Publications by authors named "Jose Canas"

58 Publications

Changes in Serum MicroRNAs after Anti-IL-5 Biological Treatment of Severe Asthma.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Immunology, IIS-Fundación Jiménez Díaz, 28040 Madrid, Spain.

There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment ( < 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the biosynthesis/degradation of glucans ( < 0.05). However, it did not correlate with an improvement in lung function. MiRNA-338-3p could be used as a biomarker of early response to reslizumab and mepolizumab in severe eosinophilic asthmatic patients. In fact, this miRNA could be involved in airway remodeling, targeting genes related to MAPK and TGF-β signaling pathways.
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http://dx.doi.org/10.3390/ijms22073558DOI Listing
March 2021

Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic mutant colon cancer.

Theranostics 2021 25;11(8):3595-3606. Epub 2021 Jan 25.

Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM (Madrid), Spain.

In hypoxic tumors, positive feedback between oncogenic KRAS and HIF-1α involves impressive metabolic changes correlating with drug resistance and poor prognosis in colorectal cancer. Up to date, designed KRAS-targeting molecules do not show clear benefits in patient overall survival (POS) so pharmacological modulation of aberrant tricarboxylic acid (TCA) cycle in hypoxic cancer has been proposed as a metabolic vulnerability of KRAS-driven tumors. Annexin V-FITC and cell viability assays were carried out in order to verify vitamin C citotoxicity in KRAS mutant SW480 and DLD1 as well as in Immortalized Human Colonic Epithelial Cells (HCEC). HIF1a expression and activity were determined by western blot and functional analysis assays. HIF1a direct targets GLUT1 and PDK1 expression was checked using western blot and qRT-PCR. Inmunohistochemical assays were perfomed in tumors derived from murine xenografts in order to validate previous observations . Vitamin C dependent PDH expression and activity modulation were detected by western blot and colorimetric activity assays. Acetyl-Coa levels and citrate synthase activity were assessed using colorimetric/fluorometric activity assays. Mitochondrial membrane potential (Δ) and cell ATP levels were assayed using fluorometric and luminescent test. PDK-1 in mutant CRC cells and murine xenografts was downregulated using pharmacological doses of vitamin C through the proline hydroxylation (Pro402) of the Hypoxia inducible factor-1(HIF-1)α, correlating with decreased expression of the glucose transporter 1 (GLUT-1) in both models. Vitamin C induced remarkable ATP depletion, rapid mitochondrial Δ dissipation and diminished pyruvate dehydrogenase E1-α phosphorylation at Serine 293, then boosting PDH and citrate synthase activity. We report a striking and previously non reported role of vitamin C in the regulation of the pyruvate dehydrogenase (PDH) activity, then modulating the TCA cycle and mitochondrial metabolism in mutant colon cancer. Potential impact of vitamin C in the clinical management of anti-EGFR chemoresistant colorectal neoplasias should be further considered.
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http://dx.doi.org/10.7150/thno.51265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914362PMC
January 2021

Durability of Changes in Biomarkers of Cardiometabolic Disease: 1-Year Family-Based Intervention in Children with Obesity.

Metab Syndr Relat Disord 2021 Mar 1. Epub 2021 Mar 1.

Nemours Biomedical Research, Nemours Children's Specialty Care, Jacksonville, Florida, USA.

The sustainability of health benefits in response to lifestyle-based interventions remains unclear in children with overweight and obesity, and cardiometabolic disease (CMD). We determined the changes in novel biomarkers of CMD in a 1-year family-based intervention (FBI) program, during 6-month active monitoring phase and at 12-month follow-up. Children with an age-adjusted body mass index (BMI) percentile ≥85 ( = 130; age 8-11 years) were recruited for a 1-year (6-month monitored and 6-month unmonitored) randomized controlled FBI program. Anthropometry and selected biomarkers of CMD were measured in 87 participants, randomly allocated to intervention (INT) and education-only (EDU) groups, at baseline, immediately after a 6-month active intervention or control period, and at 12-month unmonitored follow-up. Samples from 87 participants (age 10.00 ± 0.11 years and Tanner stage ≤3) with obesity (BMI%ile = 97.45 ± 0.15) were available. Overall intervention effect (between groups), was observed for total (T) and high molecular weight (HMW) adiponectin, ratio of total to HMW adiponectin, fibrinogen, and interleukin (IL)-6 ( < 0.05 for all). However, between-group beneficial changes after adjusting for baseline levels were limited to BMI percentile, T and HMW adiponectin and their ratio, IL-6, and fibrinogen ( < 0.05 for all) mainly during the 6-month period of monitored intervention. Changes in traditional risk factors such as lipids and triglycerides were inconsistent. During the 6-month follow-up period, the changes in biomarkers leveled-off, except for T and HMW adiponectin, IL-6, and fibrinogen that continued to show benefits ( < 0.05) from the 6- to 12-month follow-up. The FBI program beneficially altered novel biomarkers of CMD during the monitored intervention phase in school-age children with obesity, but they mostly moved back toward baseline during the unmonitored follow-up phase. The changes in novel biomarkers of CMD appear to be more sensitive compared to the traditional risk factors. The study implies the need for refinements in lifestyle-based approaches in the preservation of cardiovascular health and calls for robust biomarkers to monitor the changes. The study was registered at ClinicalTrials.gov (NCT01146314).
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http://dx.doi.org/10.1089/met.2020.0097DOI Listing
March 2021

Serum microRNAs as Tool to Predict Early Response to Benralizumab in Severe Eosinophilic Asthma.

J Pers Med 2021 Jan 28;11(2). Epub 2021 Jan 28.

Department of Immunology, IIS-Fundación Jiménez Díaz, 28040 Madrid, Spain.

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as , , , , and . In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.
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http://dx.doi.org/10.3390/jpm11020076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912443PMC
January 2021

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease.

Front Immunol 2020 8;11:608666. Epub 2021 Jan 8.

Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.

Chronic respiratory diseases (CRDs) are an important factor of morbidity and mortality, accounting for approximately 6% of total deaths worldwide. The main CRDs are asthma and chronic obstructive pulmonary disease (COPD). These complex diseases have different triggers including allergens, pollutants, tobacco smoke, and other risk factors. It is important to highlight that although CRDs are incurable, various forms of treatment improve shortness of breath and quality of life. The search for tools that can ensure accurate diagnosis and treatment is crucial. MicroRNAs (miRNAs) are small non-coding RNAs and have been described as promising diagnostic and therapeutic biomarkers for CRDs. They are implicated in multiple processes of asthma and COPD, regulating pathways associated with inflammation, thereby showing that miRNAs are critical regulators of the immune response. Indeed, miRNAs have been found to be deregulated in several biofluids (sputum, bronchoalveolar lavage, and serum) and in both structural lung and immune cells of patients in comparison to healthy subjects, showing their potential role as biomarkers. Also, miRNAs play a part in the development or termination of histopathological changes and comorbidities, revealing the complexity of miRNA regulation and opening up new treatment possibilities. Finally, miRNAs have been proposed as prognostic tools in response to both conventional and biologic treatments for asthma or COPD, and miRNA-based treatment has emerged as a potential approach for clinical intervention in these respiratory diseases; however, this field is still in development. The present review applies a systems biology approach to the understanding of miRNA regulatory networks in asthma and COPD, summarizing their roles in pathophysiology, diagnosis, and treatment.
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http://dx.doi.org/10.3389/fimmu.2020.608666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819856PMC
January 2021

Isolation and Functional Aspects of Eosinophil-Derived Exosomes.

Methods Mol Biol 2021 ;2241:149-159

Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.

Eosinophils are granulocytes involved in inflammatory processes related to type 2 immune responses as allergy and parasitic infestation. Eosinophils are scarce in homeostatic situations, comprising 3-6% of total granulocytes. In peripheral blood, they have a life span of 18-25 h. These cells are characterized by the presence of several types of granules that are very important because of their functions. Recently, we have described that these immune cells are able to release exosomes, which are nanovesicles involved in intercellular communication and implicated in development of several diseases such as cancer, cardiovascular diseases, and asthma. Here, we describe a technique for isolation of eosinophil-derived exosomes from human peripheral blood and for their utilization in cell functional assays.
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http://dx.doi.org/10.1007/978-1-0716-1095-4_13DOI Listing
March 2021

Exosomes: A Key Piece in Asthmatic Inflammation.

Int J Mol Sci 2021 Jan 19;22(2). Epub 2021 Jan 19.

Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Avenida Reyes Católicos, 2, 28040 Madrid, Spain.

Asthma is a chronic disease of the airways that has an important inflammatory component. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These cells can exert their inflammatory functions throughout extracellular vesicles (EVs), which are small vesicles released by donor cells into the extracellular microenvironment that can be taken up by recipient cells. Depending on their size, EVs can be classified as microvesicles, exosomes, or apoptotic bodies. EVs are heterogeneous spherical structures secreted by almost all cell types. One of their main functions is to act as transporters of a wide range of molecules, such as proteins, lipids, and microRNAs (miRNAs), which are single-stranded RNAs of approximately 22 nucleotides in length. Therefore, exosomes could influence several physiological and pathological processes, including those involved in asthma. They can be detected in multiple cell types and biofluids, providing a wealth of information about the processes that take account in a pathological scenario. This review thus summarizes the most recent insights concerning the role of exosomes from different sources (several cell populations and biofluids) in one of the most prevalent respiratory diseases, asthma.
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http://dx.doi.org/10.3390/ijms22020963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835850PMC
January 2021

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children.

Sci Rep 2021 Jan 13;11(1):871. Epub 2021 Jan 13.

Department of Food Science, Pennsylvania State University, University Park, PA, USA.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h = 0.98, P = 7 × 10 and h = 0.58, P = 1 × 10]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.
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http://dx.doi.org/10.1038/s41598-020-79387-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806924PMC
January 2021

Mixed carotenoid supplementation and dysmetabolic obesity: gaps in knowledge.

Int J Food Sci Nutr 2020 Dec 19:1-6. Epub 2020 Dec 19.

Pediatric Endocrinology and Diabetes, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.

Dysmetabolic obesity during childhood and adolescence currently represents one of the greatest therapeutic challenge for healthcare systems worldwide. The global rates of obesity have more than doubled in the last 30 years. Recent meta-analysis from national surveys and food composition studies suggest an inverse association between lower carotenoid levels and the prevalence of Metabolic Syndrome in the general population, independent of serum retinol (vitamin A) levels. In children, two double-blind randomised placebo-controlled studies describing the effects of diet vs. mixed carotenoid supplementation on insulin resistance, adipokines and the rate of accrual of subcutaneous abdominal fat, implicate supplementation of these compounds to achieve targetable levels may be useful in the management of obesity accrual in this population. We will discuss the role of carotenoids and their conversion products (retinoids) in adipogenesis, lipolysis, insulin resistance and the pathophysiology of the metabolic syndrome and review the animal studies, which help support these findings.
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http://dx.doi.org/10.1080/09637486.2020.1852193DOI Listing
December 2020

Association of Antioxidant Vitamins A, C, E and Carotenoids with Cognitive Performance over Time: A Cohort Study of Middle-Aged Adults.

Nutrients 2020 Nov 20;12(11). Epub 2020 Nov 20.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA.

Carotenoids may strengthen the association of antioxidant vitamins A, C, and E with favorable cognitive outcomes over time, though a few prospective studies have examined this hypothesis. We evaluated the longitudinal data from 1251 participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (Age at visit 1 in 2004-2009 (v): 30-65 years). Vitamins A, C, and E dietary intakes and total and individual dietary carotenoids were computed using two 24-h recalls at v. Cognitive tests, covering global mental status and domains of memory/learning, attention, psychomotor speed, visuo-spatial, language/verbal, and executive function were conducted at v and/or v (2009-2013); mean ± SD follow-up: 4.66 ± 0.93 years. Mixed-effects linear regression models detected an interaction between vitamin E and total (and individual) carotenoids for three of 11 cognitive tests at v, with only one meeting the statistical significance upon multiple testing correction whereby vitamin E was linked with greater verbal memory performance in the uppermost total carotenoid tertile ( = +0.26 ± 0.08, = 0.002), a synergism largely driven by carotenoid lycopene. Vitamins A and C showed no consistent interactions with carotenoids. In conclusion, we provide partial evidence for synergism between vitamin E and carotenoids in relation to better baseline cognitive performance, pending further studies with time-dependent exposures and randomized trials directly examining this synergism.
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http://dx.doi.org/10.3390/nu12113558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699702PMC
November 2020

Proton-pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis.

J Pediatr Gastroenterol Nutr 2020 12;71(6):755-763

Department of Immunology, IIS-Fundación Jiménez Díaz.

Objectives: Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton-pump inhibitors (PPI) induce disease remission but no predictive factors of PPI-responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI-R) and nonresponder patients (PPI-NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy.

Methods: This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI-R or PPI-NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum.

Results: We found several esophageal miRNAs with different expression values between PPI-R and PPI-NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI-R displayed a significant decrease in eotaxin-3, IL-5, IL-13, periostin, and major basic protein (P < 0.05) and a significant increase in filaggrin levels after PPI treatment (P < 0.01).

Conclusions: Esophageal miRNA levels found are able to discriminate between both PPI-R and PPI-NR at baseline, and before and after treatment in PPI-R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI-R patients after PPI therapy.
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http://dx.doi.org/10.1097/MPG.0000000000002957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752232PMC
December 2020

The Genomics and Metagenomics of Asthma Severity (GEMAS) Study: Rationale and Design.

J Pers Med 2020 Sep 11;10(3). Epub 2020 Sep 11.

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.

Asthma exacerbations are a major contributor to the global disease burden, but no significant predictive biomarkers are known. The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics and the microbiome in severe asthma exacerbations. Here, we present the design of GEMAS and the characteristics of patients recruited from March 2018 to March 2020. Different biological samples and demographic and clinical variables were collected from asthma patients recruited by allergy and pulmonary medicine units in several hospitals from Spain. Cases and controls were defined by the presence/absence of severe asthma exacerbations in the past year (oral corticosteroid use, emergency room visits, and/or asthma-related hospitalizations). A total of 137 cases and 120 controls were recruited. After stratifying by recruitment location (i.e., Canary Islands and Basque Country), cases and controls did not differ for most demographic and clinical variables ( > 0.05). However, cases showed a higher proportion of characteristics inherent to asthma exacerbations (impaired lung function, severe disease, uncontrolled asthma, gastroesophageal reflux, and use of asthma medications) compared to controls ( < 0.05). Similar results were found after stratification by recruitment unit. Thereby, asthma patients enrolled in GEMAS are balanced for potential confounders and have clinical characteristics that support the phenotype definition. GEMAS will improve the knowledge of potential biomarkers of asthma exacerbations.
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http://dx.doi.org/10.3390/jpm10030123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563269PMC
September 2020

Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response.

Pediatr Allergy Immunol 2021 Jan 23;32(1):51-59. Epub 2020 Jul 23.

Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.

Background: Recurrent wheezing (RW) is frequently developed in infants that have suffered bronchiolitis (BCH) during first months of life, but the immune mechanism underlying is not clear. The goal was to analyze the innate immune response that characterizes BCH and RW.

Methods: Ninety-eight and seventy hospitalized infants with BCH or RW diagnosis, respectively, were included. Nasopharyngeal aspirate (NPA) was processed. Cellular pellet was employed to evaluate type 2 innate lymphoid cells (ILC2) by flow cytometry and mRNA expression assays by semi-quantitative real-time PCR (qRT-PCR). In supernatant, twenty-seven pro-inflammatory and immunomodulatory factors, as well as lipid mediators and nitrites, were evaluated by ELISA and Luminex.

Results: Bronchiolitis patients showed higher ILC2 percentage compared with RW (P < .05). Also, ST2 /ILC2 percentage was higher in the BCH group than in the RW group (P < .01). TLR3, IL33, IFNG, IL10, and FLG mRNA levels were significantly increased in BCH vs RW (P < .05). In supernatant, no significant differences were reached, observing similar levels of parameters linked to vascular damage, monocyte activation, and fibroblast growth. Prostaglandin E2 and cysteinyl leukotrienes C4 were evaluated; a significant difference was only found in their ratio.

Conclusion: Bronchiolitis is associated with elevated nasal percentage of ILC2. This cellular population could be the key element in the differential immune response between BCH and RW which share some mechanisms such us monocyte activation, vascular damage, and fibroblast repair. Lipid mediators could play a role in the evolution of the disease later in life through innate lymphoid cells.
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http://dx.doi.org/10.1111/pai.13317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818223PMC
January 2021

Biochemical and Hematological Correlates of Elevated Homocysteine in National Surveys and a Longitudinal Study of Urban Adults.

Nutrients 2020 Mar 30;12(4). Epub 2020 Mar 30.

Laboratory of Epidemiology and Population Sciences, NIA/NIH/IRP, Baltimore, MD 21224, USA.

Elevated blood homocysteine (Hcy) among middle-aged adults can increase age-related disease risk, possibly through other biochemical and hematological markers. We selected markers for hyperhomocysteinemia among middle-aged adults, studied time-dependent Hcy-marker associations and computed highly predictive indices of hyperhomocysteinemia, with cross-sectional and longitudinal validations. We used data from the National Health and Nutrition Examination Survey (NHANES III, phase 2, = 4000), the NHANES 1999-2006 ( = 10,151) and pooled NHANES (cross-sectional validation). Longitudinal validation consisted of mixed-effects linear regression models (Hcy predicting markers' annual rates of change), applied to the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS, = 227-244 participants, k = 2.4 repeats/participant, Age: 30-65 years) data. Machine learning detected nine independent markers for Hcy > 14 µmol/L (NHANES III, phase 2): older age; lower folate and B-12 status; higher serum levels of creatinine, uric acid, alkaline phosphatase, and cotinine; mean cell hemoglobin and red cell distribution widths (RDW); results replicated in the 1999-2006 NHANES [AUC = 0.60-0.80]. Indices combining binary markers increased elevated Hcy odds by 6.9-7.5-fold. In HANDLS, first-visit Hcy predicted annual increase in creatinine, RDW and alkaline phosphatase, with third-visit index (2013-2018) directly predicting Hcy (2004-2009). We provide evidence of the internal and external validity of indices composed of several biomarkers that are strongly associated with elevated Hcy.
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http://dx.doi.org/10.3390/nu12040950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230768PMC
March 2020

Immune recovery following bronchiolitis is linked to a drop in cytokine and LTC4 levels.

Pediatr Res 2020 02 10;87(3):581-587. Epub 2019 Oct 10.

Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.

Background: Bronchiolitis is the main cause of hospitalization of children younger than 1 year; however, the immune mechanism of bronchiolitis is not completely understood. The aim of this study was to analyze the recovery of immune response after a bronchiolitis episode.

Methods: Forty-nine infants hospitalized with bronchiolitis diagnosis were enrolled. Nasopharyngeal aspirates (NPAs) were processed. Twenty-seven pro-inflammatory biomarkers linked to innate immunity, inflammation, and epithelial damage, as well as nitrites and lipid mediators, were evaluated in the NPA supernatant by ELISA (enzyme-linked immunosorbent assay) and Luminex. Also, 11 genes were analyzed in NPA cells by quantitative PCR.

Results: A widespread statistically significant decline of multiple pro-inflammatory parameters and cytokines were detected in the recovery period after respiratory infection: interferon-α2 (IFNα2), IFNγ, interleukin-10 (IL-10), IL-1β, IL-8, IFN-γ-inducible protein-10, vascular endothelial growth factor, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β. Supporting these results, a decreased nuclear factor-κB gene expression was observed (P = 0.0116). A significant diminution of cysteinyl leukotriene C4 (LTC4) soluble levels (P = 0.0319) and cyclooxygenase-2 (COX-2) gene expression were observed in the recovery sample. In children classified by post-bronchiolitis wheezing, LTC4 remains elevated in the NPA supernatant.

Conclusions: After bronchiolitis, cytokines and biomarkers linked to innate immune response in NPA decrease significantly in the recovery period accompanied by a drop in LTC4 levels; however, this reduction was lower in infants with post-bronchiolitis wheezing.
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http://dx.doi.org/10.1038/s41390-019-0606-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086521PMC
February 2020

Circulating miRNAs as diagnostic tool for discrimination of respiratory disease: Asthma, asthma-chronic obstructive pulmonary disease (COPD) overlap and COPD.

Allergy 2019 12 20;74(12):2491-2494. Epub 2019 Jun 20.

Department of Immunology, Instituto de Investigación Sanitaria Hospital Universitario Fundacion Jimenez Diaz (IIS-FJD, UAM), Madrid, Spain.

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http://dx.doi.org/10.1111/all.13916DOI Listing
December 2019

Enhancing the Ambient Assisted Living Capabilities with a Mobile Robot.

Comput Intell Neurosci 2019 2;2019:9412384. Epub 2019 Apr 2.

Institute for Computer Research, University of Alicante, P.O. Box 99, 03080 Alicante, Spain.

Ambient assisted living (AAL) environments are currently a key focus of interest as an option to assist and monitor disabled and elderly people. These systems can improve their quality of life and personal autonomy by detecting events such as entering potentially dangerous areas, potential fall events, or extended stays in the same place. Nonetheless, there are areas that remain outside the scope of AAL systems due to the placement of cameras. There also exist sources of danger in the scope of the camera that the AAL system cannot detect. These sources of danger are relatively small in size, occluded, or nonstatic. To solve this problem, we propose the inclusion of a robot which maps such uncovered areas looking for new potentially dangerous areas that go unnoticed by the AAL. The robot then sends this information to the AAL system in order to improve its performance. Experimentation in real-life scenarios successfully validates our approach.
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http://dx.doi.org/10.1155/2019/9412384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466947PMC
August 2019

Systemic inflammation is associated with depressive symptoms differentially by sex and race: a longitudinal study of urban adults.

Mol Psychiatry 2020 06 24;25(6):1286-1300. Epub 2019 Apr 24.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, USA.

Systemic inflammation may influence trajectories of depressive symptoms over time, perhaps differentially by sex and race. Inflammatory markers and the Center for Epidemiologic Studies-Depression scale [total score: CES-D and four distinctive domains: somatic complaints, depressed affect, positive affect and interpersonal problems] were examined among African-American (AA) and White urban adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study [2004-2013, Age:30-64 y, mean ± SD follow-up time: 4.64 ± 0.93 y, N = 150 (with cytokine data) to N = 1,767 (with other inflammatory markers)]. Findings suggest that serum concentrations of high-sensitivity C-reactive protein (hsCRP), z-inflammation composite score [ICS, combining elevated hsCRP and ESR with low serum albumin and iron], and serum interleukin (IL) 1β were positively associated with ΔCES-D (Δ: annual rate of increase) among Whites only. IL-12 was directly related to ΔCES-D among men and AA. The race-specific associations of hsCRP, ICS, IL-1β and the sex-specific association of IL-12 with ΔCES-D were replicated for the "depressed affect" domain. Similarly, among men, lower serum albumin and higher ICS were linked with higher baseline "somatic complaints". IL-10 among AA and IL-12 among men were inversely related to Δ"positive affect", while "interpersonal problems" were cross-sectionally associated with IL-6 among AA and IL-10 among Whites. Finally, baseline ICS was positively associated with incident "elevated depressive symptoms" (EDS: CES-D ≥ 16) among AA (HR = 1.28, 95% CI: 1.04-1.56, P = 0.017). Overall, systemic inflammation was directly linked to increased depressive symptoms over time and at baseline, differentially across sex and race groups. More longitudinal research is needed to replicate our findings.
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http://dx.doi.org/10.1038/s41380-019-0408-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813878PMC
June 2020

Exosomes: A new approach to asthma pathology.

Clin Chim Acta 2019 Aug 9;495:139-147. Epub 2019 Apr 9.

Department of Immunology, IIS-Fundación Jiménez Díaz, Av. de los Reyes Católicos 2, 28040 Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Av. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029 Madrid, Spain. Electronic address:

Asthma is a chronic inflammatory disease of the airways with a complex pathophysiology, making the development of diagnostic and therapeutic tools a challenge. Exosomes are extracellular membranous nanovesicles implicated in intercellular communication. Exosome composition and cargo are highly heterogeneous depending on their cellular origin and physiological state. They contain proteins (tetraspanins, heat-shock proteins), nucleic acids (RNA, microRNA), and lipids (ceramides, cholesterol, sphingolipids). Current scientific advances show that exosomes play a pivotal role in the pathology of asthma as well as other inflammatory diseases, and all types of inflammatory cells (neutrophils, dendritic cells, lymphocytes, eosinophils) release exosomes. Also, structural lung cells such as airway epithelial cells and airway smooth muscle cells produce and secrete these nanovesicles. Exosomes influence and modify the functionality of these inflammatory and structural cells, triggering the characteristic processes of asthma disease. Additionally, exosomes are used as biomarkers in several disorders because they are easier to collect from different biofluids, making them a non-invasive method for screening human pathologies. Also, due to their special molecular characteristics, they can be loaded with different molecules and employed as a drug-delivery vehicle. This review focuses on recent advances related to the role of exosomes in asthma disease.
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http://dx.doi.org/10.1016/j.cca.2019.04.055DOI Listing
August 2019

SDVL: Efficient and Accurate Semi-Direct Visual Localization.

Sensors (Basel) 2019 Jan 14;19(2). Epub 2019 Jan 14.

RoboticsLab-URJC, Universidad Rey Juan Carlos, Fuenlabrada, 28943 Madrid, Spain.

Visual Simultaneous Localization and Mapping (SLAM) approaches have achieved a major breakthrough in recent years. This paper presents a new monocular visual odometry algorithm able to localize in 3D a robot or a camera inside an unknown environment in real time, even on slow processors such as those used in unmanned aerial vehicles (UAVs) or cell phones. The so-called semi-direct visual localization (SDVL) approach is focused on localization accuracy and uses semi-direct methods to increase feature-matching efficiency. It uses inverse-depth 3D point parameterization. The tracking thread includes a motion model, direct image alignment, and optimized feature matching. Additionally, an outlier rejection mechanism (ORM) has been implemented to rule out misplaced features, improving accuracy especially in partially dynamic environments. A relocalization module is also included but keeping the real-time operation. The mapping thread performs an automatic map initialization with homography, a sampled integration of new points and a selective map optimization. The proposed algorithm was experimentally tested with international datasets and compared to state-of-the-art algorithms.
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http://dx.doi.org/10.3390/s19020302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358853PMC
January 2019

Carotenoids, vitamin A, and their association with the metabolic syndrome: a systematic review and meta-analysis.

Nutr Rev 2019 01;77(1):32-45

Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.

Context: Modifiable factors that reduce the burden of the metabolic syndrome (MetS), particularly plant-derived biomarkers, have been a recent focus of rising interest.

Objective: This systematic review and meta-analysis, which follows PRISMA guidelines, evaluates evidence from a period of 20 years that links vitamin A and carotenoids with the occurrence of MetS and following the PRISMA guidelines.

Data Sources: PubMed and Cochrane databases (January 1997 through March 2017) were systematically assessed for studies, including case-control, cross-sectional, and cohort studies, that evaluated the associations of MetS with carotenoids and retinyl esters and retinol (vitamin A).

Data Extraction: Key measures of associations were harmonized into odds ratios (ORs) and 95% confidence intervals (95%CI) of MetS per 1 standard deviation (SD) of exposure using forest plots and random effects models that pooled data points from 11 cross-sectional studies. Begg's funnel and harvest plots were constructed.

Results: An inverse association between total carotenoids and MetS was found [ORpooled, 0.66; 95%CI, 0.56-0.78; 1 SD ∼ 0.82 µmol/L; n = 5 studies]. This association was the strongest for β-carotene, followed by α-carotene and β-crypotoxanthin. No association was detected between retinol and MetS (ORpooled, 1.00; 95%CI, 0.88-1.13; 1 SD ∼ 2.14 µmol/L; n = 6 studies). Publication bias was absent, and harvest plots indicated consistency upon replication for β-carotene and total carotenoid exposures.

Conclusions: This review and meta-analysis suggests that, unlike retinol, total and individual carotenoids were inversely related to MetS.
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http://dx.doi.org/10.1093/nutrit/nuy044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277204PMC
January 2019

Novel causes of drug-induced occupational asthma.

J Allergy Clin Immunol Pract 2019 Feb 1;7(2):740-742.e1. Epub 2018 Aug 1.

Allergy Department, Hospital Fundación Jiménez Díaz, Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2018.07.026DOI Listing
February 2019

Asthma diagnosis using integrated analysis of eosinophil microRNAs.

Allergy 2019 03 11;74(3):507-517. Epub 2018 Oct 11.

Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.

Background: Asthma is a syndrome characterized by airway inflammation and obstruction. Due to its heterogeneity, the difficulties in asthma diagnosis and treatment make the discovery of new biomarkers a focus of research. So, we determined the differential miRNA expression of eosinophils between healthy and asthmatic patients and to establish a differentially expressed miRNA profile detectable in sera for use as biomarker.

Methods: MicroRNAs from peripheral eosinophils from healthy and asthmatic subjects were isolated and analyzed by next-generation sequencing and confirmed by quantitative PCR in 29 asthmatics and 10 healthy individuals. The levels of serum miRNAs were performed by quantitative PCR in 138 asthmatics and 39 healthy subjects. Regression analysis and Random Forest models were performed.

Results: We found a set of miRNAs whose expression differs between eosinophils from asthmatics and healthy subjects. These miRNAs can classify asthmatics into two clusters that differed in the number of eosinophils and periostin concentration in serum. Some of these miRNAs were also confirmed in sera, as miR-185-5p which discriminates asthmatics from healthy subjects. Together with other two miRNAs, miR-185-5p allowed us to create a logistic regression model to discriminate better both conditions and a Random Forest model that can even sort the asthmatics into intermittent, mild persistent, moderate persistent, and severe persistent asthma.

Conclusion: Our data show that miRNAs profile in eosinophils can be used as asthma diagnosis biomarker in serum and that this profile is able to rank asthma severity.
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http://dx.doi.org/10.1111/all.13570DOI Listing
March 2019

Vitamin D Metabolism-Related Gene Haplotypes and Their Association with Metabolic Disturbances Among African-American Urban Adults.

Sci Rep 2018 05 23;8(1):8035. Epub 2018 May 23.

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, United States.

Epidemiological studies have confirmed associations of the vitamin D receptor (VDR) and vitamin D-related gene polymorphisms with adiposity and other metabolic disturbances. Those associations may be sex-specific. We evaluated the cross-sectional and longitudinal relationships between metabolic disturbances and haplotypes constructed from single nucleotide polymorphisms of VDR (BsmI:G/A: rs1544410; ApaI:A/C: rs7975232; and TaqI:G/A: rs731236) and MEGALIN (rs3755166:G/A; rs2075252:C/T and rs2228171:C/T) genes, in a sample of African-American adults. From 1,024 African Americans participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS, 2004-2013, Baltimore, MD), our analyses included 539 participants with complete genetic, baseline covariate and metabolic outcome data (at baseline and follow-up). Mean ± SD period of follow-up was 4.64 ± 0.93 y. Multivariable-adjusted Cox proportional hazards and logistic regression models were conducted. Among key findings, in men, incident hypertension was inversely related to MEGALIN (GCC), [HR = 0.45, 95% CI: 0.23-0.90, p = 0.024]. Overall, there was a direct, linear dose-response association between VDR (AAG: BAt) and MetS at baseline [OR = 1.60, 95% CI: 1.11-2.31, p = 0.012], while among men, VDR (GAA: bAT) was inversely related to baseline MetS [OR = 0.40, 95% CI: 0.19-0.81, p = 0.011]. In conclusion, VDR and MEGALIN gene variations can affect prevalent MetS and the incidence rate of hypertension, respectively, among African-American urban adults.
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http://dx.doi.org/10.1038/s41598-018-26230-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966433PMC
May 2018

Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity in Nonvitamin D Supplemented Adolescents.

Metab Syndr Relat Disord 2018 05 13;16(4):197-203. Epub 2018 Mar 13.

2 Biomedical Analysis Laboratory , Nemours Children's Specialty Care, Jacksonville, Florida.

Background: The relationship among inadequate vitamin D status, obesity, and cardiometabolic risk and the potential impact of physical activity-based interventions on vitamin D status are poorly characterized in children. This study aimed to address these issues.

Methods: We studied a total of 21 adolescents (15 obese and 6 normal weight; age: 14-18 years; Tanner stage>IV). Adolescents with obesity (n = 15) underwent a randomized controlled (8 in the intervention group and 7 in the control group) 3-month physical activity-based lifestyle intervention. 25-Hydroxy vitamin D [25(OH)D] by mass spectrometry, adiponectin, leptin, high-sensitivity C-reactive protein (CRP), insulin, and glucose were measured and body composition was assessed by dual-energy x-ray absorptiometry (DXA). Analysis of covariance and mixed-effects model were used to compare mean change in 25(OH)D between intervention and nonintervention groups. Bootstrap method was used to validate the estimates and principle component analysis reduced the variables in the data for adjustment.

Results: 25(OH)D was lower (P < 0.001) in the obese versus lean adolescents. Homeostasis model assessment-insulin resistance, CRP, fat mass (FM), and body mass index z-score were negatively correlated with baseline 25(OH)D, while adiponectin showed a positive correlation. After adjustment for baseline biomarkers of cardiometabolic risk, the concentration of 25(OH)D increased in the obese intervention group (P = 0.06), but not in the nonintervention group. Fat-free mass increased and FM decreased (P < 0.05 for both) in the intervention group. The magnitudes of increase in 25(OH)D and decrease in FM directly correlated (P < 0.05).

Conclusions: The increase in circulating 25(OH)D concentration by physical activity-based lifestyle-only intervention in adolescents with obesity, who did not receive vitamin D supplementation, suggests a putative independent role of physical activity-based interventions in the regulation of vitamin D status and potentially in the mitigation of risk factors of cardiovascular disease.
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http://dx.doi.org/10.1089/met.2017.0171DOI Listing
May 2018

The MEGA Project: A Study of the Mechanisms Involved in the Genesis and Disease Course of Asthma. Asthma Cohort Creation and Long-Term Follow-Up.

Arch Bronconeumol 2018 Mar 19. Epub 2018 Mar 19.

Servicio de Neumología, Hospital Vall d'Hebron, Barcelona, España; CIBER de Enfermedades Respiratorias (CIBERES), España.

The general aim of this study is to create a cohort of asthma patients with varying grades of severity in order to gain greater insight into the mechanisms underlying the genesis and course of this disease. The specific objectives focus on various studies, including imaging, lung function, inflammation, and bronchial hyperresponsiveness, to determine the relevant events that characterize the asthma population, the long-term parameters that can determine changes in the severity of patients, and the treatments that influence disease progression. The study will also seek to identify the causes of exacerbations and how this affects the course of the disease. Patients will be contacted via the outpatient clinics of the 8 participating institutions under the auspices of the Spanish Respiratory Diseases Networking System (CIBER). In the inclusion visit, a standardized clinical history will be obtained, a clinical examination, including blood pressure, body mass index, complete respiratory function tests, and FENO will be performed, and the Asthma Control Test (ACT), Morisky-Green test, Asthma Quality of Life Questionnaire (Mini AQLQ), the Sino-Nasal Outcome Test 22 (SNOT-22), and the Hospital Anxiety and Depression scale (HADS) will be administered. A specific electronic database has been designed for data collection. Exhaled breath condensate, urine and blood samples will also be collected. Non-specific bronchial hyperresponsiveness testing with methacholine will be performed and an induced sputum sample will be collected at the beginning of the study and every 24 months. A skin prick test for airborne allergens and a chest CT will be performed at the beginning of the study and repeated every 5 years.
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http://dx.doi.org/10.1016/j.arbres.2017.12.012DOI Listing
March 2018

Dairy product consumption and its association with metabolic disturbance in a prospective study of urban adults.

Br J Nutr 2018 03;119(6):706-719

1Laboratory of Epidemiology and Population Sciences,National Institute on Aging,National Institute on Aging, National Institutes of Health, Intramural Research Program,Baltimore,MD 21224,USA.

The role of dairy foods and related nutrients in cardiometabolic health aetiology is poorly understood. We investigated longitudinal associations between the metabolic syndrome (MetS) and its components with key dairy product exposures. We used prospective data from a bi-racial cohort of urban adults (30-64 years at baseline (n 1371)), the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS), in Baltimore City, MD (2004-2013). The average of two 24-h dietary recalls measured 4-10 d apart was computed at baseline (V1) and follow-up (V2) waves. Annual rates of change (Δ) in dairy foods and key nutrients were estimated. Incident obesity, central obesity and the MetS were determined. Among key findings, in the overall urban adult population, both cheese and yogurt (V1 and Δ) were associated with an increased risk of central obesity (hazard ratio (HR) 1·13; 95 % CI 1·05, 1·23 per oz equivalent of cheese (V1); HR 1·21; 95 % CI 1·01, 1·44 per fl oz equivalent of yogurt (V1)]. Baseline fluid milk intake (V1 in cup equivalents) was inversely related to the MetS (HR 0·86; 95 % CI 0·78, 0·94), specifically to dyslipidaemia-TAG (HR 0·89; 95 % CI 0·81, 0·99), although it was directly associated with dyslipidaemia-HDL-cholesterol (HR 1·10; 95 % CI 1·01, 1·21). Furthermore, ΔCa and ΔP were inversely related to dyslipidaemia-HDL and MetS incidence, respectively, whereas Δdairy product fat was positively associated with incident TAG-dyslipidaemia and HDL-cholesterol-dyslipidaemia and the MetS. A few of those associations were sex and race specific. In sum, various dairy product exposures had differential associations with metabolic disturbances. Future intervention studies should uncover how changes in dairy product components over time may affect metabolic disorders.
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http://dx.doi.org/10.1017/S0007114518000028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863589PMC
March 2018

Jellyfish collagen: A new allergen in the beach.

Ann Allergy Asthma Immunol 2018 04 2;120(4):430-431. Epub 2018 Feb 2.

Departments of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2018.01.018DOI Listing
April 2018

Novel Modulators of Asthma and Allergy: Exosomes and MicroRNAs.

Front Immunol 2017 21;8:826. Epub 2017 Jul 21.

Laboratory of Immunoallergy, Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.

Intercellular communication is crucial to the immune system response. In the recent years, the discovery of exosomes has changed the way immune response orchestration was understood. Exosomes are able to operate as independent units that act as mediators in both physiological and pathological conditions. These structures contain proteins, lipidic mediators, and nucleic acids and notoriously include microRNAs (miRNAs). miRNAs are short RNA sequences (around 19-22 nucleotides) with a high phylogenetic conservation and can partially or totally regulate multiple mRNAs, inhibiting protein synthesis. In respiratory diseases such as asthma and allergic sensitization, exosomes released by several cell types and their specific content perform crucial functions in the development and continuation of the pathogenic mechanisms. Released exosomes and miRNAs inside them have been found in different types of clinical samples, such as bronchoalveolar lavage fluids and sputum supernatants, providing new data about the environmental factors and mediators that participate in the inflammatory responses that lead to the exacerbation of asthma. In this review, we summarize our current knowledge of the role of exosomes and miRNAs in asthma and allergic sensitization, paying attention to the functions that both exosomes and miRNAs are described to perform through the literature. We review the effect of exosomes and miRNAs in cells implicated in asthma pathology and the genes and pathways that they modify in them, depicting how their behavior is altered in disease status. We also describe their possible repercussion in asthma diagnosis through their possible role as biomarkers. Therefore, both exosomes and miRNAs can be viewed as potential tools to be added to the arsenal of therapeutics to treat this disease.
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http://dx.doi.org/10.3389/fimmu.2017.00826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519536PMC
July 2017

Thymic stromal lymphopoietin, IL-33, and periostin in hospitalized infants with viral bronchiolitis.

Medicine (Baltimore) 2017 May;96(18):e6787

Pediatrics Department, Severo Ochoa Hospital, Leganés, Alfonso X El Sabio University Department of Immunology, IIS-Fundación Jiménez Díaz CIBER de Enfermedades Respiratorias (CIBERES) Respiratory Virus and Influenza Unit, National Microbiology Center (ISCIII), Madrid, Spain Translational Research Network in Pediatric Infectious Diseases (RITIP) TEDDY Network (European Network of Excellence for Pediatric Clinical Research).

Much attention has recently been focused on thymic stromal lymphopoietin (TSLP), IL-33, and periostin in allergic disease, but less is known about their role in viral bronchiolitis.The aim of the study was to investigate whether infants exhibit enhanced nasal airway secretion of TSLP, IL-33, and periostin during natural respiratory viral bronchiolitis compared to healthy controls.In total, 213 infants < 2 years of age, hospitalized with bronchiolitis from October/2013 to April/2016 were enrolled alongside 45 healthy infants. Nasopharyngeal aspirates (NPA) were screened for respiratory viruses by the polymerase chain reaction. TSLP, IL-33, and periostin were measured in NPAs. Clinical data were recorded.At least 1 virus was detected in 186 (87.3%) hospitalized infants: 149 (70%) respiratory syncytial virus (RSV); 42 (19.7%) rhinovirus (HRV); 16 (7.5%) parainfluenza virus (PIV); 9 (4.2%) adenovirus; 10 (4.7%) bocavirus; and 7 (3.3%) metapneumovirus (hMPV). Infants with bronchiolitis had higher levels of TSLP (P = .02), IL-33 (P<.001), and periostin (P = .003) than healthy controls.Detectable levels of TSLP and periostin were more frequent in virus-positive than in virus-negative patients (P = .05). TSLP and IL-33 were also more common in coinfections, mainly RSV and HRV, than in single-infections (P < .05). No patient with bronchiolitis but with negative viral detection had detectable levels of nasal TSLP or IL-33. Infants with hospital stay ≥5 days were more likely to have detectable levels of nasal TSLP and periostin after adjusting by age (P = .01).Bronchiolitis by common respiratory viruses is associated with elevated nasal levels of TSLP, IL-33, and periostin, factors known to be important in the development of Th2-response. Respiratory viruses in early life might shift immune responses toward Th2, involving asthma, and allergic diseases.
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http://dx.doi.org/10.1097/MD.0000000000006787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419921PMC
May 2017