Nasopharyngeal metatranscriptome profiles of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study

2021 ◽  
pp. 2102293
Author(s):  
Yoshihiko Raita ◽  
Marcos Pérez-Losada ◽  
Robert J. Freishtat ◽  
Andrea Hahn ◽  
Eduardo Castro-Nallar ◽  
...  
Keyword(s):  
Clustering Analysis ◽  
Type I Interferon ◽  
Species Level ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
B Virus ◽  
End Products ◽  
And Function ◽  
Multicentre Prospective Study

The question addressed by the studyBronchiolitis is not only the leading cause of hospitalisation in U.S. infants but also a major risk factor for asthma development. Growing evidence supports clinical heterogeneity within bronchiolitis. To identify metatranscriptome profiles of infant bronchiolitis, and examine their relationship with host transcriptome and subsequent asthma development.Materials/patients and methodsAs part of multicentre prospective cohort study of infants (age <12 months) hospitalised for bronchiolitis, we integrated virus and nasopharyngeal metatranscriptome (species-level taxonomy and function) data measured at hospitalisation. We applied network-based clustering approaches to identify metatranscriptome profiles. We then examined their association with host transcriptome at hospitalisation and risk for developing asthma.ResultsWe identified five metatranscriptome profiles of bronchiolitis (n=244):A) virusRSVmicrobiomecommensals, B) virusRSV/RV-AmicrobiomeH.influenzae,C) virusRSVmicrobiomeS.pneumoniae, D) virusRSVmicrobiomeM.nonliquefaciens, andE) virusRSV/RV-CmicrobiomeM.catarrhalis. Compared with profile A, profile B infants were characterised by high proportion of eczema, H. influenzae abundance, and enriched virulence related to antibiotic resistance. These profile B infants also had upregulated TH17 and downregulated type I interferon pathways (FDR<0.005) and significantly higher risk for developing asthma (17.9% versus 38.9%; adjOR, 2.81; 95%CI, 1.11–7.26). Likewise, profile C infants were characterised by high proportion of parental asthma, S. pneumoniae dominance, and enriched glycerolipid and glycerophospholipid metabolism of microbiome. These profile C infants had upregulated receptor for advanced glycation end products signalling pathway (FDR<0.005) and higher risk of asthma (17.9% versus 35.6%; adjOR, 2.49; 95%CI, 1.10–5.87).Answer to the questionMetatranscriptome and clustering analysis identified biologically-distinct metatranscriptome profiles that have differential risks of asthma.

scholarly journals Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury

2009 ◽  
Vol 297 (1) ◽  
pp. L1-L5 ◽  
Author(s):  
Xiao Su ◽  
Mark R. Looney ◽  
Naveen Gupta ◽  
Michael A. Matthay
Keyword(s):  
Lung Injury ◽  
Advanced Glycation End Products ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Experimental Models ◽  
Alveolar Type ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Receptor for advanced glycation end-products (RAGE) is a marker of alveolar type I cells and is elevated in the pulmonary edema fluid of patients with acute lung injury (ALI). We tested the hypothesis that RAGE in the bronchoalveolar lavage (BAL) would be elevated in experimental models of direct ALI characterized by alveolar epithelial cell injury. We developed ELISA measurements for RAGE and studied ALI (direct and indirect) mouse models and collected BAL at specified endpoints to measure RAGE. We also tested whether levels of BAL RAGE correlated 1) with the severity of lung injury in acid and hyperoxia-induced ALI and 2) with the beneficial effect of a novel treatment, mesenchymal stem cells (MSC), in LPS-induced ALI. In ALI models of direct lung injury induced by intratracheal instillation of acid, LPS, or Escherichia coli, the BAL RAGE was 58-, 22-, and 13-fold elevated, respectively. In contrast, BAL RAGE was not detectable in indirect models of ALI induced by an intraperitoneal injection of thiourea or by an intravenous injection of MHC I monoclonal antibody that produces a mouse model of transfusion-related ALI. BAL RAGE did correlate with the severity of lung injury in acid and hyperoxia-induced ALI. In addition, with LPS-induced ALI, BAL RAGE was markedly reduced with MSC treatment. In summary, BAL RAGE is an indicator of ALI, and it may be useful in distinguishing direct from indirect models of ALI as well as assessing the response to specific therapies.

scholarly journals The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): An Overview of Its Impact on Obesity and Early Progression of Renal Pathology

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1748 ◽  
Author(s):  
Arianna Bettiga ◽  
Francesco Fiorio ◽  
Federico Di Marco ◽  
Francesco Trevisani ◽  
Annalisa Romani ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Advanced Glycation End Products ◽  
Cell Function ◽  
Advanced Glycation ◽  
Covalent Bonds ◽  
Physiological Processes ◽  
Glycation End Products ◽  
End Products ◽  
And Function

Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients’ everyday lives.

Advanced Glycation End Products Modulate the Maturation and Function of Peripheral Blood Dendritic Cells

Diabetes ◽  
2004 ◽  
Vol 53 (6) ◽  
pp. 1452-1458 ◽  
Author(s):  
C. L. Price ◽  
P. S. Sharp ◽  
M. E. North ◽  
S. J. Rainbow ◽  
S. C. Knight
Keyword(s):  
Dendritic Cells ◽  
Advanced Glycation End Products ◽  
Peripheral Blood ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Function

scholarly journals Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules

Diabetes ◽  
2017 ◽  
Vol 66 (5) ◽  
pp. 1359-1372 ◽  
Author(s):  
Atsushi Takahashi ◽  
Yoshitsugu Takabatake ◽  
Tomonori Kimura ◽  
Ikuko Maejima ◽  
Tomoko Namba ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Proximal Tubules ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Function ◽  
Kidney Proximal Tubules

In VitroGlycoxidation of Insoluble Fibrous Type I Collagen: Solubilization and Advanced Glycation End Products

2003 ◽  
Vol 22 (6) ◽  
pp. 527-531 ◽  
Author(s):  
M. Meli ◽  
R. Granouillet ◽  
E. Reynaud ◽  
A. Chamson ◽  
J. Frey ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Type I Collagen ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells

1997 ◽  
Vol 322 (2) ◽  
pp. 567-573 ◽  
Author(s):  
Bård SMEDSRØD ◽  
Jukka MELKKO ◽  
Norie ARAKI ◽  
Hiroyuki SANO ◽  
Seikoh HORIUCHI
Keyword(s):  
Advanced Glycation End Products ◽  
Kupffer Cells ◽  
Scavenger Receptor ◽  
Type I ◽  
Advanced Glycation ◽  
Liver Uptake ◽  
Glycation End Products ◽  
End Products

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Physiological aspects of the catabolism of non-enzymically glycated proteins were studied in vivo and in vitro. AGE-modified BSA (AGE-BSA) was a mixture of high-Mr (cross-linked), monomeric and low-Mr (fragmented) AGE-BSA. After intravenous administration in rat, all three fractions of AGE-BSA accumulated extremely rapidly and almost exclusively in liver. Uptake in liver endothelial, Kupffer and parenchymal cells accounted for approx. 60%, 25% and 10–15% respectively of hepatic elimination. Both cross-linked and monomeric AGE-BSA were efficiently taken up and degraded in cultures of purified liver endothelial and Kupffer cells. Endocytosis of AGE-BSA by these cells was inhibited by several ligands for the scavenger receptor. Although 125I-Hb was not endocytosed in vitro, 125I-AGE-Hb was effectively endocytosed by a mechanism that was subject to inhibition by AGE-BSA. Endocytosis of N-terminal propeptide of type I procollagen, a physiological ligand for the scavenger receptor, was effectively inhibited by AGE-Hb and AGE-BSA. We conclude that AGE-modification renders macromolecules susceptible for elimination via the scavenger receptor of both liver endothelial and Kupffer cells.

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