Berberine alleviates ischemia reperfusion injury induced AKI by regulation of intestinal microbiota and reducing intestinal inflammation.

BACKGROUND: It has been found that a variety of host disease states can exacerbate intestinal inflammation, leading to disruption of intestinal barrier function. Changes in the composition of the intestine microbiota, which affect downstream metabolites in turn, ultimately react against the host. OBJECTIVES: We revealed the mechanism of berberine as an intestinal protective agent in rats with renal ischemia-reperfusion injury acute kidney injury (AKI). METHODS: HE staining was performed to evaluate the pathological changes in the colon and kidney. 16 S rRNA analysis was performed to assess the intestinal microbiota. Intestine TLR4/NF-κB expression was assessed by western blot. Q-RT-PCR was performed to detect TLR4 in intestine and IL-6 and KIM-1 gene expression in the kidney. SPSS 22.0 was used to compare the data. RESULTS: Rats with AKI exhibited increased relative abundances of Proteobacteria and Bacteroidetes and decreased relative abundances of Lactobacillus, Ruminococcus and Lachnospiraceae belonging to the phylum Firmicutes. The Sirt1-NF-κB-TLR4 pathway was involved in the occurrence process, accompanied by intestinal inflammation and oxidation. Berberine reversed the appeal change. CONCLUSION: Berberine inhibits the intestinal biological barrier of Proteobacteria, reduces LPS production, exerts an anti-inflammatory effect, and delays the progression of AKI.

Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates.

The diagnosis and assessment of ulcerative colitis (UC) poses significant challenges, which may result in inadequate treatment and a poor prognosis for patients. This study aims to identify potential activity biomarkers for UC and investigate the role of infiltrating immune cells in the disease. To perform gene set enrichment analysis, we utilized the cluster profiler and ggplot2 packages. Kyoto encyclopedia of genes and genomes was used to analyze degenerate enrichment genes. Significant gene set enrichment was determined using the cluster profiler and ggplot2 packages. Additionally, quantitative PCR (qRT-PCR) was employed to validate the expression of each marker in the ulcerative colitis model. We identified 651 differentially expressed genes (DEGs) and further investigated potential UC activity biomarkers. Our analysis revealed that CXCL1 (AUC = 0.710), CYP2R1 (AUC = 0.863), LPCAT1 (AUC = 0.783), and NEU4 (AUC = 0.833) were promising activity markers for the diagnosis of UC. Using rat DSS model, we validated these markers through qRT-PCR, which showed statistically significant differences between UC and normal colon mucosa. Infiltrating immune cell analysis indicated that M1 macrophages, M2 macrophages, activated dendritic cells (DCs), and neutrophils played crucial roles in the occurrence and progression of UC. Moreover, the activity markers exhibited varying degrees of correlation with activated memory CD4 T cells, M0 macrophages, T follicular helper cells, memory B cells, and activated DCs. The potential diagnostic genes for UC activity, such as CXCL1, CYP2R1, LPCAT1, and NEU4, as well as the infiltration of immune cells, may contribute to the pathogenesis and progression of UC.