ABSTRACT
Background and Aims: Women with severe intrahepatic cholestasis of pregnancy (ICP) are at higher risks of fetal complications and without effective treatments. Changes in gut microbiota in pregnancy were found to be related to the altered intestinal bile acid composition, so we aimed to explore the alterations of microbiota in the gut of ICP patients. Methods: A total of 90 women were recruited, including 45 ICP patients and 45 healthy controls. The gut microbiota communities of ICP group were compared to control group through 16S ribosomal RNA gene sequencing. The results were then confirmed by real-time polymerase chain reaction (PCR) and generalized linear model (GLM). Furthermore, we analyzed the relationships between microbiota and the severity of ICP. Results: A total of seven genera and nine taxa with differential abundances between the ICP patients and the controls were identified. All of the seven genera were verified through real-time PCR, and three key genera Parabacteroides, Flavonifractor, and Megamonas were confirmed by using the GLM model. Further analysis found that the genera Escherichia_Shigella, Olsenella, and Turicibacter were enriched in the severe ICP group, the microbial gene function related to biosynthesis of unsaturated fatty acids and propanoate metabolism were also increased in them. Conclusions: Overall, our study was the first in Asia to demonstrate an association between gut microbiota and ICP. Our findings would contribute to a better understanding of the occurrence of ICP.
Subject(s)
Cholestasis, Intrahepatic , Gastrointestinal Microbiome , Pregnancy Complications , Asia , Female , Humans , PregnancyABSTRACT
Some studies suggested the prognosis value of immune gene in lower grade glioma (LGG). Recurrence in LGG is a tough clinical problem for many LGG patients. Therefore, prognosis biomarker is required. Multivariate prognosis Cox model was constructed and then calculated the risk score. And differential expressed transcription factors (TFs) and differential expressed immune genes (DEIGs) were co-analysed. Besides, significant immune cells/pathways were identified by single sample gene set enrichment analysis (ssGSEA). Moreover, gene set variation analysis (GSVA) and univariate Cox regression were applied to filter prognostic signalling pathways. Additionally, significant DEIG and immune cells/pathways, and significant DEIG and pathways were co-analysed. Further, differential enriched pathways were identified by GSEA. In sum, a scientific hypothesis for recurrence LGG including TF, immune gene and immune cell/pathway was established. In our study, a total of 536 primary LGG samples, 2,498 immune genes and 318 TFs were acquired. Based on edgeR method, 2,164 DEGs, 2,498 DEIGs and 31 differentials expressed TFs were identified. A total of 106 DEIGs were integrated into multivariate prognostic model. Additionally, the AUC of the ROC curve was 0.860, and P value of Kaplan-Meier curve < 0.001. GATA6 (TF) and COL3A1 (DEIG) were selected (R = 0.900, P < 0.001, positive) as significant TF-immune gene links. Type II IFN response (P < 0.001) was the significant immune pathway. Propanoate metabolism (P < 0.001) was the significant KEGG pathway. We proposed that COL3A1 was positively regulated by GATA6, and by effecting type II IFN response and propanoate metabolism, COL3A1 involved in LGG recurrence.
Subject(s)
Brain Neoplasms/metabolism , Collagen Type III/physiology , GATA6 Transcription Factor/physiology , Gene Expression Regulation, Neoplastic , Glioma/metabolism , Interferon alpha-2/biosynthesis , Neoplasm Proteins/physiology , Neoplasm Recurrence, Local/metabolism , Propionates/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Female , Gene Regulatory Networks , Glioma/genetics , Glioma/immunology , Glioma/pathology , Humans , Interferon alpha-2/genetics , Male , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/immunology , Middle Aged , Neoplasm Grading , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Neoplasm Recurrence, Local/pathology , Prognosis , Proportional Hazards Models , Risk , Young AdultABSTRACT
This study was aimed to analyze the plasma metabolicomics pathway in rats with heart blood stasis syn-drome. KEGG database was used in the signal pathway analysis. HMDB was used in the analysis of molecular metabolite annotation, enzyme or transporter associated and its related properties. The metPA network software was used in the visualization of metabolite path. The results showed that 9 metabolites involved in 15 metabolic pathways. Among them, the P-value of metabolic pathway of pantothenate and CoA biosynthesis, propanoate metabolism, biosynthesis of unsaturated fatty acids was less than 0.05. It was concluded that the metabolic pathways of pan-tothenate and CoA biosynthesis, propanoate metabolism, biosynthesis of unsaturated fatty acids were involved with the pathological process of rats with heart blood stasis syndrome.
