The study aimed to contribute to understanding the role of CRP, chemerin, fetuin-A and osteopontin and to assess their suitability as biomarkers of early stages of cardiovascular diseases in psoriasis vulgaris. Serum levels measured in 28 patients and 22 controls. Patients: increased levels of CRP (p<0.001), chemerin (p<0.05), osteopontin (p<0.05) and decreased levels of fetuin-A (p<0.05), significant relationships between CRP and fetuin-A (rho=0.530, p<0.01), CRP and chemerin (rho=0.543, p<0.01), CRP and age (rho=0.590, p<0.001), osteopontin and fetuin-A (r=-0.415, p<0.05), chemerin and PASI score (rho=-0.424, p<0.05). We confirmed specific roles of the biomarkers in psoriasis. CRP, fetuin-A and osteopontin could be considered appropriate markers for the detection of early stages of cardiovascular diseases.

• MeSH
• biologické markery MeSH
• C-reaktivní protein analýza   MeSH
• chemokiny krev   MeSH
• dospělí MeSH
• fetuin A analýza   MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteopontin krev   MeSH
• psoriáza komplikace   MeSH
• rizikové faktory kardiovaskulárních chorob * MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Ateroskleróza je charakterizovaná perzistujúcim zápalom cievnej steny a je považovaná za hlavnú príčinu napomáhajúcu rozvoju kardiovaskulárnych ochorení, ktoré sú celosvetovo vedúcou príčinou úmrtí. Z dôvodu rozšírenia aterosklerózy a jej komplikácií sa zvyšuje potreba včasnej a pokiaľ je to možné neinvazívnej diagnostiky, aby sa predišlo vzniku fatálnych alebo invalidizujúcich komplikácií aterosklerózy. Na detekciu aterosklerotických plátov sa využívajú zobrazovacie metódy aj klinické vyšetrenia, ktoré zachytávajú až pláty hemodynamicky významné. Lepšia prevencia aterosklerózy si žiada vyhľadávanie vysokorizikových jedincov vo včasných štádiách. Zápal sa prejavuje počas celého priebehu aterogenézy, teda aj v štádiu subklinickej aterosklerózy, kedy je možné stanoviť koncentráciu zápalových biomarkerov v krvi. Biomarkery sú predmetom záujmu pre jednoduchosť stanovenia v plazme či sére a možnosť ich využitia na diagnostické, prognostické aj terapeutické účely. Pozitívne korelácie s aterosklerózou a jej komplikáciami boli dokázané u biomarkerov asociovaných s metabolizmom kostí ako fibro­blastový rastový faktor 23, osteokalcín, osteoglycín, osteopontín či osteoprotegerín.

Atherosclerosis is characterized by persistent inflammation of the vascular wall and is considered to be a major cause contributing to the development of cardiovascular disease, which is the leading cause of death worldwide. Due to the prevalence of atherosclerosis and its complications, the need for early and, if possible, non-invasive dia­gnosis is increasing in order to prevent the development of fatal or disabling complications of atherosclerosis. Ima­ging methods as well as clinical examina­tions are used for the detection of atherosclerotic plaques, which capture up to hemodynamically significant plaques. Better prevention of atherosclerosis requires the search for high-risk indivi­duals in early stages. Inflammation manifests itself throughout the course of atherogenesis, i.e. also in the stage of subclinical atherosclerosis, when it is possible to determine the concentration of inflammatory biomarkers in the blood. Biomarkers are of interest for the simplicity of determination in plasma or serum and the possibility of their use for diagnostic, prognostic and therapeutic purposes. Positive correlations with atherosclerosis and its complications have been demonstrated in biomarkers associated with bone meta­bolism such as fibroblast growth factor 23, osteocalcin, osteoglycin, osteopontin or osteoprotegerin.

• Klíčová slova
• osteoglycin,
• MeSH
• ateroskleróza * diagnóza   patofyziologie   MeSH
• biologické markery MeSH
• fibroblastový růstový faktor 2 analýza   MeSH
• lidé MeSH
• osteokalcin analýza   MeSH
• osteopontin analýza   MeSH
• osteoporóza * diagnóza   patofyziologie   MeSH
• osteoprotegerin analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: The diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) relies on flow cytometric demonstration of loss of glycosyl-phosphatidyl inositol (GPI)-anchored proteins from red blood cells (RBC) and white blood cells (WBC). High-sensitivity multiparameter assays have been developed to detect loss of GPI-linked structures on PNH neutrophils and monocytes. High-sensitivity assays to detect PNH phenotypes in RBCs have also been developed that rely on the loss of GPI-linked CD59 on CD235a-gated mature RBCs. The latter is used to delineate PNH Type III (total loss of CD59) and PNH Type II RBCs (partial loss of CD59) from normal (Type I) RBCs. However, it is often very difficult to delineate these subsets, especially in patients with large PNH clones who continue to receive RBC transfusions, even while on eculizumab therapy. METHODS: We have added allophycocyanin (APC)-conjugated CD71 to the existing CD235aFITC/CD59PE RBC assay allowing simultaneous delineation and quantification of PNH Type III and Type II immature RBCs (iRBCs). RESULTS: We analyzed 24 medium to large-clone PNH samples (>10% PNH WBC clone size) for PNH Neutrophil, PNH Monocyte, Type III and Type II PNH iRBCs, and where possible, Type III and Type II PNH RBCs. The ability to delineate PNH Type III, Type II, and Type I iRBCs was more objective compared to that in mature RBCs. Additionally, total PNH iRBC clone sizes were very similar to PNH WBC clone sizes. CONCLUSIONS: Addition of CD71 significantly improves the ability to analyze PNH clone sizes in the RBC lineage, regardless of patient hemolytic and/or transfusion status.

• MeSH
• antigeny CD59 metabolismus   MeSH
• buněčná diferenciace MeSH
• CD antigeny krev   fyziologie   MeSH
• diferenciální diagnóza MeSH
• erytrocyty metabolismus   patologie   MeSH
• glykoforin metabolismus   MeSH
• imunofenotypizace přístrojové vybavení   metody   normy   MeSH
• kohortové studie MeSH
• leukocyty patologie   MeSH
• lidé MeSH
• monocyty metabolismus   patologie   MeSH
• neutrofily metabolismus   patologie   MeSH
• paroxysmální hemoglobinurie krev   klasifikace   diagnóza   patologie   MeSH
• počet leukocytů přístrojové vybavení   metody   MeSH
• průtoková cytometrie přístrojové vybavení   metody   normy   MeSH
• receptory transferinu krev   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as both an intracellular protein and soluble excreted cytokine, regulating tissue remodeling and immune-infiltrate in adipose tissue the heart and the kidney. In contrast, the increased expression of OPN has been correlated with the severity of the cardiovascular and renal outcomes associated with obesity. Indeed, OPN expression is at the "cross roads" of visceral fat extension, cardiovascular diseases (CVDs) and renal disorders, in which OPN orchestrates the molecular interactions, leading to chronic low-grade inflammation. The common factor associated with OPN overexpression in adipose, cardiac and renal tissues seems attributable to the concomitant increase in visceral fat size and the increase in infiltrated OPN+ macrophages. This review underlines the current knowledge on the molecular interactions between obesity and the cardiac-renal disorders ruled by OPN.

• MeSH
• inzulinová rezistence genetika   MeSH
• ledviny metabolismus   patologie   MeSH
• lidé MeSH
• myokard metabolismus   patologie   MeSH
• nemoci ledvin genetika   metabolismus   patologie   MeSH
• nemoci srdce genetika   metabolismus   patologie   MeSH
• nitrobřišní tuk metabolismus   MeSH
• obezita genetika   metabolismus   patologie   MeSH
• osteopontin genetika   metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zánět genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Elevated levels of the extracellular matrix glycoprotein osteopontin (OPN) may be detected in both myocardium and plasma under various pathological conditions affecting the heart. Several studies demonstrated increased plasma OPN levels in patients with heart failure due to dilated cardiomyopathy (DCM), while other studies showed high OPN expression levels in the myocardium of such patients. However, very little is known about OPN levels in both plasma and myocardium of the same individual with DCM. Therefore, we aimed to compare plasma OPN levels and levels of myocardial OPN expression in patients with recent-onset DCM (Ro-DCM). METHODS: We examined plasma OPN as well as creatinine, C‐reactive protein (CRP), brain natriuretic peptide (BNP), and troponin I levels in 25 patients with Ro-DCM. Furthermore, all subjects underwent transthoracic echocardiography, selective coronary angiography, and endomyocardial biopsy (EMB) for the assessment of myocardial OPN expression. RESULTS: No significant correlation between myocardial OPN expression and clinical, biochemical, or echocardiographic parameters was found. In log transformation analysis, plasma OPN levels correlated significantly with BNP levels (r = 0.46, p = 0.031), with CRP levels (r = 0.52, p = 0.015), and with early diastolic mitral annular velocity (r = -0.57, p = 0.009). There was a borderline association between the plasma OPN log value and New York Heart Association class (p = 0.053). CONCLUSION: Plasma OPN levels reflect heart failure severity in patients with Ro-DCM. Myocardial OPN expression is not associated with either plasma OPN levels or markers of heart failure in these individuals.

• MeSH
• dilatační kardiomyopatie * diagnóza   MeSH
• krevní plazma MeSH
• lidé MeSH
• myokard MeSH
• osteopontin MeSH
• srdeční selhání * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts' differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

• MeSH
• buněčná diferenciace genetika   MeSH
• buněčné linie MeSH
• extracelulární matrix metabolismus   MeSH
• kokultivační techniky MeSH
• kyselá fosfatasa rezistentní k tartarátu metabolismus   MeSH
• messenger RNA genetika   MeSH
• mikro RNA genetika   metabolismus   MeSH
• myši MeSH
• osteoblasty metabolismus   MeSH
• osteogeneze genetika   MeSH
• osteoklasty metabolismus   MeSH
• osteopontin genetika   metabolismus   MeSH
• parakrinní signalizace genetika   MeSH
• protein PEBP2alfaA genetika   metabolismus   MeSH
• resorpce kosti metabolismus   MeSH
• signální transdukce genetika   MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Signal enhancements of up to two orders of magnitude in protein NMR can be achieved by employing HDO as a vector to introduce hyperpolarization into folded or intrinsically disordered proteins. In this approach, hyperpolarized HDO produced by dissolution-dynamic nuclear polarization (D-DNP) is mixed with a protein solution waiting in a high-field NMR spectrometer, whereupon amide proton exchange and nuclear Overhauser effects (NOE) transfer hyperpolarization to the protein and enable acquisition of a signal-enhanced high-resolution spectrum. To date, the use of this strategy has been limited to 1D and 1H-15N 2D correlation experiments. Here we introduce 2D 13C-detected D-DNP, to reduce exchange-induced broadening and other relaxation penalties that can adversely affect proton-detected D-DNP experiments. We also introduce hyperpolarized 3D spectroscopy, opening the possibility of D-DNP studies of larger proteins and IDPs, where assignment and residue-specific investigation may be impeded by spectral crowding. The signal enhancements obtained depend in particular on the rates of chemical and magnetic exchange of the observed residues, thus resulting in non-uniform 'hyperpolarization-selective' signal enhancements. The resulting spectral sparsity, however, makes it possible to resolve and monitor individual amino acids in IDPs of over 200 residues at acquisition times of just over a minute. We apply the proposed experiments to two model systems: the compactly folded protein ubiquitin, and the intrinsically disordered protein (IDP) osteopontin (OPN).

• MeSH
• lidé MeSH
• nukleární magnetická rezonance biomolekulární * MeSH
• osteopontin chemie   MeSH
• ubikvitin chemie   MeSH
• vnitřně neuspořádané proteiny chemie   MeSH
• voda chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cirrhosis is a primary cause of liver-related mortality and morbidity. The basic process driving chronic liver disease to cirrhosis is accelerated fibrogenesis. Although the pathogenesis of liver cirrhosis is a multifactorial process, the essential step in the evolution of liver fibrosis is the activation of hepatic stellate cells, which are the main source of collagen produced in the extracellular matrix. This activation process is mediated by multiple growth factors, cytokines, and chemokines. One of the hepatic stellate cell-activating signaling molecules (and also one associated with cell injury and fibrosis) is osteopontin (OPN). OPN concentration in the plasma has been found to be predictive of liver fibrosis in various liver diseases. OPN concentrations correlate significantly with the stage of fibrosis, liver insufficiency, portal hypertension, and the presence of hepatocellular cancer. However, due to its versatile signaling functions, OPN not only contributes to the development of liver cirrhosis, but is also implicated in the pathogenesis of other chronic hepatic diseases such as viral hepatitis, both alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and hepatocellular cancer. Thus, the targeting of OPN pathways seems to be a promising approach in the treatment of chronic liver diseases.

• MeSH
• biologické markery MeSH
• hepatocelulární karcinom MeSH
• jaterní cirhóza metabolismus   MeSH
• jaterní hvězdicovité buňky metabolismus   MeSH
• jaterní insuficience metabolismus   MeSH
• lékové postižení jater metabolismus   MeSH
• lidé MeSH
• nádory jater metabolismus   MeSH
• nealkoholová steatóza jater metabolismus   MeSH
• nemoci jater metabolismus   MeSH
• osteopontin metabolismus   MeSH
• portální hypertenze metabolismus   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Osteopontin (OPN) is an extracellular matrix glycoprotein that plays a role in a variety of cellular activities associated with inflammatory and fibrotic responses. Increased OPN levels in myocardium and plasma have been demonstrated in patients with dilated cardiomyopathy (DCM). However, nothing is known about OPN levels in patients with hypertrophic cardiomyopathy (HCM). Therefore, the aim of our study was to compare plasma OPN levels in patients with these two most common cardiomyopathies. PATIENTS AND METHODS: We examined plasma OPN as well as creatinine, C‐reactive protein (CRP), brain-type natriuretic peptide (BNP), and troponin I levels in 64 patients with DCM, 43 patients with HCM, and 75 control subjects. Transthoracic echocardiography was also performed on all cardiomyopathy patients. RESULTS: Plasma OPN levels were significantly elevated in patients with DCM compared with HCM patients (95 ± 43 vs. 57 ± 21 ng/ml; p < 0.001) and control subjects (54 ± 19 ng/ml; p < 0.001); however, there was no difference between HCM patients and control subjects. New York Heart Association (NYHA) class III or IV disease was more frequently present in DCM patients than in HCM subjects (44 % vs. 2 %, p < 0.0001). In multivariate analysis, BNP and CRP levels together with NYHA class were found to be significant predictors of plasma OPN levels in DCM patients (p = 0.002, p = 0.029, and p < 0.001 for BNP, CRP, and NYHA, respectively). CONCLUSION: Plasma OPN levels were associated with overall heart failure severity rather than with specific cardiomyopathy subtype in patients suffering from DCM or HCM, respectively.

• MeSH
• dilatační kardiomyopatie * krev   MeSH
• hypertrofická kardiomyopatie * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myokard MeSH
• natriuretický peptid typu B MeSH
• osteopontin * krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

To gain a better understanding of the progression of progenitor cells in the odontoblast lineage, we have examined and characterized the expression of a series of GFP reporters during odontoblast differentiation. However, previously reported GFP reporters (pOBCol2.3-GFP, pOBCol3.6-GFP, and DMP1-GFP), similar to the endogenous proteins, are also expressed by bone-forming cells, which made it difficult to delineate the two cell types in various in vivo and in vitro studies. To overcome these difficulties we generated DSPP-Cerulean/DMP1-Cherry transgenic mice using a bacterial recombination strategy with the mouse BAC clone RP24-258g7. We have analyzed the temporal and spatial expression of both transgenes in tooth and bone in vivo and in vitro. This transgenic animal enabled us to visualize the interactions between odontoblasts and surrounding tissues including dental pulp, ameloblasts and cementoblasts. Our studies showed that DMP1-Cherry, similar to Dmp1, was expressed in functional and fully differentiated odontoblasts as well as osteoblasts, osteocytes and cementoblasts. Expression of DSPP-Cerulean transgene was limited to functional and fully differentiated odontoblasts and correlated with the expression of Dspp. This transgenic animal can help in the identification and isolation of odontoblasts at later stages of differentiation and help in better understanding of developmental disorders in dentin and odontoblasts.

• MeSH
• buněčná diferenciace MeSH
• extracelulární matrix - proteiny genetika   MeSH
• fluorescenční barviva MeSH
• fosfoproteiny genetika   MeSH
• myši transgenní MeSH
• myši MeSH
• odontoblasty cytologie   MeSH
• reportérové geny * MeSH
• sialoglykoproteiny genetika   MeSH
• transgeny MeSH
• zelené fluorescenční proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH