)CD25(+)FoxP3(+) Treg lymphocytes which is observed in pre-eclampsia may be associated with altered apoptosis signaling in Tregs.     

Alternating Cationic-Hydrophobic Peptide/Peptoid Hybrids: Influence of Hydrophobicity on Antibacterial Activity and Cell Selectivity

The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent antibacterial activity (e. g., MICs of 2–8 μg/mL against E. coli) and low toxicity toward mammalian cells (<10 % hemolysis at 400 μg/mL and IC₅₀>800 μg/mL for HepG2 viability). Most peptidomimetics retained activity against drug-resistant strains. These findings corroborate the hypothesis that for related peptidomimetics two hydrophobicity thresholds may be identified: i) it should exceed a certain level in order to confer antibacterial activity, and ii) there is an upper limit, beyond which cell selectivity is lost. It is envisioned that once identified for a given subclass of peptide-like antibacterials such thresholds can guide further optimisation.     

A Stochastic Petri Net-Based Model of the Involvement of Interleukin 18 in Atherosclerosis

Interleukin 18 (IL-18) is a proinflammatory and proatherogenic cytokine with pleiotropic properties, which is involved in T and NK cell maturation and the synthesis of other inflammatory cytokines and cell adhesion molecules. It plays a significant role in orchestrating the cytokine cascade, accelerates atherosclerosis and influences plaque vulnerability. To investigate the influence of IL-18 cytokine on atherosclerosis development, a stochastic Petri net model was built and then analyzed. First, MCT-sets and t-clusters were generated, then knockout and simulation-based analysis was conducted. The application of systems approach that was used in this research enabled an in-depth analysis of the studied phenomenon. Our results gave us better insight into the studied phenomenon and allow revealing that activation of macrophages by the classical pathway and IL-18-MyD88 signaling axis is crucial for the modeled process.     

Genetic Carriers and Genomic Distribution of cadA6—A Novel Variant of a Cadmium Resistance Determinant Identified in Listeria spp.

Listeria monocytogenes is a pathogen responsible for severe cases of food poisoning. Listeria spp. strains occurring in soil and water environments may serve as a reservoir of resistance determinants for pathogenic L. monocytogenes strains. A large collection of Listeria spp. strains (155) isolated from natural, agricultural, and urban areas was screened for resistance to heavy metals and metalloids, and the presence of resistance determinants and extrachromosomal replicons. Of the tested strains, 35% were resistant to cadmium and 17% to arsenic. Sequence analysis of resistance plasmids isolated from strains of Listeria seeligeri and Listeria ivanovii, and the chromosome of L. seeligeri strain Sr73, identified a novel variant of the cadAC cadmium resistance efflux system, cadA6, that was functional in L. monocytogenes cells. The cadA6 cassette was detected in four Listeria species, including strains of L. monocytogenes, isolated from various countries and sources—environmental, food-associated, and clinical samples. This resistance cassette is harbored by four novel composite or non-composite transposons, which increases its potential for horizontal transmission. Since some cadAC cassettes may influence virulence and biofilm formation, it is important to monitor their presence in Listeria spp. strains inhabiting different environments.     

New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.     

Interlaboratory study on lipid oxidation during accelerated storage trials with rapeseed and sunflower oil analyzed by conjugated dienes as primary oxidation products

Accelerated storage tests are frequently used to assess the oxidative stability of foods and related systems due to its reproducibility. Various methods and experimental conditions are used to measure lipid oxidation. Differences between laboratories make it necessary to determine the repeatability and reproducibility of oxidation tests performed under the same conditions. The objective of the present interlaboratory study was to evaluate the outcome of a storage test for two different bulk oils, sunflower oil (SFO) and rapeseed oil (RSO), during a period of 9 weeks at 20°C, 30°C, 40°C, and 60°C. Sixteen laboratories were provided with bottled oils and conducted the storage tests according to a detailed protocol. Lipid oxidation was monitored by the formation of conjugated dienes (CD) and the activation energy (E_a) was determined for comparative purposes and statistically evaluated. An increase in CD formation was observed for both oils when the storage temperature was increased in all laboratories. The E_a,1 ranged from 47.9 to 73.3 kJ mol⁻¹ in RSO and from 27.8 to 62.6 kJ mol⁻¹ in SFO, with average values of 58.2 and 46.8 kJ mol⁻¹, respectively. The reproducibility coefficients were 10.9% and 18.2% for RSO and SFO, respectively. Practical applications: In order to compare results on oxidative stability of foods derived from different studies, the reproducibility of storage tests and methods employed to evaluate the oxidation level should be considered. This study provides fundamental data on the reproducibility of lipid oxidation under accelerated storage conditions and defines important parameters to be considered for the conduction of experiments.     

The influence of food emulsifiers on fat and sugar dispersions in oils. III. Water content,purity of oils

The influence of water on the interactions between fat and sugar crystals dispersed in triglyceride (vegetable) oils was qualitatively estimated from sedimentation and rheological experiments. The experiments were performed both with and without food emulsifiers (monoglycerides and lecithins) present in the oil. The effects of minor natural oil components (nontriglycerides) on the interactions and on emulsifier adsorption to the crystals were examined by comparing a commercial refined oil and a chromatographically purified oil. The results show that water generally increases the adhesion between fat and sugar crystals in oils and also increases the surface activity of the oil-soluble food emulsifiers. Minor oil components give a small increase in the adhesion between fat and sugar crystals in oils, but do not influence the adsorption of food emulsifiers in any systematic way.     

Ozonation of Polycyclic Aromatic Hydrocarbons in Water Solution

The degradation of three polycyclic aromatic hydrocarbons (PAHs): benzo[a]pyrene (BAP), chrysene (CHR), and fluorene (FLU) in aqueous solution using ozone was investigated. The influence of pH of the reaction mixture, ozone concentration, and the presence of a radical scavenger on the reaction rate was determined. The highest rate of PAHs disappearance was achieved in acidic solutions. The radical scavenger, tert-butanol, effectively inhibited the rate of PAHs destruction. The rate constants of direct reaction of PAHs with ozone were calculated and they were equal to (3.32 ± 0.21) × 10⁴; (1.10 ± 0.15) × 10⁴ and 44.8 ± 1.1 M^?1s^?1 for BAP, CHR, and FLU, respectively. The contributions of direct ozonolysis, and radical reaction to PAHs oxidation in ozonation processes, were evaluated.     

Effects of various roasting conditions on acrylamide,acrolein, and polycyclic aromatic hydrocarbons content in cocoa bean and the derived chocolates

The effect of roasting parameters such as the temperature (135 and 150°C) and relative humidity of air (RH of 0.3 and 5.0%) on acrylamide, acrolein, and polycyclic aromatic hydrocarbon (PAH) levels in whole and crushed cocoa beans and chocolates derived from these beans was studied. Acrylamide was identified in all tested samples of roasted cocoa beans, irrespective of process conditions. Its contents in chocolates produced from these beans were similar. The highest acrylamide concentration was found in whole cocoa beans roasted at 135°C and RH of 5.0%. Small amounts of acrolein were present only in the roasted whole cocoa beans while neither the roasted crushed cocoa beans nor chocolates contained this aldehyde. Roasting conditions significantly affected the profile and content of PAHs in whole and crushed cocoa beans and the richest in PAHs were crushed cocoa beans roasted at 150°C and RH of 5.0%. The chocolates obtained in this study contained significantly higher concentrations of PAHs than the roasted cocoa beans used for their production. The results of the study demonstrate that optimization of roasting conditions may reduce levels of all these harmful substances in cocoa beans.