Background
Asthma is heterogeneous disease with different phenotypes, endotypes and severities. Definition of these subgroups requires the identification of biomarkers in biological samples, and ...serum proteomics is a useful and minimally invasive method for this purpose. Therefore, the aim of this study was to detect serum proteins whose abundance is distinctively associated with different asthma phenotypes (allergic vs nonallergic) or severities.
Methods
For each group of donors (32 healthy controls, 43 allergic rhinitis patients and 192 asthmatics with different phenotypes and severities), we generated two pools of sera that were analysed by a shotgun MS approach based on combinatorial peptide ligand libraries and iTRAQ‐LC‐MS/MS.
Results
MS analyses identified 18 proteins with a differential abundance. Functional/network study of these proteins identified key processes for asthma pathogenesis, such as complement activation, extracellular matrix organization, platelet activation and degranulation, or post‐translational protein phosphorylation. Furthermore, our results highlighted an enrichment of the “Regulation of Insulin‐like Growth Factor (IGF) transport and uptake by Insulin‐like Growth Factor Binding Proteins (IGFBPs)” route in allergic asthma and the lectin pathway of complement activation in nonallergic asthma. Thus, several proteins (eg IGFALS, HSPG2, FCN2 or MASP1) displayed a differential abundance between the different groups of donors. Particularly, our results revealed IGFALS as a useful biomarker for moderate‐severe allergic asthma.
Conclusion
Our data suggest a set of serum biomarkers, especially IGFALS, capable of differentiating allergic from nonallergic asthma. These proteins reveal different pathophysiological mechanisms and may be useful in the future for diagnosis, prognosis or targeted therapy purposes.
This study identifies serum biomarkers for asthma (allergic and nonallergic asthma) and allergic rhinitis using iTRAQ‐based proteomics. Several proteins from the IGF pathway are increased in allergic asthma. Particularly, IGFALS could be a useful biomarker for this phenotype. Proteins from the lectin pathway of complement activation (FCN2 and MASP1) are increased in non‐allergic asthma. Abbreviations: AHSG, alpha‐2‐HS‐glycoprotein; CALU, calumenin; CPN1, carboxypeptidase N subunit 1; CPLLs, combinatorial peptide ligand libraries; C1R, complement C1r subcomponent; C4B, complement component 4B; F2, prothrombin; FCN2, ficolin 2; HAP, high abundant proteins; HSPG2, basement membrane‐specific heparan sulfate proteoglycan core protein; IGF‐ALS, insulin‐like growth factor binding protein acid labile subunit; iTRAQ, isobaric tags for relative and absolute quantitation; LAP, low abundant proteins; LC‐MS/MS, liquid chromatography coupled online to tandem mass spectrometry; MASP1, mannan binding lectin serine peptidase 1; NCAM1, neural cell adhesion molecule 1 precursor
Upregulation of a cyclin D gene determined by expression microarrays is an almost universal event in multiple myeloma (MM), but this finding has not been properly confirmed at the protein level. For ...this reason, we carried out a quantitative analysis of cyclin D proteins using a capillary electrophoresis nanoimmunoassay in newly diagnosed MM patients. Exclusive expression of cyclin D1 and D2 proteins was detected in 54 of 165 (33%) and 30 of 165 (18%) of the MM patients, respectively. Of note, cyclin D1 or D2 proteins were undetectable in 41% of the samples. High levels of cyclin D1 protein were strongly associated with the presence of t(11;14) or 11q gains. Cyclin D2 protein was detected in all the cases bearing t(14;16), but in only 24% of patients with t(4;14). The presence of cyclin D2 was associated with shorter overall survival (hazard ratio =2.14; P=0.017), although patients expressing cyclin D2 protein, but without 1q gains, had a favorable prognosis. In conclusion, although one of the cyclins D is overexpressed at the mRNA level in almost all MM patients, in approximately half of the patients this does not translate into detectable protein. This suggests that cyclins D could not play an oncogenic role in a proportion of patients with MM (clinicaltrials gov. identifier: NCT01916252).
We aimed to identify the plasma miRNA profile of antiphospholipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. ...Ninety APS patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of APS patients identified a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic regression and ROC analysis identified a signature of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombosis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters representing different thrombotic risk profile groups. Significant differences between groups for several miRNA ratios were found. Moreover, miRNA signature remained stable over time, demonstrated by their analysis three months after the first sample collection. Parallel analysis in two additional cohorts of patients, including thrombosis without autoimmune disease, and systemic lupus erythematosus without antiphospholipid antibodies, each displayed specific miRNA profiles that were distinct from those of APS patients.
, antiphospholipid antibodies of IgG isotype promoted deregulation in selected miRNAs and their potential atherothrombotic protein targets in monocytes and endothelial cells. Taken together, differentially expressed circulating miRNAs in APS patients, modulated at least partially by antiphospholipid antibodies of IgG isotype, might have the potential to serve as novel biomarkers of disease features and to typify patients' atherothrombotic status, thus constituting a useful tool in the management of the disease.
Dieulafoy's lesion of the small bowel is an uncommon cause of gastrointestinal (GI) bleeding that often recurs after endoscopic treatment.
we report an observational, descriptive, retrospective, ...single-center study in 15 patients with small bowel bleeding who were diagnosed with a Dieulafoy's lesion by capsule endoscopy or double-balloon enteroscopy.
all patients underwent combined endoscopic treatment. During a median follow-up of 33.5 months (range, 2-145), three of the 12 cases that stayed in follow-up (25 %) recurred, all within 48 hours after treatment. Two were successfully re-treated with a repeat endoscopic procedure.
Preferences are essential in explaining consumer choice and have been studied from different standpoints. Some empirical studies aimed at measuring music preferences have used direct procedures ...(i.e., list of genres), while other studies have used indirect measures (i.e., listening to excerpts of music). This article focuses on analyzing music-genre preferences to identify whether they differ depending on the type of measure used (direct vs. indirect), studying their consistency. A survey was conducted among 753 individuals. The results highlight not only the discrepancies of using one measure or another but also the relevance of familiarity and experience, associated with individuals’ endowment of cultural capital. Findings explain the (in)consistency of reported preferences through direct and indirect means. All in all, the research suggests that direct and indirect methods to measure music preferences may be capturing different dimensions.
Music preferences have been shown to be determined by a diversity of factors such as cognitive, emotional, cultural, or experiential. Having studied music is also a factor that has been considered ...from a musicology standpoint and is linked to the accumulation of cultural capital, as analyzed in cultural economics, arts management, and the sociology of culture. Research on how music studies influence music genre preferences shed light on the role that music education plays in the stock of cultural capital individuals hold. To do so, an exploratory empirical survey was undertaken using self-administered questionnaires targeted to a sample of 231 students. Findings, after performing multivariate analysis, showed that knowledge or familiarity plays an important role in music genre preferences. Specifically, having studied music affects the choice of music genres. These results contribute to the literature on music preferences, and specifically on their determinants, establishing the connection of music education with the accumulation of cultural capital and its influence on the formation of music genre preferences.
Current World Health Organization recommendations for the management of malaria include the need for a parasitological confirmation prior to triggering appropriate treatment. The use of rapid ...diagnostic tests (RDTs) for malaria has contributed to a better infection recognition and a more targeted treatment. Nevertheless, low-density infections and parasites that fail to produce HRP2 can cause false-negative RDT results. Microscopy has traditionally been the methodology most commonly used to quantify malaria and characterize the infecting species, but the wider use of this technique remains challenging, as it requires trained personnel and processing capacity.
In this study, the feasibility of an on-line system for remote malaria species identification and differentiation has been investigated by crowdsourcing the analysis of digitalized infected thin blood smears by non-expert observers using a mobile app.
An on-line videogame in which players learned how to differentiate the young trophozoite stage of the five Plasmodium species has been designed. Images were digitalized with a smartphone camera adapted to the ocular of a conventional light microscope. Images from infected red blood cells were cropped and puzzled into an on-line game. During the game, players had to decide the malaria species (Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax, Plasmodium ovale, Plasmodium knowlesi) of the infected cells that were shown in the screen. After 2 months, each player's decisions were analysed individually and collectively.
On-line volunteers playing the game made more than 500,000 assessments for species differentiation. Statistically, when the choice of several players was combined (n > 25), they were able to significantly discriminate Plasmodium species, reaching a level of accuracy of 99% for all species combinations, except for P. knowlesi (80%). Non-expert decisions on which Plasmodium species was shown in the screen were made in less than 3 s.
These findings show that it is possible to train malaria-naïve non-experts to identify and differentiate malaria species in digitalized thin blood samples. Although the accuracy of a single player is not perfect, the combination of the responses of multiple casual gamers can achieve an accuracy that is within the range of the diagnostic accuracy made by a trained microscopist.
An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed ...decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.
Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established ...therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.
Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' ...prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q
Q
) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial.
Thirty-six patients with APS were randomized to receive Q
(200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q
. Q
improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis-related genes were upregulated. Q
ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease-related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Q
. Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Q
on thrombosis and endothelial function-associated molecules.
Our results highlight the potential of Q
to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Q
might act as safe adjunct to standard therapies in APS.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02218476.
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