Microglia/Astrocytes-Glioblastoma Crosstalk: Crucial Molecular Mechanisms and Microenvironmental Factors

In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes–GB interactions, which is particularly the alterations that occur in the cell’s extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes – GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB

Quantitative Detection and Biological Propagation of Scrapie Seeding Activity In Vitro Facilitate Use of Prions as Model Pathogens for Disinfection

Prions are pathogens with an unusually high tolerance to inactivation and constitute a complex challenge to the re-processing of surgical instruments. On the other hand, however, they provide an informative paradigm which has been exploited successfully for the development of novel broad-range disinfectants simultaneously active also against bacteria, viruses and fungi. Here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model pathogens for disinfection. We used specifically adapted serial protein misfolding cyclic amplification (PMCA) for the quantitative detection, on steel wires providing model carriers for decontamination, of 263K scrapie seeding activity converting normal protease-sensitive into abnormal protease-resistant prion protein. Reference steel wires carrying defined amounts of scrapie infectivity were used for assay calibration, while scrapie-contaminated test steel wires were subjected to fifteen different procedures for disinfection that yielded scrapie titre reductions of ≤101- to ≥105.5-fold. As confirmed by titration in hamsters the residual scrapie infectivity on test wires could be reliably deduced for all examined disinfection procedures, from our quantitative seeding activity assay. Furthermore, we found that scrapie seeding activity present in 263K hamster brain homogenate or multiplied by PMCA of scrapie-contaminated steel wires both triggered accumulation of protease-resistant prion protein and was further propagated in a novel cell assay for 263K scrapie prions, i.e., cerebral glial cell cultures from hamsters. The findings from our PMCA- and glial cell culture assays revealed scrapie seeding activity as a biochemically and biologically replicative principle in vitro, with the former being quantitatively linked to prion infectivity detected on steel wires in vivo. When combined, our in vitro assays provide an alternative to titrations of biological scrapie infectivity in animals that substantially facilitates the use of prions as potentially highly indicative test agents in the search for novel broad-range disinfectants

Growing up with HIV/AIDS: a study on adolescents with HIV/AIDS and their family caregivers Creciendo con VIH/SIDA: un estudio con adolescentes portadoras de VIH/SIDA y sus cuidadoras familiares Crescendo com HIV/AIDS: estudo com adolescentes portadoras de HIV/AIDS e suas cuidadoras-familiares

This is an exploratory study with a qualitative approach, which looks at the adolescent process with HIV/AIDS. The purpose is to identify how the adolescent process occurs, from the perspective of these teenagers and their family caregivers. The investigation was performed in Porto Alegre, RS between May and July 2005, and the subjects were four adolescents and three caregivers. Data were collected by means of interviews, which were subject to the content analysis technique. The study revealed that both teenagers and family caregivers did not show concern with the changes typical of the period, especially regarding sexuality questions. Yet, the underlying diagnosis and coping with HIV remain in the family core in order to protect these agents against the stigma of the disease.<br>Es un estudio exploratorio con abordaje cualitativo, que trata del proceso de desarrollo de la adolescencia en portadoras de VIH/SIDA, con el objetivo de identificar cómo ocurre el proceso de la adolescencia, en la visión de estas adolescentes y de sus cuidadoras familiares.La investigación se realizó en Porto Alegre-RS, entre los meses de mayo y julio de 2005; los sujetos fueron cuatro adolescentes y tres cuidadoras. La colecta de las informaciones se hizo por medio de entrevistas que fueron sometidas a la técnica de análisis de contenido. El estudio reveló que las adolescentes y sus cuidadoras familiares, manifestaron preocupación con los cambios propios de ese período, especialmente en asuntos relacionados a la sexualidad. Se hizo evidente que el diagnóstico y la convivencia con el VIH permanecen ocultos en el contexto familiar, con el objetivo de proteger, a estos actores, del estigma de la enfermedad.<br>Estudo exploratório com abordagem qualitativa, que trata do processo de adolescer de portadoras de HIV/AIDS, com o objetivo de identificar como ocorre o processo da adolescência, na ótica dessas adolescentes e de suas cuidadoras-familiares. A investigação foi realizada em Porto Alegre, RS, entre os meses de maio e julho de 2005, sendo que os sujeitos foram quatro adolescentes e três cuidadoras. A coleta das informações ocorreu por meio de entrevistas que foram submetidas à técnica de análise de conteúdo. O estudo revelou que tanto as adolescentes quanto suas cuidadoras-familiares não manifestaram preocupação com as transformações próprias do período, especialmente nas questões que envolvem a sexualidade. Evidenciou-se que o diagnóstico e a convivência com o HIV ainda permanecem velados no círculo familiar, visando a proteção desses atores com relação ao estigma da doença