Understanding the molecular mechanisms underlying Alzheimer’s disease (AD) is necessary for the diagnosis and treatment of this neurodegenerative disorder. It is therefore important to detect the most important genes and miRNAs, which are associated with molecular events, and studying their interactions for recognition of AD mechanisms. Here we focus on the genes and miRNAs expression profile, which we have detected the miRNA target genes involved in AD. These are the most quintessential to find the most important miRNA, to target genes and their important pathways. A total of 179 differentially expressed miRNAs (DEmiRs) and 1404 differentially expressed genes (DEGs) were obtained from a comprehensive meta-analysis. Also, regions specific genes with their molecular function in AD have been demonstrated. We then focused on miRNAs which regulated most genes in AD, alongside we analyzed their pathways. The miRNA-30a-5p and miRNA-335 elicited a major function in AD after analyzing the regulatory network, we showed they were the most regulatory miRNAs in the AD. In conclusion, we demonstrated the most important genes, miRNAs, miRNA-mRNA interactions and their related pathways in AD using Bioinformatics methods. Accordingly, our defined genes and miRNAs could be used for future molecular studies in the context of AD.

Microglial activation can release free radicals and various pro-inflammatory cytokines, which implicates the progress of a neurodegenerative disease. Therefore suppression of microglial activation can be an appropriate strategy for combating neurodegenerative diseases. Betanin is a red food dye that acts as free radical scavenger and can be a promising candidate for this purpose. In this study, purification of betanin from red beetroots was carried out by normal phase colum chromatography, yielding 500 mg of betanin from 100 g of red beetroot. The purified betanin was evaluated by TLC, UV-visible, HPLC, ESI-MASS, FT-IR spectroscopy. Investigation on the inhibitory effect of betanin on activated microglia was performed using primary microglial culture. The results showed that betanin significantly inhibited lipopolysaccharide induced microglial function including the production of nitric oxide free radicals, reactive oxygen species, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β). Moreover, betanin modulated mitochondrial membrane potential, lysosomal membrane permeabilization and adenosine triphosphate. We further investigated the interaction of betanin with TNF-α, IL-6 and Nitric oxide synthase (iNOS or NOS2) using in silico molecular docking analysis. The docking results demonstrated that betanin have significant negative binding energy against active sites of TNF-α, IL-6 and iNOS.

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Amino acids seem to have speci¢c preferences for various locations in K K-helices. These speci¢c preferences, called singlet local propensity (SLP), have been determined by calculating the preference of occurrence of each amino acid in di¡er-ent positions of the K K-helix. We have studied the occurrence of amino acids, single or pairs, in di¡erent positions, singlet or doublet, of K K-helices in a database of 343 non-homologous proteins representing a unique superfamily from the SCOP database with a resolution better than 2.5 A î from the Protein Data Bank. The preference of single amino acids for various locations of the helix was shown by the relative entropy of each amino acid with respect to the background. Based on the total relative entropy of all amino acids occurring in a single position, the N cap position was found to be the most selective position in the K K-helix. A rigorous statistical analysis of amino acid pair occurrences showed that there are exceptional pairs for which, the observed frequency of occurrence in various doublet positions of the K K-helix is signi¢cantly di¡erent from the expected frequency of occurrence in that position. The doublet local propensity (DLP) was de¢ned as the preference of occurrences of amino acid pairs in di¡erent doublet positions of the K K-helix. For most amino acid pairs, the observed DLP (DLP O ) was nearly equal to the expected DLP (DLP E ), which is the product of the related SLPs. However, for exceptional pairs of amino acids identi¢ed above, the DLP O and DLP E values were signi¢cantly di¡erent. Based on the relative values of DLP O and DLP E , exceptional amino acid pairs were divided into two categories. Those, for which the DLP O values are higher than DLP E , should have a strong tendency to pair together in the speci¢ed position. For those pairs which the DLP O values are less than DLP E , there exists a hindrance in neighboring of the two amino acids in that speci¢c position of the K K-helix. These cases have been identi¢ed and listed in various tables in this paper. The amount of mutual information carried by the exceptional pairs of amino acids was signi¢cantly higher than the average mutual information carried by other amino acid pairs. The average mutual information conveyed by amino acid pairs in each doublet position was found to be very small but non-zero. ß

Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.

No abstract

BackgroundT-cells play an important role in the immune response and are activated in response to the presentation of antigens bound to major histocompatibility complex (MHC) molecules participating with the T-cell receptor (TCR). T-cell receptor complexes also contain four CD3 (cluster of differentiation 3) subunits. The TCR-CD3 complex is vital for T-cell development and plays an important role in intervening cell recognition events. Since microRNAs (miRNAs) are highly stable in blood serum, some of which may target CD3 molecules, they could serve as good biomarkers for early cancer detection. The aim of this study was to see whether there is a relationship between cancers and the amount of miRNAs -targeted CD3 molecules.MethodsBioinformatics tools were used in order to predict the miRNA targets for these genes. Subsequently, these highly conserved miRNAs were evaluated to see if they are implicated in various kinds of cancers. Consequently, human disease databases were used. According to the latest research, this study attempted to investigate the possible down- or upregulation of miRNAs cancer patients.ResultsWe identified miRNAs which target genes producing CD3 subunit molecules. The most conserved miRNAs were identified for the CD3G gene, while CD247 and CD3EAP genes had the least number and there were no conserved miRNA associated with the CD3D gene. Some of these miRNAs were found to be responsible for different cancers, following a certain pattern.ConclusionsIt is highly likely that miRNAs affect the CD3 molecules, impairing the immune system, recognizing and destroying cancer tumor; hence, they can be used as suitable biomarkers in distinguishing cancer in the very early stages of its development.

Gastric cancer is one of the most fatal cancers in the world. Many efforts in recent years have attempted to find effective proteins in gastric cancer. By using a comprehensive list of proteins involved in gastric cancer, scientists were able to retrieve interaction information. The study of protein-protein interaction networks through systems biology based analysis provides appropriate strategies to discover candidate proteins and key biological pathways.In this study, we investigated dominant functional themes and centrality parameters including betweenness as well as the degree of each topological clusters and expressionally active sub-networks in the resulted network. The results of functional analysis on gene sets showed that neurotrophin signaling pathway, cell cycle and nucleotide excision possess the strongest enrichment signals. According to the computed centrality parameters, HNF4A, TAF1 and TP53 manifested as the most significant nodes in the interaction network of the engaged proteins in gastric cancer. This study also demonstrates pathways and proteins that are applicable as diagnostic markers and therapeutic targets for future attempts to overcome gastric cancer.