RESUMO
microRNAs (miRNAs) are post-transcriptional regulators involved in many biological processes and human diseases, including cancer. The majority of transcripts compete over a limited pool of miRNAs, giving rise to a complex network of competing endogenous RNA (ceRNA) interactions. Currently, gene-regulatory networks focus mostly on transcription factor-mediated regulation, and dedicated efforts for charting ceRNA regulatory networks are scarce. Recently, it became possible to infer ceRNA interactions genome-wide from matched gene and miRNA expression data. Here, we inferred ceRNA regulatory networks for 22 cancer types and a pan-cancer ceRNA network based on data from The Cancer Genome Atlas. To make these networks accessible to the biomedical community, we present SPONGEdb, a database offering a user-friendly web interface to browse and visualize ceRNA interactions and an application programming interface accessible by accompanying R and Python packages. SPONGEdb allows researchers to identify potent ceRNA regulators via network centrality measures and to assess their potential as cancer biomarkers through survival, cancer hallmark and gene set enrichment analysis. In summary, SPONGEdb is a feature-rich web resource supporting the community in studying ceRNA regulation within and across cancer types.
RESUMO
Phytostanyl fatty acid esters, which are being added to a variety of foods owing to their cholesterol-lowering properties, are susceptible to thermally induced oxidation reactions. Using sitostanyl oleate as an example, we, in this study, aimed at developing strategies for the detection and the quantitation of acyl chain oxidation products (ACOPs). The elaborated ultra high performance liquid chromatography-mass spectrometry MS/MS-based approach involves (i) derivatizations of hydroxy and oxo groups, (ii) combined use of atmospheric pressure chemical ionization and electrospray ionization as ionization techniques, and (iii) establishment of selective multireaction monitoring transitions. These strategies allow the identification of a broad spectrum of nonpolar short-chain as well as polar short- and long-chain hydroxy, epoxy, and oxo ACOPs. Semiquantitative assessments showed that sitostanyl 9,10-epoxystearate was the predominating ACOP resulting from thermo-oxidation of sitostanyl oleate at 180 °C for 30 min. The elaborated analytical approach paves the way to narrow the existing knowledge gap on the fate of phytostanyl fatty acid esters upon heat treatments.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácido Oleico/química , Espectrometria de Massas em Tandem/métodos , Temperatura Alta , Estrutura Molecular , OxirreduçãoRESUMO
Starting from multifunctional triazacyclononane-triphosphinate chelator cores, dendritic molecules with the ability to bind metal ions within their framework were synthesized. A cooperative interaction of the chelator cages resulted in a markedly increased affinity towards 67/68GaIII. A hexameric PSMA inhibitor conjugate with high affinity (IC50 = 1.2 nM) and favorable in vivo PET imaging properties demonstrated practical applicability. The novel scaffolds are useful for synthesis of structurally well-defined multimodal imaging probes or theranostics.