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Pathbase (http://www.pathbase.net) is a web accessible database of histopathological images of laboratory mice, developed as a resource for the coding and archiving of data derived from the analysis of mutant or genetically engineered mice and their background strains. The metadata for the images, which allows retrieval and interoperability with other databases, is derived from a series of orthogonal ontologies and controlled vocabularies. One of these controlled vocabularies, MPATH, was developed by the Pathbase Consortium as a formal description of the content of mouse histopathological images. The database currently has over 1000 images on-line with 2000 more under curation and presents a paradigm for the development of future databases dedicated to aspects of experimental biology.

Simple Summary: Epidemiological evidence supports an increased risk of cardiovascular diseases (CVD) at doses and dose rates much lower than previously believed. However, the molecular mechanism involved in cardiac damage after chronic irradiation has not been fully elucidated. Here, we studied the proteome of mice hearts chronically irradiated with a very low dose (1 mGy/day) or with a low dose (20 mGy/day) for 300 days. Changes in the proteome were further validated by immunoblotting, enzyme activity assays, immunohistochemistry, and targeted transcriptomics. The data presented here demonstrate that chronic low-dose total body irradiation induces biological changes in mouse cardiac tissue that resemble the effects of premature cardiac ageing. A comprehensive understanding of the molecular mechanisms of CVD following chronic low dose irradiation will enable the identification of target molecules or pathways which may be used in bioassays for measuring endpoints relevant to radiation risk assessment. Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE−/−) C57Bl/6 female mice chronically irradiated for 300 days at a very low dose rate (1 mGy/day) or at a low dose rate (20 mGy/day), resulting in cumulative whole-body doses of 0.3 Gy or 6.0 Gy, respectively. The heart proteomes were compared to those of age-matched sham-irradiated ApoE−/− mice using label-free quantitative proteomics. Radiation-induced proteome changes were further validated using immunoblotting, enzyme activity assays, immunohistochemistry or targeted transcriptomics. The analyses showed persistent alterations in the cardiac proteome at both dose rates; however, the effect was more pronounced following higher dose rates. The altered proteins were involved in cardiac energy metabolism, ECM remodelling, oxidative stress, and ageing signalling pathways. The changes in PPARα, SIRT, AMPK, and mTOR signalling pathways were found at both dose rates and in a dose-dependent manner, whereas more changes in glycolysis and ECM remodelling were detected at the lower dose rate. These data provide strong evidence for the possible risk of cardiac injury following chronic low dose irradiation and show that several affected pathways following chronic irradiation overlap with those of ageing-associated heart pathology. [ABSTRACT FROM AUTHOR]

Low Dose of Dipotassium Glycyrrhizate Counteracts Atherosclerosis Progression in Apoe-/- Female Mice Serum cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) concentrations were also evaluated at the same time points by Mouse Cholesterol ELISA Kit (MyBioSource and EMELCA Bioscience, Breda, The Netherlands) and by HDK and LDL/VLDL Quantitation Kit (Sigma-Aldrich), respectively. Our results showed that the cortisol level is not modulated by DPG treatment (serum cortisol: matched controls [CN]: 12.37 ng/mL ± 1.86; DPG 12.70 ng/mL ± 0.59, I p i = 0.25; Fig. Effect of DPG on serum cortisol and cholesterol levels in female ApoE-/- mice and age-matched controls (CN) 14 weeks after treatment. [Extracted from the article]

Presents a study which analyzed the involvement of Ptcl in the tumorigenic response to a single dose of 3 Gy X-rays in neonatal and adult Ptc1 heterozygous and wild type mice. Impact of irradiation on the incidence of medulloblastoma development over the spontaneous rate in neonatal; Factor attributed to medulloblastoma formation in heteryzygous Ptcl mice.

Molecular communication between irradiated and unirradiated neighbouring cells initiates radiation-induced bystander effects (RIBE) and out-of-field (abscopal) effects which are both an example of the non-targeted effects (NTE) of ionising radiation (IR). Exosomes are small membrane vesicles of endosomal origin and newly identified mediators of NTE. Although exosome-mediated changes are well documented in radiation therapy and oncology, there is a lack of knowledge regarding the role of exosomes derived from inside and outside the radiation field in the early and delayed induction of NTE following IR. Therefore, here we investigated the changes in exosome profile and the role of exosomes as possible molecular signalling mediators of radiation damage. Exosomes derived from organs of whole body irradiated (WBI) or partial body irradiated (PBI) mice after 24 h and 15 days post-irradiation were transferred to recipient mouse embryonic fibroblast (MEF) cells and changes in cellular viability, DNA damage and calcium, reactive oxygen species and nitric oxide signalling were evaluated compared to that of MEF cells treated with exosomes derived from unirradiated mice. Taken together, our results show that whole and partial-body irradiation increases the number of exosomes, instigating changes in exosome-treated MEF cells, depending on the source organ and time after exposure. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains significant and the long-term adverse effects in survivors are substantial. The fraction of cancer stem-like cells (CSCs) because of their self-renewal ability and multi-lineage differentiation potential is critical for tumor initiation, growth, and resistance to therapies. For the development of new CSC-targeted therapies, further in-depth studies are needed using enriched and stable MB-CSCs populations. This work, aimed at identifying the amount of CSCs in three available human cell lines (DAOY, D341, and D283), describes different approaches based on the expression of stemness markers. First, we explored potential differences in gene and protein expression patterns of specific stem cell markers. Then, in order to identify and discriminate undifferentiated from differentiated cells, MB cells were characterized using a physical characterization method based on a high-frequency dielectrophoresis approach. Finally, we compared their tumorigenic potential in vivo, through engrafting in nude mice. Concordantly, our findings identified the D283 human cell line as an ideal model of CSCs, providing important evidence on the use of a commercial human MB cell line for the development of new strategic CSC-targeting therapies. [ABSTRACT FROM AUTHOR]

The brain undergoes ionizing radiation (IR) exposure in many clinical situations, particularly during radiotherapy for malignant brain tumors. Cranial radiation therapy is related with the hazard of long-term neurocognitive decline. The detrimental ionizing radiation effects on the brain closely correlate with age at treatment, and younger age associates with harsher deficiencies. Radiation has been shown to induce damage in several cell populations of the mouse brain. Indeed, brain exposure causes a dysfunction of the neurogenic niche due to alterations in the neuronal and supporting cell progenitor signaling environment, particularly in the hippocampus—a region of the brain critical to memory and cognition. Consequent deficiencies in rates of generation of new neurons, neural differentiation and apoptotic cell death, lead to neuronal deterioration and lasting repercussions on neurocognitive functions. Besides neural stem cells, mature neural cells and glial cells are recognized IR targets. We will review the current knowledge about radiation-induced damage in stem cells of the brain and discuss potential treatment interventions and therapy methods to prevent and mitigate radiation related cognitive decline. [ABSTRACT FROM AUTHOR]