Studio dell’espressione di geni coinvolti in pathways metabolici regolati da nutrienti

2014-2015Il profilo sierico, con particolare riferimento ai livelli di biomarkers, rappresenta uno strumento efficace ed affidabile per la diagnosi di malattie metaboliche, come il diabete o le malattie cardiovascolari. La composizione del siero è influenzata sia dal metabolismo endogeno che dall’apporto nutrizionale. In effetti, lo stile alimentare, con particolare riferimento alla qualità e alla quantità dell’apporto nutrizionale, può fortemente influenzare il rischio e la progressione di malattia, poiché alcuni nutrienti agiscono come composti bioattivi. A questo proposito, la letteratura attuale indica un importante ruolo di specifiche molecole nutrizionali provenienti dalla dieta che interessano specifiche vie metaboliche. L'obiettivo del nostro progetto è quello di individuare pathways metabolici regolati da nutrienti, con lo scopo di identificare possibili taget terapeutici in stati patologici. [ a cura dell'autore]XIII n.s

Medullary thyroid carcinoma

Introduction: Medullary thyroid carcinoma (MTC) constitutes approximately 5–10% of all thyroid cancers. Although the tumor forms in the thyroid, it doesn’t originate from thyroid cells, but from the C cells or parafollicular cells which produce and release a hormone called calcitonin (CT). Starting from the second half of the 1900s, MTC was progressively studied and defined. Areas covered: This study aims to analyze the history, clinical presentation and biological behavior of MTC, bio-humoral and instrumental diagnosis, molecular profiling, genetic screening, preoperative staging and instrumental procedures, indispensable in expert and dedicated hands, such as high-resolution ultrasonography, CT-scan, MRI and PET/TC. We examine recommended and controversial surgical indications and procedures, prophylactic early surgery and multiple endocrine neoplasia surgery. Also, we discuss pathological anatomy classification and targeted therapies. The role of serum CT is valued both as undisputed and constant preoperative diagnostic marker, obscuring cytology and as early postoperative marker that predicts disease persistence. Expert opinion: With a complete preoperative study, unnecessary or useless, late and extended interventions can be reduced in favor of tailored surgery that also considers quality of life. Finally, great progress has been made in targeted therapy, with favorable impact on survival

Biodanza SRT: sfide educative in carcere

The contribution highlights how the educational intervention of Biodanza SRT, a pedagogy with body mediation oriented to the education of wellbeing, through an Embodied Training aims to reinforce and develop life skills in prisoners: skills, competences and personal strategies (protective factors) useful to consolidate a mode of positive coping thanks to which it is possible to effectively face the demands and trials of daily life and laying the foundations for the construction of a future life project. Emotional education, as an indispensable complement to cognitive and metacognitive development, facilitates the development of personal empowerment, the acquisition of Best Practices useful for encouraging inmates the development of possible protective factors and the acquisition of tools and personal resources for deal with stressful events and prevent or combat unease, risky behaviors and functional deviations for the reintegration into society of ex-prisoners, once they have left the criminal path. Pursuing explicit attention through an educational intentionality capable of investing in educational practices capable of generating tangible changes (especially in the long term), developing the enhancement of talents and personal and social success, concretely helps to stimulate in prisoners that sense of responsibility facilitating the “reprogramming” of a life path again.Il contributo evidenzia come l’intervento educativo della Biodanza SRT, pedagogia a mediazione corporea orientata  all’educazione del benessere, mediante un Embodied Trainining miri a rinforzare e sviluppare nei detenuti le life skills: capacità, competenze e strategie personali (fattori di protezione) utili a consolidare una modalità di fronteggiamento positivo grazie al quale è possibile affrontare efficacemente le richieste e le prove della vita quotidiana e ponendo le basi per la costruzione di un futuro progetto di vita. L’educazione emozionale, come complemento indispensabile allo sviluppo cognitivo e metacognitivo, facilita lo sviluppo dell’empowerment personale e l’acquisizione di Best Practice utili a favorire nei detenuti lo sviluppo dipossibili fattori di protezione, l’acquisizione di strumenti e risorse personali per affrontare gli eventi stressanti e prevenire o contrastare disagio, comportamenti a rischio e devianze funzionali al reinserimento nella società degli ex detenuti, una volta usciti dal percorso penale. Perseguendo una esplicita attenzione mediante una intenzionalità educativa atta ad investiresulle pratiche educative capaci di generare cambiamenti tangibili (soprattutto a lungo termine), sviluppando la valorizzazione dei talenti ed il successo personale e sociale, concretamente si va a contribuire a stimolare nei detenuti quel senso di responsabilizzazione facilitante la “riprogrammazione” di nuovo un percorso di vita

Synergistic antitumour activity of RAF265 and ZSTK474 on human TT medullary thyroid cancer cells

Medullary thyroid cancer (MTC) is an aggressive malignancy responsible for up to 14% of all thyroid cancer-related deaths. It is characterized by point mutations in the rearranged during transfection (RET) proto-oncogene. The activated RET kinase is known to signal via extracellular signal regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K), leading to enhanced proliferation and resistance to apoptosis. In the present work, we have investigated the effect of two serine/threonine-protein kinase B-Raf (BRAF) inhibitors (RAF265 and SB590885), and a PI3K inhibitor (ZSTK474), on RET-mediated signalling and proliferation in a MTC cell line (TT cells) harbouring the RETC634W activating mutation. The effects of the inhibitors on VEGFR2, PI3K/Akt and mitogen-activated protein kinases signalling pathways, cell cycle, apoptosis and calcitonin production were also investigated. Only the RAF265+ ZSTK474 combination synergistically reduced the viability of treated cells. We observed a strong decrease in phosphorylated VEGFR2 for RAF265+ ZSTK474 and a signal reduction in activated Akt for ZSTK474. The activated ERK signal also decreased after RAF265 and RAF265+ ZSTK474 treatments. Alone and in combination with ZSTK474, RAF265 induced a sustained increase in necrosis. Only RAF265, alone and combined with ZSTK474, prompted a significant drop in calcitonin production. Combination therapy using RAF265 and ZSTK47 proved effective in MTC, demonstrating a cytotoxic effect. As the two inhibitors have been successfully tested individually in clinical trials on other human cancers, our preclinical data support the feasibility of their combined use in aggressive MTC

Antibiotic-Resistant Gram Negative Bacilli in Meals Delivered at a General Hospital, Italy

This study aimed at detecting the presence of antibiotic-resistant Gram-negatives in samples of meals delivered at the University General Hospital of Palermo, Italy. Antibiotic resistant Gram negatives were isolated in July—September 2007 ffrom cold dishes and food contact surfaces and utensils. Bacterial strains were submitted to susceptibility test and subtyped by random amplification of polymorphic DNA (RAPD). Forty-six of 55 (83.6%) food samples and 14 of 17 (82.3%) environmental swabs were culture positive for Gram negative bacilli resistant to at least one group of antibacterial drugs. A total of 134 antibiotic resistant strains, 51 fermenters and 83 non-fermenters, were recovered. Fermenters and non-fermenters showed frequencies as high as 97.8% of resistance to two or more groups of antibiotics and non fermenters were 28.9% resistant to more than three groups. Molecular typing detected 34 different profiles among the fermenters and 68 among the non-fermenters. Antibiotic resistance was very common among both fermenters and non-fermenters. However, the wide heterogeneity of RAPD patterns seems to support a prominent role of cross-contamination rather than a clonal expansion of a few resistant isolates. A contribution of commensal Gram negatives colonizing foods to a common bacterial resistance pool should not been overlooked

Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer

Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA–miRNA and miRNA–miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non- tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional back- bone was fulfilled by tight micro-societies of miR- NAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signalling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA–RNA crosstalk, which mechanistically modulates several signalling path- ways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis

DMSO increases efficiency of genome editing at two non-coding loci

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) has become the tool of choice for genome editing. Despite the fact that it has evolved as a highly efficient means to edit/replace coding sequence, CRISPR/Cas9 efficiency for “clean” editing of non-coding DNA remains low. We set out to introduce a single base-pair substitution in two intronic SNPs at the FTO locus without altering nearby non-coding sequence. Substitution efficiency increased up to 10-fold by treatment of human embryonic stem cells (ESC) with non-toxic levels of DMSO (1%) before CRISPR/Cas9 delivery. Treatment with DMSO did not result in CRISPR/Cas9 off-target effects or compromise the chromosomal stability of the ESC. Twenty-four hour treatment of human ESC with DMSO before CRISPR/Cas9 delivery may prove a simple means to increase editing efficiency of non-coding DNA without incorporation of undesirable mutations

Conjugated polymers for the optical control of the electrical activity of living cells

Different conjugated polymers are proposed as bio-optical interfaces. Selected polymers are capable to sustain thermal sterilization but provide different optical coupling with living cells