BACKGROUND: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies. METHODS: Transcriptome of kidney allograft biopsies performed within the first month in presensitized patients (DSA+) who had received desensitization and did not develop active/probable AMR by histology (R-) was compared with biopsies showing active/probable AMR (R+/DSA+). As negative controls, biopsies without rejection by histology in patients without DSA at transplantation were used (R-/DSA-). RNA sequencing from biopsies selected from the biobank was used in cohort 1 (n = 32) and microarray, including the molecular microscope (Molecular Microscope Diagnostic System [MMDx]) algorithm, in recent cohort 2 (n = 30). RESULTS: The transcriptome of R-/DSA+ was similar to R+/DSA+ as these groups differed in 14 transcripts only. Contrarily, large differences were found between both DSA+ groups and negative controls. Fast gene set enrichment analyses showed upregulation of the immune system in both DSA+ groups (gene ontology terms: adaptive immune response, humoral immune response, antigen receptor-mediated signaling, and B-cell receptor signaling or complement activation) when compared with negative controls. MMDx assessment in cohort 2 classified 50% of R-/DSA+ samples as AMR and found no differences in AMR molecular scores between R+ and R- DSA+ groups. In imlifidase desensitization, MMDx series showed a gradual increase in AMR scores over time. CONCLUSIONS: Presensitized kidney transplant recipients exhibited frequent molecular calls of AMR in biopsy-based transcript diagnostics despite desensitization therapy and negative histology.
- Publikační typ
- časopisecké články MeSH
Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells. We defined circRNAs deregulated in a heterogeneous group of MDS patients and described increased circRNA formation in higher-risk MDS. We showed that the presence of SF3B1 mutations did not affect the global production of circRNAs; however, deregulation of specific circRNAs was observed. Particularly, we demonstrated that strong upregulation of circRNAs processed from the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor; this upregulation was exclusive to SF3B1-mutated patients and was not observed in those with mutations in other splicing factors or other recurrently mutated genes, or with other clinical variables. Furthermore, we focused on the most upregulated ZEB1-circRNA, hsa_circ_0000228, and, by its knockdown, we demonstrated that its expression is related to mitochondrial activity. Using microRNA analyses, we proposed miR-1248 as a direct target of hsa_circ_0000228. To conclude, we demonstrated that mutated SF3B1 leads to deregulation of ZEB1-circRNAs, potentially contributing to the defects in mitochondrial metabolism observed in SF3B1-mutated MDS.
PURPOSE: Lumbrical muscles of the upper limb belong to the middle group of intrinsic hand muscles. Their anatomical variability has been extensively studied with heterogeneous findings. Therefore, the aim of this study is to provide a systematic review and a meta-analysis of the lumbrical muscles variations in the human hand. METHODS: For this purpose, four major electronic databases were searched to identify eligible studies. Then, all relevant data were extracted, and statistical analysis performed. A new classification of lumbrical muscles variations is proposed to summarize and clearly define all described findings. We included 26 studies, making a total sample of 1340 dissected hands. FINDINGS: The most common variations for each muscle were an accessory belly for the first lumbrical muscle, a variable origin for the second lumbrical muscle, a variable innervation for the third lumbrical muscle and a variable insertion for the fourth lumbrical muscle with the prevalence 3.8%; 7.7%; 12% and 5.8%, respectively. CONCLUSIONS: We believe that results of our statistical analysis are suitable for both hand surgeons and other medical professionals dealing with hand injuries or functional problems in their daily routine.
- MeSH
- kosterní svaly * inervace MeSH
- lidé MeSH
- ruka * inervace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Deciphering the role of the aryl hydrocarbon receptor (AhR) in lung cancer cells may help us to better understand the role of toxic AhR ligands in lung carcinogenesis, including cancer progression. We employed human lung carcinoma A549 cells to investigate their fate after continuous two-week exposure to model AhR agonists, genotoxic benzo[a]pyrene (BaP; 1 μM) and non-genotoxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 nM). While TCDD increased proliferative rate of A549 cells, exposure to BaP decreased cell proliferation and induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which was associated with enhanced cell migration, invasion, and altered cell morphology. Although TCDD also suppressed expression of E-cadherin and activated some genes linked to EMT, it did not induce the EMT-like phenotype. The results of transcriptomic analysis, and the opposite effects of BaP and TCDD on cell proliferation, indicated that a delay in cell cycle progression, together with a slight increase of senescence (when coupled with AhR activation), favors the induction of EMT-like phenotype. The shift towards EMT-like phenotype observed after simultaneous treatment with TCDD and mitomycin C (an inhibitor of cell proliferation) confirmed the hypothesis. Since BaP decreased cell proliferative rate via induction of p21 expression, we generated the A549 cell model with reduced p21 expression and exposed it to BaP for two weeks. The p21 knockdown suppressed the BaP-mediated EMT-like phenotype in A549 cells, thus confirming that a delayed cell cycle progression, together with p21-dependent induction of senescence-related chemokine CCL2, may contribute to induction of EMT-like cell phenotype in lung cells exposed to genotoxic AhR ligands.
- MeSH
- benzopyren toxicita MeSH
- epitelové buňky MeSH
- fenotyp MeSH
- karcinom * MeSH
- lidé MeSH
- nádory plic * genetika MeSH
- plíce MeSH
- receptory aromatických uhlovodíků genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: The structure of the proximal margin of the superficial layer of the supinator muscle is of high interest to many researches. Its tendinous appearance, called the arcade of Frohse, may be clinically important because of its close relationship to the deep branch of the radial nerve passing beneath it and is considered to be the cause of several syndromes. Given the importance of this structure, we aimed to provide a comprehensive and evidence-based review with meta-analytic techniques. MATERIALS AND METHODS: The meta-analysis was performed in adherence to the PRISMA guidelines. Three medical databases were searched in order to identify all potentially eligible articles. Included studies were assessed for quality and the extracted morphological and morphometric data from the relevant articles was analyzed with the use of random effects meta-analysis. RESULTS: A total of 20 studies were included into this meta-analysis. The pooled prevalence of the arcade of Frohse was calculated to be 66% within the adult population and 0% in the fetuses. Other variations regarding the arcade of Frohse were identified as very rare. Analysis of the morphometric parameters revealed the average proportions to be 23.22 mm for the length, 11.05 mm for the width and the mean thickness is 0.67 mm. CONCLUSIONS: The arcade of Frohse is a commonly found structure in adults and thoughtful knowledge of its texture and morphology is especially useful in neurology, neurosurgery, orthopedics, trauma surgery and hand surgery, because it is considered to be the most common source of compression for the deep branch of the radial nerve.
- MeSH
- kosterní svaly anatomie a histologie chirurgie MeSH
- lidé MeSH
- nervus radialis zranění MeSH
- neuropatie nervus radialis etiologie MeSH
- ortopedické výkony metody MeSH
- předloktí anatomie a histologie chirurgie MeSH
- šlachy anatomie a histologie chirurgie MeSH
- úžinové syndromy etiologie chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Accessory bones in the region of the elbow are rare variants with high clinical significance as they may be confused with avulsion fractures. We investigated their prevalence and performed a statistical analysis to support their congenital origin. Their localization was mapped to show their exact site of occurrence. We evaluated anteroposterior and lateral X-ray images of 2413 elbows in a Central European population from which a group of accessory bony structures was selected. Their character was evaluated, and accessory bones were identified. We used logistic regression to evaluate the potential relationship between the occurrence of accessory bones, the age of patients, and the occurrence of calcar olecrani. The prevalence of accessory bones of the elbow in the sample was 0.77%. Our results did not show a statistically significant relationship with the occurrence of calcar olecrani or with the age of patients. The most common type was os subepicondylare mediale (type V) in 0.46%, which was located distal to the medial epicondyle of the humerus, followed by os subepicondylare laterale (type III; 0.21%), situated laterally to the lateral epicondyle of the humerus. In comparison with previous reports, os sesamoideum mediale (type IV) was located more distally. Our data suggest that congenital accessory bones are a rare entity. Knowledge of their exact localization should be considered during diagnosis of avulsion fractures and other unclear diagnoses including accessory bony structures in the elbow region.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- loket abnormality diagnostické zobrazování MeSH
- loketní kloub abnormality krevní zásobení MeSH
- mladý dospělý MeSH
- rentgendiagnostika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this study was to report PAX6 disease-causing variants in six Czech families, to describe the associated phenotypes, and to perform functional assessment of the splice site variants. Detailed ophthalmic examination was performed. The PAX6 coding region was directly sequenced in three probands. Two probands were analysed by exome sequencing and one by genome sequencing. The effect of two variants on pre-mRNA splicing was evaluated using an exon trapping assay. Six different heterozygous PAX6 variants were identified, with c.111_120del and c.1183+1G˃T being novel. Both c.1183+1G˃T and c.1032+1G>A were proved to cause aberrant splicing with exon skipping and subsequent frameshift. The phenotypic features were variable between and within families. One individual, aged 31 years, presented with mild unilateral ptosis accompanied by aniridia in the right eye, partial aniridia in the left eye, and bilateral congenital cataracts, without marked foveal hypoplasia. Bilateral microcornea, partial aniridia, congenital cataracts, and a large posterior segment coloboma were found in another proband, aged 32 years. One child, aged 8 years, had bilateral high myopia, optic nerve colobomas, anterior polar cataracts, but no iris defects. Another individual, aged 46 years, had bilateral congenital ptosis, iris hypoplasia, keratopathy with marked fibrovascular pannus, anterior polar cataract, and foveal hypoplasia combined with impaired glucose tolerance. However, his daughter, aged 11 years, showed classical features of aniridia. Our study extends the genetic spectrum of PAX6 disease-causing variants and confirms that the associated phenotypic features may be very broad and different to the 'classical' aniridia.
- MeSH
- aniridie * genetika MeSH
- dítě MeSH
- dospělí MeSH
- fenotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- oční proteiny genetika MeSH
- rodokmen MeSH
- sestřih RNA MeSH
- transkripční faktor PAX6 genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
PURPOSE: The variability of the recurrent branch (RB) of the median nerve lends itself to an increased risk of injury when performing the minimally invasive approach for carpal tunnel release without its direct visualization. This risk is less so when it is released via the more invasive open approach as the RB can be easily identified, but the drawback is that of longer postoperative patient recovery time. Therefore, performing these releases via the less invasive approach should be more favorable for patients providing it could be done safely. Hence with there being a positive link between the hypertrophy of the thenar musculature and the course of RB according to previous studies. METHODS: We dissected 28 hands of 14 donated bodies fixed using Thiel's method to try to demonstrate these findings of the associations among the RB, palmar creases and other superficial anatomical landmarks. Fisher's exact test was conducted to verify the relationship between those structures statistically. RESULTS: Statistically significant links were found between the type of the RB and the type of the palmar creases (p value = 0.0094) and between the RB type and the palmaris longus muscle presence (p value = 0.028). CONCLUSION: It was inferred that palmar creases and other superficial anatomical landmarks listed in the text could not be used to predict the variability of the RB and the choice of mini-invasive approach should not be based on their course.
- MeSH
- anatomická variace * MeSH
- anatomická značka * MeSH
- hodnocení rizik metody MeSH
- kosti zápěstní inervace MeSH
- lidé MeSH
- miniinvazivní chirurgické výkony škodlivé účinky metody MeSH
- mrtvola MeSH
- nervus medianus abnormality zranění MeSH
- peroperační komplikace etiologie prevence a kontrola MeSH
- ruka anatomie a histologie MeSH
- syndrom karpálního tunelu chirurgie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n=6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n=4) and non-rejection histologic findings (n=8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n=12) and TCMRV (n=8) samples. The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.
- MeSH
- alografty MeSH
- arteritida genetika MeSH
- dospělí MeSH
- genová ontologie MeSH
- lidé MeSH
- průřezové studie MeSH
- rejekce štěpu diagnóza genetika MeSH
- retrospektivní studie MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- studie případů a kontrol MeSH
- transkriptom * MeSH
- transplantace ledvin metody MeSH
- tunica intima metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants.
- MeSH
- aktivace transkripce účinky léků MeSH
- azosloučeniny toxicita MeSH
- benzopyren toxicita MeSH
- buňky A549 MeSH
- časové faktory MeSH
- fluoreny toxicita MeSH
- genetická transkripce účinky léků MeSH
- genové regulační sítě účinky léků MeSH
- indoly toxicita MeSH
- karbazoly toxicita MeSH
- látky znečišťující životní prostředí toxicita MeSH
- lidé MeSH
- ligandy MeSH
- nádory plic genetika metabolismus MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- pyrazoly toxicita MeSH
- receptory aromatických uhlovodíků agonisté metabolismus MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- signální transdukce účinky léků MeSH
- stanovení celkové genové exprese metody MeSH
- thiazoly toxicita MeSH
- transkripční faktory bHLH agonisté metabolismus MeSH
- transkriptom účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
