An Overview of C19MC Cluster Subgroup 3 and Cancer.

The primate-specific microRNA gene cluster on chromosome 19 (C19MC) is composed of 56 mature microRNAs (miRNAs), which are divided into three subgroups according to the sequence similarity. This cluster is principally expressed in the placenta but not in other tissues. C19MC is involved in the regulation of proliferation, migration, and invasion of trophoblastic cells, which are important for the development of the placenta. There is a growing number of studies that have found an altered expression of some miRNAs of the C19MC cluster in cancer, suggesting that these could play an important role in the development of this disease. Therefore, in this work, we provided an overview of the C19MC cluster's role in cancer through a systematic review of published articles. In particular, we focused on miRNAs of subgroup 3. These studies suggest that miRNAs such as miR-512-3p, miR-512-5p, miR-516a-5p, miR-516b-5p, and miR-498-5p could play a pivotal role in the development of therapies for cancer. Future studies are necessary to elucidate the molecular processes and pathways regulated by subgroup 3 miRNAs.

Curcumin Can Bind and Interact with CRP: An in silico Study.

Curcuminis a polyphenol with anti-inflammatory and antioxidative properties, found primarily in turmeric, a flowering plant of the ginger family. Among its numerous medical uses, curcumin has been used in the management of metabolic syndrome, and inflammatory conditions such as artrhritis, anxiety and hyperlipidemia. In this paper, we used molecular docking tools to assess the affinity of four curcumin derivatives (Curcumin, Cyclocurcumin, Demethoxycurcumin, Bisdemethoxycurcumin) as well as the endogenous ligand phosphorylcholine to C-reactive protein (CRP), a sensitive marker of systemic inflammation. Our results showed that curcumin interacts through H bond with CRP at GLN 150 and ASP 140. Similar H bond interactions were found for each of the four curcumin derivatives with CRP. Moreover, a molecular dynamic simulation were performed to further establish the interaction between CRP and the ligands in atomic details using the Nanoscale Molecular Dynamics (NAMD) and CHARMM27 force field. Importantly, our results suggest the possible interaction between curcumin and curcurmin related molecules with CRP, thus showing an important regulatory function with plausible applications in inflammatory and oxidative processes in diseases.

In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach.

Fatty Acid Binding-Protein 5 (FABP5) is a cytoplasmic protein, which binds long-chain fatty acids and other hydrophobic ligands. This protein is implicated in several physiological processes including mitochondrial ß-oxidation and transport of fatty acids, membrane phospholipid synthesis, lipid metabolism, inflammation and pain. In the present study, we used molecular docking tools to determine the possible interaction of FABP5 with six selected compounds retrieved form Drugbank. Our results showed that FABP5 binding pocket included 31 polar and non-polar amino acids, and these residues may be related to phosphorylation, acetylation, ubiquitylation, and mono-methylation. Docking results showed that the most energetically favorable compounds are NADH (-9.12 kcal/mol), 5'-O-({[(Phosphonatooxy)phosphinato]oxy}phosphinato)adenosine (-8.62 kcal/mol), lutein (-8.25 kcal/mol), (2S)-2-[(4-{[(2-Amino-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl)methyl]amino}benzoyl)amino]pentanedioate (-7.17 kcal/mol), Pteroyl-L-glutamate (-6.86 kcal/mol) and (1S,3R,5E,7Z)-9,10-Secocholesta-5,7,10-triene-1,3,25-triol (-6.79 kcal/mol). Common interacting residues of FABP5 with nutraceuticals included SER16, LYS24, LYS34, LYS40 and LYS17. Further, we used the SwissADME server to determine the physicochemical and pharmacokinetic characteristics and to predict the ADME parameters of the selected nutraceuticals after molecular analysis by docking with the FABP5 protein. Amongst all compounds, pteroyl-L-glutamate is the only one meeting the Lipinski's rule of five criteria, demonstrating its potential pharmacological use. Finally, our results also suggest the importance of FABP5 in mediating the anti-inflammatory activity of the nutraceutical compounds.

Understanding the Metabolic Consequences of Human Arylsulfatase A Deficiency through a Computational Systems Biology Study.

The nervous system is responsible for the communication between the organism and its environment. This task is possible by the presence of the myelin sheath, which is a double membrane formed by about 75% lipids and 25% proteins. The sulfatide represents one of the main lipids of the myelin band; its degradation is catabolized by the enzyme Arylsulfatase A (ARSA), to generated galactosylceramide. Mutations affecting ARSA function lead to the neurodegenerative disease Metachromatic Leukodystrophy. This disease is characterized by accumulation of sulfatide within the band of myelin affecting its functionality. The biochemical consequences of ARSA deficiency are not well understood yet. In this paper, we used an in-silico systems-biology approach to model the biochemical consequences of ARSA deficiency within a general human metabolic network (Recon2) and a glia cellular model. We expected that ARSA deficiency mainly affected the glycosphingolipid pathways. However, the results suggest that mitochondrial metabolism and amino acid transport were the main reactions affected within both cellular models. In the glia cell model, it was highlighted the high number of affected reactions of neurotransmitters metabolism, while only a reduced effect was observed in reactions involved in glycosphingolipids metabolism. We hypothesize that ARSA deficiency might lead to metabolic consequences that not only compromise the myelin band or the glycosphingolipids metabolism but also the overall metabolic function of the nervous system. Furthermore, these results offer the bases for the design of in-vitro and in-vivo experiments that allow generating new knowledge of MLD pathophysiology and other neurodegenerative diseases.