Project description:Ulcerative colitis (UC), belonging to inflammatory bowel disease (IBD), is a chronic and relapsing inflammatory disorders of the gastrointestinal tract, which is not completely cured so far. Valeriana jatamansi is a Chinese medicine used clinically to treat "diarrhea", which is closely related to UC. This study was to elucidate the therapeutic effects of V. jatamansi extract (VJE) on dextran sodium sulfate (DSS)-induced UC in mice and its underlying mechanism. In this work, VJE effectively ameliorate the symptoms, histopathological scores and reduce the production of inflammatory factors of UC mice. The colon untargeted metabolomics analysis and 16S rDNA sequencing showed remarkable differences in colon metabolite profiles and intestinal microbiome composition between the control and DSS groups, and VJE intervention can reduce these differences. Thirty-two biomarkers were found and modulated the primary pathways including pyrimidine metabolism, arginine biosynthesis and glutathione metabolism. Meanwhile, twelve significant taxa of gut microbiota were found. Moreover, there is a close relationship between endogenous metabolites and intestinal flora. These findings suggested that VJE ameliorates UC by inhibiting inflammatory factors, recovering intestinal maladjustment, and regulating the interaction between intestinal microbiota and host metabolites. Therefore, the intervention of V. jatamansi is a potential therapeutic treatment for UC.
Project description:Interventions: Colorectal cancer control group:no;Colorectal cancer probiotics group:No
Primary outcome(s): Intestinal flora metabolomics;Intestinal mucosal barrier;Inflammatory factors;Observation of clinical efficacy indicators;Intestinal flora
Study Design: Parallel
Project description:To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, we evaluated the transcriptomic profile of human airway epithelial cells grown under treatment of crude oil, the dispersants Corexit 9500 and Corexit 9527 and oil-dispersant mixtures. We identified a very strong effect of Corexit 9500 treatment, with 84 genes (response genes) differentially expressed in treatment vs. control samples. We discovered an interactive effect of oil + dispersant mixtures; while no response gene was found for Corexit 9527 treatment alone, cells treated with Corexit 9527 + oil mixture showed an increased number of response genes (46 response genes), suggesting a synergic effect of 9527 with oil on the transcriptomic perturbation of airway epithelial cells. Through GO (gene ontology) functional term and pathway-based analysis, we identified upregulation of genes involved in angiogenesis and immune responses and downregulation of genes involved in cell junctions and steroid synthesis as the prevailing transcriptomic signatures in the cells treated with Corexit 9500, oil or Corexit 9500 + oil mixture. Interestingly, these key molecular features coincide with those observed in common lung diseases, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Our study provides mechanistic insights into the detrimental effects of oil and oil dispersants to the respiratory system and suggested significant health impacts of the recent BP oil spill to those people involved in the cleaning operation.
Project description:In summary, we characterized the role of m6A modification in pulmonary fibrosis. We reveal that m6A modification is increased in bleomycin induced pulmonary fibrosis mice model, FMT-derived myofibroblasts and idiopathic pulmonary fibrosis patient lung samples. Lowering m6A level through silencing METTL3 suppress FMT process in vitro and vivo. Fundamentally, m6A modification regulates FMT by modulating the translation of KCNH6 mRNA in a YTHDF1 dependent manner. This study provides novel insights into the mechanism of FMT process and suggests m6A modification intervention may be a promising therapeutic strategy for pulmonary fibrosis.
Project description:Pulmonary arterial hypertension (PAH) is characterized by remodelling of the pulmonary arteries and right ventricle (RV), which leads to functional decline of cardiac and skeletal muscle. This study investigated the effects of a multi-targeted nutritional intervention with extra protein, leucine, fish oil and oligosaccharides on cardiac and skeletal muscle in PAH. PAH was induced in female C57BL/6 mice by weekly injections of monocrotaline (MCT) for 8 weeks. Control diet (sham and MCT group) and isocaloric nutritional intervention (MCT + NI) were administered. Compared to sham, MCT mice increased heart weight by 7%, RV thickness by 13% and fibrosis by 60% (all p < 0.05) and these were attenuated in MCT + NI mice. Microarray and qRT-PCR analysis of RV confirmed effects on fibrotic pathways. Skeletal muscle fiber atrophy was induced (P < 0.05) by 22% in MCT compared to sham mice, but prevented in MCT + NI group. Our findings show that a multi-targeted nutritional intervention attenuated detrimental alterations to both cardiac and skeletal muscle in a mouse model of PAH, which provides directions for future therapeutic strategies targeting functional decline of both tissues.
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver. To induce chronic liver fibrosis, seven-week-old mice received 0.6 ml/kg body weight of carbon-tetrachloride (CCl4) dissolved in corn-oil by intraperitoneal (i.p.) injection, twice a week for 10 weeks (n=3). As a control, same number of mice was injected with equal volume of corn-oil for 10 weeks.
Project description:Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 week treatment withfenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased byfenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism, and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for PPARα, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis, and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent towards modulating plasma free fatty acids, cholesterol and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention. Expression profiling of liver from mice fed control diet, fish oil or fenofibrate for 2 weeks.
Project description:The deficiency of n-3 PUFAs in the brain and depressive symptoms are closely related. Krill oil contains abundant amounts of n-3 PUFAs incorporated in phosphatidylcholine.However, the effect of krill oil treatment on depression-like behaviors induced by chronic stress and its molecular mechanism in the brain remain poorly understood. Here, we used a chronic unpredictable mild stress (CUMS) model to evaluate the effect of krill oil on depression-like behaviors and explored its molecular mechanism through lipid metabolomics and mRNA profiles in the whole brain.
Project description:Pulmonary fibrosis (PF) is a progressive disease with a poor prognosis and lack of effective treatments. Therefore, identifying effective therapeutic modalities is required to improve outcome. However, the lack of predictive progressive disease biomarkers in the clinic causes a significant gap in the preclinical to clinical translational process. Here, we assessed and identified progressive alterations in pulmonary function, transcriptomics, and metabolomics in mice lungs at 7, 14, 21, and 28 days after a single dose of oropharyngeal bleomycin. By integrating multi-omics data, we identified two central gene subnetworks associated with multiple critical pathological changes in transcriptomics and metabolomics as well as pulmonary function. We presented a multi-omics-based framework to establish a translational link between the bleomycin-induced PF model in mice and human idiopathic pulmonary fibrosis to identify druggable targets and test therapeutic candidates. Our study also indicated peripheral CB1R antagonism as a rational therapeutic target for clinical translation in PF.