The study aims to elucidate the therapeutic mechanism of Baicalin (BAI) in alleviating cartilage injury in osteoarthritic (OA) rat models, concentrating on its regulation of the miR-766-3p/AIFM1 axis. An OA rat model was developed with unilateral anterior cruciate ligament transection (ACLT). Interventions comprised of BAI treatment and intra-articular administration of miR-766-3p inhibitor. For evaluation, histopathological staining was conducted to investigate the pathological severity of knee cartilage injury. The levels of oxidative stress (OS) indicators including MDA, SOD, and GSH-Px, were quantified using colorimetric assays. Inflammatory factors (IFs; TNF-?, IL-1?, and IL-6) in knee joint lavage fluids were assessed using ELISA, while RT-PCR was employed to quantify miR-766-3p expression. TUNEL apoptosis staining was utilized to detect chondrocyte apoptosis, and western blotting examined autophagy-related markers (LC3, Beclin, p62), extracellular matrix (ECM) synthesis-associated indices (COL2A, ACAN, MMP13), and apoptosis-inducing factor mitochondrion-associated 1 (AIFM1). Histological examination revealed a marked amelioration of cartilage injury in the BAI-treated OA rat models compared to controls. BAI treatment significantly reduced inflammation and OS of knee joint fluid, activated autophagy, and decreased chondrocyte apoptosis and ECM degradation. Interestingly, the inhibitory effects of BAI on these pathological markers were significantly decreased by the miR-766-3p inhibitor. Further assessment revealed that BAI efficiently promoted miR-766-3p expression while inhibiting AIFM1 protein expression. BAI potentially mitigates articular cartilage injury in OA rats, likely through modulation of miR-766-3p/AIFM1 axis. Keywords: Baicalin, microRNA, AIFM1, Osteoarthritisv, Rat.

• MeSH
• apoptóza účinky léků   MeSH
• faktor vyvolávající apoptózu metabolismus   MeSH
• flavonoidy * farmakologie   terapeutické užití   MeSH
• kloubní chrupavka účinky léků   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• mikro RNA * metabolismus   genetika   biosyntéza   MeSH
• osteoartróza farmakoterapie   metabolismus   patologie   MeSH
• oxidační stres účinky léků   MeSH
• potkani Sprague-Dawley * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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

We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor beta (ERbeta) mRNA levels in tumor was tested. In males with low expression of ERbeta, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERbeta mRNA levels and in females. Accordingly, males with low expression of ERbeta and high expression of miR-30c showed a better survival that those with low expression ERbeta and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERbeta mRNA in tumor tissue.

• MeSH
• beta receptor estrogenů genetika   metabolismus   MeSH
• kohortové studie MeSH
• kolorektální nádory genetika   metabolismus   patologie   MeSH
• lidé MeSH
• mikro RNA biosyntéza   genetika   MeSH
• míra přežití MeSH
• nádorové biomarkery biosyntéza   genetika   MeSH
• prognóza MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Parasitic nematodes transition between dramatically different free-living and parasitic stages, with correctly timed development and migration crucial to successful completion of their lifecycle. However little is known of the mechanisms controlling these transitions. microRNAs (miRNAs) negatively regulate gene expression post-transcriptionally and regulate development of diverse organisms. Here we used microarrays to determine the expression profile of miRNAs through development and in gut tissue of the pathogenic nematode Haemonchus contortus. Two miRNAs, mir-228 and mir-235, were enriched in infective L3 larvae, an arrested stage analogous to Caenorhabditis elegans dauer larvae. We hypothesized that these miRNAs may suppress development and maintain arrest. Consistent with this, inhibitors of these miRNAs promoted H. contortus development from L3 to L4 stage, while genetic deletion of C. elegans homologous miRNAs reduced dauer arrest. Epistasis studies with C. elegans daf-2 mutants showed that mir-228 and mir-235 synergise with FOXO transcription factor DAF-16 in the insulin signaling pathway. Target prediction suggests that these miRNAs suppress metabolic and transcription factor activity required for development. Our results provide novel insight into the expression and functions of specific miRNAs in regulating nematode development and identify miRNAs and their target genes as potential therapeutic targets to limit parasite survival within the host.

• MeSH
• Caenorhabditis elegans genetika   MeSH
• cholesteny farmakologie   MeSH
• delece genu MeSH
• druhová specificita MeSH
• genová ontologie MeSH
• Haemonchus účinky léků   genetika   růst a vývoj   MeSH
• larva MeSH
• messenger RNA genetika   metabolismus   MeSH
• mikro RNA biosyntéza   genetika   MeSH
• proteiny Caenorhabditis elegans genetika   MeSH
• receptor inzulinu genetika   MeSH
• RNA helmintů biosyntéza   genetika   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically "open" state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.

• MeSH
• buněčné linie MeSH
• embryo savčí * MeSH
• fibroblasty cytologie   metabolismus   MeSH
• lidé MeSH
• mikro RNA * biosyntéza   genetika   MeSH
• oktamerní transkripční faktor 3 * biosyntéza   genetika   MeSH
• regulace genové exprese * MeSH
• techniky buněčného přeprogramování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: Phytochemicals are naturally occurring plant-derived compounds and some of them have the potential to serve as anticancer drugs. Based on recent evidence, aberrantly regulated expression of microRNAs (miRNAs) is closely associated with malignancy. MicroRNAs are characterized as small non-coding RNAs functioning as posttranscriptional regulators of gene expression. Accordingly, miRNAs regulate various target genes, some of which are involved in the process of carcinogenesis. RESULTS: This comprehensive review emphasizes the anticancer potential of phytochemicals, either isolated or in combination, mediated by miRNAs. The ability to modulate the expression of miRNAs demonstrates their importance as regulators of tumorigenesis. Phytochemicals as anticancer agents targeting miRNAs are widely studied in preclinical in vitro and in vivo research. Unfortunately, their anticancer efficacy in targeting miRNAs is less investigated in clinical research. CONCLUSIONS: Significant anticancer properties of phytochemicals as regulators of miRNA expression have been proven, but more studies investigating their clinical relevance are needed.

• MeSH
• fytogenní protinádorové látky aplikace a dávkování   farmakologie   MeSH
• karcinogeneze účinky léků   genetika   MeSH
• lidé MeSH
• mikro RNA biosyntéza   genetika   MeSH
• nádory farmakoterapie   genetika   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Secondary prevention of atherosclerotic vascular diseases represents a cascade of procedures to reduce the risk of future fatal and non-fatal cardiovascular events. We sought to determine whether the expression of selected microRNAs influenced mortality of stable chronic cardiovascular patients. METHODS: The plasma concentrations of five selected microRNAs (miR-1, miR-19, miR-126, miR-133 and miR-223) were quantified in 826 patients (mean age 65.2 years) with stable vascular disease (6-36 months after acute coronary syndrome, coronary revascularization or first-ever ischemic stroke). All-cause and cardiovascular mortality rates were followed during our prospective study. RESULTS: Low expression (bottom quartile) of all five miRNAs was associated with a significant increase in five-year all-cause death, even when adjusted for conventional risk factors, treatment, raised troponin I and brain natriuretic protein levels [hazard risk ratios (HRRs) were as follows: miR-1, 1.65 (95% CI: 1.16-2.35); miR-19a, 2.27 (95% CI: 1.59-3.23); miR-126, 1.64 (95% CI: 1.15-2.33); miR-133a, 1.46 (95% CI: 1.01-2.12) and miR-223, 2.05 (95% CI: 1.45-2.91)]. Nearly similar results were found if using five-year cardiovascular mortality as the outcome. However, if entering all five miRNAs (along with other covariates) into a single regression model, only low miR-19a remained a significant mortality predictor; and only in patients with coronary artery disease [3.00 (95% CI: 1.77-5.08)], but not in post-stroke patients [1.63 (95% CI: 0.94-2.86)]. CONCLUSIONS: In stable chronic coronary artery disease patients, low miR-19a expression was associated with a substantial increase in mortality risk independently of other conventional cardiovascular risk factors.

• MeSH
• ateroskleróza krev   genetika   mortalita   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• hodnocení rizik metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA biosyntéza   krev   MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• prospektivní studie MeSH
• rizikové faktory 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
• multicentrická studie MeSH
• Geografické názvy
• Česká republika MeSH

Oocyte developmental competence is acquired during folliculogenesis and regulated by complex molecular mechanisms. Several molecules are involved in these mechanisms, including microRNAs (miRNAs) that are essential for oocyte-specific processes throughout the development. The objective of this study was to identify the expression profile of miRNAs in porcine oocytes derived from follicles of different sizes using RNA deep sequencing. Oocytes were aspirated from large (LO; 3-6 mm) or small (SO; 1.5-1.9 mm) follicles and tested for developmental competence and chromatin configurations. Small RNA libraries were constructed from both groups and then sequenced in an Illumina NextSeq. 500. Oocytes from the LO group exhibited higher developmental competence and different chromatin configuration compared with oocytes from the SO group. In total, 167 and 162 known miRNAs were detected in the LO and SO groups, respectively. MiR-205, miR-16, miR-148a-3p, and miR-125b were among the top 10 highly expressed miRNAs in both groups. Eight miRNAs were differentially expressed (DE) between both groups. Target gene prediction and pathway analysis revealed 46 pathways that were enriched with miRNA-target genes. The oocyte meiosis pathway and signaling pathways including FoxO, PI3K-Akt, and cAMP were predictably targeted by DE miRNAs. These results give more insights into the potential role of miRNAs in regulating the oocyte development.

• MeSH
• chromatin genetika   metabolismus   MeSH
• mikro RNA biosyntéza   MeSH
• oocyty cytologie   metabolismus   MeSH
• oogeneze fyziologie   MeSH
• prasata MeSH
• sekvenční analýza RNA * MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Heliothis zea nudivirus-1 (HzNV-1) is an insect virus that can induce both lytic and latent infections in various insect cell lines. During latent infection, several microRNAs (miRNAs) are produced from persistency-associated gene 1 (pag1) as the only detectable HzNV-1 transcript. Previous studies have shown that the pag1 gene suppresses the immediate-early gene hhi1 and promotes host switching into a latent infection via miRNAs derived from pag1. Although other functions of the miRNAs derived from pag1 have not yet been elucidated, several studies have suggested that miRNAs encoded from latency-associated genes can regulate histone-associated enzymes. Because pag1 is a noncoding transcript, it potentially regulates host chromatin structure through miRNAs upon infection. Nevertheless, the exact mechanism by which pag1 alters viral infections remains unknown. In this study, we found that the pag1-encoded miRNA miR-420 suppresses expression of the histone modification-associated enzyme su(var)3-9. Therefore, this miRNA causes histone modification to promote HzNV-1 infection. These results suggest that HzNV-1 may directly influence epigenetic regulation in host cells through interactions with pag1 miRNAs to promote lytic infection. This study provides us with a better understanding of both the HzNV-1 infection pathway and the relationship between viral miRNAs and epigenetic regulation.

• MeSH
• epigeneze genetická * MeSH
• histony metabolismus   MeSH
• hmyzí proteiny metabolismus   MeSH
• metylace MeSH
• mikro RNA biosyntéza   MeSH
• nukleopolyhedroviry fyziologie   MeSH
• regulace exprese virových genů * MeSH
• RNA virová biosyntéza   MeSH
• Sf9 buňky MeSH
• Spodoptera * metabolismus   virologie   MeSH
• virové proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• dospělí MeSH
• gen SMARCB1 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA biosyntéza   MeSH
• nádorové biomarkery MeSH
• nádory vedlejších dutin nosních genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH