A short-term incubation with high glucose impairs VASP phosphorylation at serine 239 in response to the nitric oxide/cGMP pathway in vascular smooth muscle cells: role of oxidative stress.

A reduction of the nitric oxide (NO) action in vascular smooth muscle cells (VSMC) could play a role in the vascular damage induced by the glycaemic excursions occurring in diabetic patients; in this study, we aimed to clarify whether a short-term incubation of cultured VSMC with high glucose reduces the NO ability to increase cGMP and the cGMP ability to phosphorylate VASP at Ser-239. We observed that a 180 min incubation of rat VSMC with 25 mmol/L glucose does not impair the NO-induced cGMP increase but reduces VASP phosphorylation in response to both NO and cGMP with a mechanism blunted by antioxidants. We further demonstrated that high glucose increases radical oxygen species (ROS) production and that this phenomenon is prevented by the PKC inhibitor chelerythrine and the NADPH oxidase inhibitor apocynin.

Mimicking pregnancy as a strategy for breast cancer prevention.

Pregnancy and its effects on breast cancer risk have been widely investigated; there is consensus among researchers that early pregnancy confers protection against breast cancer later in life, whereas nulliparity and late-age parity have been associated with increased risk of developing breast cancer. The answer to the question of how pregnancy reduces breast cancer risk has been elusive; however, pregnancy, like breast cancer, is a similar hormone-dependent entity under direct control of estrogen, progesterone and, of particular importance, human chorionic gonadotropin (hCG). In this report, we emphasize the main changes, previously described by our laboratory, in morphology and gene expression levels of the mammary gland of Sprague-Dawley rats exposed to known cancer-preventative conditions (pregnancy, hCG and progesterone + estrogen).

The genomic signature of breast cancer prevention.

The breast of parous postmenopausal women exhibits a specific signature that has been induced by a full term pregnancy. This signature is centered in chromatin remodeling and the epigenetic changes induced by methylation of specific genes which are important regulatory pathways induced by pregnancy. Through the analysis of the genes found to be differentially methylated between women of varying parity, multiple positions at which beta-catenin production and use is inhibited were recognized.

LRRK2 and neuroinflammation: partners in crime in Parkinson's disease?

It is now well established that chronic inflammation is a prominent feature of several neurodegenerative disorders including Parkinson's disease (PD). Growing evidence indicates that neuroinflammation can contribute greatly to dopaminergic neuron degeneration and progression of the disease. Recent literature highlights that leucine-rich repeat kinase 2 (LRRK2), a kinase mutated in both autosomal-dominantly inherited and sporadic PD cases, modulates inflammation in response to different pathological stimuli.

The use of biochip immunofluorescence microscopy for the diagnosis of Pemphigus vulgaris.

Pemphigus vulgaris is an autoimmune intraepithelial blistering skin disease characterized by the presence of circulating autoantibodies directed against surfaces of keratinocytes. Diagnosis is generally based on clinical features, histology, direct and indirect immunofluorescence and ELISA. This study describes a new BIOCHIP mosaic-based indirect immunofluorescence technique based on recombinant antigenic substrates and transfected cells.

p140Cap regulates memory and synaptic plasticity through Src-mediated and citron-N-mediated actin reorganization.

A major challenge in the neuroscience field is the identification of molecules and pathways that control synaptic plasticity and memory. Dendritic spines play a pivotal role in these processes, as the major sites of excitatory synapses in neuronal communication. Previous studies have shown that the scaffold protein p140Cap localizes into dendritic spines and that its knockdown negatively modulates spine shape in culture.

Ability of synbiotic encapsulated Saccharomyces cerevisiae boulardii to grow in berry juice and to survive under simulated gastrointestinal conditions.

The probiotic yeast, Saccharomyces cerevisiae boulardii, was microencapsulated in a mixture of alginate-inulin-xanthan gum, and its ability to grow in berry juice and survive 4 weeks of storage at 4 °C was determined. Exposure of the yeast in these forms to artificial gastrointestinal conditions was also assessed. Encapsulation significantly enhanced cell viability after fermentation and storage compared with the free yeast (7.

A novel truncated form of eNOS associates with altered vascular function.

Aims: Nitric oxide (NO) plays a key role in vascular homeostasis and is produced by endothelial NO synthase (eNOS), encoded by NOS3 gene. We previously reported the genetic association between NOS3 rs753482-A>C polymorphism on intron 19 and coronary artery disease (CAD). In the attempt of conferring functional implication to the rs753482-A>C polymorphism, we investigated its influence on transcript maturation.

The kiwi fruit peptide kissper displays anti-inflammatory and anti-oxidant effects in in-vitro and ex-vivo human intestinal models.

Literature reports describe kiwi fruit as a food with significant effects on human health, including anti-oxidant and anti-inflammatory activity. Fresh fruit or raw kiwi fruit extracts have been used so far to investigate these effects, but the molecule(s) responsible for these health-promoting activities have not yet been identified. Kissper is a kiwi fruit peptide displaying pore-forming activity in synthetic lipid bilayers, the composition of which is similar to that found in intestinal cells.

Postresuscitation treatment with argon improves early neurological recovery in a porcine model of cardiac arrest.

Introduction: Effects of postresuscitation treatment with argon on neurologic recovery were investigated in a porcine model of cardiac arrest (CA) with an underlying acute myocardial infarction.

Methods: The left anterior descending coronary artery was occluded in 12 pigs, and CA was induced. After 8 min of untreated CA, cardiopulmonary resuscitation was performed for 5 min before defibrillation.

Oleic acid increases synthesis and secretion of VEGF in rat vascular smooth muscle cells: role of oxidative stress and impairment in obesity.

Obesity is characterized by poor collateral vessel formation, a process involving vascular endothelial growth factor (VEGF) action on vascular smooth muscle cells (VSMC). Free fatty acids are involved in the pathogenesis of obesity vascular complications, and we have aimed to clarify whether oleic acid (OA) enhances VEGF synthesis/secretion in VSMC, and whether this effect is impaired in obesity. In cultured aortic VSMC from lean and obese Zucker rats (LZR and OZR, respectively) we measured the influence of OA on VEGF-A synthesis/secretion, signaling molecules and reactive oxygen species (ROS).

To be or not to be translational.

Translational Research means different things to different people, but it seems crucial to almost everyone. This discipline, although defined differently in academia, regulatory institutions, and industry, shares the fundamental vision of Translational Medicine, which efficiently and effectively translates basic scientific findings relevant to human disease into knowledge that benefits patients. In the present perspective, we collected commentaries and descriptions about Translational Medicine to stimulate discussion and better understand what Translational Medicine is.

Identification of two regions in the p140Cap adaptor protein that retain the ability to suppress tumor cell properties.

p140Cap is an adaptor protein that negatively controls tumor cell properties, by inhibiting in vivo tumor growth and metastasis formation. Our previous data demonstrated that p140Cap interferes with tumor growth and impairs invasive properties of cancer cells inactivating signaling pathways, such as the tyrosine kinase Src or E-cadherin/EGFR cross-talk. In breast cancer p140Cap expression inversely correlates with tumor malignancy.

Early kynurenine pathway activation following cardiac arrest in rats, pigs, and humans.

Aim Of The Study: Kynurenine pathway (KP) is a major route of the tryptophan (TRP) catabolism. In the present study, TRP and KP metabolites concentrations were measured in plasma from rats, pigs and humans after cardiac arrest (CA) in order to assess KP activation and its potential role in post-resuscitation outcome.

Methods: Plasma was obtained from: (A) 24 rats, subjected to 6 min CA and 6 min of cardiopulmonary resuscitation (CPR); (B) 10 pigs, subjected to 10 min CA and 5 min CPR; and (C) 3 healthy human volunteers and 5 patients resuscitated from CA.

Melanocytic nevi in children of southern Italy: dermoscopic, constitutional, and environmental factors.

The objective was to estimate the prevalence of melanocytic nevi (MN) in children and to determine their dermoscopic characteristics and relationship with anatomic location and environmental and constitutional factors. The population was a randomly selected sample of 144 children who attended primary schools in Naples, Italy. Before physical examination of the children, standardized interviews were conducted with their parents.

Leptin and vascular smooth muscle cells.

This review concerns the influence of leptin on vascular smooth muscle cells (VSMC). VSMC express different isoforms of the leptin receptor (Ob-R) able to activate a wide range of intracellular signalling pathways, mediating many relevant biological actions. In particular, leptin promotes processes deeply involved in atherogenesis, such as VSMC migration, hypertrophy, proliferation, osteogenic differentiation and metalloproteinase expression.

Ibuprofen plus isosorbide dinitrate treatment in the mdx mice ameliorates dystrophic heart structure.

Background: Co-administration of ibuprofen (IBU) and isosorbide dinitrate (ISDN) provides synergistic beneficial effects on dystrophic skeletal muscle. Whether this treatment has also cardioprotective effects in this disease was still unknown.

Aims: To evaluate the effects of co-administration of IBU and ISDN (a) on left ventricular (LV) structure and function, and (b) on cardiac inflammatory response and fibrosis in mdx mice.

Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.

Background & Aims: Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage. In fact, there is no evidence for mucosal or serologic modifications in those individuals. We investigated immunologic responses of duodenal mucosa samples and peripheral blood basophils, isolated from NCGS patients, after exposure to gliadin.

Current practice and recent advances in pediatric pain management.

Background: Differently from the adult patients, in pediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, selection of appropriate pain assessment tools should consider age, cognitive level and the presence of eventual disability, type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drugs pharmacokinetics should facilitate a better management of childhood pain.

An - model of epithelial mesenchymal transition in triple negative breast cancer.

The loss of epithelial expression markers by neoplastic breast cancer cells in the primary tumor is believed to play a pivotal role during breast cancer metastasis. This phenomenon is the hallmark of the epithelial mesenchymal transition (EMT) process. Gene expression microarrays were performed to investigate key functional elements on an metastasis model derived from human breast epithelial cells (MCF10F) treated with 17 beta estradiol.

AMPA receptor properties are modulated in the early stages following pilocarpine-induced status epilepticus.

Glutamate over-activation and the consequent neuronal excitotoxicity have been identified as crucial players in brain dysfunctions such as status epilepticus (SE). Owing to the central function of 2-amino-3-(hydroxyl-5-methylisoxazole-4-yl) propionic acid receptors (AMPARs) in fast excitatory neurotransmission, these receptors have been recognized to play a prominent role in the development and generation of epileptic seizure. This study was undertaken to investigate both the early changes that affect glutamatergic neurons in the rat cerebral cortex and hippocampus and the level and channel properties of AMPARs in response to SE.

Safe lumbar puncture under analgo-sedation in children with acute lymphoblastic leukemia.

Background: Children with acute lymphoblastic leukemia (ALL) undergo multiple lumbar punctures (LPs) during their course of treatment for diagnostic and therapeutic purposes. LP is a stressful and painful procedure, affecting the quality of life of these children. Procedural analgo-sedation might improve the child's comfort and prevent the child's movements, reducing the risk of traumatic lumbar puncture with blasts (TLP+), mainly at diagnosis, when higher numbers of blast cells are circulating in the peripheral blood.

Exosomes-associated neurodegeneration and progression of Parkinson's disease.

Growing evidence indicates the role of exosomes in a variety of physiological pathways as conveyors of biological materials from cell-to-cell. However the molecular mechanism(s) of secretion and their interaction with receiving cells are yet unclear. Recently, it is emerging that exosomes are involved in pathological processes as potential carriers in the progression of neurodegenerative pathologies associated with misfolded proteins.

Mapping of p140Cap phosphorylation sites: the EPLYA and EGLYA motifs have a key role in tyrosine phosphorylation and Csk binding, and are substrates of the Abl kinase.

Protein phosphorylation tightly regulates specific binding of effector proteins that control many diverse biological functions of cells (e. g. signaling, migration and proliferation).