MicroRNAs (miRNAs) have emerged as important regulators of gene expression in various biological processes, including cancer. miR-182-5p has gained attention for its potential implications in gynecologic cancers, including breast, ovarian, endometrial, and cervical cancers. miR-182-5p dysregulation has been associated with multiple facets of tumor biology in gynecologic cancers, including tumor initiation, progression, metastasis, and therapeutic response. Studies have highlighted its involvement in key signaling pathways and cellular processes that contribute to cancer development and progression. In addition, miR-182-5p has shown potential as a diagnostic and prognostic biomarker, with studies demonstrating its correlation with clinicopathological features and patient outcomes. Furthermore, the therapeutic potential of miR-182-5p is being explored in gynecologic cancers. Strategies such as miRNA mimics or inhibitors targeting miR-182-5p have shown promise in preclinical and early clinical studies. These approaches aim to modulate miR-182-5p expression, restoring normal cellular functions and potentially enhancing treatment responses. Understanding the biologic and clinical implications of miR-182-5p in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized medicine approaches. Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.
- MeSH
- Humans MeSH
- MicroRNAs * genetics MeSH
- Biomarkers, Tumor genetics MeSH
- Genital Neoplasms, Female * genetics therapy MeSH
- Prognosis MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. METHODS: We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. RESULTS: The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1). CONCLUSIONS: We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
- MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell * genetics pathology MeSH
- Cyclin D1 genetics metabolism MeSH
- Cyclin-Dependent Kinase Inhibitor p21 * genetics metabolism MeSH
- Cell Cycle Checkpoints * genetics MeSH
- Humans MeSH
- MicroRNAs * genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation genetics MeSH
- Heat-Shock Proteins MeSH
- Gene Expression Regulation, Leukemic MeSH
- Carrier Proteins genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
PURPOSE: Dual velocity encoding PC-MRI can produce spurious artifacts when using high ratios of velocity encoding values (VENCs), limiting its ability to generate high-quality images across a wide range of encoding velocities. This study aims to propose and compare dual-VENC correction methods for such artifacts. THEORY AND METHODS: Two denoising approaches based on spatiotemporal regularization are proposed and compared with a state-of-the-art method based on sign correction. Accuracy is assessed using simulated data from an aorta and brain aneurysm, as well as 8 two-dimensional (2D) PC-MRI ascending aorta datasets. Two temporal resolutions (30,60) ms and noise levels (9,12) dB are considered, with noise added to the complex magnetization. The error is evaluated with respect to the noise-free measurement in the synthetic case and to the unwrapped image without additional noise in the volunteer datasets. RESULTS: In all studied cases, the proposed methods are more accurate than the Sign Correction technique. Using simulated 2D+T data from the aorta (60 ms, 9 dB), the Dual-VENC (DV) error 0.82±0.07$$ 0.82\pm 0.07 $$ is reduced to: 0.66±0.04$$ 0.66\pm 0.04 $$ (Sign Correction); 0.34±0.04$$ 0.34\pm 0.04 $$ and 0.32±0.04$$ 0.32\pm 0.04 $$ (proposed techniques). The methods are found to be significantly different (p-value <0.05$$ <0.05 $$ ). Importantly, brain aneurysm data revealed that the Sign Correction method is not suitable, as it increases error when the flow is not unidirectional. All three methods improve the accuracy of in vivo data. CONCLUSION: The newly proposed methods outperform the Sign Correction method in improving dual-VENC PC-MRI images. Among them, the approach based on temporal differences has shown the highest accuracy.
- MeSH
- Algorithms * MeSH
- Aorta * diagnostic imaging MeSH
- Artifacts * MeSH
- Phantoms, Imaging MeSH
- Image Interpretation, Computer-Assisted methods MeSH
- Intracranial Aneurysm diagnostic imaging MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain diagnostic imaging MeSH
- Computer Simulation MeSH
- Image Processing, Computer-Assisted * methods MeSH
- Signal-To-Noise Ratio * MeSH
- Reproducibility of Results MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
- MeSH
- Amphetamine pharmacology MeSH
- Amygdala physiology MeSH
- Hippocampus * physiology MeSH
- Memory Consolidation * physiology MeSH
- Rats MeSH
- Brain physiology MeSH
- Neurons physiology metabolism MeSH
- Nucleus Accumbens * physiology MeSH
- Reward * MeSH
- Memory physiology MeSH
- Cues MeSH
- Prefrontal Cortex physiology MeSH
- Mental Recall * physiology MeSH
- Machine Learning MeSH
- Ventral Tegmental Area * physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: Asymmetric or unilateral hearing loss (AHL) may cause irreversible changes in the processing of acoustic signals in the auditory system. We aim to provide a comprehensive view of the auditory processing abilities for subjects with acquired AHL, and to examine the influence of AHL on speech perception under difficult conditions, and on auditory temporal and intensity processing. DESIGN: We examined peripheral and central auditory functions for 25 subjects with AHL resulting from vestibular schwannoma, and compared them to those from 24 normal-hearing controls that were matched with the AHL subjects in mean age and hearing thresholds in the healthy ear. Besides the basic hearing threshold assessment, the tests comprised the detection of tones and gaps in a continuous noise, comprehension of speech in babble noise, binaural interactions, difference limen of intensity, and detection of frequency modulation. For the AHL subjects, the selected tests were performed separately for the healthy and diseased ear. RESULTS: We observed that binaural speech comprehension, gap detection, and frequency modulation detection abilities were dominated by the healthy ear and were comparable for both groups. The AHL subjects were less sensitive to interaural delays, however, they exhibited a higher sensitivity to sound level, as indicated by lower difference limen of intensity and a higher sensitivity to interaural intensity difference. Correlations between the individual test scores indicated that speech comprehension by the AHL subjects was associated with different auditory processing mechanisms than for the control subjects. CONCLUSIONS: The data suggest that AHL influences both peripheral and central auditory processing abilities and that speech comprehension under difficult conditions relies on different mechanisms for the AHL subjects than for normal-hearing controls.
- MeSH
- Adult MeSH
- Hearing Loss, Unilateral * physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Speech Perception * physiology MeSH
- Aged MeSH
- Auditory Perception physiology MeSH
- Auditory Threshold * MeSH
- Case-Control Studies MeSH
- Neuroma, Acoustic * physiopathology complications MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The study evaluates the efficacy of RETROICOR (Retrospective Image Correction) in mitigating physiological artifacts within multi-echo (ME) fMRI data. Two RETROICOR implementations were compared: applying corrections to individual echoes (RTC_ind) versus composite multi-echo data (RTC_comp). Data from 50 healthy participants were collected using diverse acquisition parameters, including multiband acceleration factors and varying flip angles, on a Siemens Prisma 3T scanner. Key metrics such as temporal signal-to-noise ratio (tSNR), signal fluctuation sensitivity (SFS), and variance of residuals demonstrated improved data quality in both RETROICOR models, particularly in moderately accelerated runs (multiband factors 4 and 6) with lower flip angles (45°). Differences between RTC_ind and RTC_comp were minimal, suggesting both methods are viable for practical applications. While the highest acceleration (multiband factor 8) degraded data quality, RETROICOR's compatibility with faster acquisition sequences was confirmed. These findings underscore the importance of optimizing acquisition parameters and noise correction techniques for reliable fMRI investigations.
- MeSH
- Artifacts * MeSH
- Adult MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain Mapping * methods MeSH
- Young Adult MeSH
- Brain * diagnostic imaging physiology MeSH
- Image Processing, Computer-Assisted * methods MeSH
- Signal-To-Noise Ratio MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.
- MeSH
- Cell Differentiation * drug effects MeSH
- Chondrocytes metabolism drug effects cytology MeSH
- Cartilage * drug effects MeSH
- Extracellular Matrix * metabolism drug effects MeSH
- Homeostasis drug effects MeSH
- Hydrogels * chemistry MeSH
- Cartilage, Articular drug effects MeSH
- Rats MeSH
- Matrix Metalloproteinases metabolism MeSH
- Mesenchymal Stem Cells cytology drug effects metabolism MeSH
- MicroRNAs genetics metabolism MeSH
- Osteoarthritis therapy pathology MeSH
- Zinc Oxide chemistry MeSH
- Rats, Sprague-Dawley MeSH
- Regeneration MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Only a limited number of biomarkers guide personalized management of pancreatic neuroendocrine tumors (PanNETs). Transcriptome profiling of microRNA (miRs) and mRNA has shown value in segregating PanNETs and identifying patients more likely to respond to treatment. Because miRs are key regulators of mRNA expression, we sought to integrate expression data from both RNA species into miR-mRNA interaction networks to advance our understanding of PanNET biology. METHODS: We used deep miR/mRNA sequencing on six low-grade/high-risk, well-differentiated PanNETs compared with seven non-diseased tissues to identify differentially expressed miRs/mRNAs. Then we crossed a list of differentially expressed mRNAs with a list of in silico predicted mRNA targets of the most and least abundant miRs to generate high probability miR-mRNA interaction networks. RESULTS: Gene ontology and pathway analyses revealed several miR-mRNA pairs implicated in cellular processes and pathways suggesting perturbed neuroendocrine function (miR-7 and Reg family genes), cell adhesion (miR-216 family and NLGN1, NCAM1, and CNTN1; miR-670 and the claudins, CLDN1 and CLDN2), and metabolic processes (miR-670 and BCAT1/MPST; miR-129 and CTH). CONCLUSION: These novel miR-mRNA interaction networks identified dysregulated pathways not observed when assessing mRNA alone and provide a foundation for further investigation of their utility as diagnostic and predictive biomarkers.
- MeSH
- Gene Regulatory Networks MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger * genetics MeSH
- MicroRNAs * genetics MeSH
- Biomarkers, Tumor genetics MeSH
- Pancreatic Neoplasms * genetics pathology diagnosis MeSH
- Neuroendocrine Tumors * genetics pathology diagnosis MeSH
- Pancreas * metabolism pathology MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Gene Expression Profiling MeSH
- Transcriptome MeSH
- High-Throughput Nucleotide Sequencing methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Úvod: Akutní mastoiditida je hnisavý zánět sliznice mastoidních sklípků s rozpadem mezisklípkových kostěných sept. Je to nejčastější intratemporální zánětlivá komplikace středoušního zánětu u dětí. Včasná diagnostika a léčba jsou klíčové pro prevenci šíření zánětu ze spánkové kosti extraa intrakraniálně. Cíl práce: Cílem této retrospektivní studie je analyzovat případy akutní mastoiditidy u dětí na našem pracovišti. Studie se zaměřuje na vyhodnocení incidence akutní mastoiditidy u dětské populace, identifikaci hlavních etiologických agens odpovědných za tuto infekci a analýzu současných terapeutických přístupů, prevence a její afektivity. Materiál a metody: Formou retrospektivní studie byla zpracována data pacientů ošetřených a hospitalizovaných na dětském oddělení a na oddělení ORL KZ, a. s. – Nemocnice Děčín, o.z., v období 1. 1. 2015 – 1. 9. 2022 se stanovenou diagnózou akutní mastoiditida – H-700 dle MKN-10, vyhledáno pomocí nemocničního informačního systému. Výsledky: Do hodnoceného souboru bylo zahrnuto 23 pacientů. Sledovaní pacienti v souboru byli převážně ve věku 12–18 let. Nejméně dětí bylo ve věkové skupině do 6 let. Nejčetnějším původcem v uvedené studii byl Streptococcus pneumoniae se subtypy 3 a 8, na které, jak ukázala studie, vakcína Synflorix není účinná. Všem sledovaným pacientům byla nasazena empirická antibiotická terapie. Ve skupině případů od 12 do 18 let byla terapie antibiotiky zahájena v monoterapii. U mladších pacientů sestávala antibiotická terapie vždy z dvojkombinace antibiotik, jednalo se zejména o dvojkombinaci clindamycin + gentamycin. U 13 z 23 případů byla indikována chirurgická terapie. Ve většině případů se délka hospitalizace nezměnila v závislosti na věku, ani na etiologickém agens, či místě bydliště. Nebyla nalezena závislost mezi typem léčby akutní mastoiditidy a původcem onemocnění či ovlivněním sluchu. Závěr: V naší retrospektivní studii jsme zjistili, že incidence akutní mastoiditidy koreluje se všeobecně známou incidencí v rámci České republiky a celosvětovými daty. Studie prokazuje, že jako nejčastější patogen akutní mastoiditidy u dětí je identifikován Streptococcus pneumoniae. Analýza ukázala, že vakcína Prevenar 13 vykazuje lepší účinnost v prevenci akutní mastoiditidy ve srovnání s vakcínou Synflorix. Tyto výsledky naznačují, že přehodnocení používané vakcinační strategie by mohlo přispět k dalšímu snížení incidence akutní mastoiditidy. Lze konstatovat, že délka rekonvalescence a možné ovlivnění sluchu po léčbě akutní mastoiditidy nemusí záviset na typu mikrobiálního původce. Doporučujeme pokračovat v monitorování a hodnocení účinnosti vakcín a klinických přístupů ke zlepšení prevence a léčby této závažné komplikace středoušního zánětu.
Introduction: Acute mastoiditis is a purulent inflammation of the mastoid mucosa with disintegration of the interstitial bone septa. It is the most common intratemporal inflammatory complication of otitis media in children. Early diagnosis and treatment are crucial to prevent the spread of inflammation from the temporal bone extraand intracranially. Aim of the study: The aim of this retrospective study is to analyze the cases of acute mastoiditis in children in our department. The study aims to evaluate the incidence of acute mastoiditis in the pediatric population, identify the main etiological agents responsible for this infection, and analyze current therapeutic approaches, prevention, and its effectiveness. Materials and methods: The data of patients treated and hospitalized in the children‘s ward and ENT department of KZ, a. s. – Hospital Děčín, o.z., from 1 January 2015 – 1 September 2022 with the diagnosis – acute mastoiditis – H-700 according to ICD-10, were searched using the hospital information system, and were processed in the form of a retrospective study. Results: 23 patients were included in the evaluated cohort. The study population was mainly aged 12–18 years. The smallest number of children were in the age group under 6 years. Streptococcus pneumoniae with subtypes 3 and 8 was the most frequent causative agent in the study, for which the Synflorix vaccine was shown to be ineffective. Empiric antibiotic therapy was administered to all patients studied. In the group of cases aged 12 to 18 years, antibiotic therapy was started in monotherapy. In younger patients, antibiotic therapy always consisted of a double combination of antibiotics, in particular Clindamycin and Gentamycin. Surgical therapy was indicated in 13 of 23 cases. In most cases, the length of hospital stay did not vary with age, etiologic agent, or place of residence. No dependence was found between the type of treatment for acute mastoiditis or the causative agent of the disease or the effect on hearing. Conclusion: In our retrospective study, we found that the incidence of acute mastoiditis correlates with the generally known incidence in the Czech Republic and global data.The study shows that Streptococcus pneumoniae is identified as the most common pathogen of acute mastoiditis in children. The analysis showed that the Prevenar 13 vaccine showed better efficacy in preventing acute mastoiditis compared to the Synflorix vaccine. These results suggest that reassessment of the vaccination strategy used could contribute to further reduction in the incidence of acute mastoiditis. It can be concluded that the length of recovery and possible impact on hearing after treatment of acute mastoiditis may not depend on the type of microbial agent. We recommend continued monitoring and evaluation of vaccine efficacy and clinical approaches to improve prevention and treatment of this serious complication of otitis media.
The disease currently known as frontotemporal dementia (FTD) has undergone a complex evolution from its first description by Arnold Pick and later by Alois Alzheimer, through the first clinicopathological criteria introduced by David Neary and David Mann, to its current nomenclatural perception as a complex clinicopathological entity. Currently, Frontotemporal lobar degeneration is viewed as a heterogeneous syndrome caused by progressive degeneration of the frontal and temporal lobes of the brain. Clinically, it can manifest as three syndromes of frontotemporal dementia (behavioral variant of FTD, progressive non-fluent aphasia and semantic dementia) but also as so-called "overlap" syndromes involving corticobasal degeneration and progressive supranuclear palsy. Its prevalence is about 10 % among all dementias and 40 % among dementias with onset between 45 and 65 years of age. The clinical manifestation of the different subtypes varies, the common denominator being behavioral disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visuo-spatial functions, although preserved for a relatively long time, are superimposed by personality disintegration, fatic, gnostic and executive dysfunction. Compared with Alzheimer's disease, it generally has an earlier age of onset, a more rapid course and more devastating impairment of individual cognitive domains. FTD has a heritability of more than 30 % according to current knowledge. The main genes involved are MAPT, C9orf72 and GRN. More rarely affected genes are VCP, TDP-43, FUS and CHMP2B. In our article, we focus on the genetics of FTD and the clinic-genetic-pathological correlations. We also aim to provide a plastic picture of how individual mutations affect the molecular mechanisms of neurodegeneration.
- MeSH
- Epigenesis, Genetic genetics MeSH
- Frontotemporal Dementia * diagnosis genetics classification MeSH
- Genetic Testing methods MeSH
- Humans MeSH
- Primary Progressive Nonfluent Aphasia diagnosis genetics MeSH
- Progranulins genetics MeSH
- tau Proteins genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
