AIMS: Validating mapping systems that identify atrial fibrillation (AF) sources (focal/rotational activity) is confounded by the absence of ground truth. A key concern of prior mapping technologies is spatiotemporal instability, manifesting as poor map reproducibility. Electrographic flow (EGF) employs a novel algorithm that visualizes atrial electrical wavefront propagation to identify putative AF sources. We analysed both intra- (3 min) and inter- (>3 months) procedure EGF map reproducibility. METHODS AND RESULTS: In 23 persistent AF patients, after pulmonary vein isolation (PVI), EGF maps were generated from 3 serial 1 min recordings using a 64-electrode basket mapping catheter (triplets) at right and left atrial locations. Source prevalence from map triplets was compared between recordings. Per protocol, 12 patients returned for 3-month remapping (1 non-inducible): index procedure post-PVI EGF maps were compared with initial EGF remapping at 3-month redo. Intra-procedure reproducibility: analysing 224 map triplets (111 right atrium, 113 left atrium) revealed a high degree of map consistency with minimal min-to-min shifts: 97 triplets (43%), exact match of leading sources on all 3 maps; 95 triplets (42%), leading source within 1 electrode space on 2 of 3 maps; and 32 triplets (14%), chaotic leading source pattern. Average deviation in source prevalence over 60 s was low (6.4%). Inter-procedure reproducibility: spatiotemporal stability of EGF mapping >3 months was seen in 16 of 18 (89%) sources mapped in 12 patients with (re)inducible AF. CONCLUSION: Electrographic flow mapping generates reproducible intra- and inter-procedural maps, providing rationale for randomized clinical trials targeting these putative AF sources.
- Klíčová slova
- Basket catheter, Electrographic flow mapping, Panoramic mapping, Persistent atrial fibrillation,
- MeSH
- epidermální růstový faktor MeSH
- fibrilace síní * diagnóza chirurgie MeSH
- katetrizační ablace * metody MeSH
- lidé MeSH
- reprodukovatelnost výsledků MeSH
- srdeční síně MeSH
- venae pulmonales * chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- epidermální růstový faktor MeSH
BACKGROUND: Activity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis. METHODS: We examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified. RESULTS: Levels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up. CONCLUSIONS: This small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.
- Klíčová slova
- ANCA- associated vasculitis, DKK-3, PRO-C6, biomarkers, chronic kidney disease, kidney biopsy, kidney fibrosis,
- MeSH
- ANCA-asociované vaskulitidy * patologie MeSH
- biologické markery moč MeSH
- epidermální růstový faktor MeSH
- fibróza MeSH
- ledviny patologie MeSH
- lidé MeSH
- pilotní projekty MeSH
- protilátky proti cytoplazmě neutrofilů * MeSH
- zánět patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- epidermální růstový faktor MeSH
- protilátky proti cytoplazmě neutrofilů * MeSH
Autologous serum eye drops (ASEDs) are used as a treatment for severe dry eye disease. The concentration and stability of various growth factors in ASEDs is determinative for their efficiency. We therefore assessed the concentrations of transforming growth factor beta 1 (TGF-β1), epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) in ASEDs following storage at 4-8, -20, -80 and -156 °C. Twenty % and 100% sera from eight healthy volunteers were analysed by the sandwich enzyme immunoassay at different time intervals up to seven months. The mean levels of TGF-β1 and EGF in undiluted and 20% serum did not differ significantly from the baseline levels in fresh serum for any storage conditions after 7 days at 4-8 °C, as well as after 4- and 7-month preservation at sub-zero temperatures. In 20% serum, no IGF-1 concentration decrease was found following 7 days of preservation at 4-8 °C. However, a decrease to 78 % and 81 % (P < 0.01) of baseline values was found in 20% serum after 4-month storage at -20 °C and 7-month storage at -156 °C, respectively. A more pronounced decrease in IGF-1 was observed in undiluted serum. All assessed growth factors present in 20% frozen serum remained stable for up to 7 months. The highest stability was achieved at -80 °C. At -20 and -156 °C, some decrease in IGF-1 occurred. Our results indicate that 20% ASEDs can be stored frozen up to 7 months under proper conditions.
- MeSH
- epidermální růstový faktor * MeSH
- insulinu podobný růstový faktor I * metabolismus MeSH
- lidé MeSH
- oční roztoky MeSH
- sérum metabolismus MeSH
- teplota MeSH
- transformující růstový faktor beta1 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- epidermální růstový faktor * MeSH
- insulinu podobný růstový faktor I * MeSH
- oční roztoky MeSH
- transformující růstový faktor beta1 MeSH
The epidermal growth factor (EGF) and its receptor (EGFR) gene-gene interactions were shown to increase the susceptibility to esophageal cancer. However, the role of the EGF/EGFR pathway in the development of gastroesophageal reflux disease (GERD) and its complications (reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC)) remains unclear. This association study is aimed at investigating functional EGF and EGFR gene polymorphisms, their mRNA expression in esophageal tissues, and EGF plasma levels in relation to RE, BE, and EAC development in the Central European population. 301 patients with RE/BE/EAC (cases) as well as 98 patients with nonerosive reflux disease (NERD) and 8 healthy individuals (controls) were genotyped for +61 A>G EGF (rs4444903) and +142285 G>A EGFR (rs2227983) polymorphisms using the TaqMan quantitative polymerase chain reaction (qPCR). In random subgroups, the EGF and EGFR mRNA expressions were analyzed by reverse transcription qPCR in esophageal tissue with and without endoscopically visible pathological changes; and the EGF plasma levels were determined by enzyme-linked immunosorbent assay. None of the genotyped SNPs nor EGF-EGFR genotype interactions were associated with RE, BE, or EAC development (p > 0.05). Moreover, mRNA expression of neither EGF nor EGFR differed between samples of the esophageal tissue with and without endoscopically visible pathology (p > 0.05) nor between samples from patients with different diagnoses, i.e., RE, BE, or EAC (p > 0.05). Nevertheless, the lower EGF mRNA expression in carriers of combined genotypes AA +61 EGF (rs4444903) and GG +142285 EGFR (rs2227983; p < 0.05) suggests a possible direct/indirect effect of EGF-EGFR gene interactions on EGF gene expression. In conclusion, EGF and EGFR gene variants and their mRNA/protein expression were not associated with RE, BE or EAC development in the Central European population.
- MeSH
- adenokarcinom * patologie MeSH
- Barrettův syndrom * metabolismus MeSH
- epidermální růstový faktor genetika MeSH
- erbB receptory genetika metabolismus MeSH
- gastroezofageální reflux * genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- messenger RNA MeSH
- nádory jícnu * patologie MeSH
- peptická ezofagitida * genetika MeSH
- studie případů a kontrol MeSH
- transportní proteiny genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- epidermální růstový faktor MeSH
- erbB receptory MeSH
- messenger RNA MeSH
- transportní proteiny MeSH
The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p < 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p < 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment.
- Klíčová slova
- collagen, cutaneous wounds, cyclooxygenase-2, hydroxyproline, mupirocin, nanoparticles, poly(lactic-co-glycolic) acid, polyunsaturated fatty acids n-3, transforming growth factor,
- MeSH
- epidermální růstový faktor genetika farmakologie MeSH
- hojení ran MeSH
- kolagen metabolismus MeSH
- kopolymer kyseliny glykolové a mléčné farmakologie MeSH
- mupirocin * farmakologie MeSH
- nanočástice * MeSH
- prasata MeSH
- rybí oleje farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- epidermální růstový faktor MeSH
- kolagen MeSH
- kopolymer kyseliny glykolové a mléčné MeSH
- mupirocin * MeSH
- rybí oleje MeSH
Autism spectrum disorder (ASD) represents a serious neurodevelopmental disorder associated with autonomic nervous system dysregulation. The aim was to study complex cardiovascular autonomic regulation using heart rate variability (HRV) and systolic blood pressure variability (SBPV) linear/non-linear analysis at rest and during orthostasis, and to assess plasma levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in autistic children. Twenty-five ASD boys and 25 age and gender-matched children at the age 7-15 years were examined. After venous blood taking, continuous ECG and blood pressure biosignals were recorded at rest and during orthostasis. Evaluated parameters: RR intervals, high- and low-frequency band of HRV spectral analysis (HF-HRV, LF-HRV), symbolic dynamics parameters 0V%, 1V%, 2LV%, 2UV%, low- and high-frequency band of SBPV (LF-SBPV, HF-SBPV), systolic, diastolic, mean blood pressure, EGF, VEGF plasma levels. RR intervals were significantly shortened and the HF-HRV, LF-SBPV, HF-SBPV parameters were significantly lower at rest, the HF-HRV and LF-SBPV remained lower during orthostasis in autistic children compared to controls (p<0.05). EGF plasma levels were significantly lower in ASD compared to controls (p=0.046). No significant differences were found in remaining parameters. Our study revealed tachycardia, cardiovagal underactivity, and blunted sympathetic vasomotor regulation at rest and during orthostasis in autistic children. Additionally, complex heart rate dynamics are similar in autistic children than controls. Furthermore, EGF was reduced in autistic children without significant correlations with any autonomic parameters. We suggest that the abnormal complex cardiovascular reflex control could contribute to understanding the pathway linking autonomic features and autism.
- MeSH
- autonomní nervový systém patofyziologie MeSH
- baroreflex MeSH
- biologické markery krev MeSH
- dítě MeSH
- epidermální růstový faktor krev MeSH
- krevní tlak * MeSH
- lidé MeSH
- mladiství MeSH
- poruchy autistického spektra krev diagnóza patofyziologie MeSH
- srdce inervace MeSH
- srdeční frekvence * MeSH
- vaskulární endoteliální růstový faktor A krev MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- epidermální růstový faktor MeSH
- vaskulární endoteliální růstový faktor A MeSH
- VEGFA protein, human MeSH Prohlížeč
Adrenal incidentalomas (AI) are very common and mostly they are non-functioning adenomas (NFA). NFAs are often associated with insulin resistance and metabolic syndrome. Several biomarkers, including certain growth factors, may participatein the pathogenesis ofmetabolic changes in patients with adrenal adenomas.Patients with NFA and age-matched control subjects were enrolled in the study. Data on age, gender, presence of metabolic syndrome or its components were obtained for each subject. Blood samples were obtained and glycemia, insulinemia, lipid profile, and selected growth factor levels were measured. Forty-three patients with NFA and 40 controls were included in the study. Differences were not found in the metabolic syndrome and its components prevalence or in the biochemical profile between patients and the control group. Significant differences were noticed in the levels of IGF1, IGF2, and IGFBP3 (p=0.016, p=0.005, p=0.004, respectively), but there were no differences in VEGF or EGF concentrations. In NFA patients, an association between glycemia and EGF levels was present (p=0.026). No significant correlations between tumor size and insulin or growth factor concentrations were present in AI patients. Significantly higher serum IGF1, IGF2, and IGFBP3 concentrations in NFA patients may support the role of the IGF axis in the pathogenesis of adrenocortical lesions.No correlation between IGFs or IGFBP3 and parameters of glucose or lipid metabolism was found. Present results may support the role of the growth hormone axis rather than hyperinsulinemia and insulin resistance in the pathogenesis of adrenocortical adenomas.
- MeSH
- adenom kůry nadledvin krev patologie MeSH
- adrenokortikální nádory krev patologie MeSH
- dospělí MeSH
- epidermální růstový faktor krev MeSH
- IGFBP-3 krev MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- insulinu podobný růstový faktor II metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- epidermální růstový faktor MeSH
- IGF1 protein, human MeSH Prohlížeč
- IGF2 protein, human MeSH Prohlížeč
- IGFBP-3 MeSH
- IGFBP3 protein, human MeSH Prohlížeč
- insulinu podobný růstový faktor I MeSH
- insulinu podobný růstový faktor II MeSH
- nádorové biomarkery MeSH
The effects of ER stress on protein secretion by cardiac myocytes are not well understood. In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume. In contrast, another ER stressor, tunicamycin (TM), a protein glycosylation inhibitor, induced NRVM death in all media volumes, suggesting that protective proteins were secreted in response to TG but not TM. Proteomic analyses of TG- and TM-conditioned media showed that the secretion of most proteins was inhibited by TG and TM; however, secretion of several ER-resident proteins, including GRP78 was increased by TG but not TM. Simulated ischemia, which decreases ER/SR calcium also increased secretion of these proteins. Mechanistically, secreted GRP78 was shown to enhance survival of NRVMs by collaborating with a cell-surface protein, CRIPTO, to activate protective AKT signaling and to inhibit death-promoting SMAD2 signaling. Thus, proteins secreted during ER stress mediated by ER calcium depletion can enhance cardiac myocyte viability.
- Klíčová slova
- Cardiac myocyte death, Cardiokine, Cardioprotection, ER stress, Heart failure, Proteostasis,
- MeSH
- apoptóza MeSH
- autokrinní signalizace MeSH
- biologické markery MeSH
- chaperon endoplazmatického retikula BiP MeSH
- epidermální růstový faktor metabolismus MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- membránové glykoproteiny metabolismus MeSH
- myši MeSH
- náchylnost k nemoci MeSH
- nádorové proteiny metabolismus MeSH
- parakrinní signalizace MeSH
- proteom * MeSH
- proteomika * metody MeSH
- sarkoplazmatické retikulum metabolismus MeSH
- signální transdukce účinky léků MeSH
- stres endoplazmatického retikula * účinky léků MeSH
- thapsigargin farmakologie MeSH
- vápník metabolismus MeSH
- vápníková signalizace účinky léků MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- biologické markery MeSH
- chaperon endoplazmatického retikula BiP MeSH
- epidermální růstový faktor MeSH
- Hspa5 protein, mouse MeSH Prohlížeč
- membránové glykoproteiny MeSH
- nádorové proteiny MeSH
- proteom * MeSH
- Tdgf1 protein, mouse MeSH Prohlížeč
- thapsigargin MeSH
- vápník MeSH
INTRODUCTION: The development of metabolic syndrome-associated renal dysfunction is exacerbated by a number of factors including dyslipidemia, ectopic deposition of lipids and their toxic metabolites, impairment of lipid metabolism, and insulin resistance. Renal dysfunction is also affected by the production of proinflammatory and profibrotic factors secreted from adipose tissue, which can in turn directly impair kidney cells and potentiate insulin resistance. In this study, we investigated the manifestation of renal lipid accumulation and its effect on renal dysfunction in a model of metabolic syndrome-the hereditary hypertriglyceridemic rat (HHTg)-by assessing microalbuminuria and targeted urinary proteomics. Male Wistar control rats and HHTg rats were fed a standard diet and observed over the course of ageing at 3, 12, and 20 months of age. RESULTS: Chronically elevated levels of triglycerides in HHTg rats were associated with increased levels of NEFA during OGTT and over a period of 24 hours (+80%, P < 0.01). HHTg animals exhibited qualitative changes in NEFA fatty acid composition, represented by an increased proportion of saturated fatty acids (P < 0.05) and a decreased proportion of n-3 PUFA (P < 0.01). Ectopic lipid deposition in the kidneys of HHTg rats-triglycerides (+30%) and cholesterol (+10%)-was associated with markedly elevated microalbuminuria as ageing increased, despite the absence of microalbuminuria at the young age of 3 months in these animals. According to targeted proteomic analysis, 3-month-old HHTg rats (in comparison to age-matched controls) exhibited increased urinary secretion of proinflammatory parameters (MCP-1, IL-6, IL-8, P < 0.01) and decreased urinary secretion of epidermal growth factor (EGF, P < 0.01) before manifestation of microalbuminuria. Elevation in the urinary secretion of inflammatory cytokines can be affected by increased relative expression of MCP-1 in the renal cortex (P < 0.05). CONCLUSIONS: Our results confirm dyslipidemia and ectopic lipid accumulation to be key contributors in the development of metabolic syndrome-associated renal dysfunction. Assessing urinary secretion of proinflammatory cytokines and epidermal growth factor can help in detecting early development of metabolic syndrome-associated renal dysfunction.
- MeSH
- albuminurie etiologie moč MeSH
- analýza moči MeSH
- biologické markery krev moč MeSH
- časná diagnóza MeSH
- časové faktory MeSH
- cytokiny moč MeSH
- epidermální růstový faktor moč MeSH
- hypertriglyceridemie krev komplikace genetika moč MeSH
- lipidy krev MeSH
- mediátory zánětu moč MeSH
- metabolický syndrom krev komplikace genetika moč MeSH
- modely nemocí na zvířatech MeSH
- nemoci ledvin krev etiologie moč MeSH
- potkani transgenní MeSH
- potkani Wistar MeSH
- prediktivní hodnota testů MeSH
- proteomika * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- cytokiny MeSH
- epidermální růstový faktor MeSH
- lipidy MeSH
- mediátory zánětu MeSH
Colorectal cancer (CRC) is a heterogeneous disease that includes both hereditary and sporadic types of tumors. Tumor initiation and growth is driven by mutational or epigenetic changes that alter the function or expression of multiple genes. The genes predominantly encode components of various intracellular signaling cascades. In this review, we present mouse intestinal cancer models that include alterations in the Wnt, Hippo, p53, epidermal growth factor (EGF), and transforming growth factor β (TGFβ) pathways; models of impaired DNA mismatch repair and chemically induced tumorigenesis are included. Based on their molecular biology characteristics and mutational and epigenetic status, human colorectal carcinomas were divided into four so-called consensus molecular subtype (CMS) groups. It was shown subsequently that the CMS classification system could be applied to various cell lines derived from intestinal tumors and tumor-derived organoids. Although the CMS system facilitates characterization of human CRC, individual mouse models were not assigned to some of the CMS groups. Thus, we also indicate the possible assignment of described animal models to the CMS group. This might be helpful for selection of a suitable mouse strain to study a particular type of CRC.
- Klíčová slova
- carcinoma, consensus molecular subtypes, intestine, oncogenes, signaling cascades, tumor suppressors, tumorigenesis,
- MeSH
- epidermální růstový faktor genetika MeSH
- geny p53 genetika MeSH
- karcinogeneze genetika MeSH
- kolorektální nádory klasifikace metabolismus patofyziologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorová transformace buněk genetika MeSH
- nádory tračníku genetika MeSH
- oprava chybného párování bází DNA genetika MeSH
- protein-serin-threoninkinasy genetika MeSH
- regulace genové exprese u nádorů genetika MeSH
- signální dráha Hippo MeSH
- signální dráha Wnt genetika MeSH
- transformující růstový faktor beta genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- epidermální růstový faktor MeSH
- protein-serin-threoninkinasy MeSH
- transformující růstový faktor beta MeSH
