Cytolethal distending toxin (CDT) produced by Campylobacter jejuni comprises a heterotrimeric complex formed by CdtA, CdtB, and CdtC. Among these toxin subunits, CdtA and CdtC function as essential proteins that mediate toxin binding to cytoplasmic membranes followed by delivery of CdtB into the nucleus. The binding of CdtA/CdtC to the cell surface is mediated by cholesterol, a major component in lipid rafts. Although the putative cholesterol recognition/interaction amino acid consensus (CRAC) domain of CDT has been reported from several bacterial pathogens, the protein regions contributing to CDT binding to cholesterol in C. jejuni remain unclear. Here, we selected a potential CRAC-like region present in the CdtC from C. jejuni for analysis. Molecular modeling showed that the predicted functional domain had the shape of a hydrophobic groove, facilitating cholesterol localization to this domain. Mutation of a tyrosine residue in the CRAC-like region decreased direct binding of CdtC to cholesterol rather than toxin intermolecular interactions and led to impaired CDT intoxication. These results provide a molecular link between C. jejuni CdtC and membrane-lipid rafts through the CRAC-like region, which contributes to toxin recognition and interaction with cholesterol.

The incidence and prevalence of inflammatory bowel disease (IBD) are low but increasing in Taiwan. We aimed to investigate the epidemiology and clinical outcomes of IBD in central Taiwan. We retrospectively analyzed patients with IBD diagnosed at our hospital between January 2000 and September 2018. The diagnostic criteria were based on endoscopic and pathologic findings. Clinical characteristics, treatment regimens, and treatment outcomes were analyzed. A total of 190 patients with IBD were enrolled (80 with Crohn’s disease (CD) and 110 with ulcerative colitis (UC)). The mean age at diagnosis was 38.4 years (CD: 36 years, UC: 40 years). Male patients accounted for the majority of patients (71.1%). The male-to-female ratio was 3 : 1 for CD and 2.1 : 1 for UC. Current and ever smokers accounted for 30.5% of all patients. Only 4.2% of patients had a family history of IBD. Extraintestinal manifestations (EIMs) were reported in 7.9%, and colorectal cancers (CRCs) were reported in 2.1% of all patients. In patients with CD, the ileal type was the most common disease phenotype (57.5%), and the stricturing type was the most common disease behavior (60.0%). In patients with UC, left-sided colitis was the predominant disease extent (42.7%). The seroprevalence of hepatitis B virus (HBV) was 13.3%. The incidence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in patients with UC was 22%. 5-Aminosalicylic acids were the preferred treatment for UC, whereas corticosteroids, immunomodulators, and biologic agents were preferred for CD. In patients with CD, the bowel resection rate was 38.8%, and the incidence of hip avascular necrosis was 3.8%. In Taiwan, patients with IBD showed a male predominance, lack of familial clustering, a higher prevalence of HBV infection, and a lower prevalence of p-ANCA, EIMs, and CRC. Moreover, a higher incidence of the ileal type with poor outcomes of CD and left-sided predominance in UC were found.

Background: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is the standard treatment for patients with locally advanced rectal cancer. This study developed a random forest (RF) model to predict pathological complete response (pCR) based on radiomics derived from baseline 18 F-fluorodeoxyglucose ([ 18 F] FDG)-positron emission tomography (PET)/computed tomography (CT).Methods: This study included 169 patients with newly diagnosed rectal cancer. All patients received 18 F[FDG]-PET/CT, NCRT, and surgery. In total, 68 radiomic features were extracted from the metabolic tumor volume. The numbers of splits in a decision tree and trees in an RF were determined based on their effects on predictive performance. Receiver operating characteristic curve analysis was performed to evaluate predictive performance and ascertain the optimal threshold for maximizing prediction accuracy.Results: After NCRT, 22 patients (13%) achieved pCR, and 42 features that could differentiate tumors with pCR were used to construct the RF model. Six decision trees and seven splits were suitable. Accordingly, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 81.8%, 97.3%, 81.8%, 97.3%, and 95.3%, respectively. Conclusions: By using an RF, we determined that radiomics derived from baseline 18 F[FDG]-PET/CT could accurately predict pCR in patients with rectal cancer. Highly accurate and predictive values can be achieved but should be externally validated.

Helicobacter pylori colonizes human gastric epithelial cells and contributes to the development of several gastrointestinal disorders. Interleukin (IL)-33 is involved in various immune responses, with reported proinflammatory and anti-inflammatory effects, which may be associated with colitis and colitis-associated cancer. IL-33 induces the inflammatory cascade through its receptor, suppression of tumorigenicity-2 (ST-2). Binding of IL-33 to membrane-bound ST-2 (mST-2) recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates intracellular signaling pathways. However, whether IL-33/ST-2 is triggered by H. pylori infection and whether this interaction occurs in lipid rafts remain unclear. Our study showed that both IL-33 and ST-2 expression levels were significantly elevated in H. pylori-infected cells. Confocal microscopy showed that ST-2 mobilized into the membrane lipid rafts during infection. Depletion of membrane cholesterol dampened H. pylori-induced IL-33 and IL-8 production. Furthermore, in vivo studies revealed IL-33/ST-2 upregulation, and severe leukocyte infiltration was observed in gastric tissues infected with H. pylori. Together, these results demonstrate that ST-2 recruitment into the lipid rafts serves as a platform for IL-33-dependent H. pylori infection, which aggravates inflammation in the stomach.