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The high-pathogenicity island (HPI), carried by Yersinia pestis, is an essential pathogenic component of the virulence distributed in Escherichia coli (E. coli). As an NF-κB pathway activator, Ubiquitin (Ub) is crucial in the inflammatory response. However, the molecular mechanismsof Ub in the TLR4/Myd88/NF-κB signaling pathway induced by HPI in E. coliis still unclear. In our experiment, Ub was overexpressed usingsmall intestinal epithelial cells (in vitro), and BALB/c mouse models (in vivo) infected with E. coli HPI and analysed by using qPCR, ELISA, immunofluorescence, immunohistochemistry, and H&E staining assays. We demonstrated that E. coli HPI can promote the expression of TLR4, NF-κB, and Ub in. IPEC-J2 cells. Immunofluorescence and Immunohistochemistry analysis revealed that TLR4 and NF-κB key factor in the E. coli HPI group were expressed, and the NF-κB p65 protein translocated to the nucleus. Further research showed that the mRNA expression levels of TLR4, MyD88, NF-κB, IL-1β, and TNF-α were significantly increased in the Ub overexpression group and BALB/c mice group. H&E staining assay showed that Ub overexpression with IPEC-J2 cells have thecharacteristics of elongated, rounded, fragmented, duodenal villi diminished, and the surface was covered with many sloughed necrotic cells, indicating that exacerbating cell damage and duodenitis. Taken together, this study suggested that E. coliHPI can activate NF-κB via increasing the expression of Ub, andUb can exacerbate E. coli HPI-induced duodenitis through the TLR4/MyD88/NF-κB signaling pathway.

Background: To investigate the clinical characteristics and associated factors of pediatric acute disseminated encephalomyelitis (ADEM) patients positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies.Methods: This retrospective study included pediatric ADEM patients who underwent serum MOG antibody detection from May 2017 to August 2020. The patients were divided into two groups: those with (MOG+, n=35) and without (MOG−, n=50) anti-MOG antibodies in the serum. Our study analyzed the clinical characteristics of MOG-IgG-positive ADEM pediatric patients and conducted a comparative analysis between the two groups.Results: Thirty-five MOG-IgG-positive ADEM patients (21 males and 14 females) with encephalopathy, multifocal neurological symptoms, and typical magnetic resonance imaging (MRI) abnormalities were enrolled. They usually had a favorable outcome, while some suffered from relapse. Compared to the ADEM patients without MOG antibodies, MOG-IgG-positive ADEM patients suffered from a longer disease duration (median: 10 vs. 6 days), more meningeal involvement (31.4% vs. 8%) and frontal lobe involvement (82.8% vs. 68%), higher relapse rates (14.3% vs. 2%), lower serum tumor necrosis factor (1-12.4 pg/ml, median 1.7 vs. 1-34 pg/ml, median 2.2) and interferon-gamma (1-9.4 pg/ml, median 1.3 vs. 1-64 pg/ml, median 3) (all P < 0.05). Multivariate logistic regression analysis indicated that a longer disease duration, meningeal involvement, and frontal lobe involvement were associated factors for ADEM patients with MOG antibodies (P < 0.05).Conclusions: Our findings provide clinical evidence that a longer disease duration, meningeal involvement, and frontal lobe involvement are associated with pediatric MOG-IgG-positive ADEM.