BackgroundThe ischemia-reperfusion injury (IRI) is unavoidable in vascular surgery. Damage to the microcirculation and endothelial glycocalyx might set up a shock with loss of circulatory coherence and organ failure. Sulodexide may help to protect endothelial glycocalyx and alleviate the ischemia-reperfusion injury.MethodsTwenty female piglets underwent surgery with a 30-min-long suprarenal aortic clamp, followed by two hours of reperfusion. Ten piglets received sulodexide before the clamp, and 10 received normal saline. Blood and urine samples were taken at baseline and in 20-min intervals until the 120th minute to analyze the serum syndecan-1, E-selectin, and thrombomodulin. Albumin and glycosaminoglycans were examined in the urine. The kidney biopsies before and after the protocol were examined by light microscopy with hematoxylin-eosin staining. The sublingual microcirculation was recorded by side-stream dark field imaging at the time as blood and urine.ResultsBased on the 2-way ANOVA testing, there was no statistically significant difference in the parameters of sublingual microcirculation. Serum markers of endothelial cell activation and damage (E-selectin and thrombomodulin) did not show any statistically significant difference either. Syndecan-1, a marker of glycocalyx damage, showed statistically significantly higher values based on the 2-way ANOVA testing (p < 0.0001) with the highest difference in the 80th minute: 7.8 (3.9-44) ng/mL in the control group and 1.8 (0.67-2.8) ng/mL in the sulodexide group. In the urine, the albuminuria was higher in the control group, although not statistically significant. Glycosaminoglycans were statistically significantly higher in the sulodexide group based on the mixed-effect analysis due to the intervention itself. Histological analysis of the renal biopsies showed necrosis in both groups after reperfusion.ConclusionAdministering sulodexide significantly reduced the level of endothelial markers of IRI. The study results support further research into using preemptive administration of sulodexide to modulate IRI in clinical medicine.

• MeSH
• E-selektin krev   MeSH
• glykokalyx MeSH
• glykosaminoglykany * farmakologie   terapeutické užití   MeSH
• ledviny patologie   krevní zásobení   MeSH
• mikrocirkulace účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• prasata MeSH
• reperfuzní poškození * prevence a kontrola   MeSH
• syndekan-1 krev   MeSH
• trombomodulin krev   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BackgroundSulodexide is a glycosaminoglycan-based drug prescribed to patients with angiopathy. We performed a pilot study to investigate whether sulodexide positively modulates the endothelial glycocalyx (EG) layer and the microcirculation in a porcine model of EG enzymatic damage. The EG is a sugar-based endothelial lining that is involved in the physiology of the capillary wall and the pathogenesis of many diseases.MethodsEG damage was induced in eight piglets by hyaluronidase III and heparanase I given intravenously. Four animals received sulodexide 600 IU intravenously before the enzymes and four animals after the enzymes were administered. Four animals constituted a control group. Sublingual microcirculation by side-stream dark field imaging and plasmatic concentration of syndecan-1 by ELISA were measured at baseline, 20 min after intervention, and at the 40th, and 60th minute onwards. The statistics were performed with a one-way ANOVA test with Turkey's correction for multiple comparisons testing. Timepoint comparison was performed by Student t-test or Mann-Whitney test.ResultsAt baseline, there were no statistically significant differences between the animal groups. After the intervention, the levels of syndecan-1 were significantly lower in the control group. While there were no differences between the two intervention groups. The sublingual microcirculation analysis showed that the DeBacker score was significantly higher in the control group. At 60 min, there was also a statistically significant difference in DeBacker score between the groups (8.1 ± 1.6 mm-1 in the group with enzymes given first and 11 ± 0.92 mm-1 in the group with sulodexide given first, p = 0.03). The analysis of the proportion of perused vessels did not show any statistically significant differences.ConclusionThe results of the study demonstrated a working model of EG damage but no specific action of sulodexide on EG modulation. In the sublingual microcirculation analysis, the sulodexide reduced the fall in absolute tissue perfusion in 60 min.

• MeSH
• cévní endotel * účinky léků   MeSH
• glykokalyx * účinky léků   metabolismus   MeSH
• glykosaminoglykany * farmakologie   MeSH
• hyaluronoglukosaminidasa MeSH
• mikrocirkulace účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• pilotní projekty MeSH
• prasata MeSH
• syndekan-1 krev   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The process of kidney transplantation remains the optimal treatment for end-stage renal disease, offering improved quality of life and increased survival rates compared to long-term dialysis. However, despite advances in surgical techniques, immunosuppression regimens, and post-operative care, there are still significant challenges in predicting the organ's status and long-term outcomes of transplantation. Among the many factors that influence graft survival, the quality of the donated organ plays a fundamental role. There is an ongoing need for accurate and reliable biomarkers. Syndecan-1 is found in the endothelial glycocalyx and shed at a higher rate into the blood during systemic pathological conditions. The aim of this study is to evaluate the potential of serum syndecan-1 levels as a biomarker for assessing donor kidney quality and to investigate its correlation with donor characteristics and short-term outcomes in kidney recipients. MATERIAL AND METHODS: We investigated serum syndecan-1 levels in 80 deceased donors and correlated them with donor characteristics and short-term outcomes (defined as delayed graft function - defined as the need for dialysis within the first week post-transplantation and renal function at 3 months post-transplantation - assessed using serum creatinine levels) in 104 corresponding kidney recipients. This single-center retrospective observational cohort study was conducted from April to December 2021. RESULTS: The donor pool consisted of 65% males with a median age of 53 years. Of these, 45 donors (56%) were classified as extended criteria donors. Higher syndecan-1 levels correlated with the last creatinine levels before organ procurement (R = 0.32, p = 0.01) and were marginally higher in donors with acute kidney injury (p = 0.07). However, syndecan-1 levels were not associated with short-term outcomes in kidney recipients (renal function at 3 months). CONCLUSIONS: The data suggests syndecan-1 could be a potential biomarker for assessing donor kidney quality, although its implications on recipient outcomes require further study. This pilot investigation underscores the importance of syndecan-1 in evaluating organ quality but highlights the necessity for more extensive research to validate these findings and explore their implications in transplant success.

• MeSH
• biologické markery * krev   MeSH
• chronické selhání ledvin chirurgie   krev   terapie   MeSH
• dárci tkání * MeSH
• dospělí MeSH
• ledviny patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• opožděný nástup funkce štěpu krev   MeSH
• přežívání štěpu MeSH
• retrospektivní studie MeSH
• syndekan-1 * krev   MeSH
• transplantace ledvin * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Coronavirus disease (COVID-19) associated endotheliopathy and microvascular dysfunction are of concern. OBJECTIVE: The objective of the present single-center observational pilot study was to compare endothelial glycocalyx (EG) damage and endotheliopathy in patients with severe COVID-19 (COVID-19 group) with patients with bacterial pneumonia with septic shock (non-COVID group). METHODS: Biomarkers of EG damage (syndecan-1), endothelial cells (EC) damage (thrombomodulin), and activation (P-selectin) were measured in blood on three consecutive days from admission to the intensive care unit (ICU). The sublingual microcirculation was studied by Side-stream Dark Field (SDF) imaging with automatic assessment. RESULTS: We enrolled 13 patients in the non-COVID group (mean age 70 years, 6 women), and 15 in the COVID-19 group (64 years old, 3 women). The plasma concentrations of syndecan-1 were significantly higher in the COVID-19 group during all three days. Differences regarding other biomarkers were not statistically significant. The assessment of the sublingual microcirculation showed improvement on Day 2 in the COVID-19 group. Plasma levels of C-reactive protein (CRP) were significantly higher on the first two days in the COVID-19 group. Plasma syndecan-1 and CRP were higher in patients suffering from severe COVID-19 pneumonia compared to bacterial pneumonia patients. CONCLUSIONS: These findings support the role of EG injury in the microvascular dysfunction in COVID-19 patients who require ICU.

• MeSH
• biologické markery MeSH
• COVID-19 * patologie   MeSH
• endoteliální buňky * patologie   MeSH
• glykokalyx * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• senioři MeSH
• syndekan-1 metabolismus   MeSH
• umělé dýchání MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Objective- The leukocyte heme-enzyme MPO (myeloperoxidase) exerts proinflammatory effects on the vascular system primarily linked to its catalytic properties. Recent studies have shown that MPO, depending on its cationic charge, mediates neutrophil recruitment and activation. Here, we further investigated MPO's extracatalytic properties and its effect on endothelial glycocalyx (EG) integrity. Approach and Results- In vivo staining of murine cremaster muscle vessels with Alcian Blue 8GX provided evidence of an MPO-dependent decrease in anionic charge of the EG. MPO binding to the glycocalyx was further characterized using Chinese hamster ovary cells and its glycosaminoglycan mutants-pgsA-745 (mutant Chinese hamster ovary cells lacking heparan sulfate and chondroitin sulfate glycosaminoglycan) and pgsD-677 (mutant Chinese hamster ovary cells lacking heparan sulfate glycosaminoglycan), which revealed heparan sulfate as the main mediator of MPO binding. Further, EG integrity was assessed in terms of thickness using intravital microscopy of murine cremaster muscle. A significant reduction in EG thickness was observed on infusion of catalytically active MPO, as well as mutant inactive MPO and cationic polymer polylysine. Similar effects were also observed in wild-type mice after a local inflammatory stimulus but not in MPO-knockout mice. The reduction in EG thickness was reversed after removal of vessel-bound MPO, suggesting a possible physical collapse of the EG. Last, experiments with in vivo neutrophil depletion revealed that MPO also induced neutrophil-mediated shedding of the EG core protein, Sdc1 (syndecan-1). Conclusions- These findings provide evidence that MPO, via ionic interaction with heparan sulfate side chains, can cause neutrophil-dependent Sdc1 shedding and collapse of the EG structure.

• MeSH
• aktivace neutrofilů MeSH
• břišní svaly krevní zásobení   MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   metabolismus   patologie   MeSH
• endoteliální buňky účinky léků   metabolismus   patologie   MeSH
• glykokalyx účinky léků   metabolismus   patologie   MeSH
• heparansulfát proteoglykany metabolismus   MeSH
• kationty MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• neutrofily účinky léků   metabolismus   MeSH
• peroxidasa nedostatek   genetika   metabolismus   farmakologie   MeSH
• syndekan-1 metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. METHODS: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. RESULTS: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. CONCLUSION: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.

• MeSH
• DNA virů analýza   MeSH
• dospělí MeSH
• hybridizace in situ MeSH
• infekce papilomavirem komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 izolace a purifikace   MeSH
• nádorové proteiny analýza   fyziologie   MeSH
• nádory hlavy a krku mortalita   virologie   MeSH
• nádory jazyka mortalita   virologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom mortalita   virologie   MeSH
• syndekan-1 analýza   fyziologie   MeSH
• virové receptory fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Glycosaminoglycans have anti-inflammatory properties and interact with a variety of soluble and membrane-bound molecules. Little is known about their effects on B cells and humoral immune responses. We show that CS but not dextran or other glycosaminoglycans induces a pronounced proliferation of B cells in vitro compared with TLR4 or TLR9 ligands. With the use of inhibitors and KO mice, we demonstrate that this proliferation is mediated by the tyrosine kinases BTK and Syk but independent of CD44. Antibodies against Ig-α or Ig-β completely block CS-induced B cell proliferation. Injection of CS in mice for 4-5 days expands B cells in the spleen and results in a marked increase of CD138(+) cells in the spleen that is dependent on BTK but independent of CD4(+) T cells. Long-term treatment with CS for 14 days also increases CD138(+) cells in the bone marrow. When mice were immunized with APC or collagen and treated with CS for up to 14 days during primary or after secondary immune responses, antigen-specific humoral immune responses and antigen-specific CD138(+) plasma cells in the bone marrow were reduced significantly. These data show that CD138(+) cells, induced by treatment with CS, migrate into the bone marrow and may displace other antigen-specific plasma cells. Overall, CS is able to interfere markedly with primary and fully established humoral immune responses in mice.

• MeSH
• aktivace lymfocytů účinky léků   genetika   MeSH
• antigeny CD44 genetika   imunologie   MeSH
• buňky kostní dřeně imunologie   MeSH
• chondroitinsulfáty farmakologie   MeSH
• humorální imunita účinky léků   genetika   MeSH
• intracelulární signální peptidy a proteiny genetika   imunologie   MeSH
• myši inbrední BALB C MeSH
• myši knockoutované MeSH
• myši MeSH
• plazmatické buňky imunologie   MeSH
• pohyb buněk účinky léků   imunologie   MeSH
• proliferace buněk účinky léků   MeSH
• syndekan-1 genetika   imunologie   MeSH
• toll-like receptor 4 genetika   imunologie   MeSH
• toll-like receptor 9 genetika   imunologie   MeSH
• tyrosinkinasy genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers. METHODS: Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNalpha/beta-inducible myxovirus resistance-1 protein (MX-1). RESULTS: BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08). CONCLUSIONS: The expression pattern of receptors for BAFF on B and plasma cells in muscle suggests a local role for BAFF in autoantibody production in muscle tissues of patients with myositis who have anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. BAFF production could be influenced by type-I IFN produced by pDCs. Thus, B-cell-related molecular pathways may participate in the pathogenesis of myositis in this subset of patients.

• MeSH
• antigeny CD19 metabolismus   MeSH
• antinukleární protilátky imunologie   MeSH
• autoprotilátky * imunologie   MeSH
• B-lymfocyty metabolismus   účinky léků   MeSH
• biopsie MeSH
• dospělí MeSH
• faktor aktivující B-buňky biosyntéza   MeSH
• imunohistochemie MeSH
• interferon typ I farmakologie   MeSH
• konfokální mikroskopie MeSH
• lidé středního věku MeSH
• lidé MeSH
• maturační antigen B-buněk * biosyntéza   MeSH
• myozitida * imunologie   metabolismus   patologie   MeSH
• receptor faktoru aktivujícího B-buňky * biosyntéza   MeSH
• receptor TACI * biosyntéza   MeSH
• ribonukleoproteiny imunologie   MeSH
• senioři MeSH
• svaly * metabolismus   patologie   MeSH
• syndekan-1 metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

Multiple myeloma (MM) is an incurable malignant disease of the terminal developmental stage of B-lymphocytes. While genetic heterogeneity of MM is widely described, little is known about its genetic basis as well as primary damage during plasma cells (PC) development. In this study, we focused on genome-wide screening of DNA copy number changes using oligonucleotide-based array-CGH together with I-FISH of the IgH locus rearrangements in pair samples of bone marrow B-cells (CD19+) and CD138+ PC from newly diagnosed MM patients. The IgH disruption was found in 8.9% (4/45) of CD19+ samples and in 57.8% (26/45) of CD138+ samples. The genomic profiling using array-CGH identified copy number alterations (CNAs) in 10% (2/20) of CD19+ samples in regions known to be important for MM pathogenesis. In contrast, we found CNAs in 100% (16/16) of CD138+ samples. Most common chromosomal abnormalities were trisomies of odd-numbered chromosomes (3, 5, 7, 9, 11, 15, 19 and 21), gain 1q, gain Xq and monosomy of chromosome 13. We did not find any correlation between incidence of CNAs in CD19+ and CD138+ cells. In conclusion, effective utilization of FISH and array-CGH can identify genetic lesions in premalignant stages leading to better understanding and characterization of MM.

• MeSH
• antigeny CD19 analýza   MeSH
• buněčný rodokmen * MeSH
• chromozomální aberace * MeSH
• genová dávka * MeSH
• genová přestavba MeSH
• hybridizace in situ fluorescenční * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * genetika   imunologie   MeSH
• podskupiny lymfocytů * imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srovnávací genomová hybridizace * MeSH
• syndekan-1 analýza   MeSH
• těžké řetězce imunoglobulinů genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Multiple myeloma (MM) is a low proliferative tumor of postgerminal center plasma cell (PC). Centrosome amplification (CA) is supposed to be one of the mechanisms leading to chromosomal instability. Also, CA is associated with deregulation of cell cycle, mitosis, DNA repair and proliferation. The aim of our study was to evaluate the prognostic significance and possible role of CA in pathogenesis and analysis of mitotic genes as mitotic disruption markers. DESIGN AND METHODS: A total of 173 patients were evaluated for this study. CD138+ cells were separated by MACS. Immunofluorescent labeling of centrin was used for evaluation of centrosome amplification in PCs. Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) and qRT-PCR were performed on PCs. RESULTS: Based on the immunofluorescent staining results, all patients were divided into two groups: CA positive (38.2%) and CA negative (61.8%). Among the newly diagnosed patients, worse overall survival was indicated in the CA negative group (44/74) in comparison to the CA positive group (30/74) (P = 0.019). Gene expression was significantly down-regulated in the CA positive group in comparison to CA negative in the following genes: AURKB, PLK4, TUBG1 (P < 0.05). Gene expression was significantly down-regulated in newly diagnosed in comparison to relapsed patients in the following genes: AURKA, AURKB, CCNB1, CCNB2, CETN2, HMMR, PLK4, PCNT, and TACC3 (P < 0.05). CONCLUSIONS: Our findings indicate better prognosis for CA positive newly diagnosed patients. Considering revealed clinical and gene expression heterogeneity between CA negative and CA positive patients, there is a possibility to characterize centrosome amplification as a notable event in multiple myeloma pathogenesis.

• MeSH
• centrozom ultrastruktura   MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitóza MeSH
• mnohočetný myelom farmakoterapie   genetika   MeSH
• oprava DNA MeSH
• polymerázová řetězová reakce MeSH
• prognóza MeSH
• proliferace buněk MeSH
• recidiva MeSH
• regulace genové exprese u nádorů * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• separace buněk MeSH
• stanovení celkové genové exprese MeSH
• syndekan-1 metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH