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.
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.
Cancer can take many years to develop from initiation to progression. The long period of development might represent an opportunity to use multi-functional, multi-targeted preventive drugs to block or reverse tumorigenesis. One path to cancer prevention could be to target and reverse the early epigenetic alterations. Unlike genetic mutations, they are potentially reversible and can be restored to their normal state. Epidemiological studies have revealed the close link between rich diets in bioactive compounds and the low incidence of different types of cancer. Thus, the study regarding the impact of bioactive nutrients on the epigenome has become widespread, with focus on the modulation of epigenetic mechanisms of gene expression, such as genomic DNA methylation. Following altered activity and expression of DNA methyl transferases and ten-eleven translocation enzymes, different types of cancers exert local DNA hypermethylation of gene promoters of tumor suppressor genes or of non-coding RNAs (microRNAs and long-noncoding RNAs), as well as global hypomethylation. Recently, the potential of phytochemicals to modulate epigenetic events in human health has become evident, although specific molecular mechanisms are still unclear. Phytochemicals and other bioactive dietary compounds can restore global and gene-specific promoter DNA methylation patterns by reactivating DNA methyltransferases or by providing the provision of methyl groups. Several natural products, such as EGCG, curcumin, sulforaphane, have shown DNMT inhibitory activity, but this property needs more in-depth investigations. This review focuses on the impact of modified DNA methylation pattern on early carcinogenesis and summarizes the effects/mechanism of phytochemical interventions on this type of epigenetic alterations.
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