This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort.
- MeSH
- biologické markery * krev MeSH
- C-reaktivní protein analýza MeSH
- fibrilace síní * krev diagnóza genetika MeSH
- ischemická cévní mozková příhoda * krev diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- natriuretický peptid typu B krev MeSH
- peptidové fragmenty krev MeSH
- prospektivní studie MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Background: Recent research has linked the spread of microribonucleic acid (miRNA) to numerous disorders, either as a stimulant or an inhibitor. One of these is miRNA-22, which research has connected to oxidative stress and thyroid issues. However, the underlying mechanisms are unknown. This study investigates the expression of miRNA-22 in hypothyroid women and its relationship to the rise in oxidative stress in the patient population.Materials and Methods: 40 women patients with Hypothyroid and 40 in this study, healthy volunteers who served as controls were included. The levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH) were measured by sandwich assay, while free triiodothyronine (FT3) and thyroxine (T4) levels were measured competitive binding immunoenzymatic assay. To assess lipid profiles, an automated analyzer was employed. By enzyme-linked immunosorbent assay (ELISA), Interleukin 6 (IL-6) levels were measured. Malondialdehyde (MDA), superoxide dismutase activity (SOD), catalase activity (CAT), and advanced oxidation protein products (AOPPs), and assessed using a colorimetric technique. The quantitative polymerase chain reaction was used to evaluate the expression of serum miRNA-22.Results: Significantly more SOD and CAT activity was identified in patient groups than in the control group (P<0.05), also the patient group's AOPP and MDA concentrations were discovered to significantly outweigh those of the control group. (P< 0.05). IL-6 levels were significantly higher in the patient group than in (P<0.05) the control group. The level of miRNA-22 was higher in the sick group as compared to the control groups (P<0.05).Conclusions: The pathophysiology of oxidative stress brought on by hypothyroidism involves miRNA-22 expression, there is a reciprocal relationship between the increase in gene expression of the miRNA-22 and the increase in oxidative stress, which results in the disease's development.
- MeSH
- biologické markery krev MeSH
- chemické techniky analytické metody přístrojové vybavení MeSH
- dospělí MeSH
- hormony krev MeSH
- hypotyreóza * krev MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- oxidační stres MeSH
- spektrální analýza metody přístrojové vybavení MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.
- MeSH
- biologické markery * krev MeSH
- C-reaktivní protein * analýza metabolismus MeSH
- dospělí MeSH
- glykoproteiny krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- obezita * krev genetika MeSH
- obstrukční spánková apnoe * krev genetika MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sérový amyloidový protein metabolismus analýza genetika MeSH
- sexuální faktory MeSH
- troponin I krev MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Background: Recent evidence has shown that circulating microribonucleic acid (miRNA) has been related to many diseases either as an inhibitor or a stimulant factor, among them miRNA-122 which has proven through studies its relationship with insulin resistance, an adversative lipid profile, obesity, type 2 diabetes, and metabolic syndrome in several studies; however, the mechanisms involved are unknown. This study investigates the role of miRNA-122 expression in overweight patients suffering from metabolic disorders such as diabetes and hypertension and its relationship to the development of oxidative stress in patient groups.Materials and Methods: 30 patients with type 2 diabetes mellitus (T2DM), 30 people with hypertension (HTN), 30 patients with T2DM+HTN, and 30 healthy persons who served as controls were enrolled in this study. An ARCHITECT c4000 clinical chemistry analyzer was used to assess lipid profiles. The sandwich immunodetection approach was used to assess whole blood hemoglobinA1c. By colorimetric methodology, catalase activity (CAT), superoxide dismutase activity (SOD), malondialdehyde (MDA) levels, and advanced oxidation protein products (AOPPs) levels were measured. The expression of serum miRNA-122 was determined using the quantitative polymerase chain reaction.Results: The activity of SOD and CAT in patient groups was found to be substantially lower than in the control group (p < 0.05), whereas MDA and AOPP concentrations were found to be significantly higher in patient groups compared to the control group (p < 0.05). When patient groups were compared to control groups, the miRNA-122 level was higher in the patients (p< 0.05).Conclusions: miRNA-122 expression is involved in the pathogenesis of T2DM and HTN-induced oxidative stress, there is a reciprocal relationship between the increase in gene expression of the miRNA-122 and the increase in oxidative stress accompanied by a decrease in the effectiveness of antioxidant enzymes, which leads to the development of the disease.
- MeSH
- biochemická analýza krve metody přístrojové vybavení statistika a číselné údaje MeSH
- biologické markery krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- malondialdehyd krev MeSH
- metabolické nemoci * krev patologie MeSH
- mikro RNA * krev MeSH
- oxidační stres MeSH
- produkty pokročilé oxidace proteinů krev MeSH
- superoxiddismutasa krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- klinická studie MeSH
BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is indicated in patients with recurrent and symptomatic AF episodes. Despite the strict inclusion/exclusion criteria, AF recurrence after CA remains high. Identification of a novel biomarker that would predict AF recurrence would help to stratify the patients. The aim of the study was to seek novel biomarkers among the plasmatic microRNAs (miRNAs, miRs). METHODS: A prospective monocentric study was conducted. A total of 49 consecutive AF patients indicated for CA were included. Blood sampling was performed prior to CA. RNA was isolated from plasma using commercial kits. In the exploration phase, small RNA sequencing was performed in ten AF patients (five with and five without AF recurrence) using Illumina instrument. In the validation phase, levels of selected miRNAs were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in all participants. RESULTS: Altogether, 22 miRNAs were identified as altered between the groups by next-generation sequencing (using the DESeq2 algorithm). Using qRT-PCR, levels of the five most altered miRNAs (miR-190b/206/326/505-5p/1296-5p) were verified in the whole cohort. Plasma levels of hsa-miR-206 were significantly higher in patients with early (within 6 months) AF recurrence and showed an increase of risk recurrence,2.65 times by every increase in its level by 1 unit in the binary logistic regression. CONCLUSION: We have identified a set of 22 plasmatic miRNAs that differ between the patients with and without AF recurrence after CA and confirmed hsa-miR-206 as a novel miRNA associated with early AF recurrence. Results shall be verified in a larger independent cohort.
- MeSH
- biologické markery * krev MeSH
- fibrilace síní * genetika krev diagnóza chirurgie MeSH
- katetrizační ablace * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev genetika MeSH
- prognóza MeSH
- prospektivní studie MeSH
- recidiva * MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování * 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
Sarcopenia is defined as an age-associated loss of skeletal muscle function and muscle mass and is common in older adults. Sarcopenia as a disease is currently of interest not only to orthopedists and surgeons but also to internists, endocrinologists, rheumatologists, cardiologists, diabetologists, gynaecologists, geriatricians and paediatricians. In cooperation with the 5th Internal Medicine Clinic, we, as a unit of clinical research, aimed to describe a sarcopenic specific miRNA expression profile for disease diagnostics and classification of the severity of muscle performance deterioration. This study included a total of 80 patients (age 55-86 years) hospitalized at the V. Internal medicine clinic of LFUK and UNB with different severity of muscle performance deterioration. The study participants were evaluated and classified according to short physical performance battery score (SPPB). In this study, we investigated the role of circulating miRNAs in sarcopenia in the elderly. We hypothesized that sarcopenia effects the expression of muscle tissue-specific miRNAs (MyomiRNAs), which could be potentially reflected in the blood plasma miRNA expression profile. The expression of specific circulating miRNAs in patients with different muscle performances was analyzed. Patients' blood plasma was evaluated for the expression of myomiRNAs: miRNA-29a, miRNA-29b, miRNA-1, miRNA-133a, miRNA-133b, miRNA-206, miRNA-208b and miRNA-499, and the data were correlated with diagnostic indicators of the disease. We showed a specific sarcopenia miRNA profile that could be considered a possible biomarker for the disease. Patients with low muscle performance showed increased miRNA-1, miRNA-29a and miRNA-29b expression and decreased for the miRNA-206, miRNA-133a, miRNA-133b, miRNA-208b and miRNA-499 expression. We show that the severity of muscle performance deterioration in sarcopenia correlates with specific miRNA expression. We also propose the profile of miRNAs expression in blood plasma as a specific biomarker for sarcopenia diagnostics. Future clinical studies will be necessary to eventually naturally have to elucidate the underlined molecular mechanism responsible for specific miRNAs expression in sarcopenia pathology and progression of the disease.
- MeSH
- biologické markery krev MeSH
- fyzikální vyšetření MeSH
- kosterní svaly patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev MeSH
- sarkopenie krev patofyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Hospitalized patients in internal medicine have an increased risk of low physical reserve which further declines during the hospital stay. The diagnosis requires bed-side testing of functional domains or more complex investigations of the muscle mass. Clinically useful biomarkers of functional status are needed, thus we aimed to explore the potential of microRNAs. Among hospitalized patients, we recorded the basic demographics, anthropometrics, nutritional status, and physical function domains: hand-grip strength (HGS, abnormal values M<30 kg, W<20 kg), balance (<30 s), chair-stands speed (CHSS<0.5/s) and gait speed (GS<0.8 m/s). A panel of five micro-RNAs (miRNA 1, miRNA 133a, miRNA 133b, miRNA 29a, miRNA 29b) and basic blood biochemistry and vitamin D values were recorded. We enrolled 80 patients (M40, W40), with a mean age of 68.8±8.4 years. Obesity was observed in 27.5 % and 30 %, low HGS and low CHSS in 65.0, 77.5 %, and 80, 90 % of men and women respectively. The median hospital stay was 6.5 days. MiRNA29a and miRNA29b have the strongest correlation with the triceps skinfold (miRNA 29b, r=0.377, p=0.0006) and CHSS (miRNA 29a, r=0.262, p=0.02). MiRNA 29a, miRNA 29b and 133a levels were significantly higher in patients with CHSS<0.5/s. Other anthropometric parameters, mobility domains, or vitamin D did not correlate. All miRNAs except of miRNA 1, could predict low CHSS (miRNA29b, AUROC=0.736 CI 0.56-0.91, p=0.01), particularly in patients with low HGS (miRNA 29b, AUROC=0.928 CI 0.83-0.98). Among hospitalized patients in internal medicine, low functional status was frequent. MicroRNAs were fair biomarkers of the antigravity domain, but not other domains. Larger studies with clinical endpoints are needed.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- fyzikální vyšetření statistika a číselné údaje MeSH
- hospitalizovaní pacienti statistika a číselné údaje MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev MeSH
- senioři MeSH
- tělesná výkonnost fyziologie MeSH
- vnitřní lékařství MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies.
- MeSH
- dospělí MeSH
- fyziologie výživy genetika MeSH
- kardiometabolické riziko MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA krev MeSH
- metabolický syndrom genetika prevence a kontrola MeSH
- mikro RNA krev MeSH
- nutrigenomika MeSH
- ochranné látky farmakologie MeSH
- polyfenoly farmakologie MeSH
- signální transdukce genetika MeSH
- výpočetní biologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Cardiovascular comorbidities are independent risk factors for mortality in dialysis patients. MicroRNA signaling has an important role in vascular aging and cardiac health, while physical activity is a primary nonpharmacologic treatment for cardiovascular comorbidities in dialysis patients. To identify the relationships between muscle function, miRNA signaling pathways, the presence of vascular calcifications and the severity of cardiovascular comorbidities, we initially enrolled 90 subjects on hemodialysis therapy and collected complete data from 46 subjects. A group of 26 subjects inactiv group (INC) was monitored during 12 weeks of physical inactivity and another group of 20 patients exercise group (EXC) was followed during 12 weeks of intradialytic, moderate intensity, resistance training intervention applied three times per week. In both groups, we assessed the expression levels of myo-miRNAs, proteins, and muscle function (MF) before and after the 12-week period. Data on the presence of vascular calcifications and the severity of cardiac comorbidities were collected from the patients' EuCliD® records. Using a full structural equitation modelling of the total study sample, we found that the higher the increase in MF was observed in patients, the higher the probability of a decrease in the expression of miR-206 and TRIM63 and the lower severity of cardiac comorbidities. A reduced structural model in INC patients showed that the higher the decrease in MF, the higher the probability of the presence of calcifications and the higher severity of cardiac comorbidities. In EXC patients, we found that the higher the increase in MF, the lower the probability of higher severity of cardiovascular comorbidities.
- MeSH
- cévní endotel metabolismus MeSH
- cvičení fyziologie MeSH
- dialýza ledvin * MeSH
- kardiovaskulární nemoci krev genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA biosyntéza krev genetika MeSH
- sedavý životní styl MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- stárnutí krev genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
One of the principal mechanisms of chemotherapy resistance in highly frequent solid tumors, such as colorectal cancer (CRC), is the decreased activity of drug transport into tumor cells due to low expression of important membrane proteins, such as solute carrier (SLC) transporters. Sequence complementarity is a major determinant for target gene recognition by microRNAs (miRNAs). Single-nucleotide polymorphisms (SNPs) in target sequences transcribed into messenger RNA may therefore alter miRNA binding to these regions by either creating a new site or destroying an existing one. miRSNPs may explain the modulation of expression levels in association with increased/decreased susceptibility to common diseases as well as in chemoresistance and the consequent inter-individual variability in drug response. In the present study, we investigated whether miRSNPs in SLC transporter genes may modulate CRC susceptibility and patient's survival. Using an in silico approach for functional predictions, we analyzed 26 miRSNPs in 9 SLC genes in a cohort of 1368 CRC cases and 698 controls from the Czech Republic. After correcting for multiple tests, we found several miRSNPs significantly associated with patient's survival. SNPs in SLCO3A1, SLC22A2 and SLC22A3 genes were defined as prognostic factors in the classification and regression tree analysis. In contrast, we did not observe any significant association between miRSNPs and CRC risk. To the best of our knowledge, this is the first study investigating miRSNPs potentially affecting miRNA binding to SLC transporter genes and their impact on CRC susceptibility or patient's prognosis.
- MeSH
- 3' nepřekládaná oblast genetika MeSH
- adjuvantní chemoterapie MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory krev genetika mortalita terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru epidemiologie prevence a kontrola MeSH
- messenger RNA krev genetika MeSH
- mikro RNA krev metabolismus MeSH
- následné studie MeSH
- přenašeče organických aniontů genetika MeSH
- prognóza MeSH
- proteiny přenášející organické kationty genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- transportér organických kationtů 2 genetika MeSH
- vazebná místa genetika MeSH
- výpočetní biologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH