Metabolic syndrome is a pathological condition characterized by obesity, hyperglycemia, hypertension, elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol that increase cardiovascular disease risk and type 2 diabetes. Although numerous predisposing genetic risk factors have been identified, the biological mechanisms underlying this complex phenotype are not fully elucidated. Here we introduce a systems biology approach based on network analysis to investigate deregulated biological processes and subsequently identify drug repurposing candidates. A proximity score describing the interaction between drugs and pathways is defined by combining topological and functional similarities. The results of this computational framework highlight a prominent role of the immune system in metabolic syndrome and suggest a potential use of the BTK inhibitor ibrutinib as a novel pharmacological treatment. An experimental validation using a high fat diet-induced obesity model in zebrafish larvae shows the effectiveness of ibrutinib in lowering the inflammatory load due to macrophage accumulation.

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Gamma-hydroxybutyric acid (GHB) is a drug currently used for the treatment of alcohol dependence. The aim of our study was to investigate the incidence of craving for and abuse of GHB in 47 patients enrolled and divided into four groups: group A (pure alcoholics), group B (alcoholics with a sustained full remission from cocaine dependence), group C (alcoholics with a sustained full remission from heroin dependence) and group D (alcoholics in a methadone maintenance treatment [MMT] programme). All patients were treated with an oral dose of GHB (50 mg/kg of body weight t.i.d.) for three months. Craving for GHB was statistically significant higher in group B than in group A (P < 0.001), C (P = 0.01) and D (P < 0.001), and in group C than in group D (P < 0.05). Abuse of GHB proved to be statistically significant higher in group B than in group A (P < 0.001) and D (P < 0.01), and in group C than in group A (P = 0.01) and D (P < 0.05). Thus, the administration of GHB in alcoholics with a sustained full remission from heroin or cocaine dependence is not recommended; however, this should not discourage physicians from using GHB for the treatment of pure alcoholics or alcohol dependents following a MMT.

Indexes derived from diffusion tensor imaging (DTI) are sensitive to changes of both T2-hyperintense and normal-appearing brain white matter (WM) in elderly subjects with variable cognitive status. We investigated correlations between global cognitive performance and DTI-derived indexes along the WM tracts in the brain of patients with vascular mild cognitive impairment (MCI) and small vessel disease (SVD). Seventy-six patients with vascular MCI and SVD were assessed through Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) test and underwent DTI examination on a 1.5 T MR scanner. We used Tract Based Spatial Statistics (TBSS) to assess voxel-wise in the entire brain the spatial distribution of the correlation between values of fractional anisotropy, mean, axial/radial diffusivity and global cognitive performance as assessed with MoCA and MMSE tests. All correlations were statistically tested with a significant p-value <0.05 using a family-wise error correction for multiple comparisons. The MoCA score significantly correlated with fractional anisotropy (positive correlation) and mean, axial and radial diffusivity (negative correlations) in WM tracts of cerebral hemispheres and corpus callosum, as well as in the intra-thalamic WM tracts and the superior cerebellar peduncle decussation in the midbrain. No significant correlations were observed for MMSE score. Global cognitive performance, as measured by the MoCA score, in patients with vascular MCI and SVD is associated with microstructural changes in WM tracts underlying intra- and inter-hemispheric cerebral, thalamo-cortical and cerebello-thalamic connections.