Histology and histopathology Vol.33, nº5 (2018)
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- PublicationOpen Access1p36 deletion results in a decrease in glycosaminoglycans which is associated with aggressiveness in neuroblastic tumors(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Tadeo, Irene; Gamero Sandemetrio, Esther; Berbegall, Ana P.; Navarro, Samuel; Cañete, Adela; Noguera, RosaDespite our deep understanding of neuroblastic tumors, some patients still suffer treatment failure, so pre-treatment risk stratification still requires improvement and the search for new therapeutic targets must continue. Here we correlated prognostic clinical and biological features of neuroblastic tumors with the density of extracellular matrix glycosaminoglycans (the main components of the extracellular matrix ‘ground substance’), in nearly 400 primary samples. We also studied the relationship between the density of extracellular matrix glycosaminoglycans and the expression of B3GALT6, an enzyme required for their synthesis. We associated a decrease in glycosaminoglycans with neuroblastomas that were histopathologically poorly-differentiated or undifferentiated, as well as with metastatic disease, and 1p36 deleted tumors. This decrease in glycosaminoglycans was also related to abnormal nuclear B3GALT6 expression in neuroblastic cells. These findings point towards the importance of the ground substance in the aggressiveness of neuroblastic tumors, which should therefore be considered when developing novel therapies for treating neuroblastomas.
- PublicationOpen AccessMiRNAs participate in the diagnosis, pathogenesis and therapy of Parkinson's disease(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lu, Xuexin; Cui, Zhijie; Liu, Shuang; Yin, FengMicroRNAs (miRNAs), one kind of posttranscriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes, including Parkinson’s disease. At present, the pathogenesis of Parkinson's disease is not clear, although many studies suggest that miRNAs play a very important role in the progress of Parkinsonism. This paper reviews the biological characteristics of miRNAs and summarizes the progress of miRNAs in reference to the diagnosis and pathogenesis of Parkinson’s disease. It even considers miRNAs as a potential target for Parkinson’s disease therapy
- PublicationOpen AccessAutomatic detection of DNA double strand breaks after irradiation using an γH2AX assay(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Hohmann, Tim; Kessler, Jacqueline; Grabiec, Urszula; Bache, Matthias; Dehghani, FaramarzRadiation therapy belongs to the most common approaches for cancer therapy leading amongst others to DNA damage like double strand breaks (DSB). DSB can be used as a marker for the effect of radiation on cells. For visualization and assessing the extent of DNA damage the γH2AX foci assay is frequently used. The analysis of the γH2AX foci assay remains complicated as the number of γH2AX foci has to be counted. The quantification is mostly done manually, being time consuming and leading to person-dependent variations. Therefore, we present a method to automatically analyze the number of foci inside nuclei, facilitating and quickening the analysis of DSBs with high reliability in fluorescent images. First nuclei were detected in fluorescent images. Afterwards, the nuclei were analyzed independently from each other with a local thresholding algorithm. This approach allowed accounting for different levels of noise and detection of the foci inside the respective nucleus, using Hough transformation searching for circles. The presented algorithm was able to correctly classify most foci in cases of “high” and “average” image quality (sensitivity>0.8) with a low rate of false positive detections (positive predictive value (PPV) >0.98). In cases of “low” image quality the approach had a decreased sensitivity (0.7-0.9), depending on the manual control counter. The PPV remained high (PPV >0.91). Compared to other automatic approaches the presented algorithm had a higher sensitivity and PPV. The used automatic foci detection algorithm was capable of detecting foci with high sensitivity and PPV. Thus it can be used for automatic analysis of images of varying quality
- PublicationOpen AccessHistopathological, immunohistochemical, and stereological analysis of the effect of Ginkgo biloba (Egb761) on the hippocampus of rats exposed to long-term cellphone radiation(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Gevrek, FikretCellular phones are major sources of electromagnetic radiation (EMR) that can penetrate the human body and pose serious health hazards. The increasingly widespread use of mobile communication systems has raised concerns about the effects of cellphone radiofrequency (RF) on the hippocampus because of its close proximity to radiation during cellphone use. The effects of cellphone EMR exposure on the hippocampus of rats and the possible counteractive effects of Ginkgo biloba (Egb761) were aimed to investigate. Rats were divided into three groups: Control, EMR, and EMR+Egb761. The EMR and EMR+Egb761 groups were exposed to cellphone EMR for one month. Egb761 was also administered to the EMR+Egb761 group. Specifically, we evaluated the effect of RF exposure on rat hippocampi at harmful EMR levels (0.96 W/kg specific absorption rate [SAR]) for one month and also investigated the possible impact of Egb761 using stereological, TUNEL-staining, and immunohistochemical methods. An increase in apoptotic proteins (Bax, Acas-3) and a decrease in anti-apoptotic protein (Bcl-2) immuno-reactivity along with a decrease in the total granule and pyramidal cell count were noted in the EMR group. A decrease in Bax and Acas-3 and an increase in Bcl-2 immunoreactivity were observed in rats treated with Egb761 in addition to a decrease in TUNEL-stained apoptotic cells and a higher total viable cell number. In conclusion, chronic cellphone EMR exposure may affect hippocampal cell viability, and Egb761 may be used to mitigate some of the deleterious effects.
- PublicationOpen AccessRegulation and function of sphingosine kinase 2 in diseases(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Song, Dan Dan; Zhou, Jun Hao; Sheng, RuiSphingosine kinase functions to phosphorylate sphingosine to sphingosine 1-phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Although SphK1 and SphK2 share high sequence similarity, SphK2 has distinct distribution, regulation and function. SphK2 is involved in the pathological processes of varieties of diseases including cancer, neurodegenerative disorders, stroke, cardiovascular diseases and inflammation. SphK2 may promote the proliferation of cancer cells and the progression of inflammation. The SphK2/S1P pathway is also involved in the pathogenesis of neurodegenerative disorders and stroke. S1P produced by SphK2 in the nucleus binds to HDACs, which then inhibits histone acetylation and regulates memory. The SphK2 pathway mediates platelet aggregation, thrombosis, cardioprotection and helps to ameliorate hepatic steatosis. This review focuses on the recent advances in research on SphK2 regulation and its potential roles in diseases, highlighting SphK2 may be a novel therapeutic strategy for diseases.