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Lemieszek M.K.,Polish Institute of Agricultural Medicine
Food & function | Year: 2013

The use of biologically active compounds isolated from edible mushrooms against cancer raises global interest. Anticancer properties are mainly attributed to biopolymers including mainly polysaccharides, polysaccharopeptides, polysaccharide proteins, glycoproteins and proteins. In spite of the fact that Boletus edulis is one of the widely occurring and most consumed edible mushrooms, antitumor biopolymers isolated from it have not been exactly defined and studied so far. The present study is an attempt to extend this knowledge on molecular mechanisms of their anticancer action. The mushroom biopolymers (polysaccharides and glycoproteins) were extracted with hot water and purified by anion-exchange chromatography. The antiproliferative activity in human colon adenocarcinoma cells (LS180) was screened by means of MTT and BrdU assays. At the same time fractions' cytotoxicity was examined on the human colon epithelial cells (CCD 841 CoTr) by means of the LDH assay. Flow cytometry and Western blotting were applied to cell cycle analysis and protein expression involved in anticancer activity of the selected biopolymer fraction. In vitro studies have shown that fractions isolated from Boletus edulis were not toxic against normal colon epithelial cells and in the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells. The best results were obtained in the case of the fraction designated as BE3. The tested compound inhibited cancer cell proliferation which was accompanied by cell cycle arrest in the G0/G1-phase. Growth inhibition was associated with modulation of the p16/cyclin D1/CDK4-6/pRb pathway, an aberration of which is a critical step in the development of many human cancers including colon cancer. Our results indicate that a biopolymer BE3 from Boletus edulis possesses anticancer potential and may provide a new therapeutic/preventive option in colon cancer chemoprevention. Source

Stepkowski T.M.,Institute of Nuclear Chemistry and Technology of Poland | Kruszewski M.K.,Institute of Nuclear Chemistry and Technology of Poland | Kruszewski M.K.,Polish Institute of Agricultural Medicine
Free Radical Biology and Medicine | Year: 2011

Oxidative stress, perturbations in the cellular thiol level and redox balance, affects many cellular functions, including signaling pathways. This, in turn, may cause the induction of autophagy or apoptosis. The NRF2/KEAP1 signaling pathway is the main pathway responsible for cell defense against oxidative stress and maintaining the cellular redox balance at physiological levels. The relation between NRF2/KEAP1 signaling and regulation of apoptosis and autophagy is not well understood. In this hypothesis article we discuss how KEAP1 protein and its direct interactants (such as PGAM5, prothymosin α, FAC1 (BPTF), and p62) provide a molecular foundation for a possible cross-talk between NRF2/KEAP1, apoptosis, and autophagy pathways. We present a hypothesis for how NRF2/KEAP1 may interfere with the cellular apoptosis-regulatory machinery through activation of the ASK1 kinase by a KEAP1 binding partner-PGAM5. Based on very recent experimental evidence, new hypotheses for a cross-talk between NF-κB and the NRF2/KEAP1 pathway in the context of autophagy-related "molecular hub" protein p62 are also presented. The roles of KEAP1 molecular binding partners in apoptosis regulation during carcinogenesis and in neurodegenerative diseases are also discussed. © 2010 Elsevier Inc. All rights reserved. Source

Stepkowski T.M.,Institute of Nuclear Chemistry and Technology of Poland | Brzoska K.,Institute of Nuclear Chemistry and Technology of Poland | Kruszewski M.,Institute of Nuclear Chemistry and Technology of Poland | Kruszewski M.,Polish Institute of Agricultural Medicine
Toxicology in Vitro | Year: 2014

Silver nanoparticles (AgNPs) are widely used in industry and medicine but the recent evidence for their cytotoxicity rise a concern about the safety of their use. We have previously shown that human A549 cells are resistant to AgNPs cytotoxicity, as compared with similarly treated HepG2 cells. In order to check for the role of the NF-κB signaling pathway in response of A549 and HepG2 cell lines to the treatment with 20. nm and 200. nm AgNps, we analyzed the expression of 84 key genes related to the functionality of the NF-κB signaling pathway. We observed considerable alternations in gene expression in HepG2 cells treated with 20. nm AgNPs, and minor changes when exposed to 200. nm AgNPs. Surprisingly, no changes in gene expression were observed in A549 cells treated with both size AgNPs. Using the NF-κB luciferase reporter system, we further tested the basal activity and inducibility of the NF-κB pathway in both cell lines and found that the inducibility of NF-κB signaling in A549 cells is approximately 5 times lower than this of HepG2 cells, but the basal activity is approximately 3.5 times higher. In accordance, the NF-κB activation after AgNPs treatment was observed in HepG2 but not in A549. Altogether indicate that NF-kB mediated cellular response to AgNPs is cell type specific and related to the basal activity of NF-κB. © 2014 Elsevier Ltd. Source

Bojar I.,Polish Institute of Agricultural Medicine | Szymanska J.,Medical University of Lublin
Annals of Agricultural and Environmental Medicine | Year: 2010

Infection with T. gondii is particularly dangerous for pregnant women as it may lead to the transplacental passage of the parasite. Currently, congenital toxoplasmosis is the second most frequent intrauterine infection. The risk of transmission of T. gondii to the foetus varies throughout the world and ranges from 0.6-1.7/1,000 of pregnant women. The consequences of congenital toxoplasmosis are multifarious. On the basis of current literature review, the authors discuss the epidemiological and clinical aspects of toxoplasmosis in pregnant women, the influence of climatic and environmental factors that may lead to an increase in T. gondii infections in humans, particularly in pregnant women, and the principles of prophylactics against T. gondii infections in those women. Source

Nieoczym D.,Maria Curie Sklodowska University | Socala K.,Maria Curie Sklodowska University | Raszewski G.,Polish Institute of Agricultural Medicine | Wla P.,Maria Curie Sklodowska University
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2014

Quercetin is one of the most widely occurring flavonoid which is also often present in plants as glycosidic form - rutin. These compounds are ingredients of plant diet and are also present in numerous pharmaceutical preparations and diet supplements which are taken by patients suffering from epilepsy and treating with antiepileptic drugs (AEDs). Influence of these compounds on central nervous system-related effects was proved both in experimental and clinical studies. Their influence on anxiety, depression, memory processes and convulsant activity was reported. The aim of the present study was to investigate the effect of quercetin and rutin in some models of seizures, i.e., in the model of psychomotor seizures induced by 6. Hz stimulation, in the maximal electroshock seizure threshold and intravenous pentylenetetrazole tests in mice. We also examined a possible mechanism of anticonvulsant activity of quercetin and its influence on action of two AEDs, i.e., valproic acid and levetiracetam, in the 6. Hz seizure test. Our results revealed only a weak anticonvulsant potential of the studied flavonoids because they showed anticonvulsant action at doses from 10 to 200. mg/kg only in the 6. Hz test and did not change seizure thresholds in the remaining tests. Moreover, anticonvulsant action of the studied flavonoids was short-term, noted only at pretreatment time ranging between 30 and 60. min. The highest anticonvulsant activity of quercetin was correlated with its high plasma and brain concentration, which was revealed in a pharmacokinetic study. We did not note changes in the anticonvulsant action of the used AEDs combined with quercetin in the model of psychomotor seizures in mice. Neither quercetin and rutin nor combinations of quercetin with the studied AEDs produced any significant impairments of motor coordination (assessed in the chimney test), muscular strength (investigated in the grip-strength test) and long-term memory (evaluated in the passive avoidance test) in mice. The results of the present study suggest that quercetin and rutin have only weak and short-term anticonvulsant potential. These flavonoids seem to be safe for patients with epilepsy because they neither changed activity of the studied AEDs nor produced any adverse effects. © 2014 Elsevier Inc. Source

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