Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.

Unveiling Ga(III) phthalocyanine-a different photosensitizer in neuroblastoma cellular model.

Phthalocyanines (Pc) and their metallated derivatives are strongly considered for photodynamic therapy (PDT) possessing unique properties as possible new photosensitizers (PS). We have used toxicological assessments, real-time monitoring of cellular impedance, and imagistic measurements for assessing the in vitro dark toxicity and PDT efficacy of Ga(III)-Pc in SHSy5Y neuroblastoma cells. We have established the non-toxic concentration range of Ga(III)-Pc, a compound which shows a high intracellular accumulation, with perinuclear distribution in confocal microscopy. By choosing Ga(III)Pc non-toxic dose, we performed in vitro experimental PDT hampering cellular proliferation. Our proposed Ga(III)-Pc could complete a future PS panel for neuroblastoma alternate therapy.

Long non-coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma.

Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non-coding RNAs (lncRNAs) and their main representatives, large intergenic non-coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem-like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs-induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.

Dietary Phytoestrogens and Their Metabolites as Epigenetic Modulators with Impact on Human Health.

The impact of dietary phytoestrogens on human health has been a topic of continuous debate since their discovery. Nowadays, based on their presumptive beneficial effects, the amount of phytoestrogens consumed in the daily diet has increased considerably worldwide. Thus, there is a growing need for scientific data regarding their mode of action in the human body. Recently, new insights of phytoestrogens' bioavailability and metabolism have demonstrated an inter-and intra-population heterogeneity of final metabolites' production. In addition, the phytoestrogens may have the ability to modulate epigenetic mechanisms that control gene expression. This review highlights the complexity and particularity of the metabolism of each class of phytoestrogens, pointing out the diversity of their bioactive gut metabolites. Futhermore, it presents emerging scientific data which suggest that, among well-known genistein and resveratrol, other phytoestrogens and their gut metabolites can act as epigenetic modulators with a possible impact on human health. The interconnection of dietary phytoestrogens' consumption with gut microbiota composition, epigenome and related preventive mechanisms is discussed. The current challenges and future perspectives in designing relevant research directions to explore the potential health benefits of dietary phytoestrogens are also explored.

Comprehensive In Vitro Testing of Calcium Phosphate-Based Bioceramics with Orthopedic and Dentistry Applications.

Recently, a large spectrum of biomaterials emerged, with emphasis on various pure, blended, or doped calcium phosphates (CaPs). Although basic cytocompatibility testing protocols are referred by International Organization for Standardization (ISO) 10993 (parts 1-22), rigorous in vitro testing using cutting-edge technologies should be carried out in order to fully understand the behavior of various biomaterials (whether in bulk or low-dimensional object form) and to better gauge their outcome when implanted. In this review, current molecular techniques are assessed for the in-depth characterization of angiogenic potential, osteogenic capability, and the modulation of oxidative stress and inflammation properties of CaPs and their cation- and/or anion-substituted derivatives. Using such techniques, mechanisms of action of these compounds can be deciphered, highlighting the signaling pathway activation, cross-talk, and modulation by microRNA expression, which in turn can safely pave the road toward a better filtering of the truly functional, application-ready innovative therapeutic bioceramic-based solutions.

Fabrication and toxicity characterization of a hybrid material based on oxidized and aminated MWCNT loaded with carboplatin.

This study focused on the fabrication and toxicity characterization of a hybrid material-based on the multiple functionalizations of multiwalled carbon nanotubes (MWCNTs) with carboxyl or amino groups and the anti-tumor drug carboplatin (CP). The functionalization was evidenced by Fourier transformed infrared spectroscopy (FTIR) and high performance liquid chromatography (HPLC). The amount of platinum ions released in the simulated body fluid (SBF) was assessed by inductively coupled plasma mass spectrometry (ICP-MS). Cell viability, nanotubes cellular uptake, cell proliferation, superoxide anion production, SOD activity, intracellular glutathione and protein expression of several molecules involved in breast tumor cell survival and death were investigated after 24h exposure. Exposure to the aminated carbon nanotubes loaded with carboplatin resulted in a greater decrease of viability compared to oxidized carbon nanotubes loaded with the same drug, which was in an inversely proportional relationship with the production of superoxide anions in breast cancer cells. The inhibition of Hsp60, Hsp90, p53 and Mdm2 protein expression was induced as a consequence of the cytoprotection mechanism failure. Overexpression of Beclin1 and the reduction of Bcl2 expression were also observed, suggesting that functionalized MWCNT loaded with CP trigger cell death via autophagy in breast cancer cells.