Renal Transcriptomics Reveals the Carcinogenic Mechanism of Ethyl Carbamate in Musalais.

INTRODUCTION: Musalais is a traditional fermented wine produced in southern Xinjiang (a province of China) and is protected as a form of national intangible cultural heritage. However, ethyl carbamate (EC), which is naturally produced during the fermentation process, has been shown to induce carcinogenesis and was classified as a group 2A carcinogen by The World Health Organization's International Agency for Research on Cancer. METHODS: In this work, rats were treated with musalais containing EC at varying contents (0.1, 1, or 10 mg/kg). To evaluate the toxicity of EC in musalais, the liver and kidney of the rats were subjected to transcriptomics sequencing. Differentially expressed genes (DEGs) between treated and untreated rats were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed on these genes to investigate the biological functions affected by EC in musalais. RESULTS: The results demonstrated that high EC content in musalais is possibly involved in the regulation of cytochrome P450 metabolism, chemical carcinogenesis, metabolism of xenobiotics by cytochrome P450, Wnt signaling, and p53 signaling by targeting Mgst1, Gstp1, Gsta5, Gsta1, Adh1, Gsta2, and Ccnd1, thereby inducing cancer. CONCLUSION: The present work predicted the potential carcinogenic mechanism of high EC content in musalais, providing a reference for its safety evaluation.

UHPLC-QTOFMS-based metabolomic analysis of serum and urine in rats treated with musalais containing varying ethyl carbamate content.

The aim of this work is to investigate the effect of the ethyl carbamate (EC) content in musalais on the metabolism of rats. Electron beam irradiation was performed to decrease the content of EC in musalais, and Sprague Dawley rats were subjected to intragastric administration of musalais with varying EC content (high, medium, and low groups). Control rats were fed normally without any treatment. Serum and urine samples were analyzed using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Principal component analysis and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were performed to detect changes in the metabolite profile in the serum and urine in order to identify the differential metabolites and metabolic pathways. The results demonstrated clear differences in the serum and urine metabolic patterns between control and treatment groups. Ions in treatment groups with variable importance in the projection of >1 (selected from the OPLS-DA loading plots) and Ps < 0.05 (Student t test) compared to control group were identified as candidate metabolites. Analysis of the metabolic pathways relevant to the identified differential metabolites revealed that high EC content in musalais (10 mg/kg) mainly affected rats through valine, leucine, and isoleucine biosynthesis and nicotinate and nicotinamide metabolism, which were associated with energy metabolism. In addition, this work suggests that EC can induce oxidative stress via inhibition of glycine content.

Grape seed proanthocyanidins inhibit proliferation of pancreatic cancer cells by modulating microRNA expression.

MicroRNAs (miRNAs) are small non-coding RNAs of 18-25 nucleotides that modulate gene expression at the post-transcriptional level. Grape seed proanthocyanidins (GSPs), which are biologically active components in grape seeds, have been demonstrated to exhibit anticancer effects. The current study investigated whether GSPs can regulate miRNA expression and the possible anticancer molecular mechanisms of GSPs. Pancreatic cancer (PC) cell samples, SS3, SS12 and SS24, were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control samples, SC3, SC12 and SC24, were also prepared. Using miRNA-seq, transcriptome analysis identified 24, 83 and 83 differentially expressed (DE) miRNAs in SS3 vs. SC3, SS12 vs. SC12 and SS24 vs. SC24, respectively. This indicated that treatment with GSPs could modulate the expression of miRNAs. Subsequently, 74, 598 and 1,204 target genes for the three sets of DE miRNAs were predicted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that multiple target genes were associated with the proliferation and apoptosis of PC cells. In addition, a network was constructed of the DE miRNAs and the target genes associated with PC. The associations identified suggested that treatment with GSPs may inhibit the proliferation of PC cells through the modulation of miRNA expression.

Transcriptome analysis of pancreatic cancer cell response to treatment with grape seed proanthocyanidins.

Grape seed proanthocyanidins (GSPs) have been demonstrated to exhibit potential chemotherapeutic efficacy against various cancer types. To determine the underlying molecular mechanisms involved in GSP-induced apoptosis, the present study prepared pancreatic cancer (PC) cells samples, S3, S12 and S24, which were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control cell samples, C3, C12 and C24, were also prepared. Using RNA-sequencing, transcriptome comparisons were performed, which identified 966, 3,543 and 4,944 differentially-expressed genes (DEGs) in S3 vs. C3, S12 vs. C12 and S24 vs. C24, respectively. Gene Ontology analysis of the DEGs, revealed that treatment with GSPs is associated with disruption of the cell cycle (CC) in PC cells. Additionally, disruption of transcription, DNA replication and DNA repair were associated with GSP-treatment in PC cells. Network analysis demonstrated that the common DEGs involved in the CC, transcription, DNA replication and DNA repair were integrated, and served essential roles in the control of CC progression in cancer cells. In summary, GSPs may exhibit a potential chemotherapeutic effect on PC cell proliferation.

Effect of harvest, drying and storage on the bitterness, moisture, sugars, free amino acids and phenolic compounds of jujube fruit (Zizyphus jujuba cv. Junzao).

BACKGROUND: The taste of dried jujube fruit when compared with fresh ones is less palatable, as it develops bitterness during drying and storage. Therefore, identifying the methods by which bitterness occurs is essential for developing strategies for processing and storage. RESULTS: Bitterness in fresh jujube fruit was negligible; however, it increased by 0.9-, 1.5- and 1.8-fold during drying and storage over 6 and 12 months. The moisture significantly decreased during harvesting and drying. Free amino acids, except proline and tyrosine, significantly decreased during drying and storage. Fructose, glucose and sucrose hardly changed during harvest, drying and storage. Titratable acidity, total phenolic and total flavonoids contents were stable during harvest and drying, but increased upon storage. Additionally, protocatechuic and ellagic acids were not detected in fresh jujube fruit, however, were found to increase during drying and storage. CONCLUSION: Bitterness in fresh jujube fruit tasted negligible because of meagre amount of phytochemicals, while the condensation effect of moisture reduction, the loss of free amino acids, and the formation of protocatechuic and ellagic acids could aggravate the bitterness of jujube fruit during drying and storage. © 2017 Society of Chemical Industry.