IL-6 Activities in the Tumour Microenvironment. Part 1

The predominant role of IL-6 in cancer is its key promotion of tumour growth. IL-6 binds IL-6 receptor (IL-6R) and the membrane-bound glycoprotein gp130. The complex I-6/IL-6R/gp130 starts the Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3) or JAK/STAT3 pathway. IL-6R exits in two forms: a membrane-bound IL-6Rα subunit (mIL-6R) that participates in classic signalling pathway and soluble IL-6R subunit (sIL-6R) engaged in trans-signalling. The pro-tumour functions of IL-6 are associated with STAT3, a major oncogenic transcription factor that triggers up-regulation of target genes responsible for tumour cell survival. IL-6 combined with TGF-β induces proliferation of pathogenic Th17 cells. The anti-tumour function of IL-6 is the promotion of anti-tumour immunity. IL-6 trans-signaling contributed to transmigration of lymphocytes in high endothelial venules (HEV). Dendritic cell (DC) secreted IL-6 in the lymph node influences the activation, distribution and polarisation of the immune response. Elevated serum levels of IL-6 and increased expression of IL-6 in tumour tissue are negative prognostic marker for patients’ survival

In search of dermatophytes – frequency and etiology of fungal infections in patients with and without diabetes mellitus

Introduction: Onychomycosis is a frequent nail disorder, accounting for up to 50% of all nail problems. Treatment of onychomycosis is expensive and requires a long time of antifungal medications. Consequently, a proper and faster diagnosis is necessary. Especially for those patients with diabetes mellitus, where onychomycosis is among the most significant predictors of foot ulcer and possible severe complications.Aim: To compare the sensitivity, specificity, and turnaround time between direct microscopy, culture, histology, and real-time PCR. In addition, to compare the frequency and etiology of onychomycosis in patients with and without DM.Materials and methods: This study included 102 patients, divided into two groups. One group consisted of patients with diabetes mellitus and the other – without diabetes. Nail samples were collected and examined by direct KOH microscopic examination, culture, histology, and real-time PCR.Results: From the 102 patients with clinical onychomycosis, positive KOH was found in 38 (37.3%). Culture – 82 out of 102 samples (80.4%) were positive for dermatophytes, yeasts, and/or NDM. Positive histology samples were 32 (41.6%). The PCR was positive in 57 (55.9%) out of the 102. We discovered that there is no significant statistical difference in the etiology of the fungal infections between the two groups.Conclusions: All mycological investigations have their place in the diagnosis of onychomycosis. Direct microscopy, culture, and histology are useful methods for clinicians to diagnose and follow up the post-treatment period. The advantages of RT-PCR include obtaining results faster and accurately identifying fungi, thus becoming more valued in the diagnosis of OM

Expression of Snail and Twist compared with clinical and pathological parameters in patients with gastric cancer

Introduction: Epithelial-mesenchymal transition (EMT) is a process of change in the cellular phenotype from epithelial to mesenchymal morphology. The changes at the cellular level can explain the great heterogeneity and plasticity in the different histological subtypes of gastric carcinomas, which causes difficulties in therapy. In it, epithelial cells reduce intercellular adhesion, which is crucial in the process of invasion and metastasis of gastric carcinomas. Inhibition of cell adhesion molecules such as E-cadherin is known to be influenced by a number of transcription factors, such as Snail and Twist. Materials and methods: Our study aims to examine immunohistochemically the expression of the transcription factors Snail and Twist in 69 patients with gastric cancer and to look for a link between their expression and clinical and pathological characteristics. Results: Positive expression of Snail and Twist was observed in all cases studied by us. We observed heterogeneity and different intensity of immunohistochemical expression. There is a correlation between the immunohistochemical expression and the degree of differentiation of tumor cells and the tumor stage. The cells of poorly differentiated adenocarcinomas show diffuse and strong nuclear staining. No correlation was found between the expression of the two markers, age, and sex of the patients. Conclusions: Evaluating the expression of the two markers studied may help to assess tumor progression and prognosis. They can be used for more accurate and effective diagnosis in precancerous lesions and in early gastric cancer because they are not expressed in the normal gastric mucosa

Histopathological examination of lung from infant with lethal COVID-19 with special attention on pneumocytes type II and the immune infiltrate: a case study

Abstract Background COVID-19 is a complex disease caused by SARS-CoV-2. The molecular and cellular mechanisms of the disease are unclear and their study is one of the greatest challenges for the modern science. Since the lung is the biggest target for SARS-CoV-2, the studies on cellular and molecular changes in this organ are essential to establish the pathogenesis of the disease. To date there is increasing number of reports on the lung pathology of fatal COVID-19 and the results are mainly obtained by autopsies of elderly patients, since this age group shows highest mortality. Little is known about the progression of the disease in children and especially newborn and infants and, to our knowledge, there are no reports on the lung features of fatal COVID-19 in this age group. Methods In the present case study, we have investigated the lung morphological features in 11-months old infant who has died as a result of complications from COVID-19. Immunohistochemistry for immune cell markers and transmission electron microscopy for alveolocytes type II (ATII) are made. Results Immediate cause of the death was acute respiratory failure resulting from bilateral interstitial pneumonia and subsequent acute cardiovascular failure. The histopathology shows lung edema, hyaline membranes, airway mucus plugging and interstitial inflammation. On cellular level we have observed a substantial increase in the number of ATII cells. ATII cells were marked with cytokeratin 19, TTF1 and napsin A. Transmission elec­tron microscopy reveals ongoing apoptosis in these cells with a typical chromatin clustering and condensation towards the inner nuclear membrane. Immunohisto­chemistry shows significant increase of CD68+ macro­phages in the alveoli, increase of IL-6 in immune and stromal cells, moderate elevation of FOXP3+ and IL-17+ cells and expression of CD4+ and CD8+ cells in alveolar walls. Immune cell interactions are discussed in the sense of ongoing cytokine storm. Conclusions Our findings highlight the complexity of COVID-19 lung affection, involving ATII cell hyperplasia, interstitial mononuclear cell infiltration and macrophages increase. The findings provide an additional knowledge on the pathophysiology of COVID-19 in the lung and can serve as a basis for investigation of molecular mechanisms of this disease

On the Accuracy of Appliance Identification Based on Distributed Load Metering Data.

Dynamic load management, i.e., allowing electricity utilities to remotely turn electric appliances in households on or off, represents a key element of the smart grid. Appliances should however only be disconnected from mains when no negative side effects, e.g., loss of data or thawing food, are incurred thereby. This motivates the use of appliance identification techniques, which determine the type of an attached appliance based on the continuous sampling of its power consumption. While various implementations based on different sampling resolutions have been presented in existing literature, the achievable classification accuracies have rarely been analyzed. We address this shortcoming and evaluate the accuracy of appliance identification based on the characteristic features of traces collected during the 24 hours of a day. We evaluate our algorithm using more than 1,000 traces of different electrical appliances' power consumptions. The results show that our approach can identify most of the appliances at high accuracy

Microsatellite unstable colorectal cancers are associated with increased CD1a- and CD83-positive dendritic cell infiltration

AbstractMicrosatellite instability (MSI) is characterized by a highly immunogenic tumor phenotype and abundant lymphocytic infiltrates. The aim of this study was to investigate the association between four immunohistochemically determined classes of dendritic cells (DC) with microsatellite instability status of 258 colorectal cancer (CRC) patients and to explore the possible role of those cells as prognostic factors for survival. We observed a distinct infiltration pattern of DCs both in tumor stroma (TS) and invasive front (IF), with DCs significantly prevailing in the IF (p < 0.0001). MSI cancer biopsies showed significantly higher infiltration of CD1a + and CD83+ DCs in the TS and IF compared to microsatellite stable CRCs. Survival analysis revealed that higher CD1a + and CD83+ DC numbers both in TS and IF correlated with longer survival of the patients after surgical therapy (p < 0.05, Log rank test). Cox multivariate analysis showed that lower infiltration with CD1a + DCs in TS (p = 0.039) and CD83+ DCs in IF (p = 0.022) was an independent prognostic factor for unfavorable outcome for CRC patients. The results of our study suggest that the immunohistochemically determined CD1a + and CD83+ DCs could be used as a feature of microsatellite instability and could be further explored as prognostic markers for patients’ outcome