Ricerc@Sapienza

Recently, despite the great success achieved by the so-called "magic bullets" in the treatment of different diseases through a marked and specific interaction with the target of interest, the pharmacological research is moving toward the development of "molecular network active compounds," embracing the related polypharmacology approach.

The only drug currently available for treatment of the neglected disease Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary and urgent. To this end, the targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as a promising approach. Due to the strong effects of human sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as potential therapeutic targets. In vitro testing of synthetic substrates of S.

Over time, an understanding of the molecular mechanisms of replication and differentiation of stem cells has enabled the development of various protocols and techniques to be applied with a regenerative scope, as discussed in previous chapters. Here, we will discuss the recent progress of regenerative medicine in chemical reprogramming and transdifferentiation based on the use of epi-drugs. The main epigenetic mechanisms regulating gene expression include DNA methylation and histone tails modifications.

Epigenetic pathways play a pivotal role in the development and function of the immune system. Over the last
decade, a growing body of studies has been published out seeking to explain a correlation between epigenetic
modifications and the development of autoimmune disorders. Epigenetic changes, such as DNA methylation,
histone modifications, and noncoding RNAs, are involved in the pathogenesis of autoimmune diseases mainly by
regulating gene expression. This paper reviews the importance of epigenetic alterations during the development of

Bis-(3-bromo-4-hydroxy)benzylidene cyclic compounds have been reported by us as epigenetic multiple ligands, but different substitutions at the two wings provided analogues with selective inhibition. Since the 1-benzyl-3,5-bis((E)-3-bromobenzylidene)piperidin-4-one 3 displayed dual p300/EZH2 inhibition joined to cancer-selective cell death in a panel of tumor cells and in in vivo xenograft models, we prepared a series of bis((E)-2-bromobenzylidene) cyclic compounds 4a-n to test in biochemical (p300, PCAF, SIRT1/2, EZH2, and CARM1) and cellular (NB4, U937, MCF-7, SH-SY5Y) assays.

Introduction: In recent years, sirtuins (SIRTs) gained an increasing consideration because of their multiple key roles in several biological settings such as the regulation of transcription, energetic metabolism, cell cycle progression and cytodifferentiation, apoptosis, neuro- and cardio-protection, inflammation, cancer onset and progression. Since there is mounting evidence in favour of potential therapeutic applications of SIRT modulators in various age-related disorders, the search about them is quite active.

Cancer is considered a multifactorial pathology, whose understanding involves genomic and epigenomic studies supplemented by biochemical, biological, molecular, and epidemiological data. Current cancer research strategies are based on the paradigm of “targeted” therapies. Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules (“molecular targets”) that are involved in growth, progression, and spread of cancer.

Background: The execution of many genetic programs, influenced by environmental conditions, is epigenetically controlled. Thus, small molecules of the intermediate metabolism being precursors of most of nutrition-deriving epigenetic modifications, sense the cell surrounding environment. Methods: Here we describe histone H4K16 acetylation distribution in S. cerevisiae nhp6ab mutant, using ChIP-seq analysis; its transcription profile by RNA-seq and its metabolic features by studying the metabolome. We then intersected these three -omic approaches to unveil common crosspoints (if any).

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood.

Background