Integrated mRNA and microRNA transcriptome profiling during differentiation of human nasal polyp epithelium reveals an altered ciliogenesis.

Background: Human adult basal stem/progenitor cells (BSCs) obtained from chronic rhinosinusitis with nasal polyps (CRSwNP) when differentiated in an air-liquid interface (ALI) usually provide a pseudostratified airway epithelium with similar abnormalities than original in vivo phenotype. However, the intrinsic mechanisms regulating this complex process are not well defined and their understanding could offer potential new therapies for CRSwNP (incurable disease).

Methods: We performed a transcriptome-wide analysis during in vitro mucociliary differentiation of human adult BSCs from CRSwNP, compared to those isolated from control nasal mucosa (control-NM), in order to identify which key mRNA and microRNAs are regulating this complex process in pathological and healthy conditions.

KIT as a therapeutic target for non-oncological diseases.

KIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigmentation disorders, KIT signaling was mainly considered to be involved in the regulation of hematopoiesis, gametogenesis, and melanogenesis. More recently, novel animal models and ameliorated cellular and molecular techniques have led to the discovery of a widen repertoire of tissue compartments and functions that are being modulated by KIT.

Human bronchial epithelium orchestrates dendritic cell activation in severe asthma.

The innate immune response is impaired in asthma, with increased epithelial release of C-X-C motif chemokine ligand (CXCL)8, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). We hypothesised that dendritic cells might modulate the hyperresponsive epithelium in severe asthma.For this purpose, we investigated epithelial-dendritic crosstalk in normal and diseased conditions, and because ultrafine particulate matter may affect asthmatic airways, we investigated its impact on this crosstalk.

Prostaglandin E2 Inhibits NLRP3 Inflammasome Activation through EP4 Receptor and Intracellular Cyclic AMP in Human Macrophages.

PGE2 is a potent lipid mediator involved in maintaining homeostasis but also promotion of acute inflammation or immune suppression in chronic inflammation and cancer. Nucleotide-binding domain, leucine-rich repeat-containing protein (NLR)P3 inflammasome plays an important role in host defense. Uncontrolled activation of the NLRP3 inflammasome, owing to mutations in the NLRP3 gene, causes cryopyrin-associated periodic syndromes.

Corticosteroid treatment regulates mucosal remodeling in chronic rhinosinusitis with nasal polyps.

Objectives/hypothesis: To investigate the effect of oral plus intranasal corticosteroid (CS) treatment on nasal polyp (NP) mucosa remodeling from patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP).

Study Design: Case series, retrospective study.

Methods: Patients (n = 18) with severe CRSwNP were treated with oral prednisone for 2 weeks and intranasal budesonide for 12 weeks.

Reconstituted human upper airway epithelium as 3-d in vitro model for nasal polyposis.

Background: Primary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described.

Objectives: 1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function.

The fish oil ingredient, docosahexaenoic acid, activates cytosolic phospholipase A₂ via GPR120 receptor to produce prostaglandin E₂ and plays an anti-inflammatory role in macrophages.

Docosahexaenoic acid (DHA) is one of the major ingredients of fish oil and has been reported to have anti-inflammatory properties mediated through the GPR120 receptor. Whether cytosolic phospholipase A2 (cPLA2 ) and lipid mediators produced from cPLA2 activation are involved in the anti-inflammatory role of DHA in macrophages has not been reported. We report here that DHA and the GPR120 agonist, GW9508, activate cPLA2 and cyclooxygenase 2 (COX-2), and cause prostaglandin E2 (PGE2) release in a murine macrophage cell line RAW264.

Low molecular weight hyaluronan activates cytosolic phospholipase A2α and eicosanoid production in monocytes and macrophages.

Hyaluronan (HA) is the major glycosaminoglycan in the extracellular matrix. During inflammation, there is an increased breakdown of HA, resulting in the accumulation of low molecular weight (LMW) HA and activation of monocytes and macrophages. Eicosanoids, derived from the cytosolic phospholipase A2 group IVA (cPLA2α) activation, are potent lipid mediators also attributed to acute and chronic inflammation.

Differential expression of remodeling markers by tissue structure in nasal polyposis.

Background: Data on the expression and role of matrix metalloproteinases (MMPs) and their tissue inhibitors (tissue inhibitor of metalloproteinases [TIMPs]) in chronic rhinosinusitis with nasal polyps (CRSwNPs) are contradictory, partly because or the use of different techniques of tissue analysis. The aim of this study was to establish a qualitative/semiquantitative method of analysis on the expression of these remodeling markers in different tissue structures and eosinophils in both NPs and nasal mucosa (NM).

Methods: NP tissues were obtained from patients undergoing endoscopic sinus surgery for severe CRSwNPs (n = 33) and NM tissues from patients undergoing nasal corrective surgery (n = 12).

Changes in microRNA and mRNA expression with differentiation of human bronchial epithelial cells.

We studied the changes in expression of microRNAs (miRNAs or miRs) and mRNA in normal human bronchial epithelial cells as they differentiate from an undifferentiated monolayer to a differentiated pseudostratified epithelium after 28 days of air-liquid interface (ALI) culture. After 28 days in ALI, the epithelial cells differentially expressed basal, ciliated, and goblet cell markers. Using Affymetrix microarrays, 20 human miRNAs were found to be up-regulated, whereas 35 miRNAs were found to be down-regulated in differentiated cells compared with undifferentiated cells.

Comparing crowding in human and ideal observers.

A visual target is more difficult to recognize when it is surrounded by other, similar objects. This breakdown in object recognition is known as crowding. Despite a long history of experimental work, computational models of crowding are still sparse.

Impact of an intervention to reduce prescribing errors in a pediatric intensive care unit.

Purpose: To identify and reduce medication prescribing errors in a pediatric intensive care unit (PICU) by means of an educational program designed to improve medical prescriptions.

Methods: Before-after interventional study in a tertiary-level PICU. Handwritten prescriptions were prospectively collected: 2,228 during period 1 and 1,791 during period 2.

Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes.

Background: Leukotriene B(4) (LTB(4)) and cysteinyl leukotrienes (cysLTs) are important immune mediators, often found concomitantly at sites of inflammation. Although some of the leukotriene-mediated actions are distinctive (e.g.

Montelukast reduces eosinophilic inflammation by inhibiting both epithelial cell cytokine secretion (GM-CSF, IL-6, IL-8) and eosinophil survival.

Leukotriene receptor antagonists, such as montelukast (MK), are currently used to treat rhinitis and asthma, but their anti-inflammatory role in eosinophil inflammation is not well understood. The aim of this study is to investigate the effect of MK on an in vitro model of upper-airway eosinophil inflammation by reducing pro-inflammatory cytokines from both nasal mucosa (NM) and polyp (NP) epithelial cells and reducing eosinophil survival primed by epithelial cell secretions. Epithelial cells were stimulated with fetal bovine serum (FBS) with or without MK for 24 hours, and cytokine concentrations in epithelial secretions were measured by ELISA.

Glucocorticoid therapy increases COX-2 gene expression in nasal polyps in vivo.

The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal polyps. In total, 65 patients with nasal polyps were randomly (3:1) treated with (n = 51; 33 with asthma) or without (n = 14) oral prednisone and intranasal budesonide for 2 weeks plus intranasal budesonide for 10 additional weeks. Biopsies were obtained at baseline and after 2 and 12 weeks of treatment.

Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids.

Background: Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) alpha and beta or to downregulation of GRalpha. We aimed to evaluate the in vivo regulation of GR isoforms in GC-treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels.

Methods: Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks.

Corticosteroid therapy increases membrane-tethered while decreases secreted mucin expression in nasal polyps.

Background: Mucus hypersecretion is a hallmark of nasal polyposis (NP). Corticosteroids (CS) are first-line treatment for NP, decreasing their size and inflammatory component. However, their effect on mucin production is not well-understood.

[Initial signs and symptoms of brain tumors in children].

Introduction: This is a study of the presenting features of brain tumors in children, their localization and histology which is aimed at describing the most frequent symptoms at the beginning and at the moment of diagnosis and minimize the time needed to reach a diagnosis.

Methods: Retrospective and descriptive study. Data were collected from the medical records of the patients (aged: 0-16) operated on for a brain tumor in our Department from 1999 to 2004.

Mucin genes have different expression patterns in healthy and diseased upper airway mucosa.

Background: Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper-secretion therapy.

Objective: The aim of this study was to evaluate and compare mucin gene expression at epithelial and glandular levels, and to identify potential mucin expression patterns for specific upper airways pathologies.

Mucin gene expression in rhinitis syndromes.

Rhinitis and rhinosinusitis are often associated with airway diseases such as asthma, cystic fibrosis, and nasal polyposis. In these diseases, the alteration of both the quantity and quality of mucus results in an impaired mucociliary clearance, and this produces, in extreme cases, the airway obstruction. Mucins are the major component in mucus and are responsible for its viscoelastic properties.