Kontext: Procento nezralých granulocytů (immature granulocytes, iG%) je časným markerem zánětu s prognostickou hodnotou u řady onemocnění. Cíl: V této studii jsme se pokusili zjistit, zda má procento nezralých granulocytů prognostickou hodnotu z hlediska 28denní mortality pacientů s akutním koronárním syndromem (AKS). Metoda: Jednalo se o retrospektivní studii provedenou v období mezi 1. lednem 2019 a 30. červnem 2019 na Klinice urgentní medicíny lékařské fakulty univerzity v tureckém Mersinu. Do studie byli zařazeni všichni pacienti ve věku nad 18 let, kteří byli dopraveni na kliniku urgentní medicíny s bolestí na hrudi a hospitalizováni s předběžnou diagnózou AKS. Pacienti byli rozděleni do dvou skupin, na ty, kteří přežili, a ty, kteří nepřežili. Byly zaznamenány hodnoty iG% a dalších laboratorních parametrů a následně byl analyzován vztah mezi hodnotami iG% a 28denní mortalitou. Kromě toho byla pro srovnání diagnostické přesnosti hodnot iG% a dalších proměnných provedena analýza roc. Výsledky: Do studie bylo zařazeno celkem 617 pacientů, z tohoto počtu bylo 423 (68,6 %) mužů. Průměrný věk pacientů dosahoval 63,9 ± 12,7 roku. hodnota iG% byla vyšší u nepřeživších pacientů (1,2 ± 1,4) než u přeživších (0,5 ± 0,5 ) (p = 0,007). V predikci 28denní mortality, pokud byla mezní hodnota iG% > 0,6, byla zjištěna specificita ve výši 93,70 % a senzitivita 54,55 % (Auc = 0,717; p = 0,000). V predikci 28denní mortality na AKS představovalo iG% nezávislý rizikový faktor (poměr rizik [hazard ratio, hr] 632,962; 95% interval spolehlivosti 3,389–118 206,572; p = 0,016). Závěr: u pacientů s AKS může hodnota iG% souviset s 28denní mortalitou.
Background: The percentage of immature granulocytes (IG%) is an early marker of inflammation and has a prognostic significance in many diseases. Objective: In this study, we tried to investigate whether the percentage of immature granulocytes has a prognostic value in 28-day mortality in patients with acute coronary syndrome (ACS). Method: This study was carried out retrospectively between 1.1.2019 and 30.6.2019 at Mersin University Faculty of Medicine, Department of Emergency Medicine. Patients older than 18 years who applied to the emergency department with chest pain and were hospitalized with a preliminary diagnosis of ACS were included in the study. The patients were divided into two groups as survivors and non-survivors. IG% and other laboratory parameters were recorded. The relationship between IG% and 28-day mortality was analyzed. In addition, ROC analysis was performed to compare the diagnostic accuracy of IG% and other variables. Results: A total of 617 patients, including 423 (68.6%) men, were included in the study. The mean age of the patients were 63.9 ± 12.7. IG% was higher in non-survivor patients (1.2 ± 1.4) than in surviving patients (0.5 ± 0.5) (p = 0.007). In predicting 28-day mortality, when the cut-off value for IG% was >0.6, the specifi- city was found to be 93.70% and the sensitivity to be 54.55% (AUC = 0.717, p = 0.000). In predicting 28-day mortality for ACS, IG% was an independent risk factor (hazard ratio [HR] 632.962, 95% confidence interval 3.389-118206.572, p = 0.016). Conclusion: IG% may be associated with a 28-day mortality in patients with ACS.
- MeSH
- akutní koronární syndrom * krev mortalita MeSH
- biologické markery MeSH
- granulocyty * patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- ROC křivka MeSH
- senioři MeSH
- statistika jako téma MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
The molecular basis of increased hemoglobin in Andean Aymara highlanders is unknown. We conducted an integrative analysis of whole-genome-sequencing and granulocytes transcriptomics from Aymara and Europeans in Bolivia to explore genetic basis of the Aymara high hemoglobin. Differentially expressed and spliced genes in Aymaras were associated with inflammatory and hypoxia-related pathways. We identified transcripts with 4th or 5th exon skipping of NFKB1 (AS-NFKB1), key part of NF-kB complex, and their splicing quantitative trait loci; these were increased in Aymaras. AS-NFKB1 transcripts correlated with both transcripts and protein levels of inflammatory and HIF-regulated genes, including hemoglobin. While overexpression of the AS-NFKB1 variant led to increased expression of inflammatory and HIF-targeted genes; under inflammatory stress, NF-kB protein translocation to the nucleus was attenuated, resulting in reduced expression of these genes. Our study reveals AS-NFKB1 splicing events correlating with increased hemoglobin in Aymara and their possible protective mechanisms against excessive inflammation.
- MeSH
- alternativní sestřih * genetika MeSH
- dospělí MeSH
- exony genetika MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa genetika metabolismus MeSH
- granulocyty metabolismus MeSH
- hemoglobiny * metabolismus genetika MeSH
- lidé MeSH
- lokus kvantitativního znaku MeSH
- NF-kappa B - podjednotka p50 * metabolismus genetika MeSH
- regulace genové exprese MeSH
- transkriptom MeSH
- zánět * genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Bolívie MeSH
The knowledge about the contribution of the innate immune system to health and disease is expanding. However, to obtain reliable results, it is critical to select appropriate mouse models for in vivo studies. Data on genetic and phenotypic changes associated with different mouse strains can assist in this task. Such data can also facilitate our understanding of how specific polymorphisms and genetic alterations affect gene function, phenotypes, and disease outcomes. Extensive information is available on genetic changes in all major mouse strains. However, comparatively little is known about their impact on immune response and, in particular, on innate immunity. Here, we analyzed a mouse model of chronic multifocal osteomyelitis, an autoinflammatory disease driven exclusively by the innate immune system, which is caused by an inactivating mutation in the Pstpip2 gene. We investigated how the genetic background of BALB/c, C57BL/6J, and C57BL/6NCrl strains alters the molecular mechanisms controlling disease progression. While all mice developed the disease, symptoms were significantly milder in BALB/c and partially also in C57BL/6J when compared to C57BL/6NCrl. Disease severity correlated with the number of infiltrating neutrophils and monocytes and with the production of chemokines attracting these cells to the site of inflammation. It also correlated with increased expression of genes associated with autoinflammation, rheumatoid arthritis, neutrophil activation, and degranulation, resulting in altered neutrophil activation in vivo. Together, our data demonstrate striking effects of genetic background on multiple parameters of neutrophil function and activity influencing the onset and course of chronic multifocal osteomyelitis.
- MeSH
- adaptorové proteiny signální transdukční genetika MeSH
- aktivace neutrofilů genetika MeSH
- cytoskeletální proteiny MeSH
- genetické pozadí * MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neutrofily * imunologie patologie MeSH
- osteomyelitida * genetika imunologie patologie MeSH
- přirozená imunita genetika MeSH
- stupeň závažnosti nemoci MeSH
- zánět genetika patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Background and Objectives: Initial diagnosis of brest cancer (BC) is important for fate and prognosis of the diseases profile, we sought to identify the correlation between Midkine (MK) as a new biomarker with cancer antigen (CA)15-3, liver function test, renal function test, blood cells parameters in individuals with invasive ductal carcinoma.Methods: The serum MK and CA15-3 of all subjects were measured by the ELISA technique, Liver enzymes were measured by colourimetric methods and neutrophils, and lymphocytes were measured by an Electrical Impedance Cell Counting method (automated machine).Results: The results of the correlation among serum MK and other parameters in invasive ductal carcinoma of the breast showed a considerable positive correlation among MK and CA15-3 and measured white blood cells. Moreover, there were a weak correlation with Aspartate Aminotransferase (AST) and RBC, while there is no correlation between serum MK and other liver enzymes or blood parameters. Conclusion: The study results of the correlation between serum MK and other parameters in colorectal carcinoma patients show a significant positive correlation of MK with CA15-3 markers in invasive ductal carcinoma of the breast.
- MeSH
- duktální karcinom prsu krev MeSH
- ELISA metody MeSH
- jaterní testy MeSH
- klinická studie jako téma metody MeSH
- lidé MeSH
- lymfocyty metabolismus MeSH
- midkin * analýza krev MeSH
- nádorové biomarkery * krev MeSH
- nádory prsu * diagnóza krev MeSH
- neutrofily metabolismus MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- lidé MeSH
Common variable immunodeficiency disorder (CVID) is the most common form of primary antibody immunodeficiency. Due to low antibody levels, CVID patients receive intravenous or subcutaneous immunoglobulin replacement therapy as treatment. CVID is associated with the chronic activation of granulocytes, including an increased percentage of low-density neutrophils (LDNs). In this study, we examined changes in the percentage of LDNs and the expression of their surface markers in 25 patients with CVID and 27 healthy donors (HD) after in vitro stimulation of whole blood using IVIg. An oxidative burst assay was used to assess the functionality of LDNs. CVID patients had increased both relative and absolute LDN counts with a higher proportion of mLDNs compared to iLDNs, distinguished based on the expression of CD10 and CD16. Immature LDNs in the CVID and HD groups had significantly reduced oxidative burst capacity compared to mature LDNs. Interestingly we observed reduced oxidative burst capacity, reduced expression of CD10 after stimulation of WB, and higher expression of PD-L1 in mature LDNs in CVID patients compared to HD cells. Our data indicate that that the functional characteristics of LDNs are closely linked to their developmental stage. The observed reduction in oxidative burst capacity in mLDNs in CVID patients could contribute to an increased susceptibility to recurrent bacterial infections among CVID patients.
- MeSH
- běžná variabilní imunodeficience * MeSH
- fenotyp MeSH
- lidé MeSH
- neutrofily * MeSH
- průtoková cytometrie MeSH
- respirační vzplanutí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Calcineurin-nuclear factor of activated T cells (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression, but besides their required T cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitor-treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens; however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described. Thus, we tested the response of human neutrophils to opportunistic fungal pathogens, namely Candida albicans and Aspergillus fumigatus, in the presence of CN-NFAT inhibitors. Here, we report that the NFAT pathway members were expressed in neutrophils and mediated part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes with subsequent production of effector molecules. Importantly, genes and proteins involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2, CCL3, and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils.
- MeSH
- Aspergillus fumigatus imunologie MeSH
- Candida albicans imunologie MeSH
- chemotaxe MeSH
- kalcineurin * metabolismus MeSH
- lidé MeSH
- mykózy imunologie MeSH
- neutrofily * imunologie metabolismus MeSH
- signální transdukce * MeSH
- transkripční faktory NFATC * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Helicobacter pylori colonizes the human gastric mucosa of more than half of the human population and has a unique lipopolysaccharide (LPS) structure. LPS is the most dominant and suitable pathogen-associated molecular pattern that is detected via pattern recognition receptors. Although the priming effect of H. pylori LPS on reactive oxygen species (ROS) production of PMNs is lower than that of Escherichia coli O111:B4 LPS, LPS released from H. pylori associated with antibiotics eradication therapy may activate PMNs and increase ROS production. In addition, we describe the effects of H. pylori and E. coli O111:B4 LPSs on gene expression and the anti-inflammatory effect of lansoprazole (LPZ) in human polymorphonuclear leukocytes. LPS isolated from H. pylori and E. coli O111:B4 alters toll-like receptor 2 (TLR) and TLR4 expressions similarly. However, LPS from E. coli O111:B4 and H. pylori caused a 1.8-fold and 1.5-fold increase, respectively, in CD14 expression. All LPS subtypes upregulated TNFα and IL6 expression in a concentration-dependent manner. Although E. coli O111:B4 LPS upregulated IL8R mRNA levels, H. pylori LPS did not (≦ 100 ng/mL). Gene expression levels of ITGAM demonstrated no significant change on using both LPSs. These different effects on the gene expression in PMNs may depend on variations in LPS structural modifications related to the acquired immunomodulatory properties of H. pylori LPS. Proton pump inhibitors, i.e., LPZ, are used in combination with antibiotics for the eradication therapy of H. pylori. LPZ and its acid-activated sulphenamide form AG-2000 suppress ROS production of PMNs in a dose-dependent manner. These results suggest that LPZ combination with antibiotics for H. pylori eradication reduces gastric inflammation by suppressing ROS release from PMNs.
- MeSH
- cytokiny metabolismus genetika MeSH
- Escherichia coli účinky léků genetika MeSH
- Helicobacter pylori * účinky léků genetika MeSH
- inhibitory protonové pumpy * farmakologie chemie MeSH
- lanzoprazol * farmakologie chemie MeSH
- lidé MeSH
- lipopolysacharidy * metabolismus farmakologie MeSH
- neutrofily * účinky léků imunologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- toll-like receptor 4 metabolismus genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Tuberculosis (TB) remains one of the top 10 causes of death worldwide and still poses a serious challenge to public health. Recent attention to neutrophils has uncovered unexplored areas demanding further investigation. Therefore, the aim of this study was to determine neutrophil activation and circulatory neutrophil extracellular trap (NET) formation in various types of TB. Sera from TB patients (n = 91) and healthy controls (NHD; n = 38) were analyzed for NE-DNA and MPO-DNA complexes, cell-free DNA (cfDNA), and protease activity (elastase). We show that these NET parameters were increased in TB sera. Importantly, NET formation and NE activity were elevated in TB patients with extensive tissue damage when compared to those with minor damage and in patients with relapse, compared to new cases. We discuss the importance of balancing NET formation to prevent tissue damage or even relapse and argue to analyze circulating NET parameters to monitor the risk of disease relapse. To investigate the tissues for NETs and to find the source of the circulating NET degradation products, we collected sections of granulomas in lung and lymph node biopsies. Samples from other diseases with granulomas, including sarcoidosis (SARC) and apical periodontitis (AP), served as controls. Whereas NET formation characterizes the caseating granulomas, both caseating and non-caseating granulomas harbor DNA with unusual conformation. As TB is associated with hypercoagulation and thromboembolism, we further imaged the pulmonary vessels of TB patients and detected vascular occlusions with neutrophil aggregates. This highlights the dual role of neutrophils in the pathology of TB.
- MeSH
- aktivace neutrofilů MeSH
- dospělí MeSH
- extracelulární pasti * metabolismus MeSH
- granulom * patologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutrofily * metabolismus MeSH
- studie případů a kontrol MeSH
- tuberkulóza patologie krev MeSH
- volné cirkulující nukleové kyseliny krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Chronická obstrukční plicní nemoc (CHOPN) je definována jako heterogenní onemocnění manifestující se respiračními příznaky. Podkladem jsou abnormality dýchacích cest a alveolů, které progredují a vedou k ireverzibilní obstrukční ventilační poruše. Léčba vychází z nové klasifikace CHOPN dle Globální iniciativy pro CHOPN 2023 (GOLD), kde jsou rozhodujícími kritérii symptomy onemocnění a exacerbace. Klíčovou léčbou jsou bronchodilatační léky v monoterapii, duální kombinaci či trojkombinaci. Kombinační bron- chodilatační léčba na základě rozdílných mechanismů zlepšuje stupeň dilatace bronchiálního stromu. Jedná se o kombinaci dlouhodobě působících β2-agonistů (LABA), dlouhodobě působících antagonistů muskarinových receptorů (LAMA) a případně inhalačního kortikosteroidu (IKS). Zařazení IKS směřuje především k snížení rizika a počtu exacerbací CHOPN.1 Trendem je kombinační léčba v jednom inhalačním systému, která zajišťuje lepší compliance pacien ta a i snazší inhalační techniku. Terapii je vhodné individualizovat podle konkrétních nálezů s cílem redukovat riziko exacerbací a zlepšit příznaky onemocnění s dopadem na zlepšení kvality života.
Chronic obstructive pulmonary disease (COPD) is defined as a heterogeneous disease manifesting with respiratory symptoms. Underlying abnormalities of the airways and alveoli progress and lead to irreversible obstructive ventilatory failure. Treatment is based on the new Global Initiative for COPD 2023 (GOLD) classification of COPD, where disease symptoms and exacerbations are the critical criteria. The key treatment is bronchodilators in monotherapy, dual combination or triple combination. Combination bronchodilator therapy improves the degree of bronchial tree dilatation based on different mechanisms. It is a combination of long-acting β2-agonists (LABAs), long- acting muscarinic receptor antagonists (LAMAs) and possibly an inhaled corticosteroid (ICS). The inclusion of ICS is primarily aimed at reducing the risk and number of COPD exacerbations. 1 The trend is towards combination therapy in a single inhalation system, which provides better patient compliance as well as easier inhalation technique. Therapy should be individualized according to specific findings in order to reduce the risk of exacerbations and improve disease symptoms with an impact on quality of life.
- MeSH
- agonisté beta-2-adrenergních receptorů farmakologie terapeutické užití MeSH
- antagonisté muskarinových receptorů farmakologie terapeutické užití MeSH
- aplikace inhalační MeSH
- bronchodilatancia farmakologie terapeutické užití MeSH
- chronická obstrukční plicní nemoc * diagnóza farmakoterapie klasifikace patofyziologie MeSH
- eozinofily účinky léků MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- kombinovaná farmakoterapie * MeSH
- lidé MeSH
- progrese nemoci MeSH
- respirační funkční testy metody MeSH
- rizikové faktory MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
- MeSH
- biologická terapie MeSH
- biopsie MeSH
- bronchiální astma * diagnóza farmakoterapie MeSH
- bronchoskopie MeSH
- eozinofily * fyziologie účinky léků MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- respirační funkční testy MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
