Puzyn T.,Jackson State University |
Puzyn T.,University of Gdansk |
Rasulev B.,Jackson State University |
Gajewicz A.,Jackson State University |
And 8 more authors.
It is expected that the number and variety of engineered nanoparticles will increase rapidly over the next few years, and there is a need for new methods to quickly test the potential toxicity of these materials. Because experimental evaluation of the safety of chemicals is expensive and time-consuming, computational methods have been found to be efficient alternatives for predicting the potential toxicity and environmental impact of new nanomaterials before mass production. Here, we show that the quantitative structure-activity relationship (QSAR) method commonly used to predict the physicochemical properties of chemical compounds can be applied to predict the toxicity of various metal oxides. Based on experimental testing, we have developed a model to describe the cytotoxicity of 17 different types of metal oxide nanoparticles to bacteria Escherichia coli. The model reliably predicts the toxicity of all considered compounds, and the methodology is expected to provide guidance for the future design of safe nanomaterials. © 2011 Macmillan Publishers Limited. All rights reserved. Source
Gatsios D.,Research Academic Computer Technology Institute |
Garofalakis J.,Research Academic Computer Technology Institute |
Chrysanthakopoulou T.,Research Academic Computer Technology Institute |
Tripoliti E.,Research Academic Computer Technology Institute |
And 5 more authors.
Proceedings of the IEEE/EMBS Region 8 International Conference on Information Technology Applications in Biomedicine, ITAB
the prevalence of heart failure is 2-3% of the general population and affects millions of people. In recent years, considerable progress has been made decoding the pathophysiology of this multi-factorial trait. Still the search for new variables with significant impact on the development of heart failure is an ongoing process. As part of the VPH2 project, a data mining study was conducted aiming specifically at extracting new knowledge from a population suffering from heart failure In particular, the population consists of patients suffering from post-mitral infarction development of myocardial remodelling. The aim of the study was to apply data mining methodologies in order to classify the patients in those who developed late onset heart failure against those that did not develop the trait. Data derived from a multiple genetic variant analysis added predictive value to this study. The methodology followed, the results and the clinically important findings are presented in this work. © 2010 IEEE. Source
Relja B.,Goethe University Frankfurt |
Weber R.,Goethe University Frankfurt |
Maraslioglu M.,Goethe University Frankfurt |
Wagner N.,Goethe University Frankfurt |
And 4 more authors.
Background: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-κB activation. Inhibiting JNK with a cell-penetrating, proteaseresistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection. Methods: Male mice were fed a Lieber-DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 ± 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested. Results: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-κB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c-Jun and NF-κB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. DJNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/RPLOS induced c-Jun and NF-κB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-κB phosphorylation after H/R. Conclusions: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-κB. © 2015 Relja et al. Source
Moser J.M.,University of Aarhus |
Bigini P.,Instituto Of Ricerche Farmacologiche Mario Negri |
Schmitt-John T.,University of Aarhus
Molecular Genetics and Genomics
This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now, 57 years after the first report on the wobbler mouse we summarize the progress made in understanding the disease mechanism and testing various therapeutic approaches and discuss the relevance of these advances for human ALS. The identification of the causative mutation linking the wobbler mutation to a vesicle transport factor and the research focussed on the cellular basis and the therapeutic treatment of the wobbler motor neuron degeneration has shed new light on the molecular pathology of the disease and might contribute to the understanding the complexity of ALS. © 2013 The Author(s). Source
Beeg M.,Instituto Of Ricerche Farmacologiche Mario Negri |
Beeg M.,ETH Zurich |
Stravalaci M.,Instituto Of Ricerche Farmacologiche Mario Negri |
Bastone A.,Instituto Of Ricerche Farmacologiche Mario Negri |
And 2 more authors.
Preparing reliable, seed-free stock solutions of the highly amyloidogenic peptides amyloid-β (Aβ) is difficult. Besides the formation of aggregates during synthesis and storage, dissolution of the peptide is a critical step because vortexing can induce aggregation. To overcome this, synthesis of the more water-soluble depsi-Aβ 1-42 peptide, from which the native sequence is easily obtained, has been suggested. We further refined this technique, including a cutoff filtration step and switching the depsipeptide in basic conditions, to stabilize the formed native peptide. The obtained solutions of native Aβ 1-40 and Aβ 1-42 peptides were homogeneous and aggregate free, as indicated by thioflavin T and circular dichroism analysis. © 2011 Elsevier Inc. All rights reserved. Source