Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes

The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of the tumor microenvironment (TME) collaborate to mechanically condition the extracellular matrix (ECM) making it inhospitable to immune cells. TME is composed of several cell lines besides cancer cells, including tumor-associated macrophages, cancer-associated fibroblasts, CD4⁺ and CD8⁺ lymphocytes, and innate immunity cells. These populations interface with each other to prepare a conservative response, capable of evading the defense mechanisms implemented by the host’s immune system. The presence or absence, in particular, of cytotoxic CD8⁺ cells in the vicinity of the main tumor mass, is able to predict, respectively, the success or failure of drug therapy. Among various mechanisms of immunescaping, in this study, we characterized the modulation of the phenotypic profile of CD4⁺ and CD8⁺ cells in resting and activated states, in response to the mechanical pressure exerted by a three-dimensional in vitro system, able to recapitulate the rheological and stiffness properties of the tumor ECM.     

Keratinocytes Migration Promotion,Proliferation Induction,and Free Radical Injury Prevention by 3-Hydroxytirosol

3-hydroxytyrosol (HT) is the main phenolic compound found in olive oil with known antioxidant, anti-inflammatory, and antimicrobial properties in several dermatological conditions, both when taken in the form of olive oil or pure in cosmeceutical formulations. To date, its direct effect on the wound healing process and the molecular mechanisms involved have not yet been elucidated. Thus, in the present study, we aimed to explore its effects in vitro in epidermal keratinocyte cultures focusing on the molecular mechanism implied. HT was able to induce keratinocyte proliferation in the low micromolar range, increasing the expression of cyclin dependent kinases fundamental for cell cycle progression such as CDK2 and CDK6. Furthermore, it increased cell migration through the activation of tissue remodeling factors such as matrix metalloproteinase-9 (MMP-9) protein. Then, we evaluated whether HT also showed antioxidant activity at this concentration range, protecting from H₂O₂-induced cytotoxicity. The HT prevented the activation of ATM serine/threonine kinase (ATM), Checkpoint kinase 1 (Chk1), Checkpoint kinase 2 (Chk2), and p53, reducing the number of apoptotic cells. Our study highlighted novel pharmacological properties of HT, providing the first evidence of its capability to induce keratinocyte migration and proliferation required for healing processes and re-epithelialization.     

Association of subjective health symptoms with indoor air quality in European office buildings: The OFFICAIR project

The aim of this study was to explore the association between the building-related occupants’ reported health symptoms and the indoor pollutant concentrations in a sample of 148 office rooms, within the framework of the European OFFICAIR research project. A large field campaign was performed in 37 office buildings among eight countries, which included (a) 5-day air sampling of volatile organic compounds (VOCs), aldehydes, ozone, and NO₂ (b) collection of information from 1299 participants regarding their personal characteristics and health perception at workplace using online questionnaires. Stepwise and multilevel logistic regressions were applied to investigate associations between health symptoms and pollutant concentrations considering personal characteristics as confounders. Occupants of offices with higher pollutant concentrations were more likely to report health symptoms. Among the studied VOCs, xylenes were associated with general (such as headache and tiredness) and skin symptoms, ethylbenzene with eye irritation and respiratory symptoms, a-pinene with respiratory and heart symptoms, d-limonene with general symptoms, and styrene with skin symptoms. Among aldehydes, formaldehyde was associated with respiratory and general symptoms, acrolein with respiratory symptoms, propionaldehyde with respiratory, general, and heart symptoms, and hexanal with general SBS. Ozone was associated with almost all symptom groups.     

Multi-Attribute Community Detection in International Trade Network

Networks and Spatial Economics - Understanding the structure of communities in a network has a great importance in the economic analysis. Communities are indeed characterized by specific...     

The Methyl Ester of 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic Acid Reduces Endometrial Lesions Development by Modulating the NFkB and Nrf2 Pathways

Endometriosis is a common gynecological disease. Here, we aimed to investigate the anti-fibrotic, anti-inflammatory, and anti-oxidative role of the methyl ester of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO-Me) on endometriosis. An endometriosis rat model was constructed by intraperitoneally injecting recipient rats with an equivalent of tissue from the uterus of a donor animal. Endometriosis was allowed to develop for seven days. CDDO-Me was administered on the 7th day and for the next 7 days. On day 14, rats were sacrificed, and peritoneal fluid and endometriotic implants were collected. CDDO-Me displayed antioxidant activity by activating the Nfr2 pathway and the expression of antioxidant mediators such as NQO-1 and HO-1. Moreover, it reduced lipid peroxidation and increased glutathione (GSH) levels and superoxide dismutase (SOD) activity. CDDO-Me also showed anti-inflammatory activity by decreasing the expression of pro-inflammatory cytokines in peritoneal fluids and NFkB activation. It, in turn, reduced cyclooxygenase-2 (COX-2) expression in the endometriotic loci and prostaglandin E2 (PGE2) levels in the peritoneal fluids, leading to increased apoptosis and reduced angiogenesis. The reduced oxidative stress and pro-inflammatory microenvironment decreased implants diameter, area, and volume. In particular, CDDO-Me administration reduced the histopathological signs of endometriosis and inflammatory cells recruitment into the lesions, as shown by toluidine blue staining and myeloperoxidase (MPO) activity. CDDO-Me strongly suppressed α-SMA and fibronectin expression and collagen deposition, reducing endometriosis-associated fibrosis. In conclusion, CDDO-Me treatment resulted in a coordinated and effective suppression of endometriosis by modulating the Nrf2 and NFkB pathways.     

Dietary Micronutrient Management to Treat Mitochondrial Dysfunction in Diet-Induced Obese Mice

Obesity and associated metabolic disturbances, which have been increasing worldwide in recent years, are the consequences of unhealthy diets and physical inactivity and are the main factors underlying non-communicable diseases (NCD). These diseases are now responsible for about three out of five deaths worldwide, and it has been shown that they depend on mitochondrial dysfunction, systemic inflammation and oxidative stress. It was also demonstrated that several nutritional components modulating these processes are able to influence metabolic homeostasis and, consequently, to prevent or delay the onset of NCD. An interesting combination of nutraceutical substances, named DMG-gold, has been shown to promote metabolic and physical wellness. The aim of this research was to investigate the metabolic, inflammatory and oxidative pathways modulated by DMG-gold in an animal model with diet-induced obesity. Our data indicate that DMG-gold decreases the metabolic efficiency and inflammatory state and acts as an antioxidant and detoxifying agent, modulating mitochondrial functions. Therefore, DMG-gold is a promising candidate in the prevention/treatment of NCD.     

Evaluation of the adsorption behavior of polyacetylenes onto a food-grade resin for the debittering of carrot juice

In the present study, a procedure for the adsorptive removal of bitter principles, such as the polyacetylenes falcarinol, falcarindiol, and falcarindiol-3-acetate, from carrot juice using a food-grade macroreticular, non-ionic adsorption resin was investigated. To characterize the adsorption behavior of the target compounds, the influence of the independent factors resin amount, stirring rate, pH value, and temperature was studied first in batch-scale experiments. Based on mathematical models obtained from the analysis of the D-optimal design applied, optimal adsorption conditions of each polyacetylene were deduced. Taking together these findings, the adsorption behavior of polyacetylenes was investigated in column experiments. To enhance the binding rates by increasing contact times, the carrot juice was two- and threefold re-applied to the column at 30 °C. As expected, relative amounts of polyacetylenes bound by the adsorbent increased with prolonged contact time of carrot juice and resin material. After a contact time of 64 min, nearly 90% of total polyacetylenes were sorbed onto the resin surface. Therefore, the described adsorption technique may present a valuable tool for the removal of polyacetylenes from carrot juice and thus for debittering. On the other hand, adsorption may be utilized for the recovery and enrichment of these plant secondary metabolites and their use as a functional ingredient in pharmaceutical products and dietary supplements, respectively.     

Diversity of Candida zemplinina strains from grapes and Italian wines

The aim of this research was to genetically and technologically characterize Candida zemplinina strains isolated from different sources of enological interest. Phenotypic and genotypic subtyping, as well as enological characterization, were carried out on 36 C. zemplinina isolates collected from grapes, must and wines of different regions of Italy. RAPD-PCR fingerprinting of the isolates revealed a high genetic heterogeneity. At physiological level, yeasts were grouped into different clusters on the basis of sugar and ethanol tolerance. Common enological characteristics were examined and strains resulted to be highly fructophilic while presenting low ethanol and acetic acid production, high glycerol production, capacity to metabolize malic acid and slower fermentation kinetics when compared to Saccharomyces cerevisiae.The genetic and phenotypic intraspecies biodiversity of C. zemplinina gave useful data to understand its potential technological role in winemaking. This research represents a first step for the selection of C. zemplinina strains to be used as a starter in co-culture or in sequential inoculation with S. cerevisiae to improve the complexity and to enhance the particular characteristic of wines.     

Detection of Brettanomyces spp. in Red Wines Using Real-Time PCR

The question if the "Brett character" is a favorable wine attribute is one of the most controversial issues and it is currently addressed by many researches. Actually, the presence of Brettanomyces/Dekkera in wine during barrel aging is often associated to detrimental organoleptic characteristics depending on the release of volatile phenols (for example, 4-ethylphenol and 4-ethylguaiacol); for that reason the possibility to rapidly detect the yeast at the early stage of wine production could allow preventive actions to reduce wine spoilage. In this work, 25 and 5 samples from conventional and organic vineyards, respectively, all suspected to be spoiled by Brettanomyces/Dekkera spp., were analyzed using both culture-dependent and culture-independent techniques. In particular, a DNA extraction protocol and a real-time quantitative PCR (qPCR) assay to directly detect and quantify B. bruxellensis were optimized. Results showed that B. bruxellensis was present in 22 of 30 samples, ranging from 10 to 10(4) CFU/mL, lower values being found in organic wines (10 to 10(2) CFU/mL). Overall, qPCR was proved to be a useful and valuable wine control system, since 12 samples were recorded as positive for yeast presence when analyzed by qPCR and negative in case of plate count analyses. Practical Application: Brettanomyces cells were detected using a qPCR method, optimized in this study, which allows to obtain results quickly.