Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.

• MeSH
• ankylózující spondylitida krev   diagnóza   imunologie   MeSH
• axiální spondyloartritida krev   diagnóza   MeSH
• biologické markery * krev   MeSH
• C-reaktivní protein analýza   metabolismus   MeSH
• HLA-B27 antigen genetika   imunologie   MeSH
• idiopatické střevní záněty * krev   imunologie   diagnóza   komplikace   MeSH
• leukocytární L1-antigenní komplex krev   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.

• MeSH
• adjuvancia imunologická MeSH
• aplikace intranazální MeSH
• chitosan * chemie   MeSH
• glykoproteiny MeSH
• imunizace MeSH
• imunoglobulin A MeSH
• Muromegalovirus * MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• slizniční imunita MeSH
• vakcíny * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Obesity and its related severe comorbidities are increasing rapidly. The duodenal-jejunal bypass is an endoscopically implanted device (mimicking the Roux-en-Y gastric bypass) developed to support weight reduction and improve type 2 diabetes control. MATERIALS AND METHODS: Retrospective data analysis of consecutive patients undergoing duodenal-jejunal bypass (EndoBarrier®, DJB) implantation between 2013 and 2017 was performed to evaluate safety as well as short- and long-term efficacy. RESULTS: One hundred and twenty-one patients (mean BMI of 43.1 ± 7.2 kg/m2 and weight of 138.2 ± 28.6 kg) underwent DJB implantation. The mean dwelling time was 15.5 months, the mean total body weight loss (%TBWL) after explantation was 10.3% ± 7.9% (14.2 kg, p < 0.0001), and the mean BMI was 39.5 ± 7.3 kg/m2 (p < 0.0001). There was no significant weight gain 24 months after the explantation. Seventy-seven patients had type 2 diabetes mellitus (T2DM) with a mean HbA1c before implantation of 5.6% (n = 52). The mean HbA1c after explantation was 5.1% (p = 0.0001). Significant reductions in transaminase and lipid levels before and after explantation were observed. One complication occurred during implantation and another during explantation. In 16 patients, the device had to be extracted earlier than expected (7 for severe adverse events and 9 for adverse events; 13.2%). CONCLUSION: Despite an evident rate of adverse events, the DJB shows promise as a weight-loss procedure. Our results show that some patients implanted with the device maintained reduced weight even 24 months after explantation, while many improved T2DM control.

• MeSH
• diabetes mellitus 2. typu * chirurgie   komplikace   MeSH
• duodenum chirurgie   MeSH
• glykovaný hemoglobin MeSH
• hmotnostní úbytek MeSH
• jejunum chirurgie   MeSH
• lidé MeSH
• morbidní obezita * chirurgie   MeSH
• obezita chirurgie   komplikace   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• žaludeční bypass * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cyanobacterial harmful blooms (CyanoHABs) pose a global ecological problem, and their lipopolysaccharides (LPS) are among the bioactive compounds they release. Previous studies on CyanoHAB-LPS from single cyanobacterial species have shown varying bioactivities in different in vitro cell models. In this study, we isolated LPS from 19 CyanoHAB samples collected at 18 water bodies in the Czech Republic over two consecutive seasons. The proportions of cyanobacteria, Gram-negative bacteria (G-), and other bacteria in the biomass were determined by qPCR, while the cyanobacterial genera were identified using light microscopy. In vitro models of keratinocytes (HaCaT), the intestinal epithelium (co-culture of differentiated Caco-2 cells and peripheral blood mononuclear cells - PBMC), and PBMC alone were treated with isolated LPS at concentrations of 50, 100, and 1 μg/ml, respectively. The endotoxin activities of these concentrations were within the range measured in the aquatic environment. Approximately 85-90% of the samples displayed biological activity. However, the potency of individual LPS effects and response patterns varied across the different in vitro models. Furthermore, the observed activities did not exhibit a clear correlation with the taxonomic composition of the phytoplankton community, the relative share of microbial groups in the biomass, endotoxin activity of the LPS, or LPS migration and staining pattern in SDS-PAGE. These findings suggest that the effects of CyanoHAB-LPS depend on the specific composition and abundance of various LPS structures within the complex environmental sample and their interactions with cellular receptors.

• MeSH
• biomasa MeSH
• Caco-2 buňky MeSH
• leukocyty mononukleární MeSH
• lidé MeSH
• lipopolysacharidy * toxicita   MeSH
• sinice * MeSH
• škodlivý vodní květ MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Dalbavancin is increasingly being used for long-term treatment of subacute and chronic staphylococcal infections. In this study, a new Bayesian model was implemented and validated using MwPharm software for accurately forecasting the duration of pharmacodynamic target attainment above the efficacy thresholds of 4.02 mg/L or 8.04 mg/L against staphylococci. Forecasting accuracy improved substantially with the a posteriori approach compared with the a priori approach, particularly when two measured concentrations were used. This strategy may help clinicians to estimate the duration of optimal exposure with dalbavancin in the context of long-term treatment.

• MeSH
• antibakteriální látky * terapeutické užití   farmakologie   MeSH
• Bayesova věta MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• stafylokokové infekce * farmakoterapie   MeSH
• Staphylococcus MeSH
• teikoplanin terapeutické užití   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are major causes of hospital-acquired infections and sepsis. Due to increasing antibiotic resistance, new treatments are needed. Mesenchymal stem cells (MSCs) have antimicrobial effects, which can be enhanced by preconditioning with antibiotics. This study investigated using antibiotics to strengthen MSCs against MRSA and P. aeruginosa. MSCs were preconditioned with linezolid, vancomycin, meropenem, or cephalosporin. Optimal antibiotic concentrations were determined by assessing MSC survival. Antimicrobial effects were measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antimicrobial peptide (AMP) gene expression. Optimal antibiotic concentrations for preconditioning MSCs without reducing viability were 1 μg/mL for linezolid, meropenem, and cephalosporin and 2 μg/mL for vancomycin. In MIC assays, MSCs preconditioned with linezolid, vancomycin, meropenem, or cephalosporin inhibited MRSA or P. aeruginosa growth at lower concentrations than non-preconditioned MSCs (p ≤ 0.001). In MBC assays, preconditioned MSCs showed enhanced bacterial clearance compared to non-preconditioned MSCs, especially when linezolid and vancomycin were used against MRSA (p ≤ 0.05). Preconditioned MSCs showed increased expression of genes encoding the antimicrobial peptide genes hepcidin and LL-37 compared to non-preconditioned MSCs. The highest hepcidin expression was seen with linezolid and vancomycin preconditioning (p ≤ 0.001). The highest LL-37 expression was with linezolid preconditioning (p ≤ 0.001). MSCs' preconditioning with linezolid, vancomycin, meropenem, or cephalosporin at optimal concentrations enhances their antimicrobial effects against MRSA and P. aeruginosa without compromising viability. This suggests preconditioned MSCs could be an effective adjuvant treatment for antibiotic-resistant infections. The mechanism may involve upregulation of AMP genes.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• antimikrobiální peptidy MeSH
• cefalosporiny farmakologie   MeSH
• hepcidiny farmakologie   terapeutické užití   MeSH
• lidé MeSH
• linezolid farmakologie   terapeutické užití   MeSH
• meropenem farmakologie   terapeutické užití   MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• mezenchymální kmenové buňky * MeSH
• mikrobiální testy citlivosti MeSH
• Pseudomonas aeruginosa genetika   MeSH
• stafylokokové infekce * mikrobiologie   MeSH
• vankomycin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases = 27, ncontrols = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases = 29, ncontrols = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.

• MeSH
• antigen CA-125 MeSH
• časná detekce nádoru metody   MeSH
• lidé MeSH
• metylace DNA * MeSH
• nádorové biomarkery genetika   MeSH
• nádory vaječníků * diagnóza   genetika   MeSH
• prospektivní studie MeSH
• studie případů a kontrol MeSH
• transkripční faktory Krüppel-like genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Physiology-based pharmacokinetic modeling suggests that rifabutin can out-balance P-glycoprotein (P-gp) induction by concurrent P-gp inhibition. However, clinical or experimental evidence for this Janus-faced rifabutin effect is missing. Consequently, LS180 cells were exposed to a moderately (2 μM) and strongly (10 μM) P-gp-inducing concentration of rifampicin or rifabutin for 6 days. Cellular accumulation of the fluorescent P-gp substrate rhodamine 123 was evaluated using flow cytometry, either without (induction only) or with adding rifamycin drug to the cells during the rhodamine 123 efflux phase (induction + potential inhibition). Rhodamine 123 accumulation was decreased similarly by both drugs after 6-day exposure (2 μM: 55% residual fluorescence compared to non-induced cells, P < 0.01; 10 μM: 30% residual fluorescence compared to non-induced cells, P < 0.001), indicating P-gp induction. Rhodamine 123 influx transporters mRNA expressions were not affected, excluding off-target effects. Acute re-exposure to rifabutin, however, considerably re-increased rhodamine 123 accumulation (2 μM induction: re-increase by 55%, P < 0.01; 10 μM induction: 49% re-increase, P < 0.001), suggesting P-gp inhibition. In contrast, rifampicin only had weak effects (2 μM induction: no re-increase; 10 μM induction: 16% re-increase; P < 0.05). Molecular docking analysis eventually revealed that rifabutin has a higher binding affinity to the inhibitor binding site of P-gp than rifampicin (ΔG (kcal/mol) = -11.5 vs -5.3). Together, this study demonstrates that rifabutin can at least partly mask P-gp induction by P-gp inhibition, mediated by high affinity binding to the inhibitory site of P-gp.

• MeSH
• P-glykoprotein metabolismus   MeSH
• rhodamin 123 metabolismus   MeSH
• rifabutin * farmakologie   MeSH
• rifampin * farmakologie   MeSH
• simulace molekulového dockingu MeSH
• Publikační typ
• časopisecké články MeSH

Despite the adenoids are regularly removed in patients with mucopolysaccharidoses (MPS), the underlying tissue and cellular pathologies remain understudied. We characterized an (immuno)histopathologic and ultrastructural phenotype dominated by lysosomal storage changes in a specific subset of adenotonsillar paracortical cells in 8 MPS patients (3 MPS I, 3 MPS II, and 2 MPS IIIA). These abnormal cells were effectively detected by an antibody targeting the lysosomal membrane tetraspanin CD63. Important, CD63+ storage vacuoles in these cells lacked the monocytes/macrophages lysosomal marker CD68. Such a distinct patterning of CD63 and CD68 was not present in a patient with infantile neurovisceral variant of acid sphingomyelinase deficiency. The CD63+ storage pathology was absent in two MPS I patients who either received enzyme-replacement therapy or underwent hematopoietic stem cells transplantation prior the adenoidectomy. Our study demonstrates novel features of lysosomal storage patterning and suggests diagnostic utility of CD63 detection in adenotonsillar lymphoid tissue of MPS patients.

• MeSH
• antigeny CD63 MeSH
• enzymová substituční terapie MeSH
• lidé MeSH
• lymfoidní tkáň patologie   MeSH
• lyzozomy MeSH
• mukopolysacharidózy * diagnóza   farmakoterapie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

AIM: To compare open-source AndroidAPS (AAPS) and commercially available Control-IQ (CIQ) automated insulin delivery (AID) systems in a prospective, open-label, single-arm clinical trial. METHODS: Adults with type 1 diabetes who had been using AAPS by their own decision entered the first 3-month AAPS phase then were switched to CIQ for 3 months. The results of this treatment were compared with those after the 3-month AAPS phase. The primary endpoint was the change in time in range (% TIR; 70-80 mg/dL). RESULTS: Twenty-five people with diabetes (mean age 34.32 ± 11.07 years; HbA1c 6.4% ± 3%) participated in this study. CIQ was comparable with AAPS in achieving TIR (85.72% ± 7.64% vs. 84.24% ± 8.46%; P = .12). Similarly, there were no differences in percentage time above range (> 180 and > 250 mg/dL), mean sensor glucose (130.3 ± 13.9 vs. 128.3 ± 16.9 mg/dL; P = .21) or HbA1c (6.3% ± 2.1% vs. 6.4% ± 3.1%; P = .59). Percentage time below range (< 70 and < 54 mg/dL) was significantly lower using CIQ than AAPS. Even although participants were mostly satisfied with CIQ (63.6% mostly agreed, 9.1% strongly agreed), they did not plan to switch to CIQ. CONCLUSIONS: The CODIAC study is the first prospective study investigating the switch between open-source and commercially available AID systems. CIQ and AAPS were comparable in achieving TIR. However, hypoglycaemia was significantly lower with CIQ.

• MeSH
• diabetes mellitus 1. typu * farmakoterapie   MeSH
• dospělí MeSH
• glykovaný hemoglobin MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• inzulinové infuzní systémy MeSH
• inzuliny * MeSH
• krevní glukóza MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• prospektivní studie MeSH
• selfmonitoring glykemie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH