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

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 > 0.05) by dietary treatments. Conversely, kids in linseed group reported the lower (P < 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 < 0.05) cooking loss percentage, whereas the proximate chemical composition of both meat muscles did not vary among treatments (P > 0.05). The experimental diets partially modulated the kid meat fatty acid composition in both muscles, where feeding linseed and oregano improved (P < 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

Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome.

OBJECTIVE: Metformin is widely used for the treatment of type 2 diabetes. Growing evidence supports the beneficial effects of metformin also in patients with polycystic ovary syndrome (PCOS). It was recently reported that metformin has a TSH-lowering effect in hypothyroid patients with diabetes being treated with metformin. DESIGN: Aim of this study was to evaluate the effect of metformin treatment on the thyroid hormone profile in patients with PCOS. PATIENTS AND MEASUREMENTS: Thirty-three patients with PCOS were specifically selected for being either treated with levothyroxine for a previous diagnosis of hypothyroidism (n = 7), untreated subclinically hypothyroid (n = 2) or euthyroid without levothyroxine treatment (n = 24) before the starting of metformin. The serum levels of TSH and FT(4) were measured before and after a 4-month period of metformin therapy. RESULTS: Thyroid function parameters did not change after starting metformin therapy in euthyroid patients with PCOS. In the 9 hypothyroid patients with PCOS, the basal median serum levels of TSH (3·2 mIU/l, range = 0·4-7·1 mIU/l) significantly (P < 0·05) decreased after a 4-month course of metformin treatment (1·7 mIU/l, range = 0·5-5·2 mIU/l). No significant change in the serum levels of FT4 was observed in these patients. The TSH-lowering effect of metformin was not related to the administered dose of the drug, which was similar in euthyroid as compared with hypothyroid patients with PCOS (1406 ± 589 vs 1322 ± 402 mg/day, respectively; NS). CONCLUSIONS: These results indicate that metformin treatment has a TSH-lowering effect in hypothyroid patients with PCOS, both treated with l-thyroxine and untreated

Possible added value of thyroglobulin antibody (TgAb) testing in the evaluation of thyroidal status of subjects with overweight or obesity

Purpose: An increase in serum TSH concentrations in the absence of thyroid disease, named isolated hyperthyrotropinemia, is frequently observed in subjects with obesity. It is directly associated with body mass index, and it is reversible following weight loss. Autoimmune hypothyroidism is frequently associated with obesity, it is usually progressive and needs replacement treatment with L-thyroxine. The aim of this study was to investigate the role of thyroglobulin antibodies (TgAb) to define the thyroidal status in subjects with overweight or obesity. Methods: This is a retrospective study including 749 consecutive adult patients with overweight or obesity. Of those, 76 were excluded from the analysis due to hyperthyroidism, previous thyroidectomy or radioiodine therapy for hyperthyroidism, hemiagenesis or drug-induced hypothyroidism. Serum thyrotropin (TSH), free thyroxine (FT4), free 3,5,3'-triiodothyronine (FT3), TgAb and thyroperoxidase antibodies (TPOAb) were measured in all patients. Results: Out of 673 patients, 408 did not have thyroid disease. Among patients with thyroid disease (n = 265), 130 had nodular disease with no humoral signs of thyroid autoimmunity and 135 (20%) had autoimmune thyroiditis, defined by the presence of TPOAb and/or TgAb. The prevalence of hyperthyrotropinemia, either directly measured or presumed based on L-thyroxine treatment at the time of data collection, was 63.9% in patients with both TgAb and TPOAb, 47.1% in those with isolated positivity of TPOAb, 42.8% in patients with isolated positivity of TgAb, and 14.5% in those with no detectable TgAb or TPOAb. Conclusions: Our results confirm a high prevalence of autoimmune thyroiditis (20%) in patients with obesity. TgAb may be associated with hypothyroidism in the absence of TPOAb. TgAb measurement may turn helpful to unravel a proportion of subjects that may have or may develop primary hypothyroidism requiring specific substitutive treatment