- MeSH
- biologické markery * analýza MeSH
- galektin 3 analýza metabolismus normy MeSH
- lidé MeSH
- natriuretické peptidy analýza metabolismus MeSH
- růstový diferenciační faktor 15 analýza metabolismus normy MeSH
- srdeční selhání * diagnóza MeSH
- troponin analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Aging is a natural process of gradual decrease in physical and mental capacity. Biological age (accumulation of changes and damage) and chronological age (years lived) may differ. Biological age reflects the risk of various types of disease and death from any cause. We selected potential biomarkers of aging - telomerase, AGEs, GDF11 and 15 (growth differentiation factor 11/15), sirtuin 1, NAD+ (nicotinamide adenine dinucleotide), inflammasome NLRP3, DNA/RNA damage, and klotho to investigate changes in their levels depending on age and sex. We included 169 healthy volunteers and divided them into groups according to age (under 35; 35-50; over 50) and sex (male, female; male and female under 35; 35-50, over 50). Markers were analyzed using commercial ELISA kits. We found differences in values depending on age and gender. GDF15 increased with age (under 30 and 35-50 p < 0.002; 35-50 and over 50; p < 0.001; under 35 and over 50; p < 0.001) as well as GDF11 (35-50 and over 50; p < 0.03; under 35 and over 50; p < 0.02), AGEs (under 30 and 35-50; p < 0.005), NLRP3 (under 35 over 50; p < 0.03), sirtuin 1 (35-50 and over 50; p < 0.0001; under 35 and over 50; p < 0.004). AGEs and GDF11 differed between males and females. Correlations were identified between individual markers, markers and age, and markers and sex. Markers that reflect the progression of biological aging vary with age (GDF15, GDF11, AGEs, NLRP3, sirtuin) and sex (AGEs, GDF11). Their levels could be used in clinical practice, determining biological age, risk of age-related diseases and death of all-causes, and initiating or contraindicating a therapy in the elderly based on the patient's health status.
- MeSH
- biologické markery MeSH
- DNA MeSH
- kostní morfogenetické proteiny MeSH
- lidé MeSH
- NAD * MeSH
- produkty pokročilé glykace MeSH
- protein NLRP3 MeSH
- růstové diferenciační faktory metabolismus MeSH
- senioři MeSH
- sirtuin 1 MeSH
- stárnutí genetika MeSH
- telomerasa * MeSH
- zdravotní stav MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: Growth differentiation factor 15 (GDF15) shows potential predictive value in various cardiac conditions. We investigated relationships between GDF15 and clinical or procedural outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) in order to propose clinically useful predictive risk stratification model. METHODS: This prospective single-center registry enrolled 88 consecutive patients with severe symptomatic aortic stenosis treated with TAVI. Clinical parameters were collected and biomarkers including GDF-15 were measured within 24 h before TAVI. All relevant clinical outcomes according to the Valve Academic Research Consortium-2 were collected over the follow-up period. RESULTS: The cohort included 52.3% of females. The mean age of study participants was 81 years; the mean Society of Thoracic Surgeons (STS) score and logistic EuroSCORE were 3.6% and 15.4%, respectively. The mortality over the entire follow-up period was 10.2%; no death was observed within the first 30 days following TAVI. Univariate analysis showed significant associations between GDF15 and mortality (P=0.0006), bleeding (P=0.0416) and acute kidney injury (P=0.0399). A standard multivariate logistic regression model showed GDF-15 as the only significant predictor of mortality (P=0.003); the odds ratio corresponding to an increase in GDF15 of 1000 pg/mL was 1.22. However, incremental predictive value was not observed when the STS score was combined with GDF15 in this predictive model. CONCLUSIONS: Based on our observations, preprocedural elevated GDF15 levels are associated with increased mortality and demonstrate their additional value in predicting adverse clinical outcomes in a TAVI population.
- MeSH
- aortální stenóza * chirurgie MeSH
- hodnocení rizik MeSH
- lidé MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- růstový diferenciační faktor 15 MeSH
- senioři nad 80 let MeSH
- transkatetrální implantace aortální chlopně * škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Myostatin (MSTN), an important negative regulator of skeletal muscle, plays an important role in skeletal muscle health. In previous study, we found that the expression of MSTN was different during skeletal muscle injury repair. Therefore, we explored the expression changes of MSTN at different time points during skeletal muscle injury repair after eccentric exercise. In addition, MSTN is regulated by follistatin (FST) and decorin (DCN) in vivo, so our study examined the time-specific changes of FST, DCN and MSTN in the circulation and skeletal muscle during skeletal muscle injury repair after eccentric exercise, and to explore the reasons for the changes of MSTN in the process of exercise-induced muscle injury repair, to provide a basis for promoting muscle injury repair. The rats performed one-time eccentric exercise. Blood and skeletal muscle were collected at the corresponding time points, respectively immediate after exercise (D0), one day (D1), two days (D2), three days (D3), seven days (W1) and fourteen days (W2) after exercise (n=8). The levels of MSTN, FST, DCN in serum and mRNA and protein expression in muscle were detected. MSTN changes in the blood and changes in DCN and FST showed the opposite trend, except immediately after exercise. The change trends of mRNA and protein of gastrocnemius DCN and MSTN are inconsistent, there is post-transcriptional regulation of MSTN and DCN in gastrocnemius. Acute eccentric exercise might stimulate the secretion of DCN and FST into the circulation and inhibit MSTN. MSTN may be regulated by FST and DCN after acute eccentric exercise.
- MeSH
- časové faktory MeSH
- dekorin * genetika metabolismus MeSH
- folistatin * genetika metabolismus MeSH
- kondiční příprava zvířat * MeSH
- kosterní svaly * metabolismus MeSH
- krysa rodu rattus MeSH
- messenger RNA genetika MeSH
- myostatin * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue. METHODS: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines. RESULTS: Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/β-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure. CONCLUSION: We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.
- MeSH
- adipogeneze * MeSH
- adiponektin metabolismus MeSH
- beta-katenin * metabolismus MeSH
- buněčná diferenciace fyziologie MeSH
- glukosa metabolismus MeSH
- inzulin metabolismus MeSH
- kostní morfogenetické proteiny metabolismus MeSH
- lidé MeSH
- myši MeSH
- protein Smad2 MeSH
- protein Smad3 MeSH
- receptory regulované proteiny Smad MeSH
- růstové diferenciační faktory metabolismus MeSH
- signální dráha Wnt MeSH
- TGF-beta receptor I. typu MeSH
- transformující růstový faktor beta metabolismus MeSH
- tukové buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
CONTEXT: Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. OBJECTIVE: To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI). METHODS: AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. RESULTS: During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. CONCLUSION: Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- genové regulační sítě * MeSH
- hmotnostní úbytek * MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- následné studie MeSH
- obezita metabolismus patologie MeSH
- prognóza MeSH
- redukční dieta * MeSH
- růstový diferenciační faktor 15 genetika metabolismus MeSH
- transkriptom * MeSH
- tuková tkáň metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Multimodal gadolinium fluoride nanoparticles belong to potential contrast agents useful for bimodal optical fluorescence and magnetic resonance imaging. However, the metallic nature of the nanoparticles, similarly to some paramagnetic iron oxides, might induce allergic and anaphylactic reactions in patients after administration. A reduction of these adverse side effects is a priority for the safe application of the nanoparticles. Herein, we prepared paramagnetic poly(4-styrenesulfonic acid-co-maleic acid) (PSSMA)-stabilized GdF3 nanoparticles with surface modified by Atto 488-labeled poly(styrene-grad-2-dimethylaminoethyl acrylate)-block-poly(2-dimethylaminoethyl acrylate) (PSDA-A488) with reactive amino groups for introduction of an additional imaging (luminescence) modality and possible targeting of anticancer drugs. The saturation magnetization of GdF3@PSSMA particles according to SQUID magnetometry reached 157 Am2 kg-1 at 2 K and magnetic field of 7 T. GdF3@PSSMA-PSDA-A488 nanoparticles were well tolerated by human cervical adenocarcinoma (HeLa), mouse bone marrow-derived mast cells (BMMC), and rat basophilic mast cells (RBL-2H3); the particles also affected cell morphology and protein tyrosine phosphorylation in mast cells. Moreover, the nanoparticles interfered with the activation of mast cells by multivalent antigens and inhibited calcium mobilization and cell degranulation. These findings show that the new multimodal GdF3-based nanoparticles possess properties useful for various imaging methods and might minimize mast cell degranulation incurred after future nanoparticle diagnostic administration.
- MeSH
- degranulace buněk MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mastocyty * MeSH
- myši MeSH
- nanočástice * MeSH
- polymery MeSH
- růstový diferenciační faktor 3 MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification critically dependent on circulating vitamin K status. Growth differentiation factor 15 (GDF-15) is a regulatory cytokine mainly of the inflammatory and angiogenesis pathways, but potentially also involved in bone mineralization. We sought to determine whether these two circulating biomarkers jointly influenced morbidity and mortality risk in patients with chronic coronary heart disease (CHD). METHODS AND RESULTS: 894 patients ≥6 months after myocardial infarction and/or coronary revascularization at baseline were followed in a prospective study. All-cause and cardiovascular mortality, non-fatal cardiovascular events (myocardial infarction, stroke, any revascularization), and hospitalization for heart failure (HF) were followed as outcomes. Desphospho-uncarboxylated MGP (dp-ucMGP) was used as a biomarker of vitamin K status. Both, increased concentrations of dp-ucMGP (≥884 pmol/L) and GDF-15 (≥1339 pg/mL) were identified as independent predictors of 5-year all-cause or cardiovascular mortality. However, their coincidence further increased mortality risk. The highest risk was observed in patients with high dp-ucMGP plus high GDF-15, not only when compared with those with "normal" concentrations of both biomarkers [HR 5.51 (95% CI 2.91-10.44), p < 0.0001 and 6.79 (95% CI 3.06-15.08), p < 0.0001 for all-cause and cardiovascular mortality, respectively], but even when compared with patients with only one factor increased. This pattern was less convincing with non-fatal cardiovascular events or hospitalization for HF. CONCLUSIONS: The individual coincidence of low vitamin K status (high dp-ucMGP) and high GDF-15 expression predicts poor survival of stable CHD patients.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- chronická nemoc MeSH
- extracelulární matrix - proteiny krev MeSH
- hodnocení rizik MeSH
- incidence MeSH
- koronární nemoc krev diagnóza mortalita terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nedostatek vitaminu D krev diagnóza mortalita MeSH
- prognóza MeSH
- prospektivní studie MeSH
- proteiny vázající vápník krev MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- růstový diferenciační faktor 15 krev MeSH
- senioři MeSH
- upregulace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
GDF-15 (growth differentiation factor 15) je protein, který se fyziologicky vyskytuje v nízkých koncentracích v řadě tkání a orgánů včetně jater, ledvin, srdce nebo plic. Hladiny GDF-15 stoupají v odpovědi na přítomnost zánětu, hypoxii, poškození tkáně, nádorové bujení nebo při probíhající remodelaci myokardu. Zvýšené koncentrace cirkulujícího GDF-15 jsou spojeny s nárůstem mortality u nemocných s akutními koronárními syndromy nebo srdečním selháním. Vyšší hladiny GDF-15 mohou být prediktorem i dalších komplikací akutních koronárních syndromů, včetně krvácení, rizika reinfarktu nebo rozvoje srdečního selhání. Hodnoty GDF-15 je také možné využít jako ukazatele rizika krvácivých komplikací antikoagulační léčby a rizika celkové mortality u nemocných s fibrilací síní. Role GDF-15 jako biomarkeru v kardiologii není však pevně stanovena. Článek přináší přehled aktuálních poznatků o využití GDF-15 v diagnostice kardiovaskulárních onemocnění.
GDF-15 (Growth differentiation factor 15) is a protein synthesised in some tissues including liver, kidney, heart, or lung. GDF-15 a stress-responsive cytokine. GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. GDF-15 is linked to the incidence and prognosis of heart failure. In acute coronary syndromes GDF-15 identifies risk of complications including bleeding, reinfarction, development of heart failure or mortality. In patients with atrial fibrillation, GDF-15 is a potent marker of bleeding adverse events in anticoagulated patients and a predictor of overall mortality. Role of GDF-15 in cardiology is not definitively constituted.
- MeSH
- fibrilace síní diagnóza komplikace prevence a kontrola MeSH
- ischemická choroba srdeční diagnóza komplikace prevence a kontrola MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- růstový diferenciační faktor 15 * analýza účinky léků MeSH
- srdeční selhání * diagnóza prevence a kontrola terapie MeSH
- Check Tag
- lidé MeSH
