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Préveza, Greece

Benetatos L.,Transfusion Unit | Hatzimichael E.,University of Ioannina | Hatzimichael E.,Thomas Jefferson University | Londin E.,Thomas Jefferson University | And 4 more authors.
Cellular and Molecular Life Sciences | Year: 2013

The mammalian genome is transcribed in a developmentally regulated manner, generating RNA strands ranging from long to short non-coding RNA (ncRNAs). NcRNAs generated by intergenic sequences and protein-coding loci, represent up to 98 % of the human transcriptome. Non-coding transcripts comprise short ncRNAs such as microRNAs, piwi-interacting RNAs, small nucleolar RNAs and long intergenic RNAs, most of which exercise a strictly controlled negative regulation of expression of protein-coding genes. In humans, the DLK1-DIO3 genomic region, located on human chromosome 14 (14q32) contains the paternally expressed imprinted genes DLK1, RTL1, and DIO3 and the maternally expressed imprinted genes MEG3 (Gtl2), MEG8 (RIAN), and antisense RTL1 (asRTL1). This region hosts, in addition to two long intergenic RNAs, the MEG3 and MEG8, one of the largest microRNA clusters in the genome, with 53 miRNAs in the forward strand and one (mir-1247) in the reverse strand. Many of these miRNAs are differentially expressed in several pathologic processes and various cancers. A better understanding of the pathophysiologic importance of the DLK1-DIO3 domain-containing microRNA cluster may contribute to innovative therapeutic strategies in a range of diseases. Here we present an in-depth review of this vital genomic region, and examine the role the microRNAs of this region may play in controlling tissue homeostasis and in the pathogenesis of some human diseases, mostly cancer, when aberrantly expressed. The potential clinical implications of this data are also discussed. © 2012 Springer Basel AG.

Benetatos L.,Transfusion Unit | Voulgaris E.,University of Ioannina | Vartholomatos G.,University of Ioannina
Critical Reviews in Eukaryotic Gene Expression | Year: 2012

A rapidly growing body of evidence highlights the involvement of DLK1-MEG3 imprinted domain in cell biology and cancer pathogenesis. The imprinted domain contains protein-coding genes, long non-coding RNAs, and various small non-coding RNAs. The imprinted microRNAs located here interact with important transcription factors, modulate fundamental signaling cascades, form molecular signatures with diagnostic and prognostic potential, and could differentiate chemoresistant from chemosensitive disease. Moreover, as they can be detected in patients' serum, are easy to obtain, and can be used as adjuvant diagnostic biomarkers with the potential of monitoring disease progression and response to treatment. © 2011 Begell House, Inc.

Bonaccio M.,Istituto Neurologico Mediterraneo Neuromed | Di Castelnuovo A.,Istituto Neurologico Mediterraneo Neuromed | Bonanni A.,Epicomed Research Srl | Costanzo S.,Istituto Neurologico Mediterraneo Neuromed | And 6 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

Background and aims: Adherence to Mediterranean diet (MD) is reportedly declining in the last decades. We aimed to investigate the adherence to MD over the period 2005-2010 and exploring the possible role of the global economic crisis in accounting for the changing in the dietary habits in Italy. Methods and results: Cross-sectional analysis in a population-based cohort study which randomly recruited 21,001 southern Italian citizens enrolled within the Moli-sani study. Food intake was determined by the Italian EPIC food frequency questionnaire. Adherence to MD was appraised by the Italian Mediterranean Index (IMI). A wealth score was derived to evaluate the economic position and used together with other socioeconomic indicators. Highest prevalence of adherence to MD was observed during the years 2005-2006 (31.3%) while the prevalence dramatically fell down in the years 2007-2010 (18.3%; P<. 0.0001). The decrease was stronger in the elderly, less affluent groups, and among those living in urban areas. Accordingly, we observed that in 2007-2010 socioeconomic indicators were strongly associated with higher adherence to MD, whereas no association was detected in the years before the economic crisis began; both wealth score and education were major determinants of high adherence to MD with 31% (95%CI: 18-46%) higher adherence to this pattern within the wealthier group compared to the less affluent category. Conclusion: Adherence to MD has considerably decreased over the last few years. In 2007-2010 socioeconomic indicators have become major determinants of adherence to MD, a fact likely linked to the economic downturn. © 2014 Elsevier B.V.

Bosticardo G.,Nephrology and Dialysis Unit | Malberti F.,Nephrology and Dialysis Unit | Basile C.,Nephrology and Dialysis Unit | Leardini L.,Transfusion Unit | And 4 more authors.
Nephrology Dialysis Transplantation | Year: 2012

Background. There is no consensus regarding the optimal dialysate calcium concentration (DCa) during haemodialysis (HD). Low DCa may predispose to acute arrhythmias, whereas high DCa increases the long-term risk of soft tissue calcifications. Methods. Twenty-two HD patients treated in four dialysis centres underwent two HD sessions, respectively, with 1.5 and 1.25 mmol/L total DCa. Calcium mass balance (CMB) was calculated from ionized calcium (iCa) in the dialysate and blood at the start and end of each run, using a kinetic formula to define the mean concentrations in the blood and dialysate and then estimating CMBs over the entire treatments. Results. Mean blood iCa levels increased using 1.5 DCa, whereas they remained unchanged using 1.25 DCa. Diffusive CMB positively correlated with the dialysate/blood iCa gradient. With 1.5 DCa, diffusive CMBs were strongly positive at the blood side and negative at the dialysate side, indicating transfer from dialysate to blood. With 1.25 DCa, despite a negative dialysate/blood iCa gradient, diffusive CMB was slightly positive in blood and negative in dialysate. The global balances based on both the convective and diffusive components showed a positive net transfer of Ca from dialysate to blood with 1.5 DCa and an approximately neutral Ca flux with 1.25 DCa. Conclusions. While CMB is nearly neutral when using 1.25 DCa, the use of 1.5 DCa results in a gain of Ca during HD. The risks associated with Ca load should be considered in the choice of DCa prescription for HD but need also be weighed against the risk of worse haemodynamic dialysis tolerance. © 2012 The Author.

Rutella S.,IRCCS | Rutella S.,Catholic University | Iudicone P.,Azienda Ospedaliera S. Camillo Forlanini | Bonanno G.,Azienda Ospedaliera S. Camillo Forlanini | And 13 more authors.
Cytotherapy | Year: 2012

Background aims. We have recently shown that thymoglobulin (TG) efficiently expands cytokine-induced killer (CIK) cells in combination with interferon (IFN)-γ and interleukin (IL)-2 (ITG2 protocol). It is presently unknown whether the infusion of autologous immune effector cells generated by TG, IFN-γ and IL-2 is feasible and safe. Methods. Five patients with advanced and/or refractory solid tumors were enrolled in the present phase I/II study. Peripheral blood mononuclear cells (PBMC) collected by leukapheresis were stimulated under good manufacturing practice (GMP)-conditions with IFN-γ, followed by TG and IL-2. After 2-3 weeks in culture, a median of 4.65 × 106 immune effector cells per kilogram of recipient's body weight was obtained and infused intravenously. The median time from enrollment into the study to infusion of the expanded CIK cells was 30 days. Results. ITG2 efficiently expanded immune effector cells that comprised both conventional natural killer (NK) cells and CD3+ CD16+ CD56+ CIK cells. One patient with advanced melanoma died because of disease progression before the infusion of CIK cells. The target dose of at least 2.5 × 106 CIK cells/kg of recipient's body weight was reached in four out of five evaluable patients. CIK cells were administered intravenously without any measurable toxicity. In vitro, CIK cells exerted lytic activity against cervical cancer cells. The median survival was 4.5 months (range 1-13) from the first infusion of CIK cells. Conclusions. This study has highlighted the feasibility and safety of the administration of CIK cells generated with the ITG2 protocol. Whether CIK cells can help control disease burden in patients with advanced malignancies will be determined in future clinical trials. © 2012 Informa Healthcare.

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