Obesity is considered an important factor contributing to the development of atherosclerosis. Inflammation plays a key role in endothelial dysfunction (ED), an initial stage of the atherosclerotic process. Several microRNAs (miRNAs) may play an important role in the inflammatory process, but there is a lack of information about their participation in the early stages of atherosclerosis development in patients with obesity. We aimed to assess the relations between plasma concentration of selected miRNAs, ED evaluated by reactive hyperemia index (RHI), inflammatory markers and other factors involved in the pathogenesis of atherosclerosis in adolescents and young adults with obesity. Participants (30 males, 30 females; aged 15 25 years) were divided into two groups: those with overweight/obesity (OW/O) (20 males, 20 females) and controls (C) (10 males, 10 females). The plasma concentrations of inflammatory markers, cytokines, adipocytokines, markers of lipid profile and glucose metabolism and selected miRNAs (miR 92, 126, -146a, -155) were analyzed. No significant differences in any of the miRNAs were found between the groups. MiR-146a correlated positively with RHI. Dividing the group by sex showed more significant associations between miRNA and analyzed parameters (IL-6, fasting glycemia) in men. Several observed correlations indicate a potential role of miRNAs in inflammation, the atherosclerotic process and glycemic control, primarily in male subjects with obesity. The relatively low number of observed associations between assessed parameters related to obesity and the pathogenesis of its complications could be attributed to the early stage of the atherosclerotic process in young subjects with obesity, where only subtle abnormalities are expectedly found. Key words Endothelial dysfunction, Atherosclerosis, Obesity, MicroRNA, Reactive hyperemia index.
- MeSH
- ateroskleróza * krev genetika MeSH
- biologické markery krev MeSH
- cirkulující mikroRNA * krev genetika MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- obezita * krev komplikace genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Karcinom prostaty je jedním z nejčastějších onkologických onemocnění mužů ve světě. Diagnostika a stratifikace pacientů jsou klíčové pro zajištění včasné a adekvátní terapie. Současné standardy se opírají převážně o PSA, jehož nádorová specificita je limitována. Tento přehled se zaměřuje na neinvazivní potenciální onkomarkery získané z moči včetně oxidačního stresu, metabolomiky a analýzy nukleových kyselin. V rámci některých studií se ukazuje, že zvýšené hladiny markerů jako F2-isoprostanáza, sarcosin a PCA3 mohou indikovat přítomnost a agresivitu karcinomu prostaty. Nové kombinované testy Prostarix, Mi-Prostate Score, SelectMDX nebo ExoDX nabízejí potenciál pro zlepšení stratifikace pacientů a snížení počtu negativních biopsií. Klinické využití těchto nových markerů je zatím omezené. Vzhledem k heterogenitě tohoto onemocnění je nezbytné pokračovat ve výzkumu, který usnadní personalizovaný přístup v léčbě.
Prostate cancer is one of the most common oncological diseases among men worldwide. Accurate diagnosis and patient stratification are crucial for ensuring timely and appropriate therapy. Current standards primarily rely on PSA, whose tumor specificity is limited. This review focuses on non-invasive potential oncological markers derived from urine, including oxidative stress, metabolomics and nucleic acid analysis. Some studies indicate that elevated levels of markers such as F2-isoprostane, sarcosine or PCA3 may signify the presence and aggressiveness of prostate cancer. New combined tests Prostarix, Mi-Prostate Score, SelectMDX and ExoDX offer potential for improved diagnosis and patient stratification, as well as a reduction in negative biopsies. However, the clinical application of these new markers remains limited. Considering the heterogeneity of this disease, ongoing research is essential to support a personalized approach to treatment.
- MeSH
- aminokyseliny moč MeSH
- biopsie metody MeSH
- časná detekce nádoru metody MeSH
- diagnostické techniky molekulární MeSH
- exozómy fyziologie MeSH
- lidé MeSH
- metabolomika metody MeSH
- mikro RNA moč MeSH
- nádorové biomarkery * moč MeSH
- nádory prostaty * diagnóza MeSH
- oxidační stres fyziologie MeSH
- prostatický specifický antigen krev MeSH
- Check Tag
- lidé MeSH
INTRODUCTION: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear. METHODS: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study. RESULTS: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants. DISCUSSION: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses. HIGHLIGHTS: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study.
- MeSH
- Alzheimerova nemoc * genetika metabolismus MeSH
- čichová sliznice metabolismus MeSH
- epigenomika MeSH
- faktor 2 související s NF-E2 genetika metabolismus MeSH
- látky znečišťující vzduch škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * MeSH
- mikro RNA metabolismus genetika MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transkriptom MeSH
- výfukové emise vozidel * toxicita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The potential of microRNAs to protect the female reproductive system from the toxic influence of oil-related environmental contaminants has not yet been examined. The aim of the present study was to examine the ability of the microRNA miR-152 to prevent the toxic effects of toluene on ovarian cells. Porcine ovarian granulosa cells transfected or not transfected with miR-152 mimics were cultured with or without toluene (0, 10 and 100 ng/ml). The expression of miR-152; cell viability; proliferation (accumulation of PCNA, cyclin B1 and BrdU); cytoplasmic/mitochondrial apoptosis (accumulation of bax and caspase 3); and release of progesterone, testosterone and estradiol were quantified via RT-qPCR, the Trypan blue exclusion test, quantitative immunocytochemistry, the BrdU assay and ELISA. The addition of toluene reduced cell viability, decreased the levels of all the measured markers of proliferation and the release of all the measured steroid hormones, and promoted the expression of apoptosis markers. Transfection of cells with miR-152 mimics increased the expression of miR-152, cell proliferation, and progesterone release but reduced apoptosis and the release of testosterone and estradiol. Moreover, miR-152 prevented or inhibited all the toluene effects in addition to its inhibitory effect on testosterone and estradiol release. The present results demonstrate that miR-152 can protect ovarian cells from the harmful influence of toluene.
- MeSH
- apoptóza * účinky léků MeSH
- estradiol MeSH
- folikulární buňky * účinky léků metabolismus MeSH
- kultivované buňky MeSH
- mikro RNA * metabolismus genetika MeSH
- prasata MeSH
- progesteron metabolismus MeSH
- proliferace buněk účinky léků MeSH
- toluen * toxicita MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Infiltrated and activated M1 macrophages play a role in kidney injury and fibrosis during chronic kidney disease (CKD) progression. However, the specific ways that M1 macrophage polarization contributes to renal fibrosis are not fully understood. The study seeks to investigate how miR-92a-3p regulates M1 macrophage polarization and its connection to renal fibrosis in the development of CKD. Our results revealed that miR-92a-3p overexpression increased M1-macrophage activation, iNOS, IL-6, and TNF-alpha expression in RAW264.7 upon LPS stimulation. LIN28A overexpression reversed these effects. Moreover, miR-92a-3p overexpression in RAW264.7 exacerbated NRK-52E cell apoptosis induced by LPS, but LIN28A overexpression counteracted this effect. MiR-92a-3p knockout in unilateral ureteral obstruction (UUO) C57BL/6 mice led to reduced renal infiltration and fibrosis, accompanied by decreased iNOS, alpha-SMA, IL-6, TNF-alpha, and increased LIN28A. In summary, our findings suggest that miR-92a-3p may play a role in promoting renal injury and fibrosis both in vitro and in vivo. This effect is potentially achieved by facilitating M1 macrophage polarization through the targeting of LIN28A.
- MeSH
- aktivace makrofágů MeSH
- fibróza * MeSH
- ledviny patologie metabolismus MeSH
- makrofágy * metabolismus patologie MeSH
- mikro RNA * metabolismus genetika MeSH
- myši inbrední C57BL * MeSH
- myši knockoutované MeSH
- myši MeSH
- proteiny vázající RNA * metabolismus genetika MeSH
- RAW 264.7 buňky MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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
Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3'-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.
- MeSH
- apoptóza * genetika MeSH
- cyklin-dependentní kinasa 2 * metabolismus genetika MeSH
- kruhová RNA * genetika metabolismus MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory plic * genetika patologie metabolismus MeSH
- nemalobuněčný karcinom plic * genetika patologie metabolismus MeSH
- proliferace buněk * genetika MeSH
- proteiny aktivující GTPasu genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- signální transdukce genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
DNA ligase 1 (LIG1) plays a key role in DNA synthesis and DNA damage repair pathways. LIG1 has been shown to be up-regulated in human non-small cell lung cancer (NSCLC); however, its role and molecular regulatory mechanism in NSCLC cell proliferation are still not fully understand. In this study, we aimed to explore the role of LIG1 and post-transcripional regulators in NSCLC. Utilizing bioinformatic tools and qRT-PCR, our investigation substantiated the up-regulation of LIG1 within NSCLC cell lines and tumour tissues. Remarkably, individuals exhibiting elevated levels of LIG1 had diminished survival rates. Functionally, the depletion of LIG1 inhibited cell proliferation and migration, contrasting with the increased proliferation and migration upon LIG1 over-expression. Prediction from the TargetScanHuman database and results of dual luciferase reporter assays indicated that miR-325 could directly bind to and negatively regulate LIG1. Moreover, our findings demonstrated that the mimicry of miR-325 decreased cell viability, whereas its inhibition correspondingly increased viability, indicative of the tumour-suppressive role of miR-325 through the down-regulation of LIG1. Collectively, our findings show that LIG1 could promote tumour progression and knockdown of LIG1 could exert suppressive effects on NSCLC. As the post-transcriptional factor of LIG1, miR-325 could negatively regulate the expression of LIG1 to inhibit tumour progression in vitro. These findings suggest that LIG1 and miR-325 might be potential therapeutic targets for NSCLC treatment.
- MeSH
- DNA-ligasa ATP * metabolismus genetika MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory plic * patologie genetika metabolismus MeSH
- nemalobuněčný karcinom plic * genetika patologie metabolismus MeSH
- pohyb buněk * MeSH
- proliferace buněk * MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. Lamin A KO manifested a more pronounced effect in SHSY5Y cells compared to A375 cells, evident by changes in cell morphology, increased cell proliferation, and oncogenic miRNA expression. Moreover, AGO fPAR-CLIP in Lamin A KO SHSY5Y cells revealed significantly reduced RNAi activity. Further exploration of the nuclear AGO interactome by mass spectrometry identified FAM120A, an RNA-binding protein and known interactor of AGO2. Subsequent FAM120A fPAR-CLIP, revealed that FAM120A co-binds AGO targets and that this competition reduces the RNAi activity. Therefore, loss of Lamin A triggers nuclear AGO2 translocation, FAM120A mediated RNAi impairment, and upregulation of oncogenic miRNAs, facilitating cancer cell proliferation.
- MeSH
- aktivní transport - buněčné jádro MeSH
- Argonaut proteiny * metabolismus genetika MeSH
- buněčné jádro * metabolismus MeSH
- lamin typ A * metabolismus genetika MeSH
- lidé MeSH
- melanom genetika metabolismus patologie MeSH
- mikro RNA * metabolismus genetika MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * genetika MeSH
- proteiny vázající RNA metabolismus genetika MeSH
- RNA interference * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
