Nealkoholická jaterní steatóza (NAFLD) se pojí se zvýšeným rizikem kardiovaskulárních chorob a vyšší celkovou mortalitou. U pacientů po transplantaci jater je prevalence NAFLD/NASH (steatohepatitida) ve srovnání s běžnou populací významně vyšší. Identifikace časných známek NAFLD/NASH může být relevantní pro další predikci rozvoje onemocnění nejenom u transplantovaných pacientů, ale i v běžné populaci. Zaměříme se na tyto oblasti: 1. profilace rizikových alel vybraných genů asociovaných s vyšší pravděpodobností rozvoje steatózy v genomu příjemce; 2. přítomnost inzulínové rezistence a změn v energetickém metabolismu ve svalu a v játrech příjemce; 3. identifikace změn v expresi (aktivace/suprese) specifických metabolických drah ve štěpu metodou microarray (na úrovni transkriptomu). Dále se zaměříme na validaci neinvazivních metod, které mohou indikovat časné fáze NAFLD. Využijeme možnosti vzájemně korelovat údaje získané magnetickou rezonanční spektroskopií a elastografií s histologickým hodnocením a transkriptomickými daty.; Nonalcoholic fatty liver disease (NAFLD) is associated with higher risk of cardiovascular disease and overall mortality. Identification of NAFLD/NASH (steatohepatitis) markers is relevant for NAFLD prediction or early diagnosis and treatment not only in liver transplant recipients, included into this study, but also in general population. We will focus on these indicators: 1. recipient ́s profile of genetic polymorphisms associated with higher probability of steatosis; 2. occurrence of insulin resistance and altered liver/skeletal muscle energy metabolism; 3. identification of genes and/or pathways differentially expressed in liver tissue due to NAFLD/NASH. We will also focus on the validation of non-invasive methods such as MR spectroscopy and elastography in identification of early stages of NAFLD. Results obtained from these non-invasive methods together with histological results and the identified set of genetic, metabolic and transcriptomic markers associated with NAFLD/NASH disease will be cross-correlated and assessed for its predictive value for the progression of NAFLD/NASH.

• MeSH
• alely MeSH
• biologické markery MeSH
• dárci tkání MeSH
• genotyp MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• multiomika MeSH
• nealkoholová steatóza jater etiologie   genetika   MeSH
• pooperační období MeSH
• rizikové faktory MeSH
• stanovení celkové genové exprese MeSH
• transplantace jater MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• genetika, lékařská genetika
• hepatologie
• transplantologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

V projektu budou sledovány patofyziologické mechanizmy inzulinové rezistence a možnosti ovlivnění rezistence tkání agonisty PPAR gama.Pokusy budou proveden u neobezních modelů inzulinové rezistence a u transgenních potkanů s exprimovanou translokázou MK.Sledován bude transport MK do tukové a svalové tkáně ve vztahu k transportním systémům MK (CD36, FABP), vliv dostupnosti glukosy na reesterifikaci a aktivita klíčových enzymů oxidace mastných kyselin. Testován bude vliv zvýšené akumulace derivátů mastných kyselin (diacylglycerolů a mastných kyselin s dlouhým řetězcem) v kosterním svalu na změny v expresi a buněčné lokalizaci protein kinasy C, která je zapojena do přenosu inzulinového signálu. Budou sledovány účinky a farmakogenetické aspekty léčby inzulinové rezistence agonisty nukleárních receptorů PPARgama (thiazolidindionů) ve vztahu k ukládání a mobilizaci triglyceridů a genové expresi.; The proposed project is designed to obtain new information about the pathophysiological mechanisms of insulin resistance and potential for modulating the metabolic syndrome. The experiments will be carried out on non-obese models of insulin resistance hyperlipidemic rats and in transgene rats expressing FA translocase.The fatty acid transport, their utilization, storage, and DAG and LCFA-CoA will be determined. Gene expression profiling in liver, adipose tissue and muscle provide information about localization of lipid metabolism disorderes. The attention will be also focused on the possible pharmacological and pharmacogenetical aspects of the nuclear receptors agonists (PPARgamma) therapy and the implications for the storage and mobilisation of triglycerides.

• MeSH
• inzulinová rezistence MeSH
• mastné kyseliny chemie   MeSH
• mitochondriální ADP/ATP-translokasy MeSH
• PPAR gama MeSH
• přenašeče monokarboxylových kyselin MeSH
• proteinkinasa C MeSH
• thiazolidindiony MeSH
• transportní proteiny mastných kyselin MeSH
• triglyceridy MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• diabetologie
• biochemie
• vnitřní lékařství
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Syndrom insulinové resistence je častou metabolickou poruchou výrazně zvyšující riziko rozvoje diabetu 2. typu a kardiovaskulárních onemocnění. V projektu budou sledovány mechanismy poruch lipidového metabolismu při insulinové resistenci. Studie bude provedena u experimentálních modelů insulinové resistence, u neobesní linie hereditárně hypertriglyceridemických potkanů, u spontánně hypertensních potkanů se zvýšenou expresí translokasy mastných kyselin v tukové tkáni a v kosterním svalu. Dále bude sledována úloha LPL v transportu a utilizaci mastných kyselin, aktivita LPL a účimek resistinu ve vztahu k utilizaci glukosy ve tkáních, oxidaci mastných kyselin a sensitivitě tukové a svalové tkáně k účinku insulinu. Dále bude sledován vliv nutriční a farmakologické intervence na poruchy lipidového metabolismu při insulinové resistenci.; The aim od the project is to continue studying the pathophysiological mechanisms of insulin resistance and to assess the potential for nutritional and pharmacological intervention. Experiments will be performed in unique experimental models of insulin resistance, in hereditary hypertriglyceridemic rats, SHR rats with deletion of Cd36 fatty acid transporter and transgenic SHR rats with expression of Cd36 or aP2. The role fatty acid binding proteins, fatty acid transporters and LPL activity on transport and utilization of NEFA and tissue insulin sensitivity will be evaluated. Additionally, the long-term effect of TZD on NEFA metabolism will be analyzed.

• MeSH
• hypertriglyceridemie MeSH
• inzulinová rezistence MeSH
• lipoproteinlipasa MeSH
• mastné kyseliny metabolismus   MeSH
• thiazolidindiony metabolismus   MeSH
• tuková tkáň MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• diabetologie
• vnitřní lékařství
• biochemie
• farmacie a farmakologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

INTRODUCTION: The retrospective study evaluated the clinical and radiological outcomes of conservative treatment for type II odontoid C2 fractures in octogenerians. The study aimed to assess the clinical outcomes and quality of survival of patients treated using conservative methods. Additionally, the study sought to define radiological outcomes, fracture healing success and the development of complications in correlation with clinical outcomes. MATERIALS AND METHODS: Patients aged ≥80 with dens C2 fracture were fixed with a hard cervical collar for 6 weeks, followed by early mobilization. Patients showing delayed fracture healing on computed tomography (CT) scan were subsequently immobilized in a soft neck collar for additional 6 weeks. The follow-up CT scan was then performed with consequential rehabilitation. Patients with nonunion of the C2 on the follow-up CT scan and clinical symptoms were contraindicated for physical rehabilitation for cervical spine till next CT scan after another 12 weeks. Clinical and radiographic evaluations were performed during follow-up visits, with a median follow-up was 109 days, with the range extending from 1 day to 1 year. RESULTS: In total, 33 patients were included in the study and were followed for 1 year. The 30-day mortality rate was 21.2%, and between 30 days and one year post-treatment, it was 18.2%. Mortality was higher during the study period in displaced fractures (>2 mm; 9 out of 16 patients died) compared to non-displaced fractures (≤2 mm; 4 out of 17 patients died). The Japanese Orthopaedic Association (JOA) score remained unchanged between admission (mean 16.9; SD ± 0.5) and the end of follow-up (mean 16.9; SD ± 0.5; P > 0.05), the Visual Analogue Scale (VAS) score showed improvement from values measured upon admission to the hospital (mean 7.97; SD ± 1.33) to values measured at the end of follow-up (mean 1.58; SD ± 1.62; P < 0.001) and the Neck Disability Index (NDI) showed a statistically significant difference between admission (mean 41.3; SD ± 14.92) and the end of follow-up (mean 14.29; SD ± 4.65; P < 0.001). The standard measurement of Posterior Atlantodental Interval (PADI) had an average value of 18.6 (range 16-22 mm) and primary bony union of odontoid fractures occurred in eleven cases (33.3%), while six patients (18.2%) had fibrous union with minimal clinical difficulties. CONCLUSION: This study demonstrates the safety and efficacy of conservative treatment for odontoid fractures in octogenerians and underscores the critical role of conservative management in a polymorbid elderly population.

• Publikační typ
• časopisecké články MeSH

• MeSH
• lékařská genetika MeSH
• Publikační typ
• biografie MeSH
• nekrology MeSH

• O autorovi
• Křen, Vladimír, 1931-2024 Autorita

• Publikační typ
• abstrakt z konference MeSH

Quercetin, a flavonoid present in many fruits and vegetables, exhibits beneficial effects toward abnormalities related to metabolic syndrome. In this study, to further investigate metabolic and transcriptomic responses to quercetin supplementation, we used a genetic model of metabolic syndrome. Adult male rats of the PD/Cub strain were fed either a high-sucrose diet (HSD; control PD rats) or HSD fortified with quercetin (10 g quercetin/kg diet; PD-Q rats). Morphometric and metabolic parameters, along with transcriptomic profiles of the liver and retroperitoneal fat, were assessed. The relative weights of epididymal and retroperitoneal fat were significantly decreased in quercetin-treated animals. Furthermore, a smaller area under the glycemic curve along with a decreased level of fasting insulin were detected in PD-Q rats. While no changes in total cholesterol levels were observed, the overall level of triglycerides decreased in the serum and the liver of the PD-Q rats. The transcriptomic profile of the liver and the adipose tissue corroborated the metabolic and morphometric findings, revealing the pattern consistent with insulin-sensitizing changes, with major regulator nodes being Pparg, Adipoq, Nos2, and Mir378. In conclusion, quercetin supplementation improves abnormalities related to metabolic syndrome, namely adiposity, dyslipidemia and glucose intolerance.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Several corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a limited segment of rat chromosome 20 from a metabolic syndrome model, spontaneously hypertensive rat (SHR), was introgressed into Brown Norway (BN) genomic background. We mapped the extent of the differential segment and compared the genomic sequences of BN vs. SHR within the segment in silico. The differential segment of SHR origin in BN.SHR20 spans about 9 Mb of the telomeric portion of the short arm of chromosome 20. We identified non-synonymous mutations e.g., in ApoM, Notch4, Slc39a7, Smim29 genes and other variations in or near genes associated with metabolic syndrome in human genome-wide association studies. Male rats of BN and BN.SHR20 strains were fed a standard diet for 18 weeks (control groups) or 16 weeks of standard diet followed by 14 days of high-sucrose diet (HSD). We assessed the morphometric and metabolic profiles of all groups. Adiposity significantly increased only in BN.SHR20 after HSD. Fasting glycemia and the glucose levels during the oral glucose tolerance test were higher in BN.SHR20 than in BN groups, while insulin levels were comparable. The fasting levels of triacylglycerols were the highest in sucrose-fed BN.SHR20, both compared to the sucrose-fed BN and the control BN.SHR20. The non-esterified fatty acids and total cholesterol concentrations were higher in BN.SHR20 compared to their respective BN groups, and the HSD elicited an increase in non-esterified fatty acids only in BN.SHR20. In a new genetically defined model, we have isolated a limited genomic region involved in nutrigenetic sensitization to sucrose-induced metabolic disturbances.

• MeSH
• apolipoproteiny M genetika   MeSH
• celogenomová asociační studie MeSH
• hypertenze * metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• lidské chromozomy, pár 20 metabolismus   MeSH
• mastné kyseliny MeSH
• metabolický syndrom * genetika   metabolismus   MeSH
• nutrigenomika MeSH
• omezení příjmu potravy MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• proteiny přenášející kationty * genetika   MeSH
• sacharosa škodlivé účinky   MeSH
• savci genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.

• Publikační typ
• časopisecké články MeSH