Docosahexaenoic acid (DHA) promotes immunogenic apoptosis in human multiple myeloma cells, induces autophagy and inhibits STAT3 in both tumor and dendritic cells

Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid found in fish oil, is a multi-target agent and exerts anti-inflammatory and anticancer activities alone or in combination with chemotherapies. Combinatorial anticancer therapies, which induce immunogenic apoptosis, autophagy and STAT3 inhibition have been proposed for long-term therapeutic success. Here, we found that DHA promoted immunogenic apoptosis in multiple myeloma (MM) cells, with no toxicity on PBMCs and DCs. Immunogenic apoptosis was shown by the emission of specific DAMPs (CRT, HSP90, HMGB1) by apoptotic MM cells and the activation of their pro-apoptotic autophagy. Moreover, immunogenic apoptosis was directly shown by the activation of DCs by DHA-induced apoptotic MM cells. Furthermore, we provided the first evidence that DHA activated autophagy in PBMCs and DCs, thus potentially acting as immune stimulator and enhancing processing and presentation of tumor antigens by DCs. Finally, we found that DHA inhibited STAT3 in MM cells. STAT3 pathway, essential for MM survival, contributed to cancer cell apoptosis by DHA. We also found that DHA inhibited STAT3 in blood immune cells and counteracted STAT3 activation by tumor cell-released factors in PBMCs and DCs, suggesting the potential enhancement of the anti-tumor function of multiple immune cells and, in particular, that of DCs

Our products are safe (don't tell anyone!). Why don't supermarkets advertise their private food safety standards?

Large retail chains have spent considerable resources to promote production protocols and traceability across the supply chain, aiming at increasing food safety. Yet, the majority of consumers are unaware of these private food safety standards (PFSS) and retailers are not informing them. This behavior denotes a pooling paradox: supermarkets spend a large amount of money for food safety and yet they forget to inform consumers. The result is a pooling equilibrium where consumers cannot discriminate among high quality and low quality products and supermarkets give up the potential price premium. This paper provides an economic explanation for the paradox using a contract-theory model. We found that PFSS implementation may be rational even if consumers have no willingness to pay for safety, because the standard can be used as a tool to solve asymmetric information along the supply chain. Using the PFSS, supermarkets can achieve a separating equilibrium where opportunistic suppliers have no incentive to accept the contract. Even if consumers exhibit a limited (but strictly positive) willingness to pay for safety, advertising may be profit-reducing. If the expected price margin is high enough, supermarkets have incentive to supply both certified and uncertified products. In this case, we show that, if consumers perceive undifferentiated products as “reasonably safe”, supermarkets may maximize profits by pooling the goods and selling them as undifferentiated. This result is not driven by advertising costs, as we derive it assuming free advertising.Agribusiness, Food Consumption/Nutrition/Food Safety,

La "similarità" delle categorie merceologiche dei flussi di esportazioni e di importazioni di prodotti alimentari nell'ambito dell'Unione Europea

L’articolo pone l’attenzione sul confronto dei flussi delle importazioni e delle esportazioni agro-industriali di Italia e Francia, due paesi mediterranei che hanno un interscambio intenso. La Francia è, infatti, il principale paese europeo fornitore dell’Italia e rappresenta il secondo mercato di sbocco per le produzioni agro-industriali italiane. Il lavoro propone due livelli di analisi. Nel primo livello si valutano, sulla base dell’elaborazione di dati EUROSTAT espressi in valori (euro), le caratteristiche dei flussi commerciali in entrata e in uscita dall’Italia e dalla Francia da e verso gli altri paesi dell’UE-27. Nel secondo livello, invece, l’idea è quella di stimare il grado di “similarità” dei beni scambiati sotto il profilo merceologico e di valutare in quale misura le relazioni tra i due partner siano improntate, da un lato, alla concorrenza, dall’altro alla complementarietà. L’analisi della similarità dal lato delle importazioni e delle esportazioni di prodotti agro-industriali scambiati dall’Italia e dalla Francia con l’area commerciale europea si basa su tre categorie di indici. La prima categoria degli indici di somiglianza e di specializzazione (saldo normalizzato, indice di somiglianza della struttura delle importazioni e delle esportazioni, indice di somiglianza dei prodotti dal lato delle importazioni e delle esportazioni) permette di esaminare il grado di “similarità”, di specializzazione e il trend evolutivo dei rapporti commerciali delle aree di scambio considerate. La seconda categoria di indici (Finger-Kreinen e Hirschmann) misura, invece, il cambiamento strutturale dei pattern commerciali, nell’intervallo temporale 1999-2006. Infine, l’ultima categoria (indice di Balassa sulle importazioni e sulle esportazioni) fornisce informazioni circa i vantaggi comparati rilevati dell’Italia e della Francia nell’interscambio con il mercato europeo.Q17,

Polyfunctional Melan-A-specific tumor-reactive CD8+ T cells elicited by dacarbazine treatment before peptide-vaccination depends on AKT activation sustained by ICOS

The identification of activation pathways linked to anti-tumor T-cell polyfunctionality in long surviving patients is of great relevance in the new era of immunotherapy. We have recently reported that dacarbazine (DTIC) injected one day before peptide-vaccination plus IFN-α improves the anti-tumor lytic activity and enlarges the repertoire of Melan-A-specific T-cell clones, as compared with vaccination alone, impacting the overall survival of melanoma patients. To identify the mechanisms responsible for this improvement of the immune response, we have analyzed the endogenous and treatment-induced antigen-specific response in a panel of Melan-A-specific CD8+ T-cell clones in terms of differentiation phenotype, inhibitory receptor profile, polyfunctionality and AKT activation. Here we show that Melan-A specific CD8+ T cells isolated from patients treated with chemoimmunotherapy possess a late differentiated phenotype as defined by the absence of CD28 and CD27 co-stimulatory molecules and high levels of LAG-3, TIM-3 and PD-1 inhibitory receptors. Nevertheless they show higher proliferative potential and an improved anti-tumor polyfunctional effector profile in terms of co-production of TNF-α, IFN-γ and Granzyme-B compared with cells derived from patients treated with vaccination alone. Polyfunctionality is dependent on an active AKT signalling related to the engagement of the co-stimulatory molecule ICOS. We suggest that this phenotypic and functional signature is dictated by a fine-tuned balance between TCR triggering, AKT activation, co-stimulatory and inhibitory signals induced by chemoimmunotherapy and may be associated with anti-tumor T cells able to protect patients from tumor recurrence

I luoghi della nascita: una ricerca-intervento sui fattori di rischio nelle madri migranti

El embarazo implica cambios físicos y también relacionales y afectivos. Durante los nueve meses, y en los meses posteriores al nacimiento, las mujeres desarrollan una serie de expectativas y fantasías sobre sí mismos y sus hijos. La manera en la que las las mujeres viven su maternidad expresa, además, los valores culturales, los mitos, y las reglas que la sociedad ha transmitido. Entonces, el nacimiento puede considerarse como un evento cultural con características distintivas. Pasando de estas consideraciones, nos preguntamos cómo las mujeres inmigrantes viven su experiencia de la maternidad en un país extranjero. Examinamos la manera en que las mujeres llevan a cabo la reconstrucción, la historia de su embarazo en relación con su propia identidad maternal, la identidad de su hijo y su cultura de origen, para evaluar el riesgo de depresión posparto. En este estudio, reunimos a 11 mujeres inmigrantes, que pertenecen a diferentes culturas y viven en Palermo. Las participantes realizaron una entrevista semiestructurada sobre representaciones maternas (IRMAG y IRMAN respectivamente), un dibujo simbólico del espacio de la vida familiar (DSSVF) y luego la escala de Depresión Postnatal Edimburgo (EPDS) durante el embarazo y puerperio.Pregnancy involves physical changes but also relational and affective ones. During the nine months’ period and in the months following the birth, women develop a series of expectations and fantasies about themselves and their child. The way women live their motherhood expresses, in addition, the cultural values, the myths, the rules society has transmitted to them. Then, birth can be considered as a cultural event with distinctive features. Moving from these considerations, we wondered how immigrant women live their experience of motherhood in a foreign country. We examined the way women reconstruct the history of their pregnancy in relation to their own maternal identity, the identity of their child and their culture of origin, to evaluate the risk of post-partum depression. In this study, we met 11 immigrant women, who belong to different cultures and live in Palermo. The participants were administered a semi-structured interview about maternal representations (IRMAG and IRMAN respectively),a symbolic drawing of family life space (DSSVF) and then the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and puerperium.peerReviewe

HGF modulates actin cytoskeleton remodeling and contraction in testicular myoid cells

The presence of the HGF/Met system in the testicular myoid cells was first discovered by our group. However, the physiological role of this pathway remains poorly understood. We previously reported that HGF increases uPA secretion and TGF-β activation in cultured tubular fragments and that HGF is maximally expressed at Stages VII–VIII of the seminiferous epithelium cycle, when myoid cell contraction occurs. It is well known that the HGF/Met pathway is involved in cytoskeletal remodeling; moreover, the interaction of uPA with its receptor, uPAR, as well as the activation of TGF-β have been reported to be related to the actin cytoskeleton contractility of smooth muscle cells. Herein, we report that HGF induces actin cytoskeleton remodeling in vitro in isolated myoid cells and myoid cell contraction in cultured seminiferous tubules. To better understand these phenomena, we evaluated: (1) the regulation of the uPA machinery in isolated myoid cells after HGF administration; and (2) the effect of uPA or Met inhibition on HGF-treated tubular fragments. Because uPA activates latent TGF-β, the secretion of this factor was also evaluated. We found that both uPA and TGF-β activation increase after HGF administration. In testicular tubular fragments, HGF-induced TGF-β activation and myoid cell contraction are abrogated by uPA or Met inhibitor administratio

L'IMMAGINE FILMICA NELLA FORMAZIONE: LE NARRAZIONI SULLA VIOLENZA ALL'INFANZIA

Il presente contributo rivolge l’attenzione alle risonanze emotive, alla soggettività di chi affronta il tema della violenza all’infanzia. Lo studio si propone di esplorare i processi attraverso i quali i soggetti, posti all’interno di un gruppo impegnato in attività formativa, organizzano informazioni e costruiscono rappresentazioni sull’abuso sui minori. Il gruppo dei partecipanti all’indagine è composto da 163 soggetti (122 studenti universitari, e 41 professionisti tra cui N = 12 agenti delle Forze dell’ordine e N = 29 operatori sociosanitari) ai quali è stata proposta la visione del film documentario Una storia americana (Capturing the Friedmans, USA 2003). I contenuti delle riflessioni sono stati analizzati attraverso l’analisi delle frequenze ed i test statistici del Chi2 . Lo studio conferma l’importanza dell’utilizzo, nella formazione, dei laboratori cinematografici che rendono possibile anche la narrazione interiore permessa dalla relazione, e dalla protezione, che si crea all’interno del gruppo per mezzo del quale si dà pensabilità all’accaduto ed una motivazione agli eventi e al loro senso.This paper directs its attention towards the emotional repercussions and the subjectivity of whoever is tackling the subject of child abuse. This study intends to explore the processes through which individuals placed within a group involved in educational activity organise their information and build up representations regarding child abuse. The group of participants in the study was made up of 163 individuals (122 university students and 41 professional persons, of whom N = 12 police officers and N = 29 social-medical workers), who were shown a documentary film, Capturing the Friedmans, (USA 2003). The results of the subsequent deliberations were examined via an analysis of frequency and the Chi-square statistical tests. The study confirms the importance of the utilisation, in education, of cinematographic laboratories; they also provide an opportunity for interior narration, which is permitted by the relationship (and the protection) created within the group. Through these the conceivable aspects of the event can emerge, along with the meaning and motivation behind the events

The influence of aquatic humic substances characteristics on the coagulation efficiency using ferric chloride

The aim of this study was to verify the influence of the apparent molecular size of aquatic humic substances on the effectiveness of coagulation with ferric chloride. Coagulation-filtration tests using jar test and bench-scale sand filters were carried out on samples of water with true color of approximately 100 Hazen units, prepared with aquatic humic substances of different molecular sizes (F1: < 0.45 µm, F2: 100 kDa - 0.45 µm, F3: 30 - 100 kDa and F4': < 30 kDa). For the water samples with lower apparent molecular size fractions, greater dosages of coagulant was needed to remove the color around 5.0 Hanzen units, mainly because these water samples contain higher concentrations of fulvic acids, which exhibited a larger number of negatively-charged groups.Conselho Nacional de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Pesquisa e Desenvolvimento (CNPq

The regions of the sequence most exposed to the solvent within the amyloidogenic state of a protein initiate the aggregation process.

Formation of misfolded aggregates is an essential part of what proteins can do. The process of protein aggregation is central to many human diseases and any aggregating event needs to be prevented within a cell and in protein design. In order to aggregate, a protein needs to unfold its native state, at least partially. The conformational state that is prone to aggregate is difficult to study, due to its aggregating potential and heterogeneous nature. Here, we use a systematic approach of limited proteolysis, in combination with electrospray ionisation mass spectrometry, to investigate the regions that are most flexible and solvent-exposed within the native, ligand-bound and amyloidogenic states of muscle acylphosphatase (AcP), a protein previously shown to form amyloid fibrils in the presence of trifluoroethanol. Seven proteases with different degrees of specificity have been used for this purpose. Following exposure to the aggregating conditions, a number of sites along the sequence of AcP become susceptible to proteolytic digestion. The pattern of proteolytic cleavages obtained under these conditions is considerably different from that of the native and ligand-bound conformations and includes a portion within the N-terminal tail of the protein (residues 6-7), the region of the sequence 18-23 and the position 94 near the C terminus. There is a significant overlap between the regions of the sequence found to be solvent-exposed from the present study and those previously identified to be critical in the rate-determining steps of aggregation from protein engineering approaches. This indicates that a considerable degree of solvent exposure is a feature of the portions of a protein that initiate the process of aggregation

Breastfeeding education: where are we going? A systematic review article

Background: UNICEF (United Nations International Children’s Emergency Fund) and WHO estimate that if all babies were breastfed for at least the first six months of their lives, the rate of morbidity and malnutrition would sig-nificantly decrease all over the world. In this view, these two organizations promoted a worldwide campaign for breastfeeding, creating the Baby Friendly Hospital Initiative (BFHI) that encourages good practices for the promotion of breastfeeding in hospitals. The aim of our study was to review the available evidence regarding the positive effects of breastfeeding, in order to suggest to most appropriate strategy to support it. Methods: The main databases including Scopus, PubMed, MEDLINE, Google scholar and Science Direct were researched to obtain the original papers related to breastfeeding education. The main terms used to literature search were "Breastfeeding education", Breastfeeding support", and “Breastfeeding healthcare policy”. The timeframe in-cluded the obtained articles was from 1980 to 2015. Results: Our analysis confirms that healthcare providers play a pivotal role in education and encouraging mothers to begin and continue breastfeeding. In this view, the adequate training of healthcare providers seems to be mandatory in order to support this practice. Moreover, adequate facilities are needed in order to promote and support breastfeeding. Conclusion: Considering the available evidence, breastfeeding should be supported among all the mothers. Based on the positive data emerging from the public awareness campaign in different Countries of the world, we strongly en-courage an accurate training for doctors and midwives and the implementation of adequate facilities in order to sup-port breastfeeding