Eicosanoids and exosomes : a link between macrophages and lung cancer

Chronic inflammation increases the risk of lung cancer. Macrophages (MO) are important players in inflammation, with regulatory and executive functions. Eicosanoids and exosomes can be both triggers and mediators of these functions. Cysteinyl leukotrienes (CysLTs) are the most potent mediators of broncho-constriction in the lungs, a function exerted via CysLT1 receptor. Their function in asthma is well described, but little is known about CysLTs and lung cancer. In the first study we investigated how the interaction between pulmonary epithelium and leukocytes affects CysLTs formation. Monocytic cells and eosinophils formed LTC4, which was exported and promptly converted to LTD4 by pulmonary epithelial cells in a transcellular manner. The lung cancer cell line A549 expressing γ-glutamyl transpeptidase 1 (GGT-1) showed a high activity. Exosomes released by A549 cells also contained GGT-1 and efficiently converted LTC4 to LTD4. On the other hand, healthy bronchial epithelial cells (PBEC) expressing GGT-5 formed LTD4 12 times more slowly. The results highlight an active role for epithelial cells and their exosomes in biosynthesis of LTD4, which may be of particular relevance in the lung, given that LTD4 is the most potent agonist of CysLT1. MOs can be differentiated from blood monocytes with GM-CSF and M-CSF, resulting in cells primed toward the inflammatory M1- and resolving M2-states. A comprehensive analysis of eicosanoid formation in these two in vitro models is missing and our second study focused on this gap. By LC-MS analysis, we observed that both MO phenotypes released pro-resolving lipid mediators (PGE metabolite, LXA4) in resting conditions. When the same cells were incubated (30 min) with bacterial stimuli, there was a shift to pro-inflammatory eicosanoids: M-CSF MOs produced high amounts of LTC4, relevant for M2 functions in asthma. GM-CSF cells expressed the highest levels of cPLA2, 5-LO and FLAP; and in ionophore incubations these cells also produced the highest levels of 5-HETE. However, MCSF MO formed more products apparently due to a better response to bacterial stimuli, demonstrated by enhanced mobilization and activation of cPLA2 and 5-LO. In conclusion, GM-CSF and M-CSF can regulate specific pathways in MOs, and it appears that eicosanoid biosynthesis primarily reflect the cellular response and activation mechanisms, rather than the protein expression profile. In colon cancer a pro-tumorigenic effect of LTD4 but not LTC4 has been demonstrated. A pro-tumorigenic effect has been shown also for exosomes. To extend the findings of our first study, we used pleura exudates from lung cancer patients to isolate primary cancer cells and exosomes. Both cells and exosomes metabolized LTC4 to LTD4, and we also found that exosomes stimulated CysLTs formation in the cancer cells. Cancer cells from all patients expressed CysLT1, and exosomes promoted their migration and survival in a CysLT1 dependent manner, as demonstrated by the inhibition by montelukast (MK) treatment, a CysLT1 antagonist used to treat asthma. In cancer, interactions between the transformed cancer cells and other recruited cell types in the tumor are important. Tumor associated macrophages (TAMs) provide cancer cells with a suitable low-grade inflammation milieu including growth promoting factors. Taken together, the results in this thesis suggest a novel pro-tumorigenic mechanism based on this theme, driven by the exosomes/CysLT1 cascade: TAMs provide LTC4 that lung cancer cells and their exosomes convert to LTD4. Via CysLT1 receptor this promotes survival and migration of the cancer cells. A protective effect in lung cancer has been previously described for MK and our results suggest a possible mechanism for this, driven by the exosomes/ CysLT1 cascade, further encouraging the use of this drug in lung cancer treatment

An ica algorithm for analyzing multiple data sets

In this paper we derive an independent-component analysis (ICA) method for analyzing two or more data sets simultaneously. Our model permits there to be components individual to the various data sets, and others that are common to all the sets. We explore the assumed time autocorrelation of independent signal components and base our algorithm on prediction analysis. We illustrate the algorithm using a simple image separation example. Our aim is to apply this method to functional brain mapping using functional magnetic resonance imaging (fMRI). 1

A Spatially Robust ICA Algorithm for Multiple fMRI Data Sets

In this paper we derive an independent-component analysis (ICA) method for analyzing two or more data sets simultaneously. Our model extracts independent components common to all data sets and independent data-set-specific components. We use time-delayed autocorrelations to obtain independent signal components and base our algorithm on prediction analysis. We applied this method to functional brain mapping using functional magnetic resonance imaging (fMRI). The results of our 3-subject analysis demonstrate the robustness of the algorithm to the spatial misalignment intrinsic in multiple-subject fMRI data sets. 1

A Novel Approach of Determining the Risks for the Development of Hyperinsulinemia in the Children and Adolescent Population Using Radial Basis Function and Support Vector Machine Learning Algorithm

Hyperinsulinemia is a condition with extremely high levels of insulin in the blood. Various factors can lead to hyperinsulinemia in children and adolescents. Puberty is a period of significant change in children and adolescents. They do not have to have explicit symptoms for prediabetes, and certain health indicators may indicate a risk of developing this problem. The scientific study is designed as a cross-sectional study. In total, 674 children and adolescents of school age from 12 to 17 years old participated in the research. They received a recommendation from a pediatrician to do an OGTT (Oral Glucose Tolerance test) with insulinemia at a regular systematic examination. In addition to factor analysis, the study of the influence of individual factors was tested using RBF (Radial Basis Function) and SVM (Support Vector Machine) algorithm. The obtained results indicated statistically significant differences in the values of the monitored variables between the experimental and control groups. The obtained results showed that the number of adolescents at risk is increasing, and, in the presented research, it was 17.4%. Factor analysis and verification of the SVM algorithm changed the percentage of each risk factor. In addition, unlike previous research, three groups of children and adolescents at low, medium, and high risk were identified. The degree of risk can be of great diagnostic value for adopting corrective measures to prevent this problem and developing potential complications, primarily type 2 diabetes mellitus, cardiovascular disease, and other mass non-communicable diseases. The SVM algorithm is expected to determine the most accurate and reliable influence of risk factors. Using factor analysis and verification using the SVM algorithm, they significantly indicate an accurate, precise, and timely identification of children and adolescents at risk of hyperinsulinemia, which is of great importance for improving their health potential, and the health of society as a whole

Geoecological evaluation of local surroundings for the purposes of recreational tourism

The paper presents geoecological evaluation of the city of Loznica for the purposes of sports and recreational tourism based on quantitative method of diversity, V-Wert Method. Using the GIS tool by the quantitative method, the criteria of natural components (relief, forest, water surface and climate) are evaluated for the analyzed area. In the proposed method, the climate factor was supplemented by the analysis of the bioclimatic index Universal Thermal Climate Index (UTCI). When the evaluation was completed, the final results were obtained based on which the degrees of convenience of different parts of the analyzed area have been presented. Out of the total analyzed surface, which amounts to 705 km2 , favorable surfaces comprise 21 km2 (2.98%), and very favorable surfaces comprise 33 km2 , i.e. 4.68% of the territory. The largest area consists of conditionally favorable terrains — 333 km2 (47.23%). Since one of the basic strategic priorities of the City of Loznica is improvement and development of sports and recreational tourism, the aim of this analysis is to emphasize the potential of the mentioned area in terms of general suitability of the terrain for the development of this type of tourism

4D nanoimaging of early age cement hydration.

Despite a century of research, our understanding of cement dissolution and precipitation processes at early ages is very limited. This is due to the lack of methods that can image these processes with enough spatial resolution, contrast and field of view. Here, we adapt near-field ptychographic nanotomography to in situ visualise the hydration of commercial Portland cement in a record-thick capillary. At 19 h, porous C-S-H gel shell, thickness of 500 nm, covers every alite grain enclosing a water gap. The spatial dissolution rate of small alite grains in the acceleration period, ∼100 nm/h, is approximately four times faster than that of large alite grains in the deceleration stage, ∼25 nm/h. Etch-pit development has also been mapped out. This work is complemented by laboratory and synchrotron microtomographies, allowing to measure the particle size distributionswith time. 4D nanoimagingwill allow mechanistically study dissolution-precipitation processes including the roles of accelerators and superplasticizers.Financial support from PID2019-104378RJ-I00 research grant, which is co-funded by FEDER, is gratefully acknowledged. ToScA (United Kingdom) is gratefully acknowledged for awarding Jim Elliott Award to Shiva Shirani, I.R.S. is thankful for funding from PTA2019-017513–I

Rasagiline Effects on Glucose Metabolism, Cognition, and Tau in Alzheimer’s Dementia

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer\u27s disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose–positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG-PET was analyzed for the presence of an AD-like pattern as an inclusion criterion and as a longitudinal outcome using prespecified regions of interest and voxel-based analyses. Tau PET was evaluated at baseline and longitudinally. Clinical outcomes were analyzed using an intention-to-treat (ITT) model. Results: Fifty patients were randomized and 43 completed treatment. The study met its primary end point, demonstrating favorable change in FDG-PET differences in rasagiline versus placebo in middle frontal (P \u3c 0.025), anterior cingulate (P \u3c 0.041), and striatal (P \u3c 0.023) regions. Clinical measures showed benefit in quality of life (P \u3c 0.04). Digit Span, verbal fluency, and Neuropsychiatric Inventory (NPI) showed non-significant directional favoring of rasagiline; no effects were observed in Alzheimer\u27s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or activities of daily living. Rasagiline was generally well tolerated with low rates of adverse events and notably fewer neuropsychiatric symptoms in the active treatment group. Discussion: These outcomes illustrate the potential benefits of rasagiline on clinical and neuroimaging measures in patients with mild to moderate AD. Rasagiline appears to affect neuronal activity in frontostriatal pathways, with associated clinical benefit potential warranting a more fully powered trial. This study illustrated the potential benefit of therapeutic repurposing and an experimental medicine proof-of-concept design with biomarkers to characterize patient and detect treatment response

Open House Thessaloniki - Exhibition

HERSUS Project Open House in Thessaloniki took place from the 8th till the 16th of June 2023 with an exhibition open to the public at the Centre for Architecture of the Municipality of Thessaloniki. The exhibition presented the activities and results of HERSUS Project, including six Intelectual Outputs, three International Student Workshops, awarded projects with Prize on Modern Built Heritage, as well as HERSUS international presence and media projection. The HERSUS project proposes enhancing and testing of innovative teaching practices in the field of sustainability of the built heritage and strives to enhance the competence and motivation of educators and researchers to include curricula elements that will have tangible results, preparing students and educators to become real actors of the environmental change.HERSUS Consortium Vladan Djokić, Ana Radivojević, Ana Nikezić, Jelena Živković, Nataša Ćuković Ignjatović, Milica Milojević, Jelena Ristić Trajković, Aleksandra Milovanović, Aleksandra Djordjević, Mladen Pešić, Ana Zorić, Bojana Zeković, Tamara Popović, Nevena Lukić, Emanuela Sorbo, Enrico Anguillari, Sofia Tonello, Irene Sgarro,Maria Philokyprou, Aimilios Michael, Andreas Savvides, Panayiota Pyla, Odysseas Kontovourkis, Stavroula Thravalou, Maria Nodaraki, Theodora Hadjipetrou, Konstantinos Sakantamis, Alkmini Paka, Kleoniki Axarli, Maria Doussi, Angeliki Chatzidimitriou, Sofoklis Kotsopoulos, Mar Loren-Méndez, José Peral López, Enrique Larive, Julia Rey, Marta García de Casasola Gómez, María Carrascal, Daniel Pinzón-Ayala, María Álvarez de los Corrales, Roberto Alonso-Jiménez. Учесници: Архитектонски факултет, Универзитет у Београду (Србија), IUAV University of Venice (Италија), University of Cyprus (Кипар), Aristotle University of Thessaloniki (Грчка), и University of Seville – UNESCO Chair on Built Urban Heritage CREhAR in the digital era (Шпанија)