Search

This study aimed to investigate the degeneration of the meniscal tissue in osteoarthritic knees and to adapt the Bonar score and its modifications to develop a microscopic examination. This study included consecutive patients who underwent total knee arthroplasty for symptomatic end-stage gonarthrosis. During the surgery, the menisci were completely dissected to preserve their original shapes. The samples were prepared using the hematoxylin and eosin (H&E) staining method and the Alcian blue protocol and were examined under light microscopy. The extent of histopathological changes was assessed based on the classical Bonar score assumptions. Additionally, in the second step of the examination, menisci remnants were evaluated using the modified Bonar score developed by Zabrzyński et al. The study involved 44 patients, from whom 83 samples of knee menisci were obtained. Histological examination of the meniscal specimens under a light microscope revealed tissue degeneration in all cases, in both the medial and lateral menisci. The mean classical Bonar score was 8.3571 and the mean modified Bonar score was 6.9398. There were no statistically significant differences in classical Bonar score assessment between medial and lateral menisci (p = 0.3014). There were no statistically significant differences in the modified-Bonar score assessment between medial and lateral menisci (p = 0.3620). We show that both menisci are implicated in the degenerative process, with high scores in the Bonar system, regardless of knee axial deformity. The Bonar score, along with its modifications, can be readily employed in the microscopic assessment of meniscus pathology. [ABSTRACT FROM AUTHOR]

Simple Summary: This study delves into the roles of RUVBL1 and HIF1A in the development of clear-cell renal cell carcinoma (ccRCC) and investigates their clinical relevance as prognostic biomarkers. Utilizing TCGA data and an institutional tissue cohort, mRNA and protein expressions were analyzed. Elevated RUVBL1 mRNA expression in ccRCC tissues was associated with advanced histological grade, T stage, lymph node metastasis, and clinical stage. High RUVBL1 mRNA expression correlated with poorer overall survival, serving as an adverse prognostic factor. Similarly, HIF1A mRNA expression was significantly higher in ccRCC tissues and correlated with worse overall survival. Simultaneous evaluation of RUVBL1 and HIF1A mRNA expression demonstrated enhanced prognostic capacity, surpassing individual markers. Immunohistochemical staining confirmed the upregulation of both RUVBL1 and HIF-1α proteins in ccRCC tissues, with high expression associated with shorter patient survival time. These findings emphasize RUVBL1 and HIF-1α as potential prognostic markers in ccRCC, suggesting avenues for translating these insights into clinical applications. This study investigates the roles of RUVBL1 and HIF1A in ccRCC development and explores their clinical significance as prognostic biomarkers. mRNA and protein expressions were analyzed using TCGA data and an institutional tissue cohort, respectively. Correlations with clinicopathological parameters and patient outcomes were assessed. TCGA data revealed significantly elevated RUVBL1 mRNA expression in ccRCC tissues, associated with advanced histological grade, T stage, lymph node metastasis, and clinical stage. High RUVBL1 mRNA expression correlated with inferior overall survival and served as an adverse prognostic factor. Similarly, HIF1A mRNA expression was significantly higher in ccRCC tissues, correlating with worse overall survival and acting as an adverse prognostic factor for treatment outcomes. Simultaneous evaluation of RUVBL1 and HIF1A mRNA expression demonstrated enhanced prognostic capacity, surpassing the predictive power of individual markers. Immunohistochemical staining confirmed substantial upregulation of both RUVBL1 and HIF-1α proteins in ccRCC tissues. Furthermore, high expression of both RUVBL1 and HIF-1α proteins was significantly associated with shorter patient survival time. Our findings underscore the significance of RUVBL1 and HIF-1α as potential prognostic markers in ccRCC, paving the way for further research to translate these insights into clinically relevant applications. [ABSTRACT FROM AUTHOR]

Pulmonary venous hypertension (PVH) is caused by deteriorating left ventricular function. The most common cause of PVH in dogs is myxomatous mitral valve degeneration (MMVD). It causes left ventricular volume overload and an increase in left atrial and pulmonary venous pressure (PVH), which leads to pulmonary vascular wall remodeling and contributes to the perpetuation and worsening of PVH. Pulmonary vascular wall remodeling is also characteristic of pulmonary arterial hypertension (PAH). However, the changes in PVH arise secondary to heart failure and vascular remodeling progresses as the disease progresses. On the other hand, PAH is a primary disease that can be triggered, for example, by the use of certain drugs. Similar structural changes may suggest the influence of similar pathophysiological mechanisms or the intermediation of similar mediators. Therefore, this article discusses recent and hitherto uncommented findings elucidating the pathophysiology of the processes and influences on the pattern of histological changes observed in pulmonary hypertension secondary to degenerative mitral valve disease. In particular, we focus on the activity of factors such as endothelin, serotonin, and nitric oxide, which are involved in pulmonary vascular wall remodeling in both PVH and PAH. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this research was to explore the correlation between Gleason score and pattern and the expression of the MLH1, MSH2, MDC1, TP53BP1 proteins in prostate cancer (PC). Prostate cancer development is related to errors in DNA, among others double-strand breaks (DSB) and changes in the base sequence of the DNA. These errors should be repaired through mismatch (MMR) or DSB repair proteins such as MSH2, MLH1, MDC1 and TP53BP1. Material and methods: A total of 500 prostate cancer specimens were recruited in this study. From among all gathered specimens the 52 most suitable cases were selected. The expression of examined proteins was detected by immunohistochemistry, and its correlation with the Gleason score and pattern were further analyzed through standard statistical algorithms. Results: The results show a significant correlation between Gleason pattern and the nuclear expression of the MSH2 protein and the cytoplasmic expression of the MLH1 protein. Gleason score significantly correlates with the nuclear and the cytoplasmic expression of the MSH2 protein and the cytoplasmic expression of the MDC1 protein. There is no correlation between the nuclear or cytoplasmic expression of the TP53BP1 protein and Gleason pattern or score. Conclusions: Our study suggests that the aberration in the MMR repair mechanism may be significantly more important regarding the grading among PC cells in comparison to the impact of alterations in the DSB repair mechanism. The lack of correlation between expression of the TP53BP1 protein and Gleason pattern and Gleason score suggests that the radiation resistance of PC is independent of alterations connected with TP53BP1. [ABSTRACT FROM AUTHOR]

Current strategies in urinary bladder augmentation include use of gastrointestinal segments, however, the technique is associated with inevitable complications. An acellular biologic scaffold seems to be a promising option for urinary bladder augmentation. The aim of this study was to evaluate the utility of bladder acellular matrix (BAM) for reconstruction of clinically significant large urinary bladder wall defects in a long‐term porcine model. Urinary bladders were harvested from 10 pig donors. Biological scaffolds were prepared by chemically removing all cellular components from urinary bladder tissue. A total of 10 female pigs underwent hemicystectomy and subsequent bladder reconstruction with BAM. The follow‐up study was 6 months. Reconstructed bladders were subjected to radiological, macroscopic, histological, immunohistochemical, and molecular evaluations. Six out of ten animals survived the 6‐month follow‐up period. Four pigs died during observation due to mechanical failure of the scaffold, anastomotic dehiscence between the scaffold and native bladder tissue, or occluded catheter. Tissue engineered bladder function was normal without any signs of postvoid residual urine in the bladder or upper urinary tracts. Macroscopically, graft shrinkage was observed. Urothelium completely covered the luminal surface of the graft. Smooth muscle regeneration was observed mainly in the peripheral graft region and gradually decreased toward the center of the graft. Expression of urothelial, smooth muscle, blood vessel, and nerve markers were lower in the reconstructed bladder wall compared to the native bladder. BAM seems to be a promising biomaterial for reconstruction of large urinary bladder wall defects. Further research on cell‐seeded BAM to enhance urinary bladder regeneration is required. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the role of SATB1, SMAD3, Ezrin and β-catenin as individual and combined biomarkers for the survival prediction in pancreatic adenocarcinoma (PAC). Notably, this study distinguished for the first time a potential prognostic value of SATB1 corresponding to its subcellular localization in PAC. Immunohistochemical staining on tissue macroarrays, as well as RNA-seq data from public sources, were investigated, and the results correlated with overall survival (OS) and clinicopathological features. The connectivity between the examined factors, as well as their common signaling pathways, were demonstrated by the functional enrichment analysis. Herein, the prognostic ability of cytoplasmic SATB1 in OS analysis was even superior to nuclear SATB1. Both staining patterns tended to have opposite roles in the prognosis of PAC: SATB1c was an independent prognostic factor for poor OS, whereas SATB1n expression reached no statistical significance, but Kaplan–Meier curves separated patients with low expression and adverse prognosis from patients with high expression and favorable prognosis. High levels of SATB1 mRNA appeared as an independent prognostic indicator for better OS. Furthermore, individual expression of SMAD3 or Ezrin, as well as combined expression of SATB1/SMAD3/Ezrin/β-catenin, were associated with OS independently of conventional risk factors, both in our cohort and TCGA dataset. In our series, patients with tumors harboring combined expression of SATB1n-high/SMAD3low/Ezrinlow/β-cateninlow experienced the highest survival rates, while those with SATB1c-present/SMAD3high/Ezrinhigh/β-cateninhigh had the worst survival. In conclusion, protein and/or mRNA expression levels of SATB1, SMAD3, Ezrin and β-catenin may serve as potential prognostic biomarkers for PAC, both as single predictors and even better when combined. [ABSTRACT FROM AUTHOR]

CRS is a process involving a number of adverse changes in the mucosa of the paranasal sinuses and nasal polyps, e.g. increased fibroblast proliferation, angiogenesis, increased formation of fibrous tissue (subepithelial fibrosis) and tissue destruction. There are biomarkers whose levels can be increased in chronic inflammation of the paranasal sinuses: peripheral blood eosinophilia, IgE immunoglobulin, cytokines - IL-4, IL-5, IL-13, IL-25, IL-33, periostin, P-glycoprotein, CXCL-12, CXCL-13, INF-Υ, TNFα, TGFβ1, albumins, eotaxin. These biomarkers are not pathognomonic for CRS. The concentration of biomarkers is also increased in bronchial asthma and atopic dermatitis. The TGFβ, in particular the β1 subunit, was identified as the main factor involved in the remodelling of tissue stroma. In conjunction with continuous improvement of tissue testing methods, it is advisable to search for new factors that will more accurately allow the assessment of tissue remodelling in the chronic processes of paranasal sinuses. [ABSTRACT FROM AUTHOR]

Background: The role of BRAF mutations in cancerogenesis has been demonstrated in several solid tumor types. However, in salivary gland tumors, this genetic alteration is very uncommon, and its role still remains unclear. Thus, the aim of this study was to analyze BRAF V600E (VE1) protein expression with BRAF mutation status in codon 600, in malignant and benign salivary gland tumors.Methods: Studies were performed on archived formalin-fixed paraffin-embedded tissue sections derived from 95 patients who underwent surgery for tumors of the salivary gland. Immunohistochemical staining (IHC) on tissue microarray slides was performed for evaluation of BRAF V600E (VE1) protein expression, and the automatic molecular diagnostics platform was used for the evaluation of mutations in codon 600 of BRAF gene.Results: IHC cytoplasmic expression of BRAF V600E (VE1) protein was found in two of 95 cases: one case of adenocarcinoma NOS (one of three; 33%) and one case of carcinoma ex pleomorphic adenoma (one of five; 20%). Although, in IHC studies, nuclear BRAF V600E (VE1) protein expression was found in 14 (15%) of the analyzed cases: nine of 28 (32%) cases of pleomorphic adenoma, three of five (60%) cases of ductal carcinoma, one of nine (11%) case of mucoepidermoid carcinoma, and in one of five (20%) case of carcinoma ex pleomorphic adenoma. All cases were negative for polymerase chain reaction PCR-based analyses of BRAF mutations in codon 600.Conclusions: In studied salivary gland cancers, no PCR-based prove mutations of BRAF V600 were detected. Further molecular analyses are necessary to rapid molecular arrays for the identification of specific mutations, optimal for individualized targeted therapies. [ABSTRACT FROM AUTHOR]