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

Současná hypertenze, diabetes mellitus a obezita patří v nynější klinické praxi k nejčastějším přidruženým onemocněním. Zásadní význam má vyšetření rozvoje hypertrofie levé komory (LVH) u výše uvedených komplikovaných komorbidních pacientů. Souvislost poměru neutrofilů a lymfocytů (NLR) s rozvojem LVH není dostatečně prozkoumána. Cílem práce bylo studovat roli NLR při vzniku hypertrofie levé komory u hypertoniků zatížených diabetem 2. typu a obezitou. Materiál a metoda: Do studie bylo zařazeno 297 hypertoniků s diabetes mellitus 2. typu a obezitou. Byly vytvořeny dvě skupiny: první skupina – LVH, n = 153, s hypertrofií levé komory a druhá skupina, n = 144, bez přítomnosti LVH. Výpočet hmotnosti LK použil modifikovaný Devereuxův vzorec, kde hodnoty přesahující 95 g/m2 (ženy) a 115 g/m2 (muži) byly indikativní pro LVH. Analýza dat byla provedena pomocí statistického softwaru MedCalc verze 20.111. K prozkoumání rizikových faktorů pro LVH byla použita logistická regresní analýza. Výsledky: NLR byl významně zvýšen ve skupině LVH 3,21 ± 1,33 vs 2,65 ± 1,19, p = 0,0002 a trvání esenciální hypertenze bylo také významně delší ve skupině LVH 17,87 ± 7,23 roku vs. 15,35 ± 6,41 roku, p = 0,0017. Procento cirkadiánního rytmu krevního tlaku „non-dipperů“ bylo významně vyšší ve skupině LVH 53 (34,64 %) oproti 31 (22,92 %), p = 0,0263. Zvýšené hodnoty NLR byly spojeny s vyšším rizikem LVH s poměrem šancí (OR) 1,570, 95% interval spolehlivosti (CI) = 1,080–2,911, p = 0,019. Multivariační logistická analýza odhalila, že NLR spolu s délkou trvání hypertenze jsou nadále významnými prediktory rozvoje LVH u jedinců s EH, DM a obezitou OR ‒ 1,299; 95% CI: 1,009–2,105; p = 0,037 a OR – 1,089; CI: 1,019–3,539; p = 0,043. Závěr: Výsledky studie zjistily vliv poměru neutrofilů a lymfocytů na progresi hypertrofie levé komory u jedinců s esenciální hypertenzí spojenou s diabetem a obezitou. Lze navrhnout, že NLR by se mohl objevit jako nový indikátor LVH ve stratifikaci rizika esenciální hypertenze. Identifikace NLR u hypertoniků s diabetem a obezitou by mohla být nápomocná v efektivnější léčbě těchto pacientů.

The patients with concurrent hypertension, diabetes mellitus (DM), and obesity are among the most common associated conditions in contemporary clinical practice. It is of crucial importance to investigate the development of left ventricular hypertrophy (LVH) in above mentioned complicated comorbid patients. The association of neutrophil-to-lymphocyte ratio (NLR) with the development of LVH is not researched enough. The aim of the work was to study the role of NLR in the development of LVH in hypertensive patients burdened with type 2 diabetes and obesity. Methods: 297 hypertensive patients with diabetes mellitus type 2 and obesity were enrolled into the study. Two groups were created: the first group - LVH, n = 153, with left ventricular hypertrophy and the second one, n = 144, without the presence of LVH. The calculation of LV mass employed the modified Devereux formula, where values exceeding 95 g/m2 (females) and 115 g/m2 (males) were indicative of LVH. Data analysis was conducted using MedCalc version 20.111 statistical software. Logistic regression analysis was utilized to explore the risk factors for LVH. Results: The NLR was significantly elevated in LVH group 3.21±1.33 vs 2.65±1.19, p = 0.0002, and duration of essential hypertension (EH) was also significantly longer in LVH group 17.87±7.23 years vs 15.35±6.41 years, p = 0.0017. The percentage of “non-dippers” blood pressure circadian rhythm was significantly higher in LVH group 53 (34.64%) vs 31 (22.92%), p = 0.0263. The increased NLR levels were associated with higher risk of LVH with odds ratio (OR) 1.570, 95% confidence interval (CI) = 1.080–2.911, p = 0.019. The multivariate logistic analysis revealed that NLR together with duration of hypertension continued to be substantial predictors of LVH development in individuals with EH, DM, and obesity OR ‒ 1.299; 95% CI: 1.009–2.105; p = 0.037 and OR – 1.089; CI: 1.019–3.539; p = 0.043, respectively. Conclusion: The study findings affirm the impact of the neutrophil-to-lymphocyte ratio on the progression of left ventricular hypertrophy in individuals with essential hypertension associated with diabetes and obesity. It can be suggested that NLR could emerge as a novel indicator for LVH in essential hypertension risk stratification. Identification of NLR in hypertensive patients with diabetes and obesity could be helpful in more effective management of these patients.

• Klíčová slova
• Poměr neutrofilů k lymfocytům,
• MeSH
• hodnocení rizik * MeSH
• hypertenze komplikace   MeSH
• hypertrofie levé komory srdeční * etiologie   prevence a kontrola   MeSH
• komorbidita MeSH
• komplikace diabetu MeSH
• lidé MeSH
• lymfocyty MeSH
• neutrofily MeSH
• obezita komplikace   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• Check Tag
• lidé MeSH

• MeSH
• lidé MeSH
• lymfocyty * MeSH
• nemoci štítné žlázy MeSH
• neutrofily * MeSH
• počet lymfocytů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• úvodníky MeSH

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils.

• MeSH
• imunoterapie * metody   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory * imunologie   terapie   metabolismus   patologie   MeSH
• neutrofily * imunologie   metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We present two cases from the neonatal department with cerebrospinal fluid examination. We revealed a striking discrepancy in polymorphonuclear (PMN) and mononuclear (MN) cell counts using conventional light microscopy in comparison with automated analyzer Sysmex XN-1000 (PMNs - 13 vs. 173x106/L, MNs - 200 vs. 67x106/L in case 1 and PMNs - 13 vs. 372x106/L, MNs - 411 vs. 179x106/L in case 2). We revealed the dominant presence of hemosiderophages in both cases in cytospin slide. Even though Sysmex XN-1000 offers fast examination with a low sample volume, there is possibility of misdiagnosis, with negative impact on the patient.

• MeSH
• leukocyty mononukleární patologie   cytologie   MeSH
• lidé MeSH
• mikroskopie * metody   MeSH
• mozkomíšní mok cytologie   MeSH
• neutrofily cytologie   patologie   MeSH
• novorozenec MeSH
• počet leukocytů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• srovnávací studie MeSH

INTRODUCTION: The immune systems of both the mother and the newborn face significant challenges during birth. Proper immune regulation after birth is essential for the survival of neonates. Numerous studies have demonstrated that the neonatal immune system is relatively immature, particularly in its adaptive arm, placing the primary responsibility for immune surveillance on innate immunity. METHODS: Given the significant role of neutrophils in protecting the neonate after birth, we conducted a study investigating the properties of neutrophils in newborn cord blood using various methodological approaches. RESULTS: Our findings demonstrate the presence of immature low-density neutrophils in the cord blood, which are likely responsible for the observed elevated expression of genes coding for proteins essential to antimicrobial response, including myeloperoxidase, neutrophils elastase, and defensins. DISCUSSION: We propose that these cells function normally and support the protection of newborns early after birth. Furthermore, our results suggest that the mode of delivery might significantly influence the programming of neutrophil function. The presented findings emphasize the importance of distinct neutrophil subpopulations in neonatal immunity and their potential impact on early postnatal health.

• MeSH
• antiinfekční látky * metabolismus   MeSH
• fetální krev MeSH
• lidé MeSH
• neutrofily * MeSH
• novorozenec MeSH
• přirozená imunita MeSH
• proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH