Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.
- Klíčová slova
- AC016405.3, ADAMTs9-AS2, AGAP2-AS1, AHIF, ANRIL, CASC2, CASC7, CASC9, CCND2-AS1, CRNDE, DCST1-AS1, DGCR5, DLEU1-AS1, ECONEXIN, FAM66C, GAS5, H19, HMMR-AS1, HOTAIR, HOTAIRM1, HOTTIP, HOXA-AS2, HOXB13-1, HULC, KTN1-AS1, LINC-ROR, LINC00461, LINC00467, LINC00565, LINC00641, LINC01393, LINC01426, LINC01446, LINC01494, LINC01503, LINC01711, LINC02283, MAFG-DT, MALAT1, MATN1-AS1, MDC1-AS, MEG3, MIAT, MIR210HG, MNX1-AS1, NCK1-AS1, NEAT1, PART1, PARTICLE, PCA1, PCAT1, PVT1, RBPMS-AS1, RPSAP52, RUNX1-IT1, SAMMSON, SOX2-OT, TALNEC2, TP73-AS1, TSLC1-AS1, TUG1, TUNAR, TUSC7, UCA1, XIST, ZBED3-AS1, ZEB1-AS1, biomarker, blood, glioblastoma multiforme, glioma, liquid biopsy, lnc-TALC, lncRNA, lncRNA-ATB, noncoding RNA, plasma, serum,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Currently, with the knowledge of the role of collateral circulation in the development of cerebral ischaemia, traditional therapeutic windows are being prolonged, with time not being the only criterion. Instead, a more personalised approach is applied to select additional patients who might benefit from active treatment. This review briefly describes the current knowledge of the pathophysiology of the development of early ischaemic changes, the capabilities of MRI to depict such changes, and the basics of the routinely used imaging techniques broadly available for the assessment of individual phases of cerebral ischaemia, and summarises the possible clinical use of routine MR imaging, including patient selection for active treatment and assessment of the outcome on the basis of imaging.
- Klíčová slova
- DWI-ASPECTS, DWI-FLAIR mismatch, Ischaemic stroke,
- MeSH
- cerebrální infarkt MeSH
- cévní mozková příhoda * diagnostické zobrazování terapie MeSH
- difuzní magnetická rezonance metody MeSH
- edém mozku * MeSH
- ischemická cévní mozková příhoda * MeSH
- ischemie mozku * diagnostické zobrazování terapie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The heterogeneity of the glioma subtype glioblastoma multiforme (GBM) challenges effective neuropathological treatment. The reliance on in vitro studies and xenografted animal models to simulate human GBM has proven ineffective. Currently, a dearth of knowledge exists regarding the applicability of cell line biomolecules to the realm of GBM pathogenesis. Our study's objectives were to address this preclinical issue and assess prominin-1, ICAM-1, PARTICLE and GAS5 as potential GBM diagnostic targets. The methodologies included haemoxylin and eosin staining, immunofluorescence, in situ hybridization and quantitative PCR. The findings identified that morphology correlates with malignancy in GBM patient pathology. Immunofluorescence confocal microscopy revealed prominin-1 in pseudo-palisades adjacent to necrotic foci in both animal and human GBM. Evidence is presented for an ICAM-1 association with degenerating vasculature. Significantly elevated nuclear PARTICLE expression from in situ hybridization and quantitative PCR reflected its role as a tumor activator. GAS5 identified within necrotic GBM validated this potential prognostic biomolecule with extended survival. Here we present evidence for the stem cell marker prominin-1 and the chemotherapeutic target ICAM-1 in a glioma animal model and GBM pathology sections from patients that elicited alternative responses to adjuvant chemotherapy. This foremost study introduces the long non-coding RNA PARTICLE into the context of human GBM pathogenesis while substantiating the role of GAS5 as a tumor suppressor. The validation of GBM biomarkers from cellular models contributes to the advancement towards superior detection, therapeutic responders and the ultimate attainment of promising prognoses for this currently incurable brain cancer.
AIMS: The main objective of this study was to determine the sensitivity of abdominal ultrasonography (US) in patients with isoattenuating pancreatic carcinoma and to compare the frequency of secondary signs on abdominal US and endoscopic ultrasonography (EUS) in these tumours. METHODS: Twenty-four patients with histologically or cytologically verified isoattenuating pancreatic carcinoma who underwent abdominal US, contrast-enhanced CT and EUS of the pancreas as part of the diagnostic workup were included in this retrospective study. The sensitivity of abdominal US in detecting the isoattenuating pancreatic carcinoma was investigated and the frequency of secondary signs of isoattenuating pancreatic carcinoma on abdominal US and EUS was compared. RESULTS: In 5 of 24 patients (21%) with isoattenuating pancreatic carcinoma, a hypoechogenic pancreatic lesion was directly visualised on abdominal US. Secondary signs were present on US in 21 patients (88%). These included dilatation of the common bile duct and/or intrahepatic bile ducts in 19/24 (79%), dilatation of the pancreatic duct in 3/24 (13%), abnormal contour/inhomogeneity of the pancreas in 1/24 (4%), and atrophy of the distal parenchyma in 1/24 (4%). Pancreatic duct dilatation was observed more frequently on EUS than on abdominal US (P=0.002). For other secondary signs, there was no significant difference in their detection on abdominal US and EUS (P=0.61-1.00). CONCLUSION: Abdominal US is capable of detecting secondary signs of isoattenuating pancreatic carcinoma with high sensitivity and has the potential to directly visualise these tumours.
- Klíčová slova
- computed tomography, endoscopic ultrasonography, isoattenuating, pancreatic cancer, ultrasonography, ultrasound,
- MeSH
- lidé MeSH
- nádory slinivky břišní * diagnostické zobrazování patologie MeSH
- počítačová rentgenová tomografie * MeSH
- retrospektivní studie MeSH
- ultrasonografie MeSH
- vývody pankreatu diagnostické zobrazování patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (ADME) can influence individual response to a therapeutic treatment. The study of ADME genetic diversity in human populations has led to evolutionary hypotheses of adaptation to distinct chemical environments. Population differentiation in measured drug metabolism phenotypes is, however, scarcely documented, often indirectly estimated via genotype-predicted phenotypes. We administered seven probe compounds devised to target six cytochrome P450 enzymes and the P-glycoprotein (P-gp) activity to assess phenotypic variation in four populations along a latitudinal transect spanning over Africa, the Middle East, and Europe (349 healthy Ethiopian, Omani, Greek, and Czech volunteers). We demonstrate significant population differentiation for all phenotypes except the one measuring CYP2D6 activity. Genome-wide association studies (GWAS) evidenced that the variability of phenotypes measuring CYP2B6, CYP2C9, CYP2C19, and CYP2D6 activity was associated with genetic variants linked to the corresponding encoding genes, and additional genes for the latter three. Instead, GWAS did not indicate any association between genetic diversity and the phenotypes measuring CYP1A2, CYP3A4, and P-gp activity. Genome scans of selection highlighted multiple candidate regions, a few of which included ADME genes, but none overlapped with the GWAS candidates. Our results suggest that different mechanisms have been shaping the evolution of these phenotypes, including phenotypic plasticity, and possibly some form of balancing selection. We discuss how these contrasting results highlight the diverse evolutionary trajectories of ADME genes and proteins, consistent with the wide spectrum of both endogenous and exogenous molecules that are their substrates.
- Klíčová slova
- ADME genes, drug metabolism phenotypes, genome-wide association studies, genome-wide selection scans, human evolution,
- MeSH
- celogenomová asociační studie * MeSH
- cytochrom P-450 CYP2D6 * genetika MeSH
- fenotyp MeSH
- genomika MeSH
- lidé MeSH
- xenobiotika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytochrom P-450 CYP2D6 * MeSH
- xenobiotika MeSH
Adaptive immunity changes over an individual’s lifetime, maturing by adulthood and diminishing with old age. Epigenetic mechanisms involving DNA and histone methylation form the molecular basis of immunological memory during lymphocyte development. Monocytes alter their function to convey immune tolerance, yet the epigenetic influences at play remain to be fully understood in the context of lifespan. This study of a healthy genetically homogenous cohort of children, adults and seniors sought to decipher the epigenetic dynamics in B-lymphocytes and monocytes. Variable global cytosine methylation within retro-transposable LINE-1 repeats was noted in monocytes compared to B-lymphocytes across age groups. The expression of the human leukocyte antigen (HLA)-DQ alpha chain gene HLA-DQA1*01 revealed significantly reduced levels in monocytes in all ages relative to B-lymphocytes, as well as between lifespan groups. High melting point analysis and bisulfite sequencing of the HLA-DQA1*01 promoter in monocytes highlighted variable cytosine methylation in children and seniors but greater stability at this locus in adults. Further epigenetic evaluation revealed higher histone lysine 27 trimethylation in monocytes from this adult group. Chromatin immunoprecipitation and RNA pulldown demonstrated association with a novel lncRNA TINA with structurally conserved similarities to the previously recognized epigenetic modifier PARTICLE. Seeking to interpret the epigenetic immunological landscape across three representative age groups, this study focused on HLA-DQA1*01 to expose cytosine and histone methylation alterations and their association with the non-coding transcriptome. Such insights unveil previously unknown complex epigenetic layers, orchestrating the strength and weakening of adaptive immunity with the progression of life.
- Klíčová slova
- ChIP, HLA, PARTICLE, TINA, histone, long non-coding RNA, methylation,
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: While the role of physiotherapy as part of a comprehensive inpatient rehabilitation is indisputable, clear evidence concerning the effectiveness of different rehabilitation managements [interdisciplinary implementing the International Classification of Functioning, disability and health (ICF) vs. multidisciplinary model] and physiotherapy categories (neuroproprioceptive "facilitation, inhibition" vs. motor/skill acquisitions using technologies) are still lacking. In this study, four kinds of comprehensive inpatient rehabilitation with different management and content of physical therapy will be compared. Moreover, focus will be placed on the identification of novel biological molecules reflective of effective rehabilitation. Long non-coding RNAs (lncRNAs) are transcripts (>200 bps) of limited coding potential, which have recently been recognized as key factors in neuronal signaling pathways in ischemic stroke and as such, may provide a valuable readout of patient recovery and neuroprotection during therapeutic progression. METHODS AND ANALYSIS: Adults after the first ischemic stroke in an early sub-acute phase with motor disability will be randomly assigned to one of four groups and undergo a 3 weeks comprehensive inpatient rehabilitation of different types: interdisciplinary team work using ICF model as a guide; multidisciplinary teamwork implementing neuroproprioceptive "facilitation and inhibition" physiotherapy; multidisciplinary teamwork implementing technology-based physiotherapy; and standard multidisciplinary teamwork. Primary (the Goal Attainment Scale, the Patient-Reported Outcomes Measurement Information System, and the World Health Organization Disability Assessment Schedule) and secondary (motor, cognitive, psychological, speech and swallowing functions, functional independence) outcomes will be measured. A blood sample will be obtained upon consent (20 mls; representing pre-rehabilitation molecular) before and after the inpatient program. Primary outcomes will be followed up again 3 and 12 months after the end of the program. The overarching aim of this study is to determine the effectiveness of various rehabilitation managements and physiotherapeutic categories implemented by patients post ischemic stroke via analysis of primary, secondary and long non-coding RNA readouts. This clinical trial will offer an innovative approach not previously tested and will provide new complex analysis along with public assessable molecular biological evidence of various rehabilitation methodology for the alleviation of the effects of ischemic stroke. CLINICAL TRIAL REGISTRATION: NCT05323916, https://clinicaltrials.gov/ct2/show/NCT05323916.
Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) on T lymphocytes. This fundamental mechanism of adaptive immunity has broadened upon recognition of extracellular exosomal MHC, raising awareness of an alternative means for antigen presentation. This study demonstrates that conditioned growth media (CGM) previously exposed to monocyte-derived dendritic cells from CeD significantly downregulates the CD3+ lineage marker of control T cells. Such increased activation was reflected in their elevated IL-2 secretion. Exosome localization motif identification and quantification within HLA-DQA1 and HLA-DQB1 transcripts highlighted their significant prevalence within HLA-DQB1 alleles associated with CeD susceptibility. Flow cytometry revealed the strong correlation between HLA-DQ and the CD63 exosomal marker in T cells exposed to CGM from MoDCs sourced from CeD patients. This resulted in lower concentrations of CD25+ CD127- T cells, suggestive of their compromised induction to T-regulatory cells associated with CeD homeostasis. This foremost comparative study deciphered the genomic basis and extracellular exosomal effects of HLA transfer on T lymphocytes in the context of CeD, offering greater insight into this auto-immune disease.
- Klíčová slova
- autoimmunity, exosome, gluten, major histocompatibility complex II, monocyte-derived dendritic cells,
- MeSH
- alely MeSH
- celiakie * MeSH
- gluteny genetika MeSH
- HLA-DQ antigeny genetika MeSH
- lidé MeSH
- regulační T-lymfocyty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- gluteny MeSH
- HLA-DQ antigeny MeSH
AIMS: To evaluate the estimated fetal radiation dose during prophylactic internal iliac arterial occlusion in patients with abnormal placenta and to estimate the risk of radiation induced cancer in child age. METHODS: Prophylactic occlusion of the internal iliac arteries during Caesarean section was performed in 42 patients with placenta praevia and/or placenta accreta spectrum. Fogarty embolectomy catheters were used for prophylactic occlusion of the internal iliac arteries. All procedures were performed in the hybrid operating room using Philips Allura Xper FD 20 X-ray system. Low dose X-ray fluoroscopy (7.5 frames per second) was used. The CODE (Conceptus dose estimation) Software was used to estimate the fetal dose and the risk of radiation induced carcinoma. RESULTS: Fluoroscopy times required for insertion of Fogarty catheters were 0.5-4.2 min (mean: 1.7 min, median: 1.5 min). The estimated radiation dose to the fetus was 0.26-3.36 mGy (mean: 1.49 mGy, median: 1.25 mGy). The risk of radiation induced cancer in child age was 0.01-0.04% (mean 0.02%, median 0.01%). One patient developed thrombosis of a common femoral artery. CONCLUSION: Prophylactic occlusion of the internal iliac arteries is a simple and safe procedure with minimal risk of complications and with a very low estimated radiation dose to the fetus.
- Klíčová slova
- fetus radiation dose, internal iliac arteries, placenta accreta spectrum, placenta praevia, prophylactic occlusion,
- MeSH
- balónková okluze * MeSH
- císařský řez MeSH
- dávka záření MeSH
- dítě MeSH
- krvácení při operaci MeSH
- lidé MeSH
- nádory vyvolané zářením * MeSH
- placentace MeSH
- plod MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The autoimmune condition, Celiac Disease (CeD), displays broad clinical symptoms due to gluten exposure. Its genetic association with DQ variants in the human leukocyte antigen (HLA) system has been recognised. Monocyte-derived mature dendritic cells (MoDCs) present gluten peptides through HLA-DQ and co-stimulatory molecules to T lymphocytes, eliciting a cytokine-rich microenvironment. Having access to CeD associated families prevalent in the Czech Republic, this study utilised an in vitro model to investigate their differential monocyte profile. The higher monocyte yields isolated from PBMCs of CeD patients versus control individuals also reflected the greater proportion of dendritic cells derived from these sources following lipopolysaccharide (LPS)/ peptic-tryptic-gliadin (PTG) fragment stimulation. Cell surface markers of CeD monocytes and MoDCs were subsequently profiled. This foremost study identified a novel bio-profile characterised by elevated CD64 and reduced CD33 levels, unique to CD14++ monocytes of CeD patients. Normalisation to LPS stimulation revealed the increased sensitivity of CeD-MoDCs to PTG, as shown by CD86 and HLA-DQ flow cytometric readouts. Enhanced CD86 and HLA-DQ expression in CeD-MoDCs were revealed by confocal microscopy. Analysis highlighted their dominance at the CeD-MoDC membrane in comparison to controls, reflective of superior antigen presentation ability. In conclusion, this investigative study deciphered the monocytes and MoDCs of CeD patients with the identification of a novel bio-profile marker of potential diagnostic value for clinical interpretation. Herein, the characterisation of CD86 and HLA-DQ as activators to stimulants, along with robust membrane assembly reflective of efficient antigen presentation, offers CeD targeted therapeutic avenues worth further exploration.
- Klíčová slova
- CD33, CD64, CD86, MHCDQ, autoimmunity, major histocompatibility complex II, monocyte, monocyte-derived dendritic cells,
- MeSH
- autoimunitní nemoci imunologie MeSH
- biologické markery metabolismus MeSH
- buněčná membrána metabolismus MeSH
- CD antigeny metabolismus MeSH
- celiakie epidemiologie imunologie MeSH
- cytotoxické T-lymfocyty imunologie MeSH
- dendritické buňky imunologie MeSH
- dospělí MeSH
- gliadin škodlivé účinky MeSH
- HLA-DQ antigeny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipopolysacharidy MeSH
- mladiství MeSH
- mladý dospělý MeSH
- monocyty metabolismus MeSH
- náchylnost k nemoci MeSH
- prezentace antigenu imunologie MeSH
- rodina MeSH
- rodokmen MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- biologické markery MeSH
- CD antigeny MeSH
- gliadin MeSH
- HLA-DQ antigeny MeSH
- lipopolysacharidy MeSH
