Read by QxMD icon Read


Yuan Lu, Jian-Ya Xu, Xiao-Hua Zhang, Xia Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous...
November 4, 2016: Journal of Ethnopharmacology
Fatemeh Moheimani, Alan C-Y Hsu, Andrew T Reid, Teresa Williams, Anthony Kicic, Stephen M Stick, Philip M Hansbro, Peter A B Wark, Darryl A Knight
Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium...
2016: Respiratory Research
Assem Zhakupova, Nincy Debeuf, Michiel Krols, Wendy Toussaint, Leen Vanhoutte, Irina Alecu, Zoltán Kutalik, Peter Vollenweider, Daniela Ernst, Arnold von Eckardstein, Bart N Lambrecht, Sophie Janssens, Thorsten Hornemann
ORMDL proteins are believed to be negative regulators of serine palmitoyltransferase (SPT), which catalyzes the first and rate limiting step in sphingolipid (SL) de novo synthesis. Several single nucleotide polymorphisms (SNPs) that are close to the ORMDL3 locus have been reported to increase ORMDL3 expression and to be associated with an elevated risk for early childhood asthma; however, the direct effect of ORMDL3 expression on SPT activity and its link to asthma remains elusive. In this study, we investigated whether ORMDL3 expression is associated with changes in SPT activity and total SL levels...
September 19, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Stephan Löser, Lisa G Gregory, Youming Zhang, Katrein Schaefer, Simone A Walker, James Buckley, Laura Denney, Charlotte H Dean, William O C Cookson, Miriam F Moffatt, Clare M Lloyd
BACKGROUND: Genome-wide association studies have identified the ORMDL3 (ORM (yeast)-like protein isoform 3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma. OBJECTIVE: We sought to investigate in vivo the functional role of ORMDL3 in disease inception. METHODS: An Ormdl3 deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata determined...
September 10, 2016: Journal of Allergy and Clinical Immunology
Andrew H Liu, William C Anderson, Cullen M Dutmer, Daniel A Searing, Stanley J Szefler
In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened...
August 2016: Journal of Allergy and Clinical Immunology
Lin Cai, Clement Oyeniran, Debolina D Biswas, Jeremy Allegood, Sheldon Milstien, Tomasz Kordula, Michael Maceyka, Sarah Spiegel
The bioactive sphingolipid metabolite, ceramide, regulates physiological processes important for inflammation and elevated levels of ceramide have been implicated in IL-1-mediated events. Although much has been learned about ceramide generation by activation of sphingomyelinases in response to IL-1, the contribution of the de novo pathway is not completely understood. Because yeast ORM1 and ORM2 proteins negatively regulate ceramide levels through inhibition of serine palmitoyltransferase, the first committed step in ceramide biosynthesis, we examined the functions of individual mammalian ORM orthologs, ORM (yeast)-like (ORMDL)1-3, in regulation of ceramide levels...
August 2016: Journal of Lipid Research
Mateja Žavbi, Peter Korošec, Matjaž Fležar, Sabina Škrgat Kristan, Mateja Marc Malovrh, Matija Rijavec
One of the major asthma susceptibility loci is 17q12-17q21.1, but the relationship between this locus and adult asthma is unclear. Association analysis of 13 single nucleotide polymorphisms (SNPs) and haplotypes from 17q12-17q21.1 was performed in 418 adult patients with asthma and 288 controls from Slovenia. Single SNP analysis revealed only marginal associations with adult asthma for SNPs located in GSDMA, GSDMB, ORMDL3 and ZPBP2 genes, and rs7219080 was the most highly associated. Analyses of asthma phenotypes found no association with atopy or lung function, but rs2305480 and rs8066582 were associated with childhood asthma and rs9916279 was associated with asthma in smokers...
June 2016: Human Immunology
Jose J Lopez, Letizia Albarran, Luis J Gómez, Tarik Smani, Gines M Salido, Juan A Rosado
Three decades ago, store-operated Ca(2+) entry (SOCE) was identified as a unique mechanism for Ca(2+) entry through plasma membrane (PM) Ca(2+)-permeable channels modulated by the intracellular Ca(2+) stores, mainly the endoplasmic reticulum (ER). Extensive analysis of the communication between the ER and the PM leads to the identification of the protein STIM1 as the ER-Ca(2+) sensor that gates the Ca(2+) channels in the PM. Further analysis on the biophysical, electrophysiological and biochemical properties of STIM1-dependent Ca(2+) channels has revealed the presence of a highly Ca(2+)-selective channel termed Ca(2+) release-activated Ca(2+) channel (CRAC), consisting of Orai1 subunits, and non-selective cation channels named store-operated channels (SOC), including both Orai1 and TRPC channel subunits...
August 2016: Biochimica et Biophysica Acta
Ai-Mei Yang, Rong Huang, Shi-Jie Jin
OBJECTIVE: To investigate ORMDL3 polymorphisms in children with asthma in Hunan, China, and to determine the relationship between ORMDL3 polymorphisms and serum osteopontin (OPN) and transforming growth factor-β1 (TGF-β1) levels. METHODS: Peripheral blood samples were collected in children with asthma (n=98; astma group) or without asthma (n=30; control group) from Hunan, China. The asthma group was subdivided into atopic (n=62) and non-atopic (n=36) subgroups...
April 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
T Paulenda, P Draber
A family of widely expressed ORM-like (ORMDL) proteins has been recently linked to asthma in genomewide association studies in humans and extensively explored in in vivo studies in mice. ORMDL proteins are key regulators of serine palmitoyltransferase, an enzyme catalyzing the initial step of sphingolipid biosynthesis. Sphingolipids play prominent roles in cell signaling and response to stress, and they affect the mechanistic properties of cellular membranes. Deregulation of sphingolipid biosynthesis and their recycling has been proven to support and even cause several diseases including allergy, inflammation, and asthma...
July 2016: Allergy
Zhengguang Huang, Lijuan Gao, Xia Zhao, Hao Ling, Wenjun Chen
OBJECTIVE: To investigate the effect of Guben-fangxiao decoction (GBFXD) on respiratory-syncytial-virus (RSV)-induced asthma and the expression of asthma susceptibility gene, orosomucoid 1-like protein 3 (ORMDL3) in mice. METHODS: Seventy-two female BALB/c mice were randomly assigned to normal, model, GBFXD high dose, GBFXD moderate dose, GBFXD low dose and montelukast groups. An asthma model was induced via intraperitoneal injection and aerosol inhalation of ovalbumin (OVA) and repeated intranasal instillation of RSV in all mice, except those in the normal group...
February 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
Laura Coleman, Ingrid A Laing, Anthony Bosco
PURPOSE OF REVIEW: This article discusses recent findings into the mechanisms that determine how viruses trigger asthma exacerbations. RECENT FINDINGS: Substantial progress has been made in our understanding of the pathogenesis of virus-induced asthma exacerbations. This includes new insights into the role of bacteria, the regulation of interferon responses, and the discovery of innate immune pathways that link viral infections with allergic inflammation. Progress has also been made in elucidating the genetic risk factors for asthma exacerbations, most notably the contribution of the ORMDL3/GSDMB locus on 17q, the mechanisms underlying the farming effect, and the discovery that CDHR3 binds to rhinovirus species C...
April 2016: Current Opinion in Allergy and Clinical Immunology
Jennie G Ono, Tilla S Worgall, Stefan Worgall
Asthma is a clinically heterogeneous disorder, whose onset and progression results from a complex interplay between genetic susceptibility, allergens, and viral triggers. Sphingolipids and altered sphingolipid metabolism have emerged as potential key contributors to the pathogenesis of asthma. Orosomucoid-like 3 gene (ORMDL3) and the asthma susceptibility locus 17q21 have been strongly and reproducibly linked to childhood asthma, but how this gene is functionally linked to asthma is incompletely understood...
December 2015: Molecular and Cellular Pediatrics
Xiaochun Ma, Rongfang Qiu, Jie Dang, Jiangxia Li, Qin Hu, Shan Shan, Qian Xin, Wenying Pan, Xianli Bian, Qianqian Yuan, Feng Long, Na Liu, Yan Li, Fei Gao, Chengwei Zou, Yaoqin Gong, Qiji Liu
ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is a universally confirmed susceptibility gene for asthma and has recently emerged as a crucial modulator in lipid metabolism, inflammation and endoplasmic reticulum (ER) stress-the mechanisms also closely involved in atherosclerosis (AS). Here we first presented the evidence of two single nucleotide polymorphisms regulating ORMDL3 expression (rs7216389 and rs9303277) significantly associated with AS risk and the evidence of increased ORMDL3 expression in AS cases compared to controls, in Chinese Han population...
2015: Scientific Reports
Viktor Bugajev, Ivana Halova, Lubica Draberova, Monika Bambouskova, Lucie Potuckova, Helena Draberova, Tomas Paulenda, Sergi Junyent, Petr Draber
Single-nucleotide polymorphism studies have linked the chromosome 17q12-q21 region, where the human orosomucoid-like (ORMDL)3 gene is localized, to the risk of asthma and several other inflammatory diseases. Although mast cells are involved in the development of these diseases, the contribution of ORMDL3 to the mast cell physiology is unknown. In this study, we examined the role of ORMDL3 in antigen-induced activation of murine mast cells with reduced or enhanced ORMDL3 expression. Our data show that in antigen-activated mast cells, reduced expression of the ORMDL3 protein had no effect on degranulation and calcium response, but significantly enhanced phosphorylation of AKT kinase at Ser 473 followed by enhanced phosphorylation and degradation of IκBα and translocation of the NF-κB p65 subunit into the nucleus...
March 2016: Cellular and Molecular Life Sciences: CMLS
W H Zhai, C Y Song, Z G Huang, H Sha
While increasing scientific evidence suggests that the ORMDL3 rs7216389 polymorphism may contribute to a higher susceptibility to asthma, many of the current studies have yielded inconclusive results. This meta-analysis aimed to assess the association between the ORMDL3 rs7216389 polymorphism and the risk of asthma. An extensive literature search for relevant studies was conducted in PubMed, Embase, the Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, and Google Scholar. This meta-analysis was performed using the STATA 12...
2015: Genetics and Molecular Research: GMR
X Li, A T Hastie, G A Hawkins, W C Moore, E J Ampleford, J Milosevic, H Li, W W Busse, S C Erzurum, N Kaminski, S E Wenzel, D A Meyers, E R Bleecker
BACKGROUND: Genome-wide association studies (GWASs) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms (SNPs) remain elusive. We sought to dissect functional genes/SNPs for asthma by combining expression quantitative trait loci (eQTLs) and GWASs. METHODS: Cis-eQTL analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy (BEC, n = 107) and from bronchial alveolar lavage (BAL, n = 94)...
October 2015: Allergy
Wei-Xia Yang, Rui Jin, Chun-Ming Jiang, Xiao-Hua Wang, Jin Shu, Ling Li, Liang-Hua Zhu, Li-Li Zhuang, Chao Gao, Guo-Ping Zhou
Orosomucoid 1-Like Protein 3 (ORMDL3) is an asthma candidate gene and Casitas B lineage lymphoma b (Cbl-b), an E3 ubiquitin ligase, is a critical factor in maintaining airway immune tolerance. However, the association of Cbl-b with ORMDL3 for asthma is unclear. Here, we show that expression of ORMDL3 is significantly increased and shows a strong linear correlation with decreased Cbl-b in the peripheral blood of recurrent wheeze patients. To elucidate the molecular mechanisms underlying this correlation, we identified that Cbl-b suppressed the transcriptional activity and mRNA expression of ORMDL3 in vivo...
July 8, 2015: FEBS Letters
Huimin Shi, Dan Cheng, Lingling Yi, Xiaorong Huo, Kan Zhang, Guohua Zhen
The aim of this study was to determine whether orosomucoid1- like 3 (ORMDL3) single nucleotide polymorphisms rs7216389, rs11650680, rs12603332 are associated with susceptibility to asthma. We performed a meta-analysis by searching PubMed, EMBASE, Elsevier and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. We examined the association between the three SNPs and asthma risk in four genetic models (TT + TC vs. CC, TC vs. CC, TT vs. CC, TT vs...
2015: International Journal of Clinical and Experimental Medicine
A A Toncheva, D P Potaczek, M Schedel, S W Gersting, S Michel, N Krajnov, V D Gaertner, J M Klingbeil, T Illig, A Franke, C Winkler, J M Hohlfeld, C Vogelberg, A von Berg, A Bufe, A Heinzmann, O Laub, E Rietschel, B Simma, J Genuneit, A C Muntau, M Kabesch
BACKGROUND: Genomewide association studies identified ORMDL3 as a plausible asthma candidate gene. ORMDL proteins regulate sphingolipid metabolism and ceramide homeostasis and participate in lymphocyte activation and eosinophil recruitment. Strong sequence homology between the three ORMDL genes and ORMDL protein conservation among different species suggest that they may have shared functions. We hypothesized that if single nucleotide polymorphisms (SNPs) in ORMDL3 alter its gene expression and play a role in asthma, variants in ORMDL1 and ORMDL2 might also be associated with asthma...
October 2015: Allergy
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"