TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients.

OBJECTIVE: In recent years, the role of the modern inflammatory markers TREM-1 (triggering receptors expressed on myeloid cells) and HMGB1 (high mobility group box 1 protein) in tumorigenesis has begun to be studied. Their role in gliomas is not clear. The aim of our study was to find the role of inflammation in gliomas. Patients and Methods. In 63 adult patients with gliomas and 31 healthy controls, the expressions of TREM-1 and TREM-2 on CD14+ blood cells (method: flow cytometry) and the levels of soluble sTREM-1, HMGB1, IL-6, and IL-10 (Elisa tests) were analyzed. RESULTS: Cox proportional hazard analysis showed that a TREM-1/TREM-2 ratio was associated with reduced overall survival (HR = 1.001, P = 0.023). Patients with a TREM-1/TREM-2 ratio above 125 survived significantly shorter than patients with a TREM-1/TREM-2 ratio below 125. The percentage of CD14+ TREM-1+ cells was strongly associated with a plasma IL-6/IL-10 ratio (positively) and with IL-10 (negatively). Conversely, we found a higher percentage of CD14+ TREM-2+ monocytes in better surviving patients; these cells could downregulate the exaggerated inflammation and potentiate the phagocytosis in the tumor. The serum levels of HMGB1 negatively correlated with the percentage of CD14+ TREM-1+ cells and with the TREM-1/TREM-2 ratio. The positive correlation between the serum levels of a late proinflammatory cytokine HMGB1 with the percentage of TREM2+ CD14+ monocytes can be explained as an effort for suppression of systemic inflammation by anti-inflammatory acting CD14+ TREM-2+ cells. CONCLUSION: We showed that the TREM-1/TREM-2 ratio (expression on the surface of blood monocytes) could help predict prognosis in patients with gliomas, especially in high-grade gliomas, and that systemic inflammation has an impact on the patient's overall survival. This is the first study that showed that TREM expression on monocytes in peripheral blood could help predict prognosis in patients with gliomas.

Expression of synaptic proteins in the hippocampus is modulated by neonatal oxytocin treatment.

An alteration of oxytocin signaling during postnatal maturation of the brain could be associated with etiology of neurodevelopmental disorders among them autism. The aim of the present study was to examine the role of oxytocin in the regulation of expression of selected cell-adhesion molecules and scaffolding proteins in the hippocampus in early rat development. Oxytocin treatment (1 mg/ml, i.p., 50 µl/pup) at postnatal days P2-P3 resulted in the reduction of Neuroligin 3 gene expression, and was accompanied by lower SHANK1 and SHANK3 mRNA levels in the hippocampus at P5 day. Immunostaining revealed a clear trend for the lower density of Neuroligin 3 positive cells in the hippocampus and this trend has been significant in the CA3 hippocampal area. The significantly lower Neurexin 2ß mRNA levels were observed in response to oxytocin treatment, with no effect seen in the Neurexin 2α gene expression. No change has been observed in the gene expression of Neuroligin 1 and Neuroligin 2. Oxytocin induced an increase in the mRNA levels of Neuron-Specific Enolase (NSE) and a decrease in the mRNA levels of glial fibrillary acid protein (GFAP) - marker of astrocytes. Incubation of primary neuronal cells with oxytocin (1 µM, 48 h) stimulated a proliferation of NSE-positive cells. These results suggest that synaptic proteins could be under control of oxytocin in early stages of brain development. The changes of cell-adhesion molecule and scaffolding protein levels might be linked to the modulation of number of neuronal cells.

Iron deposition in rabbit cerebellum after exposure to generated and mobile GSM electromagnetic fields.

BACKGROUND: Mobile phone application may cause structural, functional changes and accumulation of toxic elements in brain. OBJECTIVES: The aim of this study was to investigate iron accumulation in rabbit cerebellum after exposure to RF EMF with light and scanning electron microscopy. MATERIALS AND METHODS: Histochemical analysis of iron distribution by light and electron microscopy with energy-dispersive microanalysis was used. RESULTS: Light microscopy revealed dystrophic changes of Purkinje cells in irradiated groups and iron deposits located in various parts of cerebellum. Deposits consists of C, O, Na, Mg, Al, Si, P, S, Cl, Ca and Fe. CONCLUSION: Our experiment revealed structural changes of Purkinje cells and iron and aluminium accumulations in stratum granulosum of rabbit's cerebellum after exposure to RF EMF (Fig. 6, Ref. 33).

Anthocyanin-Rich Diet in Chemically Induced Colitis in Mice.

The aetiology of inflammatory bowel diseases is unclear, but oxidative stress plays a key role in the pathogenesis. Anthocyanins--plant polyphenols--were shown to have antioxidant and anti-inflammatory properties. The aim of this study was to investigate the potential protective effects of anthocyanins on the oxidative status in mice with chemically induced colitis. Adult male mice were randomly divided into a control group drinking tap water and a colitis group drinking 1% dextran sulphate sodium solution. Animals had ad libitum access to a control wheat-based diet or food based on wheat producing anthocyanins. Bodyweight and stool consistency were monitored daily for 14 days. At the end of the experiment, colon length was measured and tissue samples were collected for the assessment of histology and oxidative status. Mice with colitis had lower body weight, higher stool score and shorter colon than control mice. Anthocyanins had neither an effect on stool consistency, nor on bodyweight loss and colon length. In the colon, liver and plasma, analysis of oxidative stress markers and antioxidant status revealed no significant differences between the groups. Food made from wheat producing anthocyanins did not protect mice from the consequences of chemically induced colitis. The measured biomarkers do not confirm the role of oxidative stress in this model of colitis. Further optimization of the anthocyanin-rich food might be needed before further experiments are conducted.

Effect of Fractionated Irradiation on the Hippocampus in an Experimental Model.

BACKGROUND: Ionizing radiation induces altered brain tissue homeostasis and can lead to morphological and functional deficits. The aim of the present study was to investigate the short-term and long-term effect of ionizing radiation on cell population resides adult rat hippocampus. MATERIALS AND METHODS: Adult male Wistar rats received whole- brain irradiation with fractionated doses of gamma rays (a total dose of 20 Gy) and were investigated 30 and 100 days later. A combination of Fluoro-Jade C histochemistry for visualization of degenerating neurons, immunohistochemistry for detection of astrocytes and confocal microscopy were used to quantify the neurodegenerative changes in the hippocampal dentate gyrus and CA1 subfield. RESULTS: A significant increase of Fluoro-Jade C labelled neurons was seen in both of investigated areas through the whole experiment, predominantly 30 days after irradiation. Non- significant decrease of GFAP- immunoreactive astrocytes was found in the hippocampal dentate gyrus and CA1 subfield until 100 days after irradiation. CONCLUSION: Our recent results showed that radiation response of cell types resides the adult hippocampus may play contributory role in the development of adverse radiation-induced late effects.