• MeSH
• cystatin C analýza   krev   MeSH
• diabetes mellitus MeSH
• diabetická retinopatie diagnóza   MeSH
• diabetické nefropatie diagnóza   MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace * MeSH
• kohortové studie MeSH
• komplikace diabetu * diagnóza   MeSH
• kreatinin analýza   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• komentáře MeSH
• souhrny MeSH

• Klíčová slova
• tirzepatid,
• MeSH
• cystatin C analýza   MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• hodnoty glomerulární filtrace * účinky léků   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor pro glukagonu podobný peptid 2 terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• souhrny MeSH

Tick saliva injected into the vertebrate host contains bioactive anti-proteolytic proteins from the cystatin family; however, the molecular basis of their unusual biochemical and physiological properties, distinct from those of host homologs, is unknown. Here, we present Ricistatin, a novel secreted cystatin identified in the salivary gland transcriptome of Ixodes ricinus ticks. Recombinant Ricistatin inhibited host-derived cysteine cathepsins and preferentially targeted endopeptidases, while having only limited impact on proteolysis driven by exopeptidases. Determination of the crystal structure of Ricistatin in complex with a cysteine cathepsin together with characterization of structural determinants in the Ricistatin binding site explained its restricted specificity. Furthermore, Ricistatin was potently immunosuppressive and anti-inflammatory, reducing levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α and nitric oxide in macrophages; IL-2 and IL-9 levels in Th9 cells; and OVA antigen-induced CD4+ T cell proliferation and neutrophil migration. This work highlights the immunotherapeutic potential of Ricistatin and, for the first time, provides structural insights into the unique narrow selectivity of tick salivary cystatins determining their bioactivity.

• MeSH
• cystatiny * farmakologie   MeSH
• cystein metabolismus   MeSH
• endopeptidasy metabolismus   MeSH
• kathepsiny metabolismus   MeSH
• klíště * chemie   MeSH
• obratlovci MeSH
• proteasy metabolismus   MeSH
• slinné cystatiny chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Saccharides form one of the major constituents of biological macromolecules in living organisms. Many biological processes including protein folding, stability, immune response and receptor activation are regulated by glycosylation. In this work, we optimized a capillary electrophoresis method with capacitively coupled contactless conductivity detection for the separation of eight monosaccharides commonly found in glycoproteins, namely D-glucose, D-galactose, D-mannose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-fucose, N-acetylneuraminic acid, and D-xylose. A highly alkaline solution of 50 mM sodium hydroxide, 22.5 mM disodium phosphate, and 0.2 mM CTAB (pH 12.4) was used as a background electrolyte in a 10 μm id capillary. To achieve baseline separation of all analytes, a counter-directional pressure of -270 kPa was applied during the separation. The limits of detection of our method were below 7 μg/ml (i.e., 1.5 pg or 1 mg/g protein) and the limits of quantification were below 22 μg/ml (i.e., 5 pg or 3 mg/g protein). As a proof of concept of our methodology, we performed an analysis of monosaccharides released from fetuin glycoprotein by acid hydrolysis. The results show that, when combined with an appropriate pre-concentration technique, the developed method can be used as a monosaccharide profiling tool in glycoproteomics and complement the routinely used LC-MS/MS analysis.

• MeSH
• acetylgalaktosamin MeSH
• acetylglukosamin MeSH
• cetrimonium MeSH
• chromatografie kapalinová MeSH
• elektroforéza kapilární metody   MeSH
• elektrolyty chemie   MeSH
• fetuiny MeSH
• fosfáty MeSH
• fukosa MeSH
• galaktosa MeSH
• glukosa MeSH
• glykoproteiny chemie   MeSH
• hydroxid sodný MeSH
• kyselina N-acetylneuraminová * MeSH
• mannosa MeSH
• monosacharidy * analýza   MeSH
• tandemová hmotnostní spektrometrie MeSH
• xylosa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• albuminurie moč   MeSH
• cystatin C analýza   MeSH
• hodnoty glomerulární filtrace * MeSH
• kreatinin analýza   MeSH
• lidé MeSH
• proteinurie * klasifikace   moč   MeSH
• radioisotopová renografie metody   MeSH
• vyšetření funkce ledvin metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• antipsychotika farmakokinetika   MeSH
• chronická renální insuficience * komplikace   MeSH
• cystatin C krev   MeSH
• depresivní poruchy farmakoterapie   komplikace   MeSH
• dospělí MeSH
• eliminace ledvinami MeSH
• hodnoty glomerulární filtrace MeSH
• klostridiové infekce diagnóza   farmakoterapie   komplikace   MeSH
• lidé MeSH
• psychotropní léky * farmakokinetika   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Přesné hodnocení funkce ledvin u pacientů se závažným jaterním poškozením je velmi důležité pro posouzení stupně ledvinného poškození (chronic kidney disease – CKD), bezpečné podávání léků, určení další prognózy, intenzivních léčebných postupů včetně hemodialýzy, hemodiafiltrace či hemoperfuze, ale i indikace k transplataci jater. Všechny metody užívající sérový kreatinin ke stanovení glomerulární filtrace (GF) u nemocných s chorobami jater jsou nepřesné: přeceňují (overestimate) hodnotu GF a stupeň nadhodnocení je tím větší, čím je poškození jater závažnější, a to především v důsledku snížené tvorby endogenního kreatininu (creatinine generation rate – CGR). Použití cystatinu C k odhadu GF u nemocí jater je slibné především ve stavech s akutním poškozením a selháním ledvin (AKI), ale získané výsledky zatím nejsou zcela jednoznačné a vyžadují většinově srovnání více metod stanovení GF.

Accurate measurement of renal function in serious liver disease is very important not only for the estimation of renal damage (chronic kidney disease – CKD), safe drug management, prediction of illness follow-up, intensive methods including hemodialysis, hemodiafiltration or hemoperfusion, but also for the indication of liver transplantation. All methods of renal function measurement using serum creatinine for the estimation of glomerular filtration rate (GFR) are not accurate: they overestimate the value of GFR; the worse the liver damage is, the higher the level of overestimation; predominantly due to decreased endogenous creatinine production (creatinine generation rate – CGR). Using of cystatin C for GFR in liver disease is mainly promising in acute kidney injury (AKI), but obtained results have not been definitive yet and need more relevant data from different methods of GFR estimation. Conflict of Interest: The authors declare that the article/ manuscript complies with ethical standards, patient anonymity has been respected, and they state that they have no financial, advisory or other commercial interests in relation to the subject matter. Publication Ethics: This article/ manuscript has not been published or is currently being submitted for another review with the exception of congressional abstracts and best practices. The authors agree to publish their names and e-mails in the published article/ manuscript. Dedication: The article/ manuscript is not supported by a grant nor has it been created with the support of any company. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

• MeSH
• cystatin C analýza   MeSH
• hodnoty glomerulární filtrace MeSH
• kreatinin analýza   MeSH
• lidé MeSH
• nemoci jater komplikace   MeSH
• renální insuficience * diagnóza   MeSH
• Check Tag
• lidé MeSH

The hard tick Ixodes ricinus is a vector of Lyme disease and tick-borne encephalitis. Host blood protein digestion, essential for tick development and reproduction, occurs in tick midgut digestive cells driven by cathepsin proteases. Little is known about the regulation of the digestive proteolytic machinery of I. ricinus. Here we characterize a novel cystatin-type protease inhibitor, mialostatin, from the I. ricinus midgut. Blood feeding rapidly induced mialostatin expression in the gut, which continued after tick detachment. Recombinant mialostatin inhibited a number of I. ricinus digestive cysteine cathepsins, with the greatest potency observed against cathepsin L isoforms, with which it co-localized in midgut digestive cells. The crystal structure of mialostatin was determined at 1.55 Å to explain its unique inhibitory specificity. Finally, mialostatin effectively blocked in vitro proteolysis of blood proteins by midgut cysteine cathepsins. Mialostatin is likely to be involved in the regulation of gut-associated proteolytic pathways, making midgut cystatins promising targets for tick control strategies.

• MeSH
• cystatiny metabolismus   MeSH
• fylogeneze MeSH
• kathepsin L metabolismus   MeSH
• klíšťata metabolismus   MeSH
• klíště metabolismus   MeSH
• krevní proteiny metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• proteolýza MeSH
• sekvence aminokyselin MeSH
• trávicí systém metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Surface plasmon resonance imaging biosensors have a number of advantages that make them superior to other analytical methods. These include the possibility of label-free detection, speed and high sensitivity to low protein concentrations. The aim of this study was to create and analyze biochips, with the help of which it is possible to test cystatin C in patient urine samples and compare the results with the one-time traditional ELISA method. The main advantage of the surface plasmon resonance imaging method is the possibility of repeated measurements over a long period of time in accordance with clinical practice. The surface of the biochip was spotted with anticystatin C and a negative control of mouse IgG at a ratio of 1:1. The aforementioned biochip was first verified using standard tests and then with patient samples, which clearly confirmed the required sensitivity even for very low concentrations of cystatin C.

• MeSH
• biosenzitivní techniky * MeSH
• cystatin C analýza   moč   MeSH
• lidé MeSH
• mikročipová analýza MeSH
• myši MeSH
• povrchová plasmonová rezonance * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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