Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics.

One of the main challenges in cancer management relates to the discovery of reliable biomarkers, which could guide decision-making and predict treatment outcome. In particular, the rise and democratization of high-throughput molecular profiling technologies bolstered the discovery of "biomarker signatures" that could maximize the prediction performance. Such an approach was largely employed from diverse OMICs data (i.e., genomics, transcriptomics, proteomics, metabolomics) but not from epitranscriptomics, which encompasses more than 100 biochemical modifications driving the post-transcriptional fate of RNA: stability, splicing, storage, and translation. We and others have studied chemical marks in isolation and associated them with cancer evolution, adaptation, as well as the response to conventional therapy. In this study, we have designed a unique pipeline combining multiplex analysis of the epitranscriptomic landscape by high-performance liquid chromatography coupled to tandem mass spectrometry with statistical multivariate analysis and machine learning approaches in order to identify biomarker signatures that could guide precision medicine and improve disease diagnosis. We applied this approach to analyze a cohort of adult diffuse glioma patients and demonstrate the existence of an "epitranscriptomics-based signature" that permits glioma grades to be discriminated and predicted with unmet accuracy. This study demonstrates that epitranscriptomics (co)evolves along cancer progression and opens new prospects in the field of omics molecular profiling and personalized medicine.

Laccases 2 & 3 as biomarkers of Botrytis cinerea infection in sweet white wines.

Botrytized sweet wines are made with berries infected by the fungus Botrytis cinerea. The aim of this study was to identify biomarkers of B. cinerea infection in sweet wines with a focus on laccases which are exocellular oxidase enzymes produced by this fungus during fruit contamination. Total proteins from six commercial sweet wines, including three naturally botrytized wines and three non-botrytized wines were analysed by LC-QTOF-MS. Five laccases, namely laccase-1-BcLCC1, laccase-2-BcLCC2, laccase-3-BcLCC7, laccase-8-BcLCC8 and laccase-12-BcLCC12, were identified in both types of wine. Then, a targeted proteomic approach by LC-MRM was used to semi-quantify laccase-2-BcLCC2 and laccase-3-BcLCC7, in the six samples. LC-MRM targeted analysis of the two enzymes allowed the discrimination of botrytized versus non-botrytized sweet white wines.

Study of thrombinic activation indexes, in patients with lower limb critic ischaemia, before and after prostaglandin E1 therapy.

BACKGROUND: In this study the action of a prostaglandin, PGE1, was studied in a group of patients with peripheral arterial occlusive disease (PAOD). METHODS: In 16 patients (14 men and 2 women, aged 47-70 years, mean 57 +/- 7) with PAOD, Fontaine stage IIb and III in critical ischemia, the effects on two indexes of thrombin generation and action of the endovenous administration (2 hours) of 60 micrograms of Alprostadil-PGE1 for four weeks were evaluated. In all artheriopathic patients, before and after pharmacological treatment, the following haemostatic parameters were evaluated: the prothrombin fragment 1 + 2 (F1 + 2) and the fibrinopeptide A(FPA). RESULTS: The patients showed plasma levels of FPA significantly decreased at the end of the treatment. On the other hand, no significant difference in plasma F1 + 2 levels was observed after treatment. CONCLUSIONS: These results seem to indicate that plasma F1 + 2 levels are significantly elevated, as a marker of thrombosis status, in patients with PAOD before and after treatment with PGE1.

Clinical and haemostatic effects of intravenous prostaglandin E1 therapy in patients with peripheral arterial occlusive disease.

BACKGROUND: In this study the action of an antiaggregatory prostaglandin, PGE1, was studied in a group of patients with peripheral arterial occlusive disease (PAOD). METHODS: In 16 patients with PAOD Fontaine stage IIb and III the clinical and haemostatic effects of the endovenous administration of 60 micrograms/die of alprostadil-PGE1 for four weeks, were evaluated. Before and after pharmacological treatment, were evaluated the clinical symptoms (claudicatio intermittens and rest pain) and the following haemostatic parameters: plasma thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1). RESULTS: No significant difference in plasma TM, t-PA and PAI-1 levels was observed after the treatment. On the other hand the patients showed plasma levels of beta-TG and DD significantly decreased at the end of the treatment. From the clinical point of view both claudicatio intermittens and rest pain satisfactorily improved in all patients. CONCLUSIONS: This data confirmed the therapeutic efficacy of PGE1 in the treatment of PAOD patients.

Haemostatic parameters in patients with primitive venous hypertension.

In twenty patients with primitive venous hypertension and in ten healthy subjects we have determined the plasmatic levels of: Thrombomodulin (TM), beta-Thromboglobulin (beta-TG), D-Dimer (DD), the tissue activator of the plasminogen (t-PA) and the inhibitor of the activator of the plasminogen (PAI-1). The levels of the parameter we studied have shown in the patients a significant difference of beta-TG (p < 0.01) and PAI-1 (p < 0.01) compared to the controls, whereas there was no significant difference in the other parameters we studied. Our data underline, in patients with primitive venous hypertension, the importance that the activation of the platelets and the reduction of the potential fibrinolytic can assume, together with the stasis, regarding the onset of thrombotic complications.

Relationships between swallowing pattern, mode of respiration, and development of malocclusion.

A study of children in northern Italy finds positive but complex relationships between malocclusion and both respiration and swallowing patterns.