RESUMO
RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.
Assuntos
Adenoma , Neoplasias Colorretais , MicroRNAs , Ácido Pirúvico , RNA Longo não Codificante , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Ácido Pirúvico/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Reprogramação MetabólicaRESUMO
Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O. hosiei have been used as traditional Chinese medicine to treat hernia, abdominal pain, blood stasis and amenorrhea. Cytisine-like and angustifoline type alkaloids were main components identified from this plant. In our research on the bioactive alkaloids from the promising Chinese medicinal plants, four new angustifoline type alkaloids (1-4) and a new cytisine-like alkaloid (5), named hosimosine A-E, together with 13 known analogues (6-18) were isolated from the seeds of O. hosiei. Their structures were elucidated by the extensive spectroscopic methods, especially the interpretation of NMR spectra and specific rotations, along with the methods of NMR and ECD calculation. Compounds 1-4 were identified as two pairs of epimers, whose relative configurations were deduced from density functional theory (DFT) calculations of NMR chemical shifts and DP4+ analysis, and absolute configurations were determined by comparison of their experimental and theoretical ECD spectra. Compound 5 displayed two sets of NMR data caused by the existence of tautomeric forms. Compounds 14, 17 and 18 were determined to be enantiomers of literature compounds. Some of the isolates exhibited moderate cytotoxic effects against HepG2, A2780 and MCF-7 cells.
Assuntos
Alcaloides , Fabaceae , Neoplasias Ovarianas , Humanos , Feminino , Estrutura Molecular , Linhagem Celular Tumoral , Alcaloides/farmacologia , Alcaloides/química , SementesRESUMO
The di-sulfonated di-phthalimidomethyl phthalocyanine zinc (ZnPcS2P2) was an amphiphilic photosensitizer for photodynamic therapy of cancer. According to fluorescence analytical method, extracting efficiencies of 2.0% SDS (Wt%), 1.5% Triton X-100 (phi) and DMF for ZnPcS2P2 in K562 cells were compared. The results showed that 1.5% Triton X-100 was the most efficient reagent for the first time extracting. Using 1.5% Triton X-100 as extracting reagent, the kinetic curves of cellular uptake of ZnPcS2P2 as well as LDL-ZnPcS2P2 complex by K562 cells were determined. Compared with ZnPcS2P2, the maximum cellular uptake of LDL-ZnPcS2P2 by K562 was doubled, which indicated that LDL was an effective targeting delivery vehicle for ZnPcS2P2.