Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.

• Klíčová slova
• acute cellular rejection, checkpoint inhibitors, immunohistochemistry, luminex, lung transplantation,
• MeSH
• akutní nemoc MeSH
• antigeny CD274 * metabolismus   krev   MeSH
• antigeny CD31 * metabolismus   MeSH
• biologické markery * krev   metabolismus   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• plíce patologie   MeSH
• rejekce štěpu * diagnóza   krev   MeSH
• senioři MeSH
• transplantace plic * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD274 * MeSH
• antigeny CD31 * MeSH
• biologické markery * MeSH
• CD274 protein, human MeSH Prohlížeč
• PECAM1 protein, human MeSH Prohlížeč

Bordetella pertussis infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiation of incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which B. pertussis evades host sentinel phagocytes to achieve proliferation on airway mucosa.IMPORTANCETo establish a productive infection of the nasopharyngeal mucosa and proliferate to sufficiently high numbers that trigger rhinitis and aerosol-mediated transmission, the pertussis agent Bordetella pertussis deploys several immunosuppressive protein toxins that compromise the sentinel functions of mucosa patrolling phagocytes. We show that cAMP signaling elicited by very low concentrations (22 pM) of Bordetella adenylate cyclase toxin downregulates the iron acquisition systems of CD14+ monocytes. The resulting iron deprivation of iron, a key micronutrient, then represents an additional aspect of CyaA toxin action involved in the inhibition of differentiation of monocytes into the enlarged bactericidal macrophage cells. This corroborates the newly discovered paradigm of host defense evasion mechanisms employed by bacterial pathogens, where manipulation of cellular cAMP levels blocks monocyte to macrophage transition and replenishment of exhausted phagocytes, thereby contributing to the formation of a safe niche for pathogen proliferation and dissemination.

• Klíčová slova
• Bordetella pertussis, adenylate cyclase toxin, cyclic AMP, differentiation, iron acquisition, macrophages, monocytes,
• MeSH
• adenylátcyklasový toxin * metabolismus   genetika   MeSH
• AMP cyklický * metabolismus   MeSH
• antigeny CD14 * metabolismus   MeSH
• antigeny diferenciační myelomonocytární MeSH
• Bordetella pertussis * MeSH
• buněčná diferenciace * MeSH
• CD antigeny metabolismus   genetika   MeSH
• lidé MeSH
• monocyty * metabolismus   imunologie   mikrobiologie   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• receptory buněčného povrchu metabolismus   genetika   MeSH
• signální transdukce * MeSH
• upregulace MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenylátcyklasový toxin * MeSH
• AMP cyklický * MeSH
• antigeny CD14 * MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD14 protein, human MeSH Prohlížeč
• CD163 Antigen MeSH
• proteinkinasy závislé na cyklickém AMP MeSH
• receptory buněčného povrchu MeSH
• železo MeSH

Selectins and their ability to interact with specific ligands are a cornerstone in cell communication. Over the last three decades, a considerable wealth of experimental and molecular modeling insights into their structure and modus operandi were gathered. Nonetheless, explaining the role of individual selectin residues on a quantitative level remained elusive, despite its importance in understanding the structure-function relationship in these molecules and designing their inhibitors. This work explores essential interactions of selectin-ligand binding, employing a multiscale approach that combines molecular dynamics, quantum-chemical calculations, and residue interaction network models. Such an approach successfully reproduces most of the experimental findings. It proves to be helpful, with the potential for becoming an established tool for quantitative predictions of residue contribution to the binding of biomolecular complexes. The results empower us to quantify the importance of particular residues and functional groups in the protein-ligand interface and to pinpoint differences in molecular recognition by the three selectins. We show that mutations in the E-, L-, and P-selectins, e.g., different residues in positions 46, 85, 97, and 107, present a crucial difference in how the ligand is engaged. We assess the role of sulfation of tyrosine residues in PSGL-1 and suggest that TyrSO3- in position 51 interacting with Arg85 in P-selectin is a significant factor in the increased affinity of P-selectin to PSGL-1 compared to E- and L-selectins. We propose an original pharmacophore targeting five essential PSGL-binding sites based on the analysis of the selectin···PSGL-1 interactions.

• MeSH
• antigen sialyl-Lewis-X MeSH
• buněčná adheze MeSH
• ligandy MeSH
• P-selektin * metabolismus   MeSH
• selektiny * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen sialyl-Lewis-X MeSH
• ligandy MeSH
• P-selektin * MeSH
• selektiny * MeSH

Sepsis has evolved as an enormous health issue amongst critically ill patients. It is a major risk factor that results in multiple organ failure and shock. Acute kidney injury (AKI) is one of the most frequent complications underlying sepsis, which portends a heavy burden of mortality and morbidity. Thus, the present review is aimed to provide an insight into the recent progression in the molecular mechanisms targeting dysregulated immune response and cellular dysfunction involved in the development of sepsis-associated AKI, accentuating the phytoconstituents as eligible candidates for attenuating the onset and progression of sepsis-associated AKI. The pathogenesis of sepsis-mediated AKI entails a complicated mechanism and is likely to involve a distinct constellation of hemodynamic, inflammatory, and immune mechanisms. Novel biomarkers like neutrophil gelatinase-associated lipocalin, soluble triggering receptor expressed on myeloid cells 1, procalcitonin, alpha-1-microglobulin, and presepsin can help in a more sensitive diagnosis of sepsis-associated AKI. Many bioactive compounds like curcumin, resveratrol, baicalin, quercetin, and polydatin are reported to play an important role in the prevention and management of sepsis-associated AKI by decreasing serum creatinine, blood urea nitrogen, cystatin C, lipid peroxidation, oxidative stress, IL-1β, TNF-α, NF-κB, and increasing the activity of antioxidant enzymes and level of PPARγ. The plant bioactive compounds could be developed into a drug-developing candidate in managing sepsis-mediated acute kidney injury after detailed follow-up studies. Lastly, the gut-kidney axis may be a more promising therapeutic target against the onset of septic AKI, but a deeper understanding of the molecular pathways is still required.

• Klíčová slova
• Acute kidney injury, Biomarkers, Gut-kidney axis, Plant bioactive compounds, Pyroptosis, Sepsis,
• MeSH
• akutní poškození ledvin * farmakoterapie   etiologie   diagnóza   MeSH
• antigeny CD14 metabolismus   MeSH
• biologické markery MeSH
• lidé MeSH
• lipokaliny terapeutické užití   MeSH
• peptidové fragmenty metabolismus   MeSH
• proteiny akutní fáze analýza   metabolismus   terapeutické užití   MeSH
• sepse * komplikace   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antigeny CD14 MeSH
• biologické markery MeSH
• lipokaliny MeSH
• peptidové fragmenty MeSH
• presepsin protein, human MeSH Prohlížeč
• proteiny akutní fáze MeSH

Growing evidence suggests that diabetes mellitus is associated with impairment of the intestinal barrier. However, it is not clear so far if the impairment of the intestinal barrier is a consequence of prolonged hyperglycemia or the consequence of external factors influencing the gut microbiota and intestinal mucosa integrity. Aim of the study was to perform an estimation of relationship between serological markers of impairment of the intestinal barrier: intestinal fatty acid-binding protein (I-FABP), cytokeratin 18 caspase-cleaved fragment (cCK-18), and soluble CD14 (sCD14) and markers of prolonged hyperglycemia, such as the duration of diabetes mellitus and glycated hemoglobin (HbA1c) via a correlation analysis in patients with diabetes mellitus. In 40 adult patients with type 1 diabetes mellitus and 30 adult patients with type 2 diabetes mellitus the estimation has been performed. Statistically significant positive correlation was found between cCK-18 and HbA1c (r=0.5047, p=0.0275) in patients with type 1 diabetes mellitus with fading insulitis (T1D). In patients with type 1 diabetes mellitus with ongoing insulitis (T1D/INS) and in patients with type 2 diabetes mellitus (T2D), no statistically significant positive correlations were found between serological markers of intestinal barrier impairment (I-FABP, cCK-18, sCD14) and duration of diabetes or levels of HbA1c. Similarly, in cumulative cohort of patients with T1D/INS and patients with T1D we revealed statistically positive correlation only between HbA1c and cCK-18 (r=0.3414, p=0.0311). Surprisingly, we found statistically significant negative correlation between the duration of diabetes mellitus and cCK-18 (r=-0.3050, p=0.0313) only in cumulative group of diabetic patients (T1D, T1D/INS, and T2D). Based on our results, we hypothesize that the actual condition of the intestinal barrier in diabetic patients is much more dependent on variable interactions between host genetic factors, gut microbiota, and environmental factors rather than effects of long-standing hyperglycemia (assessed by duration of diabetes mellitus or HbA1c).

• MeSH
• antigeny CD14 MeSH
• biologické markery MeSH
• diabetes mellitus 1. typu * diagnóza   metabolismus   MeSH
• diabetes mellitus 2. typu * diagnóza   MeSH
• dospělí MeSH
• glykovaný hemoglobin analýza   MeSH
• hyperglykemie * MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD14 MeSH
• biologické markery MeSH
• glykovaný hemoglobin MeSH

BACKGROUND: Plaque-induced gingivitis is the most prevalent periodontal disease associated with pathogenic biofilms. The host immune system responds to pathogens through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and their co-receptor cluster of differentiation 14 (CD14). AIM: This study investigated the association between the functional polymorphism in the CD14 gene and the dental plaque microbiota in children with gingivitis. DESIGN: A total of 590 unrelated children (307 with plaque-induced gingivitis and 283 controls, aged 13-15 years) were enrolled in this case-control study. Dental plaque was processed using a ParoCheck® 20 detection kit. The CD14 -260C/T (rs2569190) polymorphism was determined with the PCR-RFLP method. RESULTS: Gingivitis was detected in 64.2% of boys and 35.8% of girls (P < .001). Children with gingivitis had a significantly higher occurrence of dental caries (P < .001). No significant differences in the CD14 -260C/T allele and genotype distribution among individuals with or without gingivitis in the whole cohort were found. Children with gingivitis and P gingivalis, however, were significantly more frequent carriers of the CT and TT genotypes than children with gingivitis without P gingivalis or healthy controls (P < .05). CONCLUSIONS: The CD14 -260C/T polymorphism acts in cooperation with P gingivalis to trigger plaque-induced gingivitis in Czech children.

• Klíčová slova
• CD14, bacteria, gingivitis, polymorphism,
• MeSH
• antigeny CD14 * MeSH
• dítě MeSH
• gingivitida * genetika   MeSH
• lidé MeSH
• mladiství MeSH
• polymorfismus genetický MeSH
• Porphyromonas gingivalis MeSH
• studie případů a kontrol MeSH
• zubní kaz * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD14 * MeSH
• CD14 protein, human MeSH Prohlížeč

PURPOSE OF THE STUDY The aim of the study was to determine miR-146a-5p, miR-223-3p and miR-23a-3p by an enzyme immunoassay in patients with inflammatory and non-inflammatory joint effusion and to verify the usefulness of these miRNAs as biomarkers of joint inflammation. MATERIAL AND METHODS Synovial fluid (SF) samples were collected from 82 patients. The group consisted of 60 non-inflammatory, 11 inflammatory-non-pyogenic, 11 inflammatory-pyogenic SF. SF miRNA was isolated by RNA Isolation Kit Plasma/Serum. The concentrations of miRNA were determined by enzyme-linked immunosorbent assays (ELISA), C-reactive protein, interleukin-6 and procalcitonin on automatic analyser, presepsin on POCT system, interleukin-1 and human neutrofil defensins 1-3 by ELISA. RESULTS A statistically significant negative correlation was found between miR-146-5p and miR-223-3p, WBC, IL-1β, IL-6 and CRP (P < 0.05) in all groups; a statistically significant positive correlation was found between miR-223-3p and miR-23a-3p, WBC, PMN, IL-1beta, IL-6 and HNP1-3, as well as a positive correlation of miR-23a-3p with IL-1β, IL-6 and HNP1-3. A statistically significant difference was found between miR-146a-5p, miR-223-3p and miR-23a-3p and individual SF groups, P = 0.006, P < 0.001, respectively. PMN, WBC, Il-1β, IL-6, HNP 1-3 predicted the inflammatory processes with excellent diagnostic power (AUC > 0.9). The clinical relevance expressed by effect size was the strongest in miR-223-3p, PMN, IL-1 , HNP 1-3 between non-inflammatory and inflammatory-pyogenic group. CONCLUSIONS Our study quantified the SF miRNA by ELISA. We have shown that miR-146a-5p, miR-223-3p and miR-23a-3p can be an important group of biomarkers for the detection and monitoring of various pathophysiological conditions in synovial fluid, including inflammatory conditions. Key words: miRNA, synovial fluid, inflammatory joint disease, enzyme-linked immunosorbent assay.

• MeSH
• antigeny CD14 MeSH
• biologické markery MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• peptidové fragmenty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD14 MeSH
• biologické markery MeSH
• mikro RNA * MeSH
• peptidové fragmenty MeSH
• presepsin protein, human MeSH Prohlížeč

AIMS: The study aims were to verify the serum (S) and synovial fluid (SF) reference intervals (RIs) for human neutrophil defensins (HNP1-3); measure S and SF defensin concentrations in different types of SF, including non-inflammatory, inflammatory non-pyogenic, inflammatory pyogenic, and hemorrhagic; and to compare the HNP1-3 concentrations in SF and S with those of other inflammatory biomarkers. METHODS: SF and S samples were collected from 92 patients. HNP1-3 concentrations were determined using enzyme-linked immunosorbent assays; glucose, lactate, interleukin-6, and procalcitonin using an automatic analyzer; and presepsin using a Pathfast system. There were 61 non-inflammatory, 11 inflammatory non-pyogenic, 11 inflammatory pyogenic, and 9 hemorrhagic SF. Non-inflammatory SF was divided into non-inflammatory normal and non-inflammatory osteoarthritis. The former was used to estimate the HNP1-3 RI in SF and S. RESULTS: The estimated HNP1-3 RIs of SF and S were 12.47-437.42 mg/L and 5.45-44.75 µg/L, respectively. HNP1-3 differed significantly between S and SF and individual groups of SF (P<0.001 and P=0.001, respectively). There were significant relationships between SF HNP1-3 and S HNP1-3 (P<0.001), S C-reactive protein (P<0.001), and S interleukin-6 (P=0.007), and between SF HNP1-3 and SF C-reactive protein (P=0.004) and SF interleukin-6 (P<0.001). The highest kappa coefficient was between SF HNP1-3 and SF interleukin-6 (κ=0.507). CONCLUSIONS: We validated the SF HNP1-3 diagnostic kit and demonstrated that SF and S HNP1-3 are promising biomarkers for distinguishing inflammatory from non-inflammatory joint diseases.

• Klíčová slova
• alpha-defensins, enzyme-linked immunosorbent assay, inflammatory joint disease, synovial fluid,
• MeSH
• alfa-defensiny * MeSH
• antigeny CD14 MeSH
• biologické markery MeSH
• C-reaktivní protein MeSH
• ELISA * MeSH
• interleukin-6 MeSH
• lidé MeSH
• peptidové fragmenty MeSH
• synoviální tekutina MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-defensiny * MeSH
• antigeny CD14 MeSH
• biologické markery MeSH
• C-reaktivní protein MeSH
• interleukin-6 MeSH
• peptidové fragmenty MeSH
• presepsin protein, human MeSH Prohlížeč

This investigation studied the effect of concentrated growth factor and nanofat on aging skin of nude mice induced by D-galactose. BALB/c mice were randomly divided into five groups: 5 mice in the control group were fed normally without any intervention, 9 mice were treated with concentrated growth factor (CGF), 9 mice were treated with nanofat (NF), 9 mice were treated with CGF+NF, and 9 mice in the model group (no treatment after subcutaneous injection of D-galactose). Relevant indicators are measured and recorded. In skin and serum, SOD and GSH content in the model group were significantly lower than those in other groups (P<0.05), and the MDA of the three treatment groups was significantly lower than that of the model group (P<0.05). Compared with the control group, the contents of total collagen, type I collagen and type III collagen in the NF group and model group were decreased in different degrees (P<0.05); the contents of elastin and elastic fiber in the skin of nude mice in the model group and NF group were significantly decreased. Compared with the model group, he number of CD31 and VEGF in the treatment group was significantly increased (P<0.01); the skin AGE content of three treatment groups was significantly lower (P<0.05). These findings suggest that concentrated growth factor and nanofat may have a significant effect on delaying aging skin induced by D-galactose in nude mice.

• MeSH
• antigeny CD31 metabolismus   MeSH
• elastin metabolismus   MeSH
• galaktosa farmakologie   MeSH
• glutathion metabolismus   MeSH
• kolagen metabolismus   MeSH
• mezibuněčné signální peptidy a proteiny farmakologie   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• stárnutí kůže účinky léků   MeSH
• superoxiddismutasa metabolismus   MeSH
• tuková tkáň transplantace   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD31 MeSH
• elastin MeSH
• galaktosa MeSH
• glutathion MeSH
• kolagen MeSH
• mezibuněčné signální peptidy a proteiny MeSH
• superoxiddismutasa MeSH
• vaskulární endoteliální růstový faktor A MeSH

AIMS: The aim of the study was to analyse the prognostic and predictive value of LC3A positive' 'Stone Like Structures'' (SLSs) in a large cohort of patients with non-small cell lung carcinoma (NSCLC) and to check its relationship with tumor infiltrating lymphocytes (TILs) and PD-L1 expression. METHODS: Tissue microarrays from 1015 patients diagnosed at the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland, were stained for LC3A, PD-L1, CD3 and CD68 using automated tissue stainer Ventana Benchmark Ultra (Roche). TILs were assessed in matched haematoxylin and eosin stained slides. RESULTS: LC3A positive SLSs, were significantly associated with worse overall (OS) and disease-free survival (DFS) outcomes in patients with lung adenocarcinoma (LADC) (HR = 2.4, 95 %CI(.994-1.008, p = 0.029) and HR = 3.9, 95 %CI (1.002-1.014), p = 0.002 respectively), whilst it was associated with better OS and DFS in patients with lung squamous cell carcinoma (LUSC), with marginal significance (HR = .99, 95 %CI(.975-1.011),p = 0.042 and HR = .99, 95 %CI (.975-1.008), p = 0.026). Multivariate analysis showed that LC3A SLSs are independent poor prognostic factor only in patients with LADC. In addition, LC3A SLSs, were negatively associated with CD68 count in LADC, whilst there was a positive correlation in LSCC. CONCLUSIONS: LC3A SLSs are differentially associated with the survival outcomes and CD68 count in LADC and LSCC. Further studies are justified for the understanding the underlying biological mechanisms of this phenomenon.

• Klíčová slova
• LC3A, Lung adenocarcinoma, Lung squamous cell carcinoma, Prognosis, Stone like structures,
• MeSH
• adenokarcinom plic * MeSH
• antigeny CD274 MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• lidé MeSH
• makrofágy * MeSH
• nádory plic * MeSH
• prognóza MeSH
• proteiny asociované s mikrotubuly MeSH
• spinocelulární karcinom * MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Švýcarsko MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD68 antigen, human MeSH Prohlížeč
• MAP1LC3A protein, human MeSH Prohlížeč
• proteiny asociované s mikrotubuly MeSH