Aim: To find a practical biomonitoring method for researchers exposed to nanoparticles causing oxidative stress. Methods: In a continuation of a study in 2016-2018, biological samples (plasma, urine and exhaled breath condensate [EBC]) were collected in 2019-2020 from 43 researchers (13.8 ± 3.0 years of exposure) and 45 controls. Antioxidant status was assessed using glutathione (GSH) and ferric-reducing antioxidant power, while oxidative stress was measured as thiobarbituric acid reactive substances, all using spectrophotometric methods. Researchers' personal nanoparticle exposure was monitored. Results: Plasma GSH was elevated in researchers both before and after exposure (p < 0.01); postexposure plasma GSH correlated with nanoparticle exposure, and GSH in EBC increased. Conclusion: The results suggest adaptation to chronic exposure to nanoparticles, as monitored by plasma and EBC GSH.
Extracelulární vezikuly (EV) jsou transportní váčky derivované ze zdrojové buňky do extracelulárního prostředí. Představují nový pilíř mezibuněčné komunikace, neboť přenáší nukleové kyseliny, proteiny a různé signální molekuly, které jsou chráněny před degradací v extracelulárním prostředí a posléze jsou uvolněny fúzí vezikuly s cílovou buňkou. Transportní mechanismus je zajištěn povrchovými strukturami účastnícími se buněčné adheze. Je všeobecně známé, že všechny buněčné organismy jsou schopné tvořit EV. Většina lidských buněk je schopna produkovat EV, díky tomu je možná jejich detekce ve všech tělesných kompartmentech. EV při svém objevu byly vnímány jako nepotřebné odpadní váčky a stály na okraji zájmů. Zásluhou nově popsaným mechanismům transportu biologicky aktivních molekul je známo, že se EV účastní celé řady homeostatických mechanismů. V infekčním lékařství je nejvíce studována oblast modulace imunitní odpovědi, kdy jsou vnímány jako potenciální biomarkery, neboť jejich produkce či nesený obsah může být alterován za patologických stavů. U mikrobů stojí v popředí interakce na úrovni patogen-patogen a patogen-hostitel. Další možností je potenciální využití EV jako transportních lékových systémů a nových cílů farmakoterapie.
Extracellular vesicles (EVs) are mother cell derived transport units released into the extracellular environment. They are a new pillar of intercellular communication as they carry nucleic acids, proteins, and other signalling molecules, protecting them from degradation in the extracellular environment until fusion of the vesicle with the target cell. The transport mechanism relies on surface structures involved in cell adhesion. It is well known that all cellular organisms are capable of producing EVs. Most human cells have this capability, and EVs can be detected in all body compartments. At the time of their discovery, EVs were considered as useless waste vesicles of marginal interest. Thanks to the newly described transport mechanisms of biologically active molecules, EVs are currently known to participate in a variety of homeostatic mechanisms. In infectious diseases, the most studied area is the modulation of the immune response, where they are seen as potential biomarkers, as their production or the content they carry can be altered under pathological conditions. For microbes, interactions at the pathogen-pathogen and pathogen-host level are at the forefront of attention. EVs also have potential for use as drug delivery systems and novel targets for pharmacotherapy.
- MeSH
- biologické markery metabolismus MeSH
- exozómy klasifikace mikrobiologie MeSH
- extracelulární vezikuly * fyziologie klasifikace mikrobiologie MeSH
- fyziologie bakterií MeSH
- fyziologie virů MeSH
- mezibuněčná komunikace genetika MeSH
- transportní vezikuly fyziologie klasifikace mikrobiologie MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies.NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.
- MeSH
- biologické markery metabolismus MeSH
- diabetes mellitus 2. typu * metabolismus MeSH
- inzulinová rezistence * MeSH
- lidé MeSH
- morbidní obezita * metabolismus MeSH
- nitrobřišní tuk metabolismus MeSH
- obezita metabolismus MeSH
- podkožní tuk metabolismus MeSH
- proteiny metabolismus MeSH
- proteomika MeSH
- průřezové studie MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Alzheimer's disease (AD) is the most common form of progressively disabling dementia. The chitinases CHI3L1 and CHI3L2 have long been known as biomarkers for microglial and astrocytic activation in neurodegeneration. Here, we collected microarray datasets from the National Center for Biotechnology Information (NCBI) brain samples of non-demented controls (NDC) (n = 460), and of deceased patients with AD (n = 697). The AD patients were stratified according to sex. Comparing the high CHI3L1 and CHI3L2 expression group (75th percentile), and low CHI3L1 and CHI3L2 expression group (25th percentile), we obtained eight signatures according to the sex of patients and performed a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to twelve cell populations. Expression analysis revealed significantly higher CHI3L1 and CHI3L2 expression in AD compared with NDC, and positive correlations of these genes with GFAP and TMEM119. Furthermore, deconvolution analysis revealed that CHI3L1 and CHI3L2 high expression was associated with inflammatory signatures in both sexes. Neuronal activation profiles were significantly activated in AD patients with low CHI3L1 and CHI3L2 expression levels. Furthermore, gene ontology analysis of common genes regulated by the two chitinases unveiled immune response as a main biological process. Finally, microglia NIS significantly correlated with CHI3L2 expression levels and were more than 98% similar to microglia NIS determined by CHI3L1. According to our results, high levels of CHI3L1 and CHI3L2 in the brains of AD patients are associated with inflammatory transcriptomic signatures. The high correlation between CHI3L1 and CHI3L2 suggests strong co-regulation.
- MeSH
- Alzheimerova nemoc * genetika metabolismus MeSH
- biologické markery metabolismus MeSH
- chitinasy * genetika metabolismus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- transkriptom genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- 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
Dysregulated systemic immune responses during infectious spondylodiscitis (IS) may impair microbial clearance and bone resorption. Therefore, the aim of the study was to examine whether circulating regulatory T cells (Tregs) are elevated during IS and whether their frequency is associated with alterations in T cells and the presence of markers of bone resorption in the blood. A total of 19 patients hospitalized with IS were enrolled in this prospective study. Blood specimens were obtained during hospitalization and 6 weeks and 3 months after discharge. Flow cytometric analysis of CD4 and CD8 T cell subsets, the percentage of Tregs and serum levels of collagen type I fragments (S-CrossLap) were performed. Out of 19 enrolled patients with IS, microbial etiology was confirmed in 15 (78.9%) patients. All patients were treated with antibiotics for a median of 42 days, and no therapy failure was observed. Next, a significant serum C-reactive protein (S-CRP) decrease during the follow-up was observed, whereas the frequencies of Tregs remained higher than those of controls at all-time points (p < 0.001). In addition, Tregs demonstrated a weak negative correlation with S-CRP and S-CrossLap levels were within the norm at all-time points. Circulating Tregs were elevated in patients with IS and this elevation persisted even after the completion of antibiotic therapy. Moreover, this elevation was not associated with treatment failure, altered T cells, or increased markers of bone resorption.
- MeSH
- antibakteriální látky terapeutické užití metabolismus MeSH
- biologické markery metabolismus MeSH
- discitida * diagnóza farmakoterapie metabolismus MeSH
- lidé MeSH
- prospektivní studie MeSH
- regulační T-lymfocyty * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term "eosinophils" was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of "LIAR" (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, "sine qua non", for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma.
- MeSH
- alergie * metabolismus MeSH
- biologické markery metabolismus MeSH
- bronchiální astma * farmakoterapie MeSH
- eozinofily metabolismus MeSH
- lidé MeSH
- počet leukocytů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Subjective social status has a known association with health, whereby better health outcomes are observed for those with higher perceived status. In this research, we offer new evidence on the status-health relationship using a rigorous methodological approach that considers both observed and unobserved confounders. METHODS: We use 5 waves of data spanning 15 years from the English Longitudinal Study of Ageing and derive a measure of allostatic load with biomarkers as an objective measure of health. We apply 'within-between' panel regression models. RESULTS: Models reveal the expected association between subjective status and health when comparing participants (the 'between' estimate), but no association when examining temporal variation within participants (the 'within' estimate). When controlling for personality traits including optimism, and parental education, the 'between' association between subjective status and allostatic load is reduced but does not disappear. CONCLUSIONS: Person-level confounders play some role in explaining the observed link between subjective status and health. The exact nature of the link, including the role of psychological pathways and early-life confounders, remains a question for future research.
- MeSH
- alostáza * MeSH
- biologické markery metabolismus MeSH
- lidé MeSH
- longitudinální studie MeSH
- senioři MeSH
- sociální status * MeSH
- stárnutí MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children. A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables. Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (-15.1% change per IQR increase, 95% CI = -23.6, -5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition. Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- lidé MeSH
- metylace DNA MeSH
- oxidační stres MeSH
- pesticidy * analýza MeSH
- pyrethriny * moč MeSH
- vystavení vlivu životního prostředí analýza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Lipidomics as a branch of metabolomics provides unique information on the complex lipid profile in biological materials. In clinically focused studies, hundreds of lipids together with available clinical information proved to be an effective tool in the discovery of biomarkers and understanding of pathobiochemistry. However, despite the introduction of lipidomics nearly twenty years ago, only dozens of big data studies using clinical lipidomics have been published to date. In this review, we discuss the lipidomics workflow, statistical tools, and the challenges of standartisation. The consequent summary divided into major clinical areas of cardiovascular disease, cancer, diabetes mellitus, neurodegenerative and liver diseases is demonstrating the importance of clinical lipidomics. In these publications, the potential of lipidomics for prediction, diagnosis or finding new targets for the treatment of selected diseases can be seen. The first of these results have already been implemented in clinical practice in the field of cardiovascular diseases, while in other areas we can expect the application of the results summarized in this review in the near future.
- MeSH
- big data MeSH
- biologické markery metabolismus MeSH
- lidé MeSH
- lipidomika * MeSH
- metabolismus lipidů MeSH
- metabolomika metody MeSH
- nádory * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
