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Abstract Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.

The most common complications of percutaneous coronary interventions and other endovascular procedures include minor hemorrhage, hematoma, or infection at the insertion site [1]. Much more serious ones include damage to the vessel wall, dissection, shock from contrast administration, acute kidney injury, myocardial infarction [2] and ischemic stroke [3]. Ischemic complications can be caused by an embolic incident due to a thrombus formation or detachment of atherosclerotic plaque fragments [3]. A rarely diagnosed complication is ischemia caused by microembolisms from the material covering the equipment inserted into the vessel – hydrophilic polymer coating (HPC)[4]. We present an interesting case of HPC revealed in coronary vessels within myocardial preparations taken in forensic post-mortem examination conducted at the Department of Forensic Medicine in Bydgoszcz (L.dz. 676/19). This article raises the issue of clinical implications and forensic aspects.

Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial–mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT‐related genes and transcription factors are associated with poor prognosis in ccRCC. EMT‐related factors suppress E‐cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), β‐catenin, and E‐cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan–Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm‐c levels compared to those with low MIFn and MIFm‐c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p

Abstract The present study aimed to investigate expression levels and prognostic significance of RUVBL1 and HNRNPU in stage I and II non–small-cell lung cancer (NSCLC) patients. Therefore, we evaluated immunohistochemical staining of RUVBL1 and HNRNPU, as well as RNA-seq data from public sources, and the results were evaluated concerning overall survival (OS) and clinicopathological features. We found that RUVBL1 and HNRNPU proteins and mRNA levels were higher in tumor tissues as compared to adjacent/normal tissues. RUVBL1 (p = 0.013) and HNRNPU (p = 0.021) high protein levels were independent prognostic factors for poor OS. Also, the multivariate analysis in the TCGA dataset revealed that high RUVBL1 (p = 0.064) and HNRNPU (p = 0.181) mRNA levels were not significantly associated with prognosis. However, the co-expression status of these markers (R + H +) was independently associated with poor OS both in the TCGA dataset (p = 0.027) and in our cohort (p = 0.001). In conclusion, combined and individual expression of RUVBL1 and HNRNPU proteins, as well as R + H + mRNA status, may serve as potential prognostic biomarkers for NSCLC. This study adds to the previous observations that RUVBL1 and HNRNPU might be novel and promising therapeutic targets and markers for prognostic evaluation.

Résumé Contexte La sarcoïdose est une maladie multisystémique caractérisée par la formation de granulomes non caséeux dans divers organes. Les poumons restent l’organe le plus fréquemment touché, alors que les lésions du système génito-urinaire affectent environ 0,2% des patients. La découverte d’un site principal dans le cordon spermatique est extrêmement rare. Présentation du cas Nous présentons le cas d’un patient où l’atteinte du cordon spermatique a été la première manifestation d’une sarcoïdose. Pendant plusieurs mois, un certain nombre de tests ont été effectués, qui montraient, entre autres, des granulomes non caséeux dans le matériel pathomorphologique, une lymphadénopathie hilaire bilatérale, et une leucopénie avec lymphopénie. Les marqueurs tumoraux étaient normaux. Une infection par des agents pathogènes urogénitaux (y compris Chlamydia Trachomatis, Neisseria gonorrhea, Mycoplasma hominis) a été exclue. Le patient n’a signalé aucun symptôme général tel que fièvre, fatigue excessive, ou perte de poids. Il a nié toute œdème ou essoufflement. Dans le même temps, un diagnostic différentiel complet a été effectué et l’étendue de la maladie a été évaluée. Grâce à la prise en charge interdisciplinaire, la qualité de vie et la fertilité du patient ont été préservées. Dans la discussion, nous présentons le diagnostic, le traitement et le pronostic de ces patients. Conclusion La sarcoïdose est une maladie multisystémique, qui ne doit pas être omise dans le diagnostic différentiel. L’excision sélective de la lésion, avec examen peropératoire, joue un rôle important lors de l’établissement d’un diagnostic. Cependant, en cas de localisation du site primaire dans le système génito-urinaire, le diagnostic est difficile.

Abstract The use of an ileal segment is a standard method for urinary diversion after radical cystectomy. Unfortunately, utilization of this method can lead to numerous surgical and metabolic complications. This study aimed to assess the tissue-engineered artificial conduit for urinary diversion in a porcine model. Tissue-engineered tubular polypropylene mesh scaffolds were used for the right ureter incontinent urostomy model. Eighteen male pigs were divided into three equal groups: Group 1 (control ureterocutaneostomy), Group 2 (the right ureter-artificial conduit-skin anastomoses), and Group 3 (4 weeks before urostomy reconstruction, the artificial conduit was implanted between abdomen muscles). Follow-up was 6 months. Computed tomography, ultrasound examination, and pyelogram were used to confirm the patency of created diversions. Morphological and histological analyses were used to evaluate the tissue-engineered urinary diversion. All animals survived the experimental procedures and follow-up. The longest average patency was observed in the 3rd Group (15.8 weeks) compared to the 2nd Group (10 weeks) and the 1st Group (5.8 weeks). The implant’s remnants created a retroperitoneal post-inflammation tunnel confirmed by computed tomography and histological evaluation, which constitutes urostomy. The simultaneous urinary diversion using a tissue-engineered scaffold connected directly with the skin is inappropriate for clinical application.

Summary: Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are expressed in precursors of insulin-producing pancreatic β-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent pancreatic and endocrine progenitors in vitro. Moreover, we investigated mechanisms by which SARS-CoV-2 enters pancreatic cells, and found that ACE2 mediates the entry, while NRP1 and TMPRSS2 do not. Surprisingly, we found that in pancreatic progenitors, SARS-CoV-2 enters cells via cathepsin-dependent endocytosis, which is a different route than in respiratory tract. Therefore, pancreatic spheroids might serve as a model to study candidate drugs for endocytosis-mediated viral entry inhibition and to investigate whether SARS-CoV-2 infection may affect pancreas development, possibly causing lifelong health consequences.

The aim of this study was to test the effect of hyaluronic acid cross-linked with polyethylene glycol containing micronized portions of calcium hydroxyapatite (Neauvia Stimulate) on both local tissue and systemic consequences, which are crucial from the perspective of long-term safety, in patients suffering from Hashimoto’s disease. This most common autoimmune disease is a frequently mentioned contraindication to the use of fillers based on hyaluronic acid as well as biostimulants based on calcium hydroxyapatite. Broad-spectrum aspects of histopathology were analyzed to identify key features of inflammatory infiltration before the procedure and 5, 21, and 150 days after the procedure. A statistically significant effect on the reduction of the intensity of the inflammatory infiltration in the tissue in relation to the state before the procedure was demonstrated, combined with a reduction in the occurrence of both antigen-recognizing (CD4) and cytotoxic (CD8) T lymphocytes. With complete statistical certainty, it was demonstrated that the treatment with Neauvia Stimulate had no effect on the levels of these antibodies. All this corresponds with the risk analysis that showed no alarming symptoms during the time of observation. The choice of hyaluronic acid fillers cross-linked with polyethylene glycol should be considered justified and safe in the case of patients suffering from Hashimoto’s disease.

Abstract The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial–mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial–mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial–mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.

Tumor cells have the ability to induce platelet activation and aggregation. This has been documented to be involved in tumor progression in several types of cancers, such as lung, colon, breast, pancreatic, ovarian, and brain. During the process, platelets protect circulating tumor cells from the deleterious effects of shear forces, shield tumor cells from the immune system, and provide growth factors, facilitating metastatic spread and tumor growth at the original site as well as at the site of metastasis. Herein, we present a wider view on the induction of platelet aggregation by specific factors primarily developed by cancer, including coagulation factors, adhesion receptors, growth factors, cysteine proteases, matrix metalloproteinases, glycoproteins, soluble mediators, and selectins. These factors may be presented on the surface of tumor cells as well as in their microenvironment, and some may trigger more than just one simple receptor–ligand mechanism. For a better understanding, we briefly discuss the physiological role of the factors in the platelet activation process, and subsequently, we provide scientific evidence and discuss their potential role in the progression of specific cancers. Targeting tumor cell-induced platelet aggregation (TCIPA) by antiplatelet drugs may open ways to develop new treatment modalities. On the one hand, it may affect patients’ prognosis by enhancing known therapies in advanced-stage tumors. On the other hand, the use of drugs that are mostly easily accessible and widely used in general practice may be an opportunity to propose an unparalleled antitumor prophylaxis. In this review, we present the recent discoveries of mechanisms by which cancer cells activate platelets, and discuss new platelet-targeted therapeutic strategies.

Matrin 3 (MATR3) is one of the most abundant inner nuclear matrix proteins involved in multiple nuclear processes. However, to date, the biological role and prognostic relevance of MATR3 in human cancers still need to be explored. Therefore, the present study aimed to examine the expression levels and prognostic significance of MATR3 in clear cell renal cell carcinoma (ccRCC) patients. We assessed MATR3 immunohistochemical staining and RNA-seq data from publicly available data sets, and the results were analyzed with reference to clinicopathological characteristics and the overall survival of patients. Furthermore, the protein–protein interaction (PPI) network for MATR3 and its neighbors was constructed, functionally annotated, and screened for survival-related genes. MATR3 protein and mRNA levels were lower in tumor tissues compared to control tissues. Lower MATR3 protein (HR 2.36, 95%CI 1.41–3.97; p = 0.001) and mRNA (HR 2.01, 95%CI 1.46–2.75; p < 0.0001) expression levels were found to be a significant independent adverse prognostic factor for the patient’s overall survival (OS). Moreover, of the candidate genes, the MRPL23 gene was identified as being the most predictive of OS, and combined MRPL23/MATR3 expression status predicted patient survival better than looking at each marker individually (HR 3.15, 95%CI 2.05–4.83; p < 0.0001). In conclusion, the results from the present investigation warrant further research into the biological and prognostic value of MATR3 and MRPL23 in ccRCC patients.

This study aimed to explore the prognostic value of SATB1, SMAD3, and TLR2 expression in non–small-cell lung carcinoma patients with clinical stages I-II. To investigate, we evaluated immunohistochemical staining to each of these markers using tissue sections from 69 patients from our cohort and gene expression data for The Cancer Genome Atlas (TCGA) cohort. We found that, in our cohort, high expression levels of nuclear SATB1 n and SMAD3 were independent prognostic markers for better overall survival (OS) in NSCLC patients. Interestingly, expression of cytoplasmic SATB1 c exhibited a significant but inverse association with survival rate, and it was an independent predictor of unfavorable prognosis. Likewise, TLR2 was a negative outcome biomarker for NSCLC even when adjusting for covariates. Importantly, stratification of NSCLCs with respect to combined expression of the three biomarkers allowed us to identify subgroups of patients with the greatest difference in duration of survival. Specifically, expression profile of SATB1 n-high /SMAD3 high /TLR2 low was associated with the best OS, and it was superior to each single protein alone in predicting patient prognosis. Furthermore, based on the TCGA dataset, we found that overexpression of SATB1 mRNA was significantly associated with better OS, whereas high mRNA levels of SMAD3 and TLR2 with poor OS. In conclusion, the present study identified a set of proteins that may play a significant role in predicting prognosis of NSCLC patients with clinical stages I-II.

Background: The face is the area most exposed to the normal course of skin aging, both intrinsically and extrinsically. The aim of the study was to evaluate the cellular and clinical response of a therapeutic protocol aimed at countering facial skin aging. Materials and Methods: Twenty female patients with facial skin laxity and photodamage underwent combined therapy including mesotherapy using non-cross-linked hyaluronic acid with calcium hydroxyapatite and an infrared energy-based device treatment with subsequent implementation of PEG-cross-linked hyaluronic acid soft tissue fillers. To evaluate the benefits, patients underwent histological, immunological, and biomechanical evaluations before the treatment and at 21 and 150 days after the treatment. Results: The histological results at 21 days and 150 days after the procedure showed an increase in the number of fibroblasts and angiogenesis. As for the immunological aspect, it was shown that the treatment has an immunomodulating action, avoiding the activation of CD4 and CD8 cells. Biomechanical data showed that, at 150 days after treatment, the average changes in skin elasticity increased by 72% and the skin hydration increased by 49%. Conclusions: A combination of an infrared energy-based device treatment with both non-cross-linked hyaluronic acid and novel PEG-cross-linked hyaluronic acid leads to numerous positive cutaneous changes after histological, immunological, and biomechanical evaluations.

Tumor necrosis factor α (TNFα) is one of the most important proinflammatory cytokines, which affects many processes associated with the growth and characteristics of endothelial, smooth muscle, and immune system cells. However, there is no correlation between most in vivo and in vitro studies on its role in endothelial cell proliferation and migration. In this study, we examined the effect of recombinant human (rh) TNFα produced in HEK293 cells on primary human coronary artery endothelial cells (pHCAECs) in the context of F-actin organization and such processes as migration and adhesion. Furthermore, we evaluated the possibility of the inhibition of the endothelial inflammatory response by the CRISPR-based regulation of TPM1 gene expression. We showed that TNFα-induced activation of pHCAECs was related to the reorganization of the actin cytoskeleton into parallel-arranged stress fibers running along the longer axis of pHCAECs. It allowed for the directed and parallel motion of the cells during coordinated migration. This change in F-actin organization promoted strong but discontinuous cell–cell contacts involved in signalization between migrating cells. Moreover, this form of intercellular connections together with locally increased adhesion was related to the formation of migrasomes and further migracytosis. Stabilization of the actin cytoskeleton through the CRISPR-based activation of endogenous expression of TPM1 resulted in the inhibition of the inflammatory response of pHCAECs following treatment with rh TNFα and stabilization of cell–cell junctions through reduced cleavage of vascular endothelial cadherin (VE-cadherin) and maintenance of the stable levels of α- and β-catenins. We also showed that CRISPR-based activation of TPM1 reduced inflammatory activation, proliferation, and migration of primary human coronary artery smooth muscle cells. Therefore, products of the TPM1 gene may be a potential therapeutic target for the treatment of proinflammatory vascular disorders.

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.

Smoking has a damaging effect on the musculoskeletal system, which was presented by authors in the rotator cuff and Achilles tendons studies; however, there are a lack of data about the effect of smoking on disorders of the long head of the biceps tendon (LHBT), particularly at the microscopic level. The purpose of this study was to investigate the effect of the tobacco smoking on the histopathologic alterations of the LHBT. Thirty-six patients with preoperatively diagnosed tendinopathy of the LHBT were referred to the Orthopaedics Department. All patients underwent arthroscopic treatment with further macroscopic and microscopic evaluation of biceps tendon samples. The active and former smokers were characterised by more advanced degenerative process of the tendinous tissue; moreover, it was intensified in the group of former smokers. Subjects who smoke more than 20 cigarettes per day also had more advanced microscopic alterations. The most severe microscopic alterations occurred in the former smokers who used tobacco for more than 20 years. However, the non-smokers group revealed moderate degeneration in all LHBT samples. Tobacco smoking is an important risk factor of the LHBT disease, which essentially intensifies the degeneration of the tendinous tissue.

Abstract Low-grade ovarian cancers represent up to 8% of all epithelial ovarian carcinomas (EOCs). Recent studies demonstrated that epithelial-mesenchymal transition (EMT) is crucial for the progression of EOCs. EMT plays a key role in cancer invasion, metastasis formation and chemotherapy resistance. An array of novel EMT transcription factors from the zinc finger protein family have been described recently, among them zinc finger protein 143 (ZNF143) and zinc finger protein 281 (ZNF281). The study included tissue specimens from 42 patients. Based on histopathological examination of surgical specimens, eight lesions were classified as serous borderline ovarian tumors (sBOTs) and 34 as low-grade EOCs. The proportions of the ovarian tumors that tested positively for ZNF143 and ZNF281 were 90 and 57%, respectively. No statistically significant differences were found in the expressions of ZNF143 and ZNF281 transcription factors in SBOTs and low-grade EOCs. Considering the expression patterns for ZNF143 and ZNF281 identified in this study, both sBOTs and low-grade EOCs might undergo a dynamic epithelial-mesenchymal interconversion. The lack of statistically significant differences in the expressions of the zinc finger proteins in sBOTs and low-grade serous EOCs might constitute an evidence for common origin of these two tumor types.

The chronic inflammation influences a microenvironment, where as a result of losing control over tissue homeostatic mechanisms, the carcinogenesis process may be induced. Inflammatory response cells can secrete a number of factors that support both initiation and progression of cancer and also they may consequently induct an epithelial-mesenchymal transition (EMT), the process responsible for development of distant metastasis. Macrophage migration inhibitory factor (MIF) acts as a pro-inflammatory cytokine that is considered as a link between chronic inflammation and tumor development. MIF can function as a modulator of important cancer-related genes expression, as well as an activator of signaling pathways that promotes the development of prostate cancer. The study was performed on FFPE tissues resected from patients who underwent radical prostatectomy. To investigate the relationship of studied proteins with involvement in tumor progression and initiation of epithelial-to-mesenchymal transition (EMT) process, we selected clinicopathological parameters related to tumor progression. Immunohistochemical analyses of MIF, SOX-4, β-catenin and E-cadherin were performed on TMA slides. We found a statistically significant correlation of overall β-catenin expression with the both lymph node metastasis (p

Aims: The purpose of this study was to investigate whether smoking is associated with neovascularization in the tendinopathy of the long head of the biceps tendon (LHBT). Methods: The study included 40 consecutive patients who underwent arthroscopic biceps tenotomy/tenodesis due to chronic biceps tendinopathy and divided into three groups: (1) non-smokers, (2) former smokers, (3) smokers. LHBT tissue samples were stained with H&E, Alcian blue and Trichrome staining. Immunohistochemical examination was performed using anti-CD31 and anti-CD34. The neovessel density score (NDS) was scored by Bonar criteria. Results: The mean period of smoking was 15.50 years with an average number of 24 cigarettes/day in the former smokers and 21.69 years with an average number of 15 cigarettes/day in the active smokers. The mean NDS was 2.23/3 in non-smokers, whereas it was 1.60/3 in former smokers and 1.31/3 in active smokers. The mean American Shoulder and Elbow Surgeons score equaled 46 in never smoked patients, 43.60 in former smokers, and 41.46 in active smokers. In the patients with smoking history, the disorganized tendinous tissue islands were avascular and composed of compact acidic polysaccharides and mucopolysaccharides. We observed negative correlation between the NDS and the smoking indexes, including cigarettes per day ( p = 0.0150), smoking years ( p = 0.0140), pack-years ( p = 0.0088). Conclusion: In conclusion, the present study revealed that smoking impairs the vascularization of the biceps tendon in chronic tendinopathy. Clinically, we observed a negative correlation between smoking and neovascularization. Furthermore, there was no correlation between neovascularization and functional preoperative status.

Abstract Background The tissue engineering of urinary bladder advances rapidly reflecting clinical need for a new kind of therapeutic solution for patients requiring urinary bladder replacement. Majority of the bladder augmentation studies have been performed in small rodent or rabbit models. Insufficient number of studies examining regenerative capacity of tissue-engineered graft in urinary bladder augmentation in a large animal model does not allow for successful translation of this technology to the clinical setting. The aim of this study was to evaluate the role of adipose-derived stem cells (ADSCs) in regeneration of clinically significant urinary bladder wall defect in a large animal model. Methods ADSCs isolated from a superficial abdominal Camper’s fascia were labeled with PKH-26 tracking dye and subsequently seeded into bladder acellular matrix (BAM) grafts. Pigs underwent hemicystectomy followed by augmentation cystoplasty with BAM only (n = 10) or BAM seeded with autologous ADSCs (n = 10). Reconstructed bladders were subjected to macroscopic, histological, immunofluoresence, molecular, and radiological evaluations at 3 months post-augmentation. Results Sixteen animals (n = 8 for each group) survived the 3-month follow-up without serious complications. Tissue-engineered bladder function was normal without any signs of post-voiding urine residual in bladders and in the upper urinary tracts. ADSCs enhanced regeneration of tissue-engineered urinary bladder but the process was incomplete in the central graft region. Only a small percentage of implanted ADSCs survived and differentiated into smooth muscle and endothelial cells. Conclusions The data demonstrate that ADSCs support regeneration of large defects of the urinary bladder wall but the process is incomplete in the central graft region. Stem cells enhance urinary bladder regeneration indirectly through paracrine effect.

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.

This study aimed to perform a comprehensive systematic review, which reports the role of the Bonar score in the histopathological assessment of tendinopathy and its clinical relevance. To identify all of the studies that reported relevant information on the Bonar scoring system and tendinopathy, an extensive search of the major and the most significant electronic databases (PubMed, Cochrane Central, ScienceDirect, SciELO, Web of Science) was performed. A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The extracted data included—year of study, geographical location, type of the study, radiological modifications, gender, number of patients, region of tendinopathy, mean age, control group, characteristics of the Bonar score and alterations in the scale, mean Bonar score, number of investigators, area of tendon investigation, clinical and radiological implications. An extensive search of the databases and other sources yielded a total of 807 articles. Eighteen papers were finally included in this systematic review, and of these, 13 original papers included the clinical and radiological implications of tendinopathy. Radiological evaluation was present in eight studies (both magnetic resonance imaging (MRI) and ultrasound (US)). The clinical implications were more frequent and present in 10 studies. Using the Bonar score, it is easy to quantify the pathological changes in tendinous tissue. However, its connection with clinical and radiological evaluation is much more complicated. Based on the current state of knowledge, we concluded that the neovascularization variable in the Bonar system should be reconsidered. Ideally, the microscopic assessment score should follow the established classification scale with the radiological and clinical agreement and should have a prognostic value.

Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction–based Idylla™ system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction–based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3–60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue.

Actin is one of the cytoskeletal proteins that take part in many cellular processes. The aim of this study was to show the influence of Trisenox (arsenic trioxide), on the cytoplasmic and nuclear F-actin organization. Arsenic trioxide is the proapoptotic factor. Together with increasing doses, it caused the increase in the number of cells undergoing apoptosis. Under arsenic trioxide treatment, cytoplasmic and nuclear F-actin (polymerized form of G-actin) was found reorganized. It was transformed into granulated structures. In cytometer studies fluorescence intensity of cytoplasmic F-actin after ATO treatment decreasing urgently in comparison to control. The obtained results may suggest the involvement of F-actin in apoptosis, especially in chromatin reorganization.

Currently, information regarding the influence of growth factors on the cytoskeleton, including G-CSF and GMCSF, remains limited. In the present study we show alterations in F-actin distribution and cell cycle progression in HL-60 promyelocytic leukemia cells, resulting from treatment with these cytokines in vitro. We found that both agents caused F-actin reorganization. Although multiple potential effects of various growth factors have been described previously, in our experimental conditions, we observed some rather subtle differences between the effects of G-CSF and GM-CSF on studied cells. The presence of these cytokines in the cell environment caused not only increased F-actin labeling in the cytoplasm, but also a weaker intensity of peripheral ring staining in comparison with control cells. In spite of the fact that HL60 cells exposed to G-CSF and GM-CSF contained different F-actin structures such as aggregates and F-actin network, the rate of actin polymerization was not significantly enhanced. Moreover, alterations were mainly related to considerable changes in the relative proportion of these different structures, what might be reflected by specific features of the differentiation process, with regard to the kind of stimulating factor used. Thus, reorganization of F-actin and other results obtained in our experimental conditions, might reflect unique characteristics of the differentiation process in HL-60 cells, involving low apoptosis frequency, the G1 to S phase transition in the cell cycle, as well as possible alternative ways of the cell death.