Pacienti s chronickým onemocněním ledvin, zejména starší osoby, jsou v nepřiměřeně vysokém riziku kardiovaskulárních komplikací a úmrtí. Patofyziologické a klinické souvislosti mezi ledvinami a kardiovaskulárním systémem jsou výstižně shrnuty v terminologii kardiorenálních syndromů. Chronický renokardiální syndrom (kardiorenální syndrom typ 4) je společným důsledkem známých tradičních, ale také tzv. netradičních rizikových faktorů vyplývajících z poškození renální tkáně a renální funkce. Chronické onemocnění ledvin samo o sobě představuje nezávislý rizikový kardiovaskulární faktor. Článek upozorňuje na vysokou mortalitu pacientů s chronickými nemocemi ledvin, a to již od časných funkčních stadií chronického onemocnění ledvin, a připomíná základní patogenezi a klinický význam nejdůležitějších renálně podmíněných netradičních kardiovaskulárních rizik, včetně těch, která jsou důležitá zejména pro pacienty vysokého věku. Korespondenční adresa: prof. MUDr. Sylvie Dusilová Sulková, DrSc. Nefrologická klinika, LF UK a FN Sokolská 581 500 05 Hradec Králové e-mail: sylvie.dusilova@fnhk.cz
Patients with chronic kidney disease, especially the elderly, are at disproportionately high risk of cardiovascular complications and death. The pathophysiological and clinical links between the kidney and the cardiovascular system are aptly summarized in the terminology of cardiorenal syndromes. Chronic renal syndrome (cardiorenal syndrome type 4) is a common consequence of known traditional but also so-called non-traditional risk factors resulting from renal tissue damage and renal function. Chronic kidney disease itself is an independent cardiovascular risk factor. The article highlights the high mortality rate of patients with chronic kidney disease, starting from the early functional stages of chronic kidney disease, and recalls the basic pathogenesis and clinical significance of the most important renal-related nontraditional cardiovascular risks, including those that are particularly important for elderly patients.
- MeSH
- chronická renální insuficience * komplikace patofyziologie MeSH
- extracelulární tekutina fyziologie MeSH
- fibroblastový růstový faktor 23 MeSH
- kardiorenální syndrom * klasifikace komplikace patofyziologie prevence a kontrola MeSH
- lidé MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- senioři MeSH
- uremické toxiny fyziologie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
INTRODUCTION: Fibroblast growth factor 20 (Fgf20), a member of the Fgf9 subfamily, was identified as an important regulator of bone differentiation and homeostasis processes. However, the role of Fgf20 in bone physiology has not been approached yet. Here we present a comprehensive bone phenotype analysis of mice with functional ablation of Fgf20. METHODS: The study conducts an extensive analysis of Fgf20 knockout mice compared to controls, incorporating microCT scanning, volumetric analysis, Fgf9 subfamily expression and stimulation experiment and histological evaluation. RESULTS: The bone phenotype could be detected especially in the area of the lumbar and caudal part of the spine and in fingers. Regarding the spine, Fgf20-/- mice exhibited adhesions of the transverse process of the sixth lumbar vertebra to the pelvis as well as malformations in the distal part of their tails. Preaxial polydactyly and polysyndactyly in varying degrees of severity were also detected. High resolution microCT analysis of distal femurs and the fourth lumbar vertebra showed significant differences in structure and mineralization in both cortical and trabecular bone. These findings were histologically validated and may be associated with the expression of Fgf20 in chondrocytes and their progenitors. Moreover, histological sections demonstrated increased bone tissue formation, disruption of Fgf20-/- femur cartilage, and cellular-level alterations, particularly in osteoclasts. We also observed molar dysmorphology, including root taurodontism, and described variations in mineralization and dentin thickness. DISCUSSION: Our analysis provides evidence that Fgf20, together with other members of the Fgf9 subfamily, plays a crucial regulatory role in skeletal development and bone homeostasis.
- MeSH
- fenotyp MeSH
- fibroblastové růstové faktory * metabolismus genetika MeSH
- fyziologická kalcifikace MeSH
- kosti a kostní tkáň metabolismus patologie diagnostické zobrazování abnormality MeSH
- myši inbrední C57BL MeSH
- myši knockoutované * MeSH
- myši MeSH
- osteogeneze MeSH
- rentgenová mikrotomografie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The FGF system is the most complex of all receptor tyrosine kinase signaling networks with 18 FGF ligands and four FGFRs that deliver morphogenic signals to pattern most embryonic structures. Even when a single FGFR is expressed in the tissue, different FGFs can trigger dramatically different biological responses via this receptor. Here we show both quantitative and qualitative differences in the signaling of one of the FGF receptors, FGFR1c, in response to different FGFs. We provide an overview of the recent discovery that FGFs engage in biased signaling via FGFR1c. We discuss the concept of ligand bias, which represents qualitative differences in signaling as it is a measure of differential ligand preferences for different downstream responses. We show how FGF ligand bias manifests in functional data in cultured chondrocyte cells. We argue that FGF-ligand bias contributes substantially to FGF-driven developmental processes, along with known differences in FGF expression levels, FGF-FGFR binding coefficients and differences in FGF stability in vivo.
- MeSH
- chondrocyty metabolismus MeSH
- fibroblastové růstové faktory * metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- receptor fibroblastových růstových faktorů, typ 1 * metabolismus MeSH
- receptory fibroblastových růstových faktorů * metabolismus MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to evaluate the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR. METHODS: Plasma bile salts, FGF19, and C4 (bile salt synthesis marker) were assessed in patients with pCCA and controls (colorectal liver metastases), before and after resection on postoperative days (PODs) 1, 3, and 7. Hepatic bile salts were determined in intraoperative liver biopsies. RESULTS: Partial liver resection in pCCA elicited a sharp decline in bile salt and FGF19 plasma levels on POD 1 and remained low thereafter, unlike in controls, where bile salts rose gradually. Preoperatively, suppressed C4 in pCCA normalized postoperatively to levels similar to those in the controls. The remnant liver volume and postoperative bilirubin levels were negatively associated with postoperative C4 levels. Furthermore, patients who developed postoperative liver failure had nearly undetectable C4 levels on POD 7. Hepatic bile salts strongly predicted hyperbilirubinemia on POD 7 in both groups. Finally, postoperative bile salt levels on day 7 were an independent predictor of LR. CONCLUSIONS: Partial liver resection alters the bile salt-FGF19 axis, but its derailment is unrelated to LR in pCCA. Postoperative monitoring of circulating bile salts and their production may be useful for monitoring LR.
- MeSH
- fibroblastové růstové faktory * krev MeSH
- hepatektomie * MeSH
- játra metabolismus chirurgie MeSH
- Klatskinův nádor * chirurgie patologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory žlučových cest * chirurgie patologie krev MeSH
- regenerace jater * fyziologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- žlučové kyseliny a soli * krev metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In this article, we focused on the impact of precisely chemically modified FLI maturation medium enriched with fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), insulin-like growth factor 1 (IGF1), and polyvinyl alcohol (PVA) and its potential to improve the efficiency of in vitro production of porcine embryos. We hypothesized that enhancing the composition of the maturation medium could result in an elevated production of embryos in vitro and can affect EGA. FLI medium resulted in a significantly higher rate of oocyte blastocyst maturation and formation compared to the control DMEM medium. In addition, immunocytochemical labelling confirmed the detection of UBF in 4-cell FLI parthenogenic embryos, suggesting similarities with natural embryo development. Through RNAseq analysis, upregulated genes present in 4-cell FLI embryos were found to play key roles in important biological processes such as cell proliferation, cell differentiation, and transcriptional regulation. Based on our findings, we demonstrated the positive influence of FLI medium in the evaluation of in vitro embryo production, EGA detection, transcriptomic and proteomic profile, which was confirmed by the positive activation of the embryonal genome in the 4-cell stage of parthenogenetically activated embryos.
- MeSH
- blastocysta účinky léků metabolismus MeSH
- fertilizace in vitro MeSH
- fibroblastový růstový faktor 2 * farmakologie MeSH
- insulinu podobný růstový faktor I * farmakologie MeSH
- kultivační média * chemie farmakologie MeSH
- leukemický inhibiční faktor * farmakologie MeSH
- oocyty MeSH
- prasata embryologie genetika MeSH
- proteomika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model. METHODS: Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 μg ‧ cm-2. The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale. RESULTS: The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres. CONCLUSION: The formation of scars with the best elasticity was exhibited by addition 1.0 μg ‧ cm-2of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research.
- MeSH
- chitosan * MeSH
- fibroblastový růstový faktor 2 * MeSH
- hojení ran účinky léků MeSH
- jizva hypertrofická MeSH
- kolagen MeSH
- kůže MeSH
- modely nemocí na zvířatech MeSH
- nanovlákna terapeutické užití MeSH
- popálení MeSH
- prasata MeSH
- pružnost * MeSH
- tkáňové podpůrné struktury MeSH
- umělá kůže * MeSH
- viskozita MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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.
Fibroblast growth factor 21 (FGF21) reduces body weight, which was attributed to induced energy expenditure (EE). Conflicting data have been published on the role of uncoupling protein 1 (UCP1) in this effect. Therefore, we aimed to revisit the thermoregulatory effects of FGF21 and their implications for body weight regulation. We found that an 8-day treatment with FGF21 lowers body weight to similar extent in both wildtype (WT) and UCP1-deficient (KO) mice fed high-fat diet. In WT mice, this effect is solely due to increased EE, associated with a strong activation of UCP1 and with excess heat dissipated through the tail. This thermogenesis takes place in the interscapular region and can be attenuated by a β-adrenergic inhibitor propranolol. In KO mice, FGF21-induced weight loss correlates with a modest increase in EE, which is independent of adrenergic signaling, and with a reduced energy intake. Interestingly, the gene expression profile of interscapular brown adipose tissue (but not subcutaneous white adipose tissue) of KO mice is massively affected by FGF21, as shown by increased expression of genes encoding triacylglycerol/free fatty acid cycle enzymes. Thus, FGF21 elicits central thermogenic and pyretic effects followed by a concomitant increase in EE and body temperature, respectively. The associated weight loss is strongly dependent on UCP1-based thermogenesis. However, in the absence of UCP1, alternative mechanisms of energy dissipation may contribute, possibly based on futile triacylglycerol/free fatty acid cycling in brown adipose tissue and reduced food intake.
- MeSH
- adrenergní látky MeSH
- energetický metabolismus MeSH
- fibroblastové růstové faktory * MeSH
- hmotnostní úbytek * MeSH
- kyseliny mastné neesterifikované * MeSH
- myši obézní MeSH
- myši MeSH
- tělesná hmotnost MeSH
- triglyceridy MeSH
- uncoupling protein 1 genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- fibroblastový růstový faktor 2 * MeSH
- fibroblasty MeSH
- hojení ran MeSH
- lidé MeSH
- popálení * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
