INTRODUCTION: Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate and vitamin D metabolism in the kidney, and its higher levels in plasma are associated with poorer outcomes in kidney and cardiovascular diseases. It is produced by bone cells upon enhanced oxidative stress and inhibits renal phosphate reabsorption and calcitriol (active form of vitamin D) production. Bilirubin, the final product of the heme catabolic pathway in the vascular bed, has versatile biological functions, including antioxidant and anti-inflammatory effects. This study explored whether bilirubin alters FGF23 production. METHODS: Experiments were performed using UMR106 osteoblast-like cells. Fgf23 transcript levels were determined by quantitative real-time polymerase chain reaction, C-terminal and intact FGF23 protein levels were determined by enzyme-linked immunosorbent assay, and cellular oxidative stress was assessed by CellROX assay. RESULTS: Unconjugated bilirubin down-regulated Fgf23 gene transcription and FGF23 protein abundance; these effects were paralleled by lower cellular oxidative stress levels. Also, conjugated bilirubin reduced Fgf23 mRNA abundance. CONCLUSION: Bilirubin down-regulates FGF23 production in UMR106 cells, an effect likely to be dependent on the reduction of cellular oxidative stress.
(1) Objectives: Intestinal failure in home parenteral nutrition patients (HPNPs) results in oxidative stress and liver damage. This study investigated how a high dose of fish oil (FO) added to various lipid emulsions influences antioxidant status and liver function markers in HPNPs. (2) Methods: Twelve HPNPs receiving Smoflipid for at least 3 months were given FO (Omegaven) for a further 4 weeks. Then, the patients were randomized to subsequently receive Lipoplus and ClinOleic for 6 weeks or vice versa plus 4 weeks of Omegaven after each cycle in a crossover design. Twelve age- and sex-matched healthy controls (HCs) were included. (3) Results: Superoxide dismutase (SOD1) activity and oxidized-low-density lipoprotein concentration were higher in all baseline HPN regimens compared to HCs. The Omegaven lowered SOD1 compared to baseline regimens and thus normalized it toward HCs. Lower paraoxonase 1 activity and fibroblast growth factor 19 (FGF19) concentration and, on the converse, higher alkaline phosphatase activity and cholesten concentration were observed in all baseline regimens compared to HCs. A close correlation was observed between FGF19 and SOD1 in baseline regimens. (4) Conclusions: An escalated dose of FO normalized SOD1 activity in HPNPs toward that of HCs. Bile acid metabolism was altered in HPNPs without signs of significant cholestasis and not affected by Omegaven.
BACKGROUND: Although regular physical activity improves immune competency and reduces the prevalence of inflammatory diseases, strenuous training in elite athletes is associated with an increased susceptibility to infectious complications. Therefore, the objective of our study was to assess the routinely examined parameters of the complement system in elite athletes. The study was carried out in a cohort of elite athletes (n = 134) and healthy control subjects (n = 110). In all subjects, besides a routine laboratory check-up, serum concentrations of the C3 and C4 complement components, mannose-binding lectin (MBL), as well as activation of all three complement pathways were determined. RESULTS: Compared to healthy controls, lower C3 and C4 complement component concentrations were observed in elite athletes (0.96 ± 0.1 vs. 1.08 ± 0.2 mg/L, and 0.18 ± 0.1 vs. 0.25 ± 0.1 mg/L, respectively, p < 0.05); with much higher frequency rates of C3 and C4 deficiencies in athletes (31.3 vs. 14.5%, and 6 vs. 0%, p < 0.05). Simultaneously, athletes had much higher frequency rates of deficiencies of activation of classical and alternative complement pathways; while, deficiency of activation of the lectin pathway was similar in both cohorts. CONCLUSIONS: We confirmed a high frequency of defects in the complement system in elite athletes. Lower concentrations of C3 and C4 complement components, with high frequencies of deficiencies of the classical and alternative complement activation pathways were the most prevalent disorder of the complement system in elite athletes. Further studies are needed to uncover the functional impacts of these observations upon the susceptibility to infectious diseases.
- Publikační typ
- časopisecké články MeSH
The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the "yellow players-YP") are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life.
- Publikační typ
- abstrakt z konference MeSH
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.
- MeSH
- cholesterol metabolismus MeSH
- cholin metabolismus MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- játra metabolismus MeSH
- kyseliny mastné neesterifikované metabolismus MeSH
- kyseliny mastné omega-3 * farmakologie terapeutické užití metabolismus MeSH
- methionin metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nealkoholová steatóza jater * etiologie genetika MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- Racemethionin metabolismus farmakologie MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND & AIMS: Severity of portal hypertension is usually quantified by measuring the hepatic venous pressure gradient (HVPG). However, due to its invasiveness, alternative markers are being sought. Bile acids (BA), being synthesized, metabolized, and transported by the liver, seem to have the potential to serve as endogenous markers. The aim of the present study was to determine whether serum BA reflect the severity of portal hypertension. METHODS: We correlated serum concentrations of individual BA with portal pressure (as HVPG) in an exploratory cohort of 21 cirrhotic patients with portal hypertension. The predictive potential of selected candidates was then confirmed in an independent validation cohort (n = 214). Additionally, nine previously published noninvasive markers were added to the stepwise logistic regression model to identify the most relevant ones, which were eventually used to create a prognostic index of portal hypertension. RESULTS: Serum levels of taurochenodeoxycholic acid (TCDCA) significantly correlated with HVPG and showed a high potential to predict clinically significant portal hypertension (HVPG ≥ 10 mm Hg: AUROC = 0.97 ± 0.06). This was confirmed in the validation cohort (AUROC = 0.96 ± 0.01). The predictive index (constructed based on AST/ALT, spleen diameter, and TCDCA concentration) was able to distinguish clinically significant portal hypertension with 95% sensitivity and 76% specificity. CONCLUSIONS: TCDCA seems to be a promising noninvasive marker of clinically significant portal hypertension. Its predictive potential may be further enhanced when it is combined with both the AST/ALT ratio and spleen diameter.
Doporučené diagnostické a terapeutické postupy pro všeobecné praktické lékaře
29 stran ; 30 cm
Příručka a směrnice, které se zaměřují na klinické laboratorní diagnostické metody. Určeno odborné veřejnosti, praktickým lékařům.
- MeSH
- klinické laboratorní techniky MeSH
- praktické lékařství MeSH
- Publikační typ
- příručky MeSH
- směrnice pro lékařskou praxi MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- diagnostika
- všeobecné lékařství
- NLK Publikační typ
- brožury
Gilbert's syndrome, also known as benign hyperbilirubinaemia, was described more than 100 years ago. It has usually been considered a physiological abnormality characterised by a mild elevation of the systemic level of unconjugated bilirubin, in the absence of any underlying liver or overt haemolytic disease. However, since the re-discovery of the potent antioxidant effects of bilirubin in the late 1980s, as well as multiple intracellular signalling pathways affected by bilirubin, an ever-increasing body of evidence suggests that individuals with Gilbert's syndrome may benefit from the mild hyperbilirubinaemia and are actually protected from the development of a wide variety of "diseases of civilisation" such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases. This review analyses the current state of medical knowledge given recent discoveries in this rapidly developing field, as well as their possible clinical significance, and provides a new perspective on this condition.
- MeSH
- antioxidancia MeSH
- bilirubin metabolismus MeSH
- Gilbertova nemoc * metabolismus MeSH
- hyperbilirubinemie metabolismus MeSH
- játra metabolismus MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Bilirubin has potent biological beneficial effects, protecting against atherosclerosis, obesity, and metabolic syndrome. The aim of this study was to assess serum bilirubin concentrations and (TA)n and (GT)n microsatellite variations in the promoter regions of the UGT1A1 and HMOX1 genes, respectively, in patients with type 2 diabetes mellitus (T2DM). The study was carried out in 220 patients with T2DM and 231 healthy control subjects, in whom standard biochemical tests were performed. The (TA)n and (GT)n dinucleotide variations were determined by means of fragment (size-based) analysis using an automated capillary DNA sequencer. Compared to controls, both male and female patients with T2DM had lower serum bilirubin concentrations (9.9 vs. 12.9 μmol/L, and 9.0 vs. 10.6 μmol/L, in men and women, respectively, p < 0.001). Phenotypic Gilbert syndrome was much less prevalent in T2DM patients, as was the frequency of the (TA)7/7UGT1A1 genotype in male T2DM patients. (GT)nHMOX1 genetic variations did not differ between diabetic patients and controls. Our results demonstrate that the manifestation of T2DM is associated with lower serum bilirubin concentrations. Consumption of bilirubin due to increased oxidative stress associated with T2DM seems to be the main explanation, although (TA)n repeat variations in UGT1A1 partially contribute to this phenomenon.
- MeSH
- bilirubin metabolismus MeSH
- diabetes mellitus 2. typu * genetika MeSH
- genotyp MeSH
- glukuronosyltransferasa genetika metabolismus MeSH
- hemoxygenasa-1 genetika metabolismus MeSH
- lidé MeSH
- polymorfismus genetický * MeSH
- promotorové oblasti (genetika) MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
