117 research outputs found
A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED
RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement. RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity
Clinical phenotypes of asthma in childhood and adolescence: clustering analysis from the paediatric u-biopred cohorts
Effect of Dietary Zinc Oxide on Morphological Characteristics, Mucin Composition and Gene Expression in the Colon of Weaned Piglets
The trace element zinc is often used in the diet of weaned piglets, as high
doses have resulted in positive effects on intestinal health. However, the
majority of previous studies evaluated zinc supplementations for a short
period only and focused on the small intestine. The hypothesis of the present
study was that low, medium and high levels of dietary zinc (57, 164 and 2,425
mg Zn/kg from zinc oxide) would affect colonic morphology and innate host
defense mechanisms across 4 weeks post-weaning. Histological examinations were
conducted regarding the colonic morphology and neutral, acidic, sialylated and
sulphated mucins. The mRNA expression levels of mucin (MUC) 1, 2, 13, 20,
toll-like receptor (TLR) 2, 4, interleukin (IL)-1β, 8, 10, interferon-γ
(IFN-γ) and transforming growth factor-β (TGF-β) were also measured. The
colonic crypt area increased in an age-depending manner, and the greatest area
was found with medium concentration of dietary zinc. With the high
concentration of dietary zinc, the number of goblet cells containing mixed
neutral-acidic mucins and total mucins increased. Sialomucin containing goblet
cells increased age-dependently. The expression of MUC2 increased with age and
reached the highest level at 47 days of age. The expression levels of TLR2 and
4 decreased with age. The mRNA expression of TLR4 and the pro-inflammatory
cytokine IL-8 were down-regulated with high dietary zinc treatment, while
piglets fed with medium dietary zinc had the highest expression. It is
concluded that dietary zinc level had a clear impact on colonic morphology,
mucin profiles and immunological traits in piglets after weaning. Those
changes might support local defense mechanisms and affect colonic physiology
and contribute to the reported reduction of post-weaning diarrhea
Towards the Human Colorectal Cancer Microbiome
Multiple factors drive the progression from healthy mucosa towards sporadic
colorectal carcinomas and accumulating evidence associates intestinal bacteria
with disease initiation and progression. Therefore, the aim of this study was to
provide a first high-resolution map of colonic dysbiosis that is associated with
human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon
tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA
sequencing. The results revealed striking differences in microbial colonization
patterns between these two sites. Although inter-individual colonization in CRC
patients was variable, tumors consistently formed a niche for
Coriobacteria and other proposed probiotic bacterial
species, while potentially pathogenic Enterobacteria were
underrepresented in tumor tissue. As the intestinal microbiota is generally
stable during adult life, these findings suggest that CRC-associated
physiological and metabolic changes recruit tumor-foraging commensal-like
bacteria. These microbes thus have an apparent competitive advantage in the
tumor microenvironment and thereby seem to replace pathogenic bacteria that may
be implicated in CRC etiology. This first glimpse of the CRC microbiome provides
an important step towards full understanding of the dynamic interplay between
intestinal microbial ecology and sporadic CRC, which may provide important leads
towards novel microbiome-related diagnostic tools and therapeutic
interventions
Expression of the blood-group-related glycosyltransferase B4galnt2 influences the intestinal microbiota in mice
Glycans on mucosal surfaces have an important role in host–microbe interactions. The locus encoding the blood-group-related glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2) is subject to strong selective forces in natural house-mouse populations that contain a common allelic variant that confers loss of B4galnt2 gene expression in the gastrointestinal (GI) tract. We reasoned that altered glycan-dependent intestinal host–microbe interactions may underlie these signatures of selection. To determine whether B4galnt2 influences the intestinal microbial ecology, we profiled the microbiota of wild-type and B4galnt2-deficient siblings throughout the GI tract using 16S rRNA gene pyrosequencing. This revealed both distinct communities at different anatomic sites and significant changes in composition with respect to genotype, indicating a previously unappreciated role of B4galnt2 in host–microbial homeostasis. Among the numerous B4galnt2-dependent differences identified in the abundance of specific bacterial taxa, we unexpectedly detected a difference in the pathogenic genus, Helicobacter, suggesting Helicobacter spp. also interact with B4galnt2 glycans. In contrast to other glycosyltransferases, we found that the host intestinal B4galnt2 expression is not dependent on presence of the microbiota. Given the long-term maintenance of alleles influencing B4galnt2 expression by natural selection and the GI phenotypes presented here, we suggest that variation in B4galnt2 GI expression may alter susceptibility to GI diseases such as infectious gastroenteritis
The Digital Fish Library: Using MRI to Digitize, Database, and Document the Morphological Diversity of Fish
Museum fish collections possess a wealth of anatomical and morphological data that are essential for documenting and understanding biodiversity. Obtaining access to specimens for research, however, is not always practical and frequently conflicts with the need to maintain the physical integrity of specimens and the collection as a whole. Non-invasive three-dimensional (3D) digital imaging therefore serves a critical role in facilitating the digitization of these specimens for anatomical and morphological analysis as well as facilitating an efficient method for online storage and sharing of this imaging data. Here we describe the development of the Digital Fish Library (DFL, http://www.digitalfishlibrary.org), an online digital archive of high-resolution, high-contrast, magnetic resonance imaging (MRI) scans of the soft tissue anatomy of an array of fishes preserved in the Marine Vertebrate Collection of Scripps Institution of Oceanography. We have imaged and uploaded MRI data for over 300 marine and freshwater species, developed a data archival and retrieval system with a web-based image analysis and visualization tool, and integrated these into the public DFL website to disseminate data and associated metadata freely over the web. We show that MRI is a rapid and powerful method for accurately depicting the in-situ soft-tissue anatomy of preserved fishes in sufficient detail for large-scale comparative digital morphology. However these 3D volumetric data require a sophisticated computational and archival infrastructure in order to be broadly accessible to researchers and educators
The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults
Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier
A computational framework for complex disease stratification from multiple large-scale datasets.
BACKGROUND: Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-'omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-'omics signatures of disease states. METHODS: The framework is divided into four major steps: dataset subsetting, feature filtering, 'omics-based clustering and biomarker identification. RESULTS: We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-'omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. CONCLUSIONS: This framework will help health researchers plan and perform multi-'omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine
Prospective Observational Study on acute Appendicitis Worldwide (POSAW)
Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments.info:eu-repo/semantics/publishedVersio
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