Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

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Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

Int Immunopharmacol. 2016 Dec 22;43:179-186

Authors: Kang GD, Kim DH

Abstract
BACKGROUND: Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo.
METHODS: The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol. Levels of inflammatory markers were measured by enzyme-linked immunosorbent assay, immunoblotting, and quantitative polymerase chain reaction.
RESULTS: Treatment with PT or PO inhibited the secretion of interleukin (IL)-8 and tumor necrosis factor (TNF) in ethanol- or LPS-stimulated KATO III cells. They also reduced the activation of nuclear factor kappa B (NF-?B). Pre-treatment with PT or PO significantly protected against ethanol-induced hemorrhagic gastritis, characterized by edema, tissue erosions, and mucosal friability in mice. Treatment with PT or PO suppressed ethanol-induced NF-?B activation and the release of TNF, IL-8, and IFN-?. The protective effect of PT was greater than that of PO and comparable to ranitidine, a positive control.
CONCLUSION: PT may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, including neutrophils, via the regulation of CXCL4 (or IL-8) secretion and the activation NF-?B.

PMID: 28013186 [PubMed – as supplied by publisher]

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Webinar Examines Pediatric Asthma Community Paramedic Project, Out-of-Hospital Death Responses – EMSWorld (press release) (blog)

Webinar Examines Pediatric Asthma Community Paramedic Project, Out-of-Hospital Death Responses
EMSWorld (press release) (blog)
In children, asthma is the most common chronic illness. In Indiana, one in 10 children have asthma, and statistics show that 30% of children who have been hospitalized require readmission shortly following discharge. To help combat this trend

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TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease.

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TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease.

J Immunol. 2016 Mar 25;

Authors: Kourepini E, Paschalidis N, Simoes DC, Aggelakopoulou M, Grogan JL, Panoutsakopoulou V

Abstract
T cell Ig and ITIM domain receptor (TIGIT), expressed on T, NK, and regulatory T cells, is known as an inhibitory molecule that limits autoimmunity, antiviral and antitumor immunity. In this report, we demonstrate that TIGIT enhances Th2 immunity. TIGIT expression was upregulated in activated Th2 cells from mice with experimental allergic disease and in Th2 polarization cultures. In addition, its high-affinity ligand CD155 was upregulated in mediastinal lymph node dendritic cells from allergic mice. In an in vitro setting, we observed thatTigitexpression in Th2 cells and its interaction with CD155 expressed in dendritic cells were important during the development of Th2 responses. In addition, blockade of TIGIT inhibited Th2, but had no effect on either Th1 or Th17 polarization. In vivo blockade of TIGIT suppressed hallmarks of allergic airway disease, such as lung eosinophilia, goblet cell hyperplasia, Ag-specific Th2 responses, and IgE production, and reduced numbers of T follicular helper and effector Th2 cells. Thus, TIGIT is critical for Th2 immunity and can be used as a therapeutic target, especially in light of recent findings showing TIGIT locus hypomethylation in T cells from pediatric patients with allergic asthma.

PMID: 27016609 [PubMed – as supplied by publisher]

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Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.

Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.

BMC Med Genomics. 2016;9(1):9

Authors: Troy NM, Hollams EM, Holt PG, Bosco A

Abstract
BACKGROUND: Asthma is strongly associated with allergic sensitization, but the mechanisms that determine why only a subset of atopics develop asthma are not well understood. The aim of this study was to test the hypothesis that variations in allergen-driven CD4 T cell responses are associated with susceptibility to expression of asthma symptoms.
METHODS: The study population consisted of house dust mite (HDM) sensitized atopics with current asthma (n?=?22), HDM-sensitized atopics without current asthma (n?=?26), and HDM-nonsensitized controls (n?=?24). Peripheral blood mononuclear cells from these groups were cultured in the presence or absence of HDM extract for 24 h. CD4 T cells were then isolated by immunomagnetic separation, and gene expression patterns were profiled on microarrays.
RESULTS: Differential network analysis of HDM-induced CD4 T cell responses in sensitized atopics with or without asthma unveiled a cohort of asthma-associated genes that escaped detection by more conventional data analysis techniques. These asthma-associated genes were enriched for targets of STAT6 signaling, and they were nested within a larger coexpression module comprising 406 genes. Upstream regulator analysis suggested that this module was driven primarily by IL-2, IL-4, and TNF signaling; reconstruction of the wiring diagram of the module revealed a series of hub genes involved in inflammation (IL-1B, NFkB, STAT1, STAT3), apoptosis (BCL2, MYC), and regulatory T cells (IL-2Ra, FoxP3). Finally, we identified several negative regulators of asthmatic CD4 T cell responses to allergens (e.g. IL-10, type I interferons, microRNAs, drugs, metabolites), and these represent logical candidates for therapeutic intervention.
CONCLUSION: Differential network analysis of allergen-induced CD4 T cell responses can unmask covert disease-associated genes and pin point novel therapeutic targets.

PMID: 26922672 [PubMed – as supplied by publisher]

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New approaches to qualitative interviewing: Development of a card sort technique to understand subjective patterns of symptoms and responses.

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New approaches to qualitative interviewing: Development of a card sort technique to understand subjective patterns of symptoms and responses.

Int J Nurs Stud. 2016 Jan 9;

Authors: Mammen JR, Norton SA, Rhee H, Butz AM

Abstract
BACKGROUND: Ability to elicit individuals’ perceptions of complex behavioral processes can be challenging, as it hinges not only upon the skill of the researcher, but also upon assumptions of a shared language and individuals’ ability to recall, analyze, and effectively communicate events. In a case-based qualitative-descriptive study about teens’ experiences of asthma self-management, we found that variations in terminology and descriptions of events, symptoms, and responses made it difficult to understand teens’ experiences of asthma. In particular, teens’ conceptualization of their asthma symptoms and self-management responses differed from situation to situation, from other teens in the study, from the interviewer, and from prior reports in the literature. These differences across many levels made it difficult to identify patterns in individual processes of self-management, and among teens in general..
OBJECTIVES: To address these challenges, we developed a card sorting activity to facilitate in-depth exploration of teens’ experiences of asthma.
DESIGN: Case-based qualitative description.
SETTING: Teen-parent dyads (N=28) were recruited from the community, Emergency Department, Pediatric Pulmonary Department, and prior study subjects of a major medical center.
METHODS: Teens first identified and then sequenced their own unique sets of asthma symptoms and self-management responses. Teens then developed contextually grounded narratives using the card sort they had created as a visual aid.
RESULTS: This technique not only allowed us to bridge teen-interviewer communication barriers and develop shared terminology, but also resulted in a visible sequence of asthma symptoms and self-management responses.
CONCLUSIONS: The card sort technique facilitated researcher-teen discussion and enabled comparison of self-management patterns across teens in our study. This technique is potentially useful for other areas of research exploring behavioral processes with complex and individual-specific experiences, in particular those involving sequences of events and self-management responses. This paper delineates the development, utility, and potential applications of the symptom-response card sorting technique for research and clinical practice.

PMID: 26897540 [PubMed – as supplied by publisher]

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Soluble Guanylate Cyclase Modulators Blunt Hyperoxia Effects on Calcium Responses of Developing Human Airway Smooth Muscle.

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Soluble Guanylate Cyclase Modulators Blunt Hyperoxia Effects on Calcium Responses of Developing Human Airway Smooth Muscle.

Am J Physiol Lung Cell Mol Physiol. 2015 Aug 7;:ajplung.00232.2015

Authors: Britt RD, Thompson MA, Kuipers I, Stewart A, Vogel ER, Thu J, Martin RJ, Pabelick CM, Prakash YS

Abstract
Exposure to moderate hyperoxia in prematurity contributes to subsequent airway dysfunction and increases the risk of developing recurrent wheeze and asthma. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic GMP (cGMP) axis modulates airway tone by regulating airway smooth muscle (ASM) intracellular Ca(2+) ([Ca(2+)]i) and contractility. However, the effects of hyperoxia on this axis in the context of Ca(2+)/contractility are not known. In developing human ASM, we explored the effects of novel drugs that activate sGC independent of NO, on alleviating hyperoxia (50% oxygen)-induced enhancement of Ca(2+) responses to bronchoconstrictor agonist. Treatment with BAY 41-2272 (sGC stimulator) and BAY 60-2770 (sGC activator) increased cGMP levels during exposure to 50% O2. Although 50% O2 did not alter sGC?1 and sGC?1 expression, BAY 60-2770 did increase sGC?1 expression. BAY 41-2272 and BAY 60-2770 blunted Ca(2+) responses to histamine in cells exposed to 50% O2. The effects of BAY 41-2272 and BAY 60-2770 were reversed by protein kinase G inhibition. These novel data demonstrate that BAY 41-2272 and BAY 60-2770 stimulate production of cGMP and blunt hyperoxia-induced increases in Ca(2+) responses in developing ASM. Accordingly, sGC stimulators/activators may be a useful therapeutic strategy in improving bronchodilation in preterm infants.

PMID: 26254425 [PubMed – as supplied by publisher]

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No Adjuvant Effect of Bacillus thuringiensis-Maize on Allergic Responses in Mice.

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No Adjuvant Effect of Bacillus thuringiensis-Maize on Allergic Responses in Mice.

PLoS One. 2014;9(8):e103979

Authors: Reiner D, Lee RY, Dekan G, Epstein MM

Abstract
Genetically modified (GM) foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt)-maize (MON810) on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA)-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma.

PMID: 25084284 [PubMed – in process]

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Passive smoking impairs children’s responses to asthma treatment – Eureka! Science News

Passive smoking impairs children's responses to asthma treatment
Eureka! Science News
Children exposed to cigarette smoke at home have lower levels of an enzyme that helps them respond to asthma treatment, a study has found. Passive smoking is known to worsen asthma symptoms in children and impair their response to inhaled steroid 

and more »

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Passive smoking impairs children’s responses to asthma treatment – Medical Xpress


The Information Daily

Passive smoking impairs children's responses to asthma treatment
Medical Xpress
Passive smoking is known to worsen asthma symptoms in children and impair their response to inhaled steroid treatment, but how this effect occurs was not known. Researchers at Imperial College London found that children with severe asthma with a parent 
Children exposed to passive smoke respond less to asthma treatmentThe Information Daily

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