Melleatin, an antibiofilm multitasking protein with rRNA N-glycosylase and nuclease activity from Armillaria mellea fruiting bodies.

Several studies highlight the identification of some enzymes with additional abilities, especially those involved in metabolic pathways and/or host defence processes, classified as multitasking proteins. In this context, we report the characterization of melleatin (17.5-kDa), a multitasking enzyme isolated from Armillaria mellea fruiting bodies.

Multiple aspects of matrix stiffness in cancer progression.

The biophysical and biomechanical properties of the extracellular matrix (ECM) are crucial in the processes of cell differentiation and proliferation. However, it is unclear to what extent tumor cells are influenced by biomechanical and biophysical changes of the surrounding microenvironment and how this response varies between different tumor forms, and over the course of tumor progression. The entire ensemble of genes encoding the ECM associated proteins is called matrisome.

Neuro-Nutraceutical Polyphenols: How Far Are We?

The brain, composed of billions of neurons, is a complex network of interacting dynamical systems controlling all body functions. Neurons are the building blocks of the nervous system and their impairment of their functions could result in neurodegenerative disorders. Accumulating evidence shows an increase of brain-affecting disorders, still today characterized by poor therapeutic options.

High-Resolution Conformational Analysis of RGDechi-Derived Peptides Based on a Combination of NMR Spectroscopy and MD Simulations.

The crucial role of integrin in pathological processes such as tumor progression and metastasis formation has inspired intense efforts to design novel pharmaceutical agents modulating integrin functions in order to provide new tools for potential therapies. In the past decade, we have investigated the biological proprieties of the chimeric peptide RGDechi, containing a cyclic RGD motif linked to an echistatin C-terminal fragment, able to specifically recognize αvβ3 without cross reacting with αvβ5 and αIIbβ3 integrin. Additionally, we have demonstrated using two RGDechi-derived peptides, called RGDechi1-14 and ψRGDechi, that chemical modifications introduced in the C-terminal part of the peptide alter or abolish the binding to the αvβ3 integrin.

Ruta graveolens water extract (RGWE) ameliorates ischemic damage and improves neurological deficits in a rat model of transient focal brain ischemia.

Introduction And Aims: The limited therapeutic options for ischemic stroke treatment render necessary the identification of new strategies. In recent years, it has been shown that natural compounds may represent a valid therapeutic opportunity. Therefore, the present study aimed to evaluate the protective effect of Ruta graveolens water extract (RGWE) in an in vivo experimental model of brain ischemia.

Angiogenesis and Multiple Sclerosis Pathogenesis: A Glance at New Pharmaceutical Approaches.

Multiple sclerosis is a chronic disease of the central nervous system characterized by demyelination and destruction of axons. The most common form of the disease is the relapsing-remitting multiple sclerosis in which episodic attacks with typical neurological symptoms are followed by episodes of partial or complete recovery. One of the underestimated factors that contribute to the pathogenesis of multiple sclerosis is excessive angiogenesis.

Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent Gene Variants and Correlations with Neurocognitive Phenotype.

Neurofibromatosis type 1 (NF1) is one of the most common genetic tumor predisposition syndrome, caused by mutations in the . To date, few genotype-phenotype correlations have been discerned in NF1, due to a highly variable clinical presentation. We aimed to study the molecular spectrum of NF1 and genotype-phenotype correlations in a monocentric study cohort of 85 NF1 patients (20 relatives, 65 sporadic cases).

A novel approach for studying receptor-ligand interactions on living cells surface by using NUS/T1ρ-NMR methodologies combined with computational techniques: The RGDechi15D-αβ integrin complex.

Structural investigations of receptor-ligand interactions on living cells surface by high-resolution Nuclear Magnetic Resonance (NMR) are problematic due to their short lifetime, which often prevents the acquisition of experiments longer than few hours. To overcome these limitations, we developed an on-cell NMR-based approach for exploring the molecular determinants driving the receptor-ligand recognition mechanism under native conditions. Our method relies on the combination of high-resolution structural and dynamics NMR data with Molecular Dynamics simulations and Molecular Docking studies.

ZBTB2 protein is a new partner of the Nucleosome Remodeling and Deacetylase (NuRD) complex.

ZBTB2 is a protein belonging to the BTB/POZ zinc-finger family whose members typically contain a BTB/POZ domain at the N-terminus and several zinc-finger domains at the C-terminus. Studies have been carried out to disclose the role of ZBTB2 in cell proliferation, in human cancers and in regulating DNA methylation. Moreover, ZBTB2 has been also described as an ARF, p53 and p21 gene repressor as well as an activator of genes modulating pluripotency.

Interactome mapping defines BRG1, a component of the SWI/SNF chromatin remodeling complex, as a new partner of the transcriptional regulator CTCF.

The highly conserved zinc finger CCCTC-binding factor (CTCF) regulates genomic imprinting and gene expression by acting as a transcriptional activator or repressor of promoters and insulator of enhancers. The multiple functions of CTCF are accomplished by co-association with other protein partners and are dependent on genomic context and tissue specificity. Despite the critical role of CTCF in the organization of genome structure, to date, only a subset of CTCF interaction partners have been identified.

Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice.

Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures. Due to structural differences between human and mouse, the mechanisms by which mutations of the H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined. To address this issue, we previously generated a mouse line carrying a humanized IC1 (hIC1) and now replaced the wildtype with a mutant IC1 identified in the overgrowth-associated Beckwith-Wiedemann syndrome.

Ruta graveolens water extract inhibits cell-cell network formation in human umbilical endothelial cells via MEK-ERK1/2 pathway.

Angiogenesis is a process encompassing several steps such as endothelial cells proliferation, differentiation and migration to form a vascular network, involving different signal transduction pathways. Among these, ERK1/2 signaling mediates VEGF-dependent signaling pathway. Here we report that the water extract of Ruta graveolens (RGWE), widely known as a medicinal plant, is able to impair in a dose-dependent manner, cell network formation without affecting cell viability.

Functional characterization of the neuron-restrictive silencer element in the human tryptophan hydroxylase 2 gene expression.

Tryptophan hydroxylase 2 (TPH2) is the key enzyme in the synthesis of neuronal serotonin. Although previous studies suggest that TPH2 neuron-restrictive silencer element (NRSE) functions as a negative regulator dependent on neuron-restrictive silencer factor (NRSF) activity, the underlying mechanisms are yet to be fully elucidated. Here, we show a detailed analysis of the NRSE-mediated repression of the human TPH2 (hTPH2) promoter activity in RN46A cells, a cell line derived from rat raphe neurons.

GRN deletion in familial frontotemporal dementia showing association with clinical variability in 3 familial cases.

Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns.

Ruta graveolens L. induces death of glioblastoma cells and neural progenitors, but not of neurons, via ERK 1/2 and AKT activation.

Glioblastoma multiforme is a highly aggressive brain tumor whose prognosis is very poor. Due to early invasion of brain parenchyma, its complete surgical removal is nearly impossible, and even after aggressive combined treatment (association of surgery and chemo- and radio-therapy) five-year survival is only about 10%. Natural products are sources of novel compounds endowed with therapeutic properties in many human diseases, including cancer.

Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity.

Serotonin (5-HT) is a neurotransmitter involved in many aspects of the neuronal function. The synthesis of 5-HT is initiated by the hydroxylation of tryptophan, catalyzed by tryptophan hydroxylase (TPH). Two isoforms of TPH (TPH1 and TPH2) have been identified, with TPH2 almost exclusively expressed in the brain.

Amyloid-β protein precursor regulates phosphorylation and cellular compartmentalization of microtubule associated protein tau.

Tau is a multifunctional protein detected in different cellular compartments in neuronal and non-neuronal cells. When hyperphosphorylated and aggregated in atrophic neurons, tau is considered the culprit for neuronal death in familial and sporadic tauopathies. With regards to Alzheimer's disease (AD) pathogenesis, it is not yet established whether entangled tau represents a cause or a consequence of neurodegeneration.

Pressure-induced vascular oxidative stress is mediated through activation of integrin-linked kinase 1/betaPIX/Rac-1 pathway.

High blood pressure induces a mechanical stress on vascular walls and evokes oxidative stress and vascular dysfunction. The aim of this study was to characterize the intracellular signaling causing vascular oxidative stress in response to pressure. In carotid arteries subjected to high pressure levels, we observed not only an impaired vasorelaxation, increased superoxide production, and NADPH oxidase activity, but also a concomitant activation of Rac-1, a small G protein.

Tumor necrosis factor-alpha mediates hemolysis-induced vasoconstriction and the cerebral vasospasm evoked by subarachnoid hemorrhage.

Hypertension can lead to subarachnoid hemorrhage and eventually to cerebral vasospasm. It has been suggested that the latter could be the result of oxidative stress and an inflammatory response evoked by subarachnoid hemorrhage. Because an unavoidable consequence of hemorrhage is lysis of red blood cells, we first tested the hypothesis on carotid arteries that the proinflammatory cytokine tumor necrosis factor-alpha contributes to vascular oxidative stress evoked by hemolysis.

Resistin impairs insulin-evoked vasodilation.

Objective: Since vascular dysfunction is a main trait of obese subjects, in the present study we evaluated the vascular impact of resistin, a recently discovered hormone markedly increased in obesity.

Research Design And Methods: We performed our analysis on aortic and mesenteric segments from young and old C57BL/6 mice and on cultured endothelial cells. Resistin-induced vascular effect was evaluated in vitro and in vivo.

Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension.

There are conflicting evidence regarding the association of hypertension with Alzheimer's disease (AD), and so far it is still unexplored whether increased blood pressure levels can be mechanistically related to the pathophysiology of AD. Since the deposition of beta-amyloid (A beta) in brain represents the first pathogenetic event in the onset of AD, in this study we investigated the role of hypertension in the brain deposition of A beta. We analyzed two independent mouse models of hypertension.

Nebivolol induces nitric oxide release in the heart through inducible nitric oxide synthase activation.

Nebivolol is a beta1-adrenergic receptor antagonist that also reduces blood pressure by evoking endothelial NO production and vasodilation. We aimed at assessing whether nebivolol induces NO production also in the heart and delineating the molecular mechanisms involved. Using the fluorescent probe diaminofluorescein, we found that nebivolol induces a dose-dependent NO production in the heart, statistically significant already at 10(-7) mol/L.

Characterization of nitric oxide release by nebivolol and its metabolites.

Background: Nebivolol is a selective beta(1)-adrenergic receptor antagonist that causes a direct vasodilator effect attributed to the action on vascular nitric oxide (NO). This study aimed to investigate whether nebivolol or its metabolites induces NO production and to explore the mechanisms underlying this pharmacologic effect.

Methods: Conductance and resistance arteries from Wistar-Kyoto rats (WKY) (n = 33) incubated with the fluorescent probe diaminofluorescein-2 (DAF-2) were stimulated with increasing concentrations of nebivolol or its enantiomers and metabolites, and NO release was histologically evaluated.