Nejvíce citovaný článek - PubMed ID 17499605
Inflammatory bowel diseases (IBD) are systemic immune-mediated conditions with predilection for the gastrointestinal tract and include Crohn's disease and ulcerative colitis. Despite the advances in the fields of basic and applied research, the etiopathogenesis remains largely unknown. As a result, only one third of the patients achieve endoscopic remission. A substantial portion of the patients also develop severe clinical complications or neoplasia. The need for novel biomarkers that can enhance diagnostic accuracy, more precisely reflect disease activity, and predict a complicated disease course, thus, remains high. Genomic and transcriptomic studies contributed substantially to our understanding of the immunopathological pathways involved in disease initiation and progression. However, eventual genomic alterations do not necessarily translate into the final clinical picture. Proteomics may represent a missing link between the genome, transcriptome, and phenotypical presentation of the disease. Based on the analysis of a large spectrum of proteins in tissues, it seems to be a promising method for the identification of new biomarkers. This systematic search and review summarize the current state of proteomics in human IBD. It comments on the utility of proteomics in research, describes the basic proteomic techniques, and provides an up-to-date overview of available studies in both adult and pediatric IBD.
- Klíčová slova
- Crohn’s disease, inflammatory bowel disease, pediatric, proteome, proteomics, ulcerative colitis,
- MeSH
- biologické markery metabolismus MeSH
- Crohnova nemoc * metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- idiopatické střevní záněty * metabolismus MeSH
- lidé MeSH
- proteomika metody MeSH
- ulcerózní kolitida * metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
PURPOSE: About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology but evolves from a distinct, poorly defined pathogenesis that has been linked in some cases to chronic norovirus (NV) infection. Interferon-driven inflammation is a prominent feature of CVID enteropathy, but it remains unknown how NV infection may contribute. METHODS: Duodenal biopsies of CVID patients, stratified according to the presence of villous atrophy (VA), IgA plasma cells (PCs), and chronic NV infection, were investigated by flow cytometry, multi-epitope-ligand cartography, bulk RNA-sequencing, and RT-qPCR of genes of interest. RESULTS: VA development was connected to the lack of intestinal (IgA+) PC, a T helper 1/T helper 17 cell imbalance, and increased recruitment of granzyme+CD8+ T cells and pro-inflammatory macrophages to the affected site. A mixed interferon type I/III and II signature occurred already in the absence of histopathological changes and increased with the severity of the disease and in the absence of (IgA+) PCs. Chronic NV infection exacerbated this signature when compared to stage-matched NV-negative samples. CONCLUSIONS: Our study suggests that increased IFN signaling and T-cell cytotoxicity are present already in mild and are aggravated in severe stages (VA) of CVID enteropathy. NV infection preempts local high IFN-driven inflammation, usually only seen in VA, at milder disease stages. Thus, revealing the impact of different drivers of the pathological mixed IFN type I/III and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination.
- Klíčová slova
- CVID, Cytotoxic T cell response, Duodenum, Interferon response genes, Norovirus, Villous atrophy,
- MeSH
- atrofie komplikace patologie MeSH
- běžná variabilní imunodeficience * komplikace imunologie MeSH
- CD8-pozitivní T-lymfocyty MeSH
- imunoglobulin A MeSH
- infekce viry z čeledi Caliciviridae * imunologie MeSH
- interferony MeSH
- lidé MeSH
- Norovirus * fyziologie MeSH
- zánět komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imunoglobulin A MeSH
- interferony MeSH
Capillary electrophoresis coupled online with mass detection is a modern tool for analyzing wide ranges of compounds in complex samples, including urine. Capillary electrophoresis with mass spectrometry allows the separation and identification of various analytes spanning from small ions to high molecular weight protein complexes. Similarly to the much more common liquid chromatography-mass spectrometry techniques, the capillary electrophoresis separation reduces the complexity of the mixture of analytes entering the mass spectrometer resulting in reduced ion suppression and a more straightforward interpretation of the mass spectrometry data. This review summarizes capillary electrophoresis with mass spectrometry studies published between the years 2017 and 2021, aiming at the determination of various compounds excreted in urine. The properties of the urine, including its diagnostical and analytical features and chemical composition, are also discussed including general protocols for the urine sample preparation. The mechanism of the electrophoretic separation and the instrumentation for capillary electrophoresis with mass spectrometry coupling is also included. This review shows the potential of the capillary electrophoresis with mass spectrometry technique for the analyses of different kinds of analytes in a complex biological matrix. The discussed applications are divided into two main groups (capillary electrophoresis with mass spectrometry for the determination of drugs and drugs of abuse in urine and capillary electrophoresis with mass spectrometry for the studies of urinary metabolome).
- Klíčová slova
- capillary electrophoresis, drugs, mass spectrometry, metabolome, urine analysis,
- MeSH
- elektroforéza kapilární metody trendy MeSH
- hmotnostní spektrometrie metody trendy MeSH
- léčivé přípravky moč MeSH
- lidé MeSH
- metabolomika MeSH
- moč chemie MeSH
- odhalování abúzu drog metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- léčivé přípravky MeSH
Gut bacteria occupy the interface between the organism and the external environment, contributing to homeostasis and disease. Yet, the causal role of the gut microbiota during host aging is largely unexplored. Here, using the African turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate, we show that the gut microbiota plays a key role in modulating vertebrate life span. Recolonizing the gut of middle-age individuals with bacteria from young donors resulted in life span extension and delayed behavioral decline. This intervention prevented the decrease in microbial diversity associated with host aging and maintained a young-like gut bacterial community, characterized by overrepresentation of the key genera Exiguobacterium, Planococcus, Propionigenium and Psychrobacter. Our findings demonstrate that the natural microbial gut community of young individuals can causally induce long-lasting beneficial systemic effects that lead to life span extension in a vertebrate model.
- Klíčová slova
- Nothobranchius furzeri, Turquoise killifish, aging, evolutionary biology, genomics, infectious disease, life span, longevity, microbiology, microbiome,
- MeSH
- dlouhověkost MeSH
- Fundulidae mikrobiologie fyziologie MeSH
- gastrointestinální trakt mikrobiologie MeSH
- stárnutí * MeSH
- střevní mikroflóra * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH