Project description:Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by dysregulated oncogenic signaling and metabolic reprogramming. PSY, an herbal formula derived from Patriniae Radix, Coix Seed, and Mori Cortex Radicis, has shown potential anti-cancer effects, but its mechanisms in CRC remain unclear. Purpose: PSY’s multi-targeted effects on oncogenic signaling, metabolic pathways, and inflammation in CRC. Materials and Methods: Transcriptomic profiling (RNA sequencing), in vitro assays, and in vivo xenograft models were used to elucidate PSY’s mechanisms. Metabolic profiling via LC-MS/MS and serum lipid analysis were performed to assess its impact on lipid metabolism. Results: PSY activated the PERK/eIF2α/ATF4 stress pathway and suppressed PI3K/Akt/mTOR signaling, inducing apoptosis and inhibiting CRC cell proliferation. Xenograft models showed significant tumor growth suppression and reduced proliferation (Ki67) and inflammation markers (COX2, p-STAT3). Metabolic profiling revealed reduced cholesterol and fatty acid biosynthesis, including arachidonic acid, correlating with COX2 downregulation. Serum LDL and HDL levels decreased, with an increased LDL/HDL ratio. Conclusion: PSY demonstrates potential as a multi-targeted agent by disrupting oncogenic signaling, lipid metabolism, and inflammation in CRC. These findings support its further exploration for clinical applications.
Project description:RNAseq and LC/MS metabolomics analysis of C. difficile strain 630 grown in BHIS media with 50% (vol/vol) faecal water added, compared with control BHIS containing only the additional PBS used for prep of Faecal water. Cells grown in biological triplicates to late log phase (T=6h) prior to harvest. Goal was to determine changes in gene expression caused by exposure to Faecal water, and changes in the metabolite profile of faecal water containing medium when incubated with actively growing C. difficile cells
Project description:mccc-1(ww4) mutant animals has no obvious developmental defect, but we observed different abundance of many metabolites by LC-MS/MS analysis. Then, we assumed different metabolite abundance is associated with different metabolic gene expression, sucha that RNA-seq was performed to examine differently expressed gene.
Project description:The cardioprotective effects of long chain (LC) 3PUFA can be achieved at the gene expression level, notably in liver. However, the complexity of biological pathways modulations and the nature of the bioactive molecules are still under investigation. The present study aimed to investigate the dose-response effects of LC 3PUFA on the production of peroxidated metabolites and on global gene expression in liver. The intake of LC ?3PUFA increased, in a dose-dependent manner, their incorporation in liver phospholipids but also the hepatic production of 4-HHE. Pathways related to inflammation were dose-dependently associated with the 3 groups but Group 2 was rather associated with inflammatory effects while Group 3 was anti-inflammatory. LC ?3PUFA had no effect on PPAR-controlled genes. However, they modified, in a dose-dependent manner, the expression of major genes related to lipoprotein metabolism (LDLR, VLDLR, INSIG1 and MTTP), possibly through the FXR signaling pathway. In conclusion, the effect of LC ?3PUFA is dependent on the dose possibly because of the production of peroxidated metabolites such as 4-HHE. New-Zealand white rabbits were fed (7 wk) a high cholesterol diet and received by daily oral gavages either oleic acid rich oil or a mixture of oils providing 0.1% (Group 1), 0.5% (Group 2) or 1% (Group 3) of energy as docosahexaenoic acid. Specific peroxidated metabolite issued from LC 3PUFA (4-hydroxyhexenal or 4-HHE) were measured by GC/MS/MS and transcription profiling was conducted in liver. Differentially expressed genes were identified using Bioconductor (Moderated p<0.05, Fold Change>1.20) and clustered into pathways (Ingenuity Pathway Analysis 7.0).
Project description:Accurate DNA replication is essential for genome integrity, with dysregulated replication dynamics, replication stress and genomic instability-hallmarks of cancer and aging. Here, we identify NAT10-mediated β-hydroxybutyrylation (Kbhb) of histones that safeguards replication fork progression, alleviates replication stress, and preserves genomic stability. DNA fiber analyses show β-hydroxybutyrate (BHB) treatment enhances replication efficiency while maintaining fork symmetry, effects abolished by NAT10 depletion or inhibition. BrdU/EdU labeling, FACS analyses reveal that NAT10-mediated Kbhb accelerates replication fork velocity and shortens S-phase duration. LC-MS/MS profiling shows no significant changes in origin firing following BHB treatment. Mechanistically, NAT10-mediated Kbhb modulates chromatin association, thereby modulating chromatin accessibility to establish a replication-permissive environment. This epigenetic remodeling mitigates replication stress markers and genomic instability. Conserved effects in transformed and primary cell models position NAT10 as a metabolic-epigenetic nexus linking nutrient signaling to replication fidelity. Our findings suggest targeting Kbhb signaling as a potential therapeutic strategy against replication stress-associated pathologies.
Project description:Vitamin B1 (VB1) is a key dietary nutrient and crucial cofactor, which exhibits a series of regulatory functions on cellular processes and the activation of the immune system. To date, the precise effect of VB1 on Mycobacterium tuberculosis has not been fully described. In the present study, the direct influence of VB1 treatment on M. bovis BCG was determined using RNA-sequencing and LC/MS. The selection of this strain was used due to its common physiological features with M.tuberculosis. The investigation of the M. bovis BCG transcription demonstrated significant changes in certain metabolic and cellular process such as the decrease in fatty acid, cholesterol and glycolipid catabolism, the decrease in DNA replication and protein translation, the reduction in cell division and cell wall formation. LC/MS indicated that most of amino acids and ADP decreased in VB1 processed culture. In addition, growth assays indicated that VB1 inhibited the BCG growth rate in vitro. This study will be benefit for our deeply understanding for impact of VB1 to M.tuberculosis.