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BACKGROUND: Camelina sativa oil is one of the richest dietary sources of omega-3, with polyunsaturated fatty acids amounts of over 50%, linolenic acid content of around 40-45%, and linoleic acid of about 15%. Moreover, this oil is a valuable source of antioxidants which provide oxidative stability. All those features raise interest in considering Camelina oil as an alternative and sustainable oil source providing stable omega-3-rich emulsions for functional food production. OBJECTIVES: The present study aimed to investigate the effects of Camelina oil-enriched crackers on serum omega-3 concentration, inflammatory markers and serum lipid profile. DESIGN: Randomized placebo-controlled pilot trial. SETTING: Research and Development Center (Complife Italia s.r.l.). PARTICIPANTS: Sixty-six free-living older volunteers (aged≥65 years). INTERVENTION: Older adults were enrolled and randomly assigned to one of two groups: the camelina group or the placebo group. Subjects consumed daily 35 g of crackers (Camelina enriched crackers or placebo ones) twice daily for 12 weeks. MEASUREMENTS: Serum polyunsaturated fatty acid profile, inflammatory status and serum lipid panel parameters were recorded pre and post-intervention. RESULTS: In the camelina group, alpha-linolenic acid serum concentration was significantly higher (p<0.01) compared to the placebo group at the end of the study. Concerning inflammatory plasma markers, a significant mean pro-inflammatory interleukin-18 plasma concentration decrease in the placebo group compared to the camelina one was observed (p<0.05). No significant differences in other mean inflammatory markers concentrations post-intervention were noted in either group. Lastly, examining the change in lipid profile, it is noteworthy that a higher reduction of total cholesterol, low-density lipoprotein and triglycerides in the camelina group post-intervention, despite the lack of statistical significance. CONCLUSION: Camelina oil significantly elevated the serum alpha-linolenic acid concentration with no significant changes in inflammatory markers and lipid profile.

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Inflammatory bowel disease (Crohn's disease (CD) and ulcerative colitis (UC)) is a multifactorial disease resulting from immune dysregulation in the gut. The underlying colitis is characterized by high levels of inflammatory cytokines, including TNFα. Biological intervention for IBD patients using anti-TNFα antibodies is often an effective therapeutic solution. However, TNFα neutralization fails to induce remission in a subgroup of IBD patients, primarily in UC patients. There is a dearth of suitable animal models representing TNFα non-responders. Here we have combined one of the best UC models currently available, namely Winnie and the TNFαKO mouse to generate a TNFα-deficient Winnie to study early onset colitis. The induced TNFα deficiency with underlying colitis does not influence general health (viability and body weight) or clinical parameters (colon weight, colon length and histological colitis) when compared with the Winnie genotype alone. The molecular characterization resulted in identification of Il1ß as the major elevated cytokine during early phases of colitis. Further, in vitro functional assay using bone marrow-derived dendritic cells confirmed IL-1ß as the major cytokine released in the absence of TNFα. This study has generated a successful model of colitis that remains TNFα non-responsive and has demonstrated that IL-1ß expression is a major pathway for the progression of colitis in this system. These data also suggest that IL-1ß can be a potential target for clinical intervention of UC patients who fail to respond to TNFα neutralization.

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BACKGROUND: p53 is a transcription factor with tumour suppressor properties, which is able to induce mitochondrial apoptosis independently of its transcriptional activity. We recently synthesised two new compounds (ISA27 and SM13), which block p53-MDM2 interaction and induce apoptosis in p53 wild-type (WT) tumour cells. The aim of this study was to verify the effectiveness of these compounds in tumours carrying a mutated form of p53 gene with no transcriptional activity. METHODS: In vitro we evaluated the effectiveness of our compounds in cancer cell lines carrying WT, mutated and null p53 gene. In vivo study was performed in Balb/c nude mice and the mitochondrial-dependent apoptotic signalling was evaluated by western blot. RESULTS: Both ISA27 and SM13 reduced cell proliferation and induced apoptosis in vitro in cells carrying either p53 WT or mutated gene, suggesting that its effect is independent from p53 transcriptional activity. On the contrary, SM13 had no effect in a p53 null cell line. In vivo, ISA27 and SM13 induced cancer cell death in a dose-dependent manner through the activation of the mitochondrial-dependent death signalling in p53-mutated cells. In vivo, SM13 reduced tumour growth. CONCLUSIONS: Our study proposes SM13 as anticancer compound to use for the treatment of p53-dependent tumours, even in the absence of p53 transcriptional activity.

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Vascular smooth muscle cell (VSMC) proliferation contributes to vascular remodeling in atherosclerosis and hypertension. Calcium-dependent signaling through calcium/calmodulin-dependent kinase II (CaMKII) and ERK1/2 activation plays an important role in the regulation of VSMC proliferation by agents such as alpha-adrenergic receptor agonists. Nevertheless, how the CaMKII and ERK pathways interact in VSMCs has yet to be characterized. The aim of the present study was to clarify this interaction in response to alpha(1)-adrenergic receptor-mediated VSMC proliferation. We discovered that phenylephrine stimulation resulted in complex formation between CaMKII and ERK in a manner that facilitated phosphorylation of both protein kinases. To assess the effects of CaMKII/ERK association on VSMC proliferation, we inhibited endogenous CaMKII either pharmacologically or by adenoviral-mediated gene transfer of a kinase-inactive CaMKII mutant. Inhibition of CaMKII activation but not CaMKII autonomous activity significantly decreased formation of the CaMKII/ERK complex. On the contrary, the expression of constitutively active CaMKII enhanced VSMC growth and CaMKII/ERK association. In addressing the mechanism of this effect, we found that CaMKII could not directly phosphorylate ERK but instead enhanced Raf1 activation. By contrast, ERK interaction with CaMKII facilitated CaMKII phosphorylation and promoted its nuclear localization. Our results reveal a critical role for CaMKII in VSMC proliferation and imply that CaMKII facilitates assembly of the Raf/MEK/ERK complex and that ERK enhances CaMKII activation and influences its subcellular localization.

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The incorporation of a Freidinger-like lactam structure into the backbone of peptides has been proven to be an useful strategy in the design of a variety of conformationally restricted targets. Several different strategies have been developed toward Freidinger lactams but no one resulted to be completely facile. Here, we report an efficient strategy that involves the iodo-derivatives in side chain of an appropriate amino acid used as electrophilic agent, and the standard solid phase peptide synthesis assisted by microwave irradiation. The methodology developed could be useful to perform Freidinger-like lactams with defined stereochemistry for routine use in solid phase peptide chemistry.

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