Role of Chemokines in Thyroid Cancer Microenvironment: Is CXCL8 the Main Player?

Tumor-related inflammation does influence the biological behavior of neoplastic cells and ultimately the patient's outcome. With specific regard to thyroid cancer, the issue of tumor-associated inflammation has been extensively studied and recently reviewed. However, the role of chemokines, which play a crucial role in determining the immuno-phenotype of tumor-related inflammation, was not addressed in previous reviews on the topic. Experimental evidence shows that thyroid cancer cells actively secrete a wide spectrum of chemokines and, at least for some of them, solid scientific data support a role for these immune-active molecules in the aggressive behavior of the tumor. Our proposal for a review article on chemokines and thyroid cancer stems from the notion that chemokines, besides having the ability to attract and maintain immune cells at the tumor site, also produce several pro-tumorigenic actions, which include proangiogenetic, cytoproliferative, and pro-metastatic effects. Studies taking into account the role of CCL15, C-X-C motif ligand 12, CXCL16, CXCL1, CCL20, and CCL2 in the context of thyroid cancer will be reviewed with particular emphasis on CXCL8. The reason for focusing on CXCL8 is that this chemokine is the most studied one in human malignancies, displaying multifaceted pro-tumorigenic effects. These include enhancement of tumor cells growth, metastatization, and angiogenesis overall contributing to the progression of several cancers including thyroid cancer. We aim at reviewing current knowledge on the (i) ability of both normal and tumor thyroid cells to secrete CXCL8; (ii) direct/indirect pro-tumorigenic effects of CXCL8 demonstrated by in vitro and in vivo studies specifically performed on thyroid cancer cells; and (iii) pharmacologic strategies proven to be effective for lowering CXCL8 secretion and/or its effects on thyroid cancer cells

Nuova formulazione delle procedure per la stima dell’intensità macrosismica da dati epicentrali o da risentimenti in zone vicine

Vengono presentate nuove relazioni empiriche, definite per il territorio italiano, per la stima dell’intensità in un dato sito a partire da informazioni epicentrali o relative a località vicine. Queste relazioni, espresse in forma probabilistica e quindi direttamente utilizzabili per la stima della pericolosità sismica, condividono la stessa formalizzazione e la medesima base informativa. In particolare, sono state seguite tre diverse strategie: le prime due hanno portato alla definizione di una relazione di attenuazione per la stima dell’intensità al sito da dati epicentrali utilizzando una forma parametrica rispettivamente Gaussiana e Binomiale; la terza analisi è stata invece mirata a definire le modalità di “correzione” del valore locale di intensità, dedotto dalle informazioni epicentrali, con dati di risentimenti osservati in località vicine al sito in esame

Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds

Human mesenchymal stem/stromal cells (hMSCs) present a key therapeutic cellular intervention for use in cell and gene therapy (CGT) applications due to their immunomodulatory properties and multi-differentiation capability. Some of the indications where hMSCs have demonstrated pre-clinical or clinical efficacy to improve outcomes are cartilage repair, acute myocardial infarction, graft versus host disease, Crohn’s disease and arthritis. The current engineering challenge is to produce hMSCs at an affordable price and at a commercially-relevant scale whilst minimising process variability and manual, human operations. By employing bioreactors and microcarriers (due to the adherent nature of hMSCs), it is expected that production costs would decrease due to improved process monitoring and control leading to better consistency and process efficiency, and enabling economies of scale. This approach will result in off the shelf (allogeneic) hMSC-based products becoming more accessible and affordable. Importantly, cell quality, including potency, must be maintained during the bioreactor manufacturing process. This review aims to examine the various factors to be considered when developing a hMSC manufacturing process using microcarriers and bioreactors and their potential impact on the final product. As concluding remarks, gaps in the current literature and potential future areas of research are also discussed

Paving the way to food grade analytical chemistry: use of a natural deep eutectic solvent to determine total hydroxytyrosol and tyrosol in extra virgin olive oils

Extra virgin olive oil (EVOO) is well known for containing relevant amounts of healthy phenolic compounds. The European Food Safety Authority (EFSA) allowed a health claim for labelling olive oils containing a minimum amount of hydroxytyrosol (OHTyr) and its derivatives, including tyrosol (Tyr). Therefore, harmonized and standardized analytical protocols are required in support of an effective application of the health claim. Acid hydrolysis performed after extraction and before chromatographic analysis has been shown to be a feasible approach. Nevertheless, other fast, green, and easy methods could be useful for on-site screening and monitoring applications. In the present research, a natural deep eutectic solvent (NADES) composed of lactic acid and glucose was used to perform a liquid/liquid extraction on EVOO samples, followed by UV-spectrophotometric analysis. The spectral features of the extracts were related with the content of total OHTyr and Tyr, determined by the acid hydrolysis method. The second derivative of spectra allowed focusing on three single wavelengths (i.e., 299 nm, 290 nm, and 282 nm) significantly related with total OHTyr, total Tyr, and their sum, respectively. In particular, the sum of OHTyr and Tyr could be determined with a root mean square error of prediction of 29.5 mg/kg, while the limits of quantitation and detection were respectively 11.8 and 4.9 mg/kg. The proposed method, therefore, represents an easy screening tool, with the use of a green, food-derived solvent, and could be considered as an attempt to pave the way for food grade analytical chemistry

The effect of pregnancy on subsequent relapse from Graves' disease after a successful course of antithyroid drug therapy.

OBJECTIVE: Pregnancy and the postpartum (PP) period are associated with profound changes of the immune system, which largely influence the clinical activity of autoimmune diseases. The aim of this study was to evaluate the effect of pregnancy and/or the PP period in driving a clinical relapse of hyperthyroidism in patients with Graves' disease (GD) who are in remission after antithyroid drug (ATD) treatment. Data were retrospectively collected from 150 female patients with GD, who were assigned to two groups according to the occurrence of a successful pregnancy after ATD withdrawal. RESULTS: Relapsing Graves' hyperthyroidism was observed in 70 of 125 patients in group I (no pregnancy after ATD withdrawal) (56.0%) and 21 of 25 patients in group II (pregnancy after ATD withdrawal) (84.0%) (P < 0.05). Logistic regression analysis (dependent variable: relapse/nonrelapse; covariates: age, positive family history for autoimmune thyroid disease, duration of treatment with ATD, number pregnancies at diagnosis, number of pregnancies after ATD withdrawal) showed a significant effect only for the number of pregnancies after ATD withdrawal [4.257 (1.315-13.782)]. The effect was ascribed to the PP period rather than to pregnancy itself because in 20 of 21 patients of group II (95.2%), the relapse of Graves' hyperthyroidism occurred between 4 and 8 months after delivery. CONCLUSIONS: The PP period is significantly associated with a relapse of hyperthyroidism in GD patients being in remission after ATD. We therefore recommend that patients with GD in remission after a course of ATD should have their thyroid function tested at 3 and 6 months after delivery

Applying the Disruption Index Procedure to Evaluate the Urban Seismic Risk in the Mt. Etna Area (Italy)

The Disruption Index is used here for the assessment of urban disruption in the Mt. Etna area after a natural disaster. The first element of the procedure is the definition of the seismic input, which is based on information about the historical seismicity and seismogenic faults. The second element is the computation of the seismic impact on the building stock and infrastructure in the region considered. Information on urban-scale vulnerability was collected and a geographic information system was used to organize the data relating to buildings and network systems (e.g., typologies, schools, strategic structures, lifelines). The central idea underlying the definition of the Disruption Index is the identification and evaluation of the impacts on a target community, considering the physical elements that contribute most to the severe disruption. The results of this study are therefore very useful for earthquake preparedness planning and for the development of strategies to minimize the risks from earthquakes. This study is a product of the European “Urban Disaster Prevention Strategies using Macroseismic Fields and Fault Sources” project (UPStrat-MAFA European project 2013)

Type I and type II interferons inhibit both basal and tumor necrosis factor-α-induced CXCL8 secretion in primary cultures of human thyrocytes.

Interferons (IFNs) and tumor necrosis factor-α (TNF-α) cooperate in activating several inflammation-related genes, which sustain chronic inflammation in autoimmune thyroid disease (AITD). Much is known about the positive signaling of IFNs to activate gene expression in AITD, while the mechanisms by which IFNs negatively regulate genes remain less studied. While IFNs inhibit CXCL8 secretion in several human cell types, their effects on thyroid cells were not evaluated. Our aim was to study the interplay between TNF-α and type I or type II IFNs on CXCL8 secretion by human thyroid cells. CXCL8 was measured in supernatants of primary cultures of thyroid cells basally and after a 24-h incubation with TNF-α. CXCL8 was detected in thyroid cell supernatants in basal conditions (96.2±23.5 pg/mL) being significantly increased (784.7±217.3 pg/mL; PIFN-β>IFN-α. This study demonstrates that type I and type II IFNs downregulate both basal and TNF-α-induced CXCL8 secretion by human thyrocytes, IFN-γ being the most powerful inhibitor. Future studies aimed at a better comprehension of the interplay between CXCL8 and thyroid diseases appear worthwhile

Effects of Dietary Extruded Linseed (Linum usitatissimum) and Oregano (Origanum vulgare) on Growth Traits, Carcass Composition and Meat Quality of Grigia di Potenza Suckling Kids

The aim of this trial was to compare the influence of supplementing diets with extruded linseed and oregano on growth parameters and meat qualitative traits in Grigia di Potenza breed suckling kids. Twenty-four male kids, exclusively fed milk from their dams, were assigned to the following diets: C) group control fed without any supplement; L) group fed control feed containing 3% extruded linseed (Linum usitatissimum L.); and LO) group fed control diet with 0.6% dried oregano (Origanum vulgare) and 3% extruded linseed. Growth performance as well as slaughtering traits and meat cuts of kids were not significantly influenced (P &gt; 0.05) by dietary treatments. Conversely, kids in linseed group reported the lower (P &lt; 0.05) percentage of dissectible fat in leg and loin. The meat from Longissimus lumborum and Semimembranosus muscles of kids in linseed diet had the lowest (P &lt; 0.05) cooking loss percentage, whereas the proximate chemical composition of both meat muscles did not vary among treatments (P &gt; 0.05). The experimental diets partially modulated the kid meat fatty acid composition in both muscles, where feeding linseed and oregano improved (P &lt; 0.05) the content of DPA and reduced MUFA. Based on the current findings, it can be concluded that linseed and oregano supplementation can be used in goat diet as no significant detrimental effects on productive performance and meat quality of suckling kids were observed