DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells

We investigated the genotoxic responses to two types of TiO2 nanoparticles (<25 nm anatase: TiO2-An, and <100 nm rutile: TiO2-Ru) in human hepatoma HepG2 cells. Under the applied exposure conditions the particles were agglomerated or aggregated with the size of agglomerates and aggregates in the micrometer range, and were not cytotoxic. TiO2-An, but not TiO2-Ru, caused a persistent increase in DNA strand breaks (comet assay) and oxidized purines (Fpg-comet). TiO2-An was a stronger inducer of intracellular reactive oxygen species (ROS) than TiO2-Ru. Both types of TiO2 nanoparticles transiently upregulated mRNA expression of p53 and its downstream regulated DNA damage responsive genes (mdm2, gadd45α, p21), providing additional evidence that TiO2 nanoparticles are genotoxic. The observed differences in responses of HepG2 cells to exposure to anatase and rutile TiO2 nanoparticles support the evidence that the toxic potential of TiO2 nanoparticles varies not only with particle size but also with crystalline structure

Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma

Glioblastoma is the most aggressive cancer among primary brain tumours. As with other cancers, the incidence of glioblastoma is increasing; despite modern therapies, the overall mean survival of patients post-diagnosis averages around 16 months, a figure that has not changed in many years. Cannabigerol (CBG) has only recently been reported to prevent the progression of certain carcinomas and has not yet been studied in glioblastoma. Here, we have compared the cytotoxic, apoptotic, and anti-invasive effects of the purified natural cannabinoid CBG together with CBD and THC on established differentiated glioblastoma tumour cells and glioblastoma stem cells. CBG and THC reduced the viability of both types of cells to a similar extent, whereas combining CBD with CBG was more efficient than with THC. CBD and CBG, both alone and in combination, induced caspase-dependent cell apoptosis, and there was no additive THC effect. Of note, CBG inhibited glioblastoma invasion in a similar manner to CBD and the chemotherapeutic temozolomide. We have demonstrated that THC has little added value in combined-cannabinoid glioblastoma treatment, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies of glioblastoma therapy

Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain

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New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX–XXX

Co-operation relationship between the parents and specialised staff members in training, occupation and care centres

The aim of this research has been to check the co-operation relationship between the parents of the persons with moderate, severe and profound deficiencies in mental and physical development and specialised staff members in social welfare institutions, particularly in training, occupation and care centres in Slovenia. The co-operation is importantly connected with the interactive style and the relationship competence of the families of these parents and the families of the specialised staff members. We have been interested in the data on what the interactive style and relationship competence in the families with persons with deficiencies who are included in these centres are like, and what the interactive style and relationship competence in the families of specialised staff members who work with these persons in these centres are like. The co-operative relationship which is established plays an important role in planning and co-ordination of the needs of these persons and the interests of everybody involved in the co-operation relationship. Furthermore, we have established the connectedness of the co-operation relationship with the inclusion of the parents into the self-assistance groups for the parents and the staff into groups having to do with supervision, intervision and key persons. Survey questionnaires for parents and specialised staff members have been used for the purpose of the exploratory quantitative research method. The first, translated part of the survey questionnaire checks the co-operation relationship and interactive style of the families of the parents and the families of the specialised staff members. The second part of the survey questionnaire, which checks the co-operation relationship between the parents and specialised staff members, has been formed on the basis of theoretical starting points and professional practice. The research has been the means of ascertaining the structural difference between the group of parents and the group of specialised staff members; on the basis of the results obtained via statistical analyses we have defined the system which best anticipates the degree of mutual co-operation relationship. In order to establish the connectedness of the interactive style and relationship competence with the co-operation relationship, Pearson’s correlation coefficient has been used. The results have shown that the interactive style and relationship competence in the families of the parents as well as in those of specialised staff members critically connected with the degree of the co-operation relationship between the parents and specialised staff members. On the basis of the system of variables we have assumed that there is a structural difference between the parents who are involved in self-assistance groups for parents and those who are not. Individual bi-variant calculations have been applied with categorical variables, to wit, point-biserial correlation coefficient with non-categorical variables in order to establish the differences. It has been established that mothers are substantially more involved in these groups than fathers and unmarried parents are more so than those living in a partnership relation; it has furthermore been established that in the units with around-the-clock-care and training of persons with deficiencies their parents participate in the self-assistance groups for parents significantly less frequently as opposed to the parents with of persons with deficiencies who are involved in the units with day care and training. In addition, on the basis of the system of variables structural differences among specialised staff members who are included in the groups for the staff and those who are not have been assumed. We have come to the conclusion that the groups for the staff are least frequented by the specialised staff members with a pre-university degree of education and most frequented by those with a higher education degree or post-graduate degree; moreover, guardians as compared with pedagogical and health care workers are involved in the groups for the staff in a significantly smaller number. The establishment of the differences in the degree of the co-operation relationship of the parents who are involved in the groups for self-assistance for parents and those who are not, as well as that of the specialised staff members who are involved in the groups for self-assistance for the staff and those who are not, has been checked by means of a one-way analysis of variance. The results have not confirmed differences in parents as opposed to the surprising fact that the specialised staff members who are involved in the groups for the staff have displayed a significantly lower degree of the co-operation relationship with parents. The statistical method of two-way analysis of variance has been applied to establish the differences in the degree of the co-operation relationship given the gender and the age of the parents and the staff. The results have confirmed the differences in the age of the male staff, namely, that with their age the degree of co-operation relationship with parents increases. On the basis of the results of the research we have substantiated and proposed the concepts of a successful co-operation relationship between the parents and specialised staff members which enable the understanding of this relationship and contribute to a more effective realisation of the programme for persons with moderate, severe and profound deficiencies in mental and physical development. The differences which have been demonstrated between the centres indicate the need for a more coordinated operation of the centres knowledge exchange in the area of the attitude in the relations with parents. It is particularly necessary to encourage those parents to co-operate who have persons with deficiencies included in around-the-clock-care and training, primarily fathers. In addition, the method of work in the day care and training practices needs to be brought as close as possible to the work in the around-the-clock-care and training practices; moreover, more recruitment of more male staff members should be attempted. Furthermore, we have proposed a revision and organisation of the groups for the staff such as intervision and particularly supervision which includes specialised staff members with the highest degree of education. All this requires new forms of work and co-operation with parents, new forms of co-operation between centres and, last but not least, training of parents and specialised staff members

Brain malignancies

Brain, the major organ of the central nervous system controls and processes most of body activities. Therefore, the most aggressive brain tumor – glioblastoma and metastases from other organs to the brain are lethal leaving the patients with very short time of survival. The brain tissue landscape is very different from any other tissues and the specific microenvironment, comprising stem cells niches and blood-brain barrier, significantly influences the low rate of glioblastoma metastasis out of the brain, but better accommodates brain-invading cancer. In contrast to low frequency (0.5%) of all glioblastoma metastases, 10%–45% of other primary cancers do metastasize to the brain. This review addresses general cellular and molecular pathways that are to some extent similar in both types of metastases, involving circulating tumor cells (CTCs) with cancer stem cells (CSCs) characteristics, and metastatic niches. The invasion is a dynamic process involving reversible epithelial-to-mesenchymal (EMT) cell process, creating a transient gradient state that is inter-connected with epigenetic plasticity of the metastasizing (m)CSCs. These cells can switch between stationary, low proliferating/dormant state to a migratory, mesenchymal-like state. Settling in their respective niches as dormant CSCs in the secondary organ is a common feature in all types of metastases. In glioblastoma metastasis, the malignant mGSC cells express markers of mesenchymal GSC subtype (MES-GSC), such as CD44 and YK-40 and their major obstacle seems to be propagating in the in various organs’ microenvironments, different from the niches that home GSCs in the primary glioblastoma. Focusing on one stromal component in the glioblastoma niches, the mesenchymal stem cells (MSCs), we report herein on their differential effects on glioblastoma cells, highly depending on their genetic subtype. On the other hand, in brain metastases, the major hindrance to metastatic progression of mCSCs seem to be crossing the blood-brain-barrier. Novel therapeutic approaches for brain metastases from various cancer types are advancing slowly, and the general trends involve targeting metastatic sub-clones and selective determinants of their niches. The update on the four most common brain metastases from lung, breast, melanoma and colorectal carcinoma is presented