The regulatory role of differential microRNA expressions on cellular inflammatory factors IL-6 and IL-10 in Echinococcus granulosus-induced anaphylaxis.

OBJECTIVE: To determine the pathogenesis and molecular targets of anaphylaxis caused by hydatid cyst fluid leakage. METHODS: First, Balb/c mice were infected with Echinococcus granulosus, and then the anaphylaxis model was developed. The mice were separated into: anaphylaxis caused by the cystic echinococcosis group (ANPC), the cystic echinococcosis without anaphylaxis group (CE group), and the normal control group (CTRL). Following this, the spleen tissue was collected for microRNA (miRNA) sequencing. Using bioinformatics analysis, differentially expressed miRNAs (DEMs) were identified. Then, through the use of protein-protein interaction (PPI) networks, the key target genes for miRNA regulation associated with echinococcosis-induced anaphylaxis were identified. RESULTS: ANPC and CE groups have 29 and 39 DEMs compared to the CTRL group, respectively. Based on these 25 DEMs, interactions between miRNA and mRNA were screened, and 174 potential target genes were identified. We performed gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on these 174 target genes, and the results revealed that the three pathways with the highest enrichment were the PI3K-Akt signaling pathway, FoxO signaling pathway, and Focal adhesion. The interaction analysis of PPI and miRNA-hub gene networks revealed that interleukin 6 (IL-6) was regulated by miR-146a-5p and miR-149-5p, while IL-10 was regulated by miR-29b-3p and miR-29c-3. Using reverse transcription polymerase chain reaction, we found that the miRNAs regulating IL-6 and IL-10 were significantly upregulated in the ANPC group, and there are three pathways involved in that process: Pathways of PI3K-Akt signaling, FoxO signaling, and Focal adhesion. IL-6 and IL-10 play an important role in cellular pyroptosis and apoptosis. Therefore, the aforementioned results provide significant reference value for elucidating the mechanism of cellular pyroptosis and apoptosis in echinococcosis-induced anaphylaxis, and for formulating tissue and organ protection strategies for patients with cystic echinococcosis when anaphylaxis is triggered by hydatid cyst rupture.

Transcriptional changes in orthotopic liver transplantation and ischemia/reperfusion injury.

Background There are few effective targeting strategies to reduce liver ischemia-reperfusion injury (IRI), which is one of the reasons for the poor prognosis of liver transplant recipients. Methods A systematic approach combining gene expression with protein interaction (PPI) network was used to screen the characteristic genes and related biological functions of post-transplant. Differentially expressed genes (DEGs) between IRI+ and IRI- were identified. Logistic regression model and receiver operating characteristic (ROC) curve were used to identify potential target genes of IRI. The expression of key genes was verified by qRT-PCR and Western-blot experiments. Finally, the ssGSEA was used to identify the immune cell infiltration in patients with IRI. Results The 283 common DEGs in GSE87487 and GSE151648 were mainly related to apoptosis and IL-17 signaling pathway. Through PPI network and logistic regression analysis, we identified that IL6, CCL2 and CXCL8 may be involved in the ischemia/reperfusion (IR) process. In addition, 32 genes were showed associated with IRI through inflammatory and metabolic pathways. Among the key genes identified, the differential expression of AGBL4, CILP2 and IL4I1 was verified by molecular experiments. Th17 cells of differentially infiltrated immune cells were positively correlated with CILP2 and IL4I1. The difference of Th17 cells between IRI+ and IRI- was verified by flow cytometry. Conclusion The study showed that AGBL4, CILP2 and IL4I1 were associated with IRI. Th17 cells may be associated with the regulation of IRI by key genes. These genes and related pathways may be targets for improving IRI.