In patients treated for prostate cancer (PCa) with radical prostatectomy (RP), determining the risk of extraprostatic extension (EPE) and nodal involvement (NI) remains crucial for planning ...nerve-sparing and extended lymphadenectomy. The study aimed to determine proteins that could serve as immunohistochemical markers of locally advanced PCa. To select candidate proteins associated with adverse pathologic features (APF) reverse-phase protein array data of 498 patients was retrieved from The Cancer Genome Atlas. The analysis yielded 6 proteins which were then validated as predictors of APF utilizing immunohistochemistry in a randomly selected retrospective cohort of 53 patients. For univariate and multivariate analysis, logistic regression was used. Positive expression of TfR1 (OR 13.74;
= 0.015), reduced expression of CD49b (OR 10.15;
= 0.013), and PSA (OR 1.29;
= 0.013) constituted independent predictors of EPE, whereas reduced expression of e-cadherin (OR 10.22;
= 0.005), reduced expression of CD49b (OR 24.44;
= 0.017), and PSA (OR 1.18;
= 0.002) were independently associated with NI. Both models achieved high discrimination (AUROC 0.879 and 0.888, respectively). Immunohistochemistry constitutes a straightforward tool that might be easily utilized before RP. Expression of TfR1 and CD49b is associated with EPE, whereas expression of e-cadherin and CD49b is associated with NI. Since following immunohistochemical markers predicts respective APFs independently from PSA, in the future they might supplement existing preoperative nomograms or be implemented in novel tools.
Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo ...appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens.
In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen.
Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients.
The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.
Electrical and optical properties of TiO
2
:Pd thin films deposited from Ti-Pd mosaic targets sputtered in reactive oxygen plasma have been studied. The properties were investigated for thin films ...with the Pd amount of 5.5 at. %, 8.4 at. % and 23 at. %. Based on resistivity measurements a drop from 10
3
down to almost 10
−3
Ωcm has been recorded when the Pd amount was varied from 5.5 at. % to 23 at. %, respectively. Moreover, it was shown that doping with different amounts of Pd results in the possibility of obtaining both types of electrical conduction: n-type for the TiO
2
with 5.5 at. % and 8.4 at. % of Pd and p-type for the TiO
2
with 23 at. % of Pd thin films. From optical measurements it has been found that as the Pd amount was increased the transmission through the thin films was reduced and position of the fundamental absorption edge was shifted toward a longer wavelength range of up to 600 nm. The optical band gap was calculated for direct and indirect transitions from optical absorption spectra. Structural properties were characterized by X-ray diffraction (XRD) and atomic force microscopy (AFM). The XRD patterns displayed occurrence of the crystalline, TiO
2
-rutile for lower Pd amounts (5.5 at. %, 8.4 at. %), while the TiO
2
:Pd (23 at. %) thin films displayed XRD-amorphous behaviour. Images obtained from AFM displayed dense, nanocrystalline structure with homogenous distribution of crystallites. Additionally performed secondary ion mass spectroscopy investigation confirmed homogenous distribution of Pd in the whole thickness of the prepared thin films.
Context:
A single microRNA gene may give rise to several mature products that differ in length, called isomiRs. IsomiRs are known to be tissue specific and functionally relevant. The microRNA ...sequence heterogeneity of the thyroid gland has yet to be determined.
Objective:
The objective of the study was to provide a comprehensive view of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma (PTC).
Design:
We used next-generation deep sequencing to analyze microRNA length heterogeneity and expression profiles of PTC tumors (n = 14), unaffected tissue adjacent to tumors (n = 14), and control, noncancerous thyroid tissue (n = 14). The results were validated with a microarray on an additional set of 9 PTC tumor/normal tissue pairs.
Results:
Eighty-nine microRNAs were significantly deregulated in PTC compared with normal thyroid tissue (false discovery rate < 0.05, fold change 0.13–20.7). Top deregulated miRNAs included miR-146b-5p, miR-221-3p, miR-7-3p, miR-551b-3p, miR-486-3p, and miR-144-3p, confirming previous microarray profiling. The expression of miRNAs did not depend on the BRAF mutation status. Interestingly, 85% of the most abundant microRNAs consisted of isoforms that differed from the standard reference sequence deposited in miRBase. Moreover, the reference microRNAs were completely absent in 42.4% and 35.9% of the microRNAs expressed in normal thyroid and PTC tumors, respectively. Numerous isomiRs had altered seed sequences, which led to a different set of target genes. For highly deregulated miR-146b-5p, we detected 6 isoforms (tumor/normal fold change 14.4–28.7, false discovery rate < 0.002) that varied at their 5′ ends with a 1-nt difference that created 2 alternative seeds. The target genes for those 2 seeds overlapped in only 13.1% of genes.
Conclusions:
Almost all microRNAs exhibit isoforms of variable length and potentially distinct function in thyroid tumorigenesis.
Background and aims: Previous studies demonstrated a close correlation between transient elastography (TE) and liver histology in chronic liver diseases. Data on the accuracy of TE in primary ...sclerosing cholangitis (PSC) remains scarce. Here, we investigated the association between TE, serum marker of liver injury and histology of explanted livers in PSC patients.
Methods: Thirty patients were prospectively recruited. TE (Fibroscan
®
) and blood sampling were performed during evaluation for liver transplantation (LT); the second blood sampling was performed on the day of LT. Fibrosis of explanted livers according to the seven-point Laennec staging system and liver collagen contents were measured.
Results: TE correlated with Laennec stages of fibrosis (p = .001), collagen contents (p < .001) and with diameter of thickest septa (p = .034) in explanted livers. It also correlated with serum indices of liver injury, namely AST, bilirubin as well as FIB-4 and APRI scores (all p < .05). In a multivariate model, only liver fibrosis, according to either Laennec score (p = .035) or collagen contents (p = .005), was significantly associated with TE. Finally, patients with cirrhosis had increased liver stiffness (p = .002) and the TE cut-off of 13.7 kPa showed the best predictive value (AUC = .90, 95% CI: 0.80-1.00, p < .001) for detecting cirrhosis.
Conclusions: TE correlates with liver fibrosis and markers of liver injury in patients with PSC. However, liver fibrosis seems to be the strongest predictor of liver stiffness assessed with TE. Hence, we postulate that TE is a reliable tool for non-invasive monitoring of PSC.
Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological ...characteristics in TTS.
Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining.
The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084).
The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.
The sample area of 2.8 ha, divided into 100 m2 square quadrats, comprised two, distinguishable by traditional methods, oak forest patches and a fragment of a neighbouring mixed oak-hornbeam forest. ...The classification of quadrats was conducted by association analysis. Their identification and interpretation were performed on the basis of the systematic value and fraction of species of the characteristic oak forest combination in each distinguished quadrat group, as well as the range of distinguished communities. It appeared that due to the hornbeam invasion into the oak forest habitat, species forming the characteristic oak forest combination receded and the community area decreased. The data enabled reconstruction of the phases of oak forest recession. They corresponded to the successive phases of the encroachment of hornbeam undergrowth in the analysed area.
MicroRNAs, non-coding regulators of gene expression, are known culprits of thyroid cancer. Using next-generation sequencing, we identified a novel microRNA gene, encoded within an important thyroid ...regulator - thyroglobulin, and analyzed its functionality in the thyroid gland. In vitro and in silico analyses proved that the novel miR-TG is processed from the precursor, and co-expressed with thyroglobulin. Both genes are specific for thyroid tissue and downregulated in papillary thyroid carcinoma by 44% (p = 0.04) and 48% (p = 0.001), respectively. Putative target genes for miR-TG were identified using in silico tools, which pinpointed MAP4K4, an oncogene upregulated in thyroid cancer. Analysis of transcriptome by RNA-seq revealed that overexpression of miR-TG in PTC-derived cell line led to downregulation of several genes, including MAP4K4 (fold change 0,82; p = 0.036). The finding was confirmed by SQ-PCR (fold change 071; p = 0.004). Direct interaction between miR-TG and MAP4K4 was confirmed in the luciferase assay (p = 0.0006). Functional studies showed increase proliferation in K1 cell line transfected with miR-TG. We propose that in normal thyroid miR-TG plays a fine-tuning effect on the maintenance of MAPK pathway, inhibiting the expression of miR's target MAP4K4. This regulation is disturbed in cancer due to downregulation of the novel, thyroglobulin-embedded microRNA, characterized in this study.
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