Diamine Oxidase Activity Deficit and Idiopathic Rhinitis: A New Subgroup of Non-Allergic Rhinitis?

Idiopathic rhinitis represents more than 50% of non-allergic rhinitis, a heterogeneous group that involves the symptomatic inflammation of the nasal mucosa. The TRPV1 receptor of unmyelinated C-type neurons appears to be involved in its pathophysiology. Histamine, whose main catabolic enzyme is DAO, is one of the mediators that can activate this receptor.

Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease.

The E3 ubiquitin-ligases are important for cellular protein homeostasis and their deregulation is implicated in cancer. The E3 ubiquitin-ligase Hakai is involved in tumour progression and metastasis, through the regulation of the tumour suppressor E-cadherin. Hakai is overexpressed in colon cancer, however, the implication in colitis-associated cancer is unknown.

Preclinical Evaluation of Fingolimod in Rodent Models of Stroke With Age or Atherosclerosis as Comorbidities.

Preclinical data indicate that fingolimod improves outcome post-ischaemia. This study used a rigorous study design in normal male C57BL/6JOlaHsd mice and in mice with common stroke comorbidities to further evaluate the translational potential of fingolimod. Stroke was induced via middle cerebral artery electrocoagulation in 8-9-week old mice (young mice), 18 month old mice (aged mice), and in high-fat diet-fed 22-week old ApoE-/- mice (hyperlipidaemic mice).

Relationship between allergic rhinitis and diamine oxidase activity: A preliminary report.

Aim: To analyze the diamine oxidase (DAO), the main catabolic enzyme of histamine, degradation activity and its relation with symptoms of persistent allergic rhinitis.

Methods: In this descriptive and analytical observational study, we collected DAO activity levels and the nasal peak inspiratory flow.

Results: Enzymatic activity deficit in 108 patients was 46.

Histological, behavioural and flow cytometric datasets relating to acute ischaemic stroke in young, aged and ApoE mice in the presence and absence of immunomodulation with fingolimod.

In this work, the sphingosine-1-phosphate receptor modulator fingolimod was assessed as a preclinical candidate for the treatment of acute ischaemic stroke according to the Stroke Therapy Academic Industry Roundtable (STAIR) preclinical recommendations. Young (15-17 weeks), aged (72-73 weeks), and ApoE mice (20-21 weeks) fed a high fat diet (all C57BL/6 mice) underwent permanent electrocoagulation of the left middle cerebral artery. Mice received either saline or fingolimod (0.

The effect of fingolimod on regulatory T cells in a mouse model of brain ischaemia.

Background: The role of the immune system in stroke is well-recognised. Fingolimod, an immunomodulatory agent licensed for the management of relapsing-remitting multiple sclerosis, has been shown to provide benefit in rodent models of stroke. Its mechanism of action, however, remains unclear.

Acute Treatment With Fingolimod Does Not Confer Long-Term Benefit in a Mouse Model of Intracerebral Haemorrhage.

Intracerebral haemorrhage (ICH) has no specific treatment, but accounts for up to 15% of all strokes and has the highest mortality. Fingolimod (FTY720) is an immunomodulator approved for the management of multiple sclerosis, with abundant evidence of efficacy in experimental ischemic stroke, and more limited evidence in experimental ICH. The goal of this study was to confirm the efficacy of fingolimod in experimental ICH using rigorous and statistically well-powered studies.

Hakin-1, a New Specific Small-Molecule Inhibitor for the E3 Ubiquitin-Ligase Hakai, Inhibits Carcinoma Growth and Progression.

The requirement of the E3 ubiquitin-ligase Hakai for the ubiquitination and subsequent degradation of E-cadherin has been associated with enhanced epithelial-to-mesenchymal transition (EMT), tumour progression and carcinoma metastasis. To date, most of the reported EMT-related inhibitors were not developed for anti-EMT purposes, but indirectly affect EMT. On the other hand, E3 ubiquitin-ligase enzymes have recently emerged as promising therapeutic targets, as their specific inhibition would prevent wider side effects.

Heat Shock Protein 90 Chaperone Regulates the E3 Ubiquitin-Ligase Hakai Protein Stability.

The E3 ubiquitin-ligase Hakai binds to several tyrosine-phosphorylated Src substrates, including the hallmark of the epithelial-to-mesenchymal transition E-cadherin, and signals for degradation of its specific targets. Hakai is highly expressed in several human cancers, including colon cancer, and is considered as a drug target for cancer therapy. Here, we report a link between Hakai and the heat shock protein 90 (Hsp90) chaperone complex.

Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis.

Gravin, an A-kinase anchoring protein, is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development, namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat diet (HFD)-induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed a normal diet or an HFD for 16 wk.

Kidney dopamine D-like receptors and angiotensin 1-7 interaction inhibits renal Na transporters.

The role of dopamine D-like receptors (DR) in the regulation of renal Na transporters, natriuresis, and blood pressure is well established. However, the involvement of the angiotensin 1-7 (ANG 1-7)-Mas receptor in the regulation of Na balance and blood pressure is not clear. The present study aimed to investigate the hypothesis that ANG 1-7 can regulate Na homeostasis by modulating the renal dopamine system.

Anti-proliferative and Anti-invasive Effect of Polysaccharide-rich Extracts from in Colon Cancer Cells.

Colorectal cancer (CRC) is one of leading causes of mortality in western countries and novel treatment strategies are required. The medicinal application of mushrooms has been used in traditional medicine in many oriental countries. Polysaccharide-rich extracts obtained from certain medicinal mushroom species have shown antitumor effects in different experimental models.

Hakai overexpression effectively induces tumour progression and metastasis in vivo.

At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated-dependent manner and induces its degradation; thus modulating cell adhesions. Here, we show that Hakai expression is gradually increased in adenoma and in different TNM stages (I-IV) from colon adenocarcinomas compared to human colon healthy tissues.

Proteomic Analysis of the E3 Ubiquitin-Ligase Hakai Highlights a Role in Plasticity of the Cytoskeleton Dynamics and in the Proteasome System.

Carcinoma, the most common type of cancer, arises from epithelial cells. The transition from adenoma to carcinoma is associated with the loss of E-cadherin and, in consequence, the disruption of cell-cell contacts. E-cadherin is a tumor suppressor, and it is down-regulated during epithelial-to-mesenchymal transition (EMT); indeed, its loss is a predictor of poor prognosis.

Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts.

Mesp1 directs multipotential cardiovascular cell fates, even though it's transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment.

Enhanced cardiac function in Gravin mutant mice involves alterations in the β-adrenergic receptor signaling cascade.

Gravin, an A-kinase anchoring protein, targets protein kinase A (PKA), protein kinase C (PKC), calcineurin and other signaling molecules to the beta2-adrenergic receptor (β2-AR). Gravin mediates desensitization/resensitization of the receptor by facilitating its phosphorylation by PKA and PKC. The role of gravin in β-AR mediated regulation of cardiac function is unclear.