Gastric Antimicrobial Peptides Fail to Eradicate Helicobacter pylori Infection Due to Selective Induction and Resistance
PLOS ONE
Authors: Nuding, Sabine; Gersemann, Michael; Hosaka, Yoshio; Konietzny, Sabrina; Schaefer, Christian; Beisner, Julia; Schroeder, Bjoern O.; Ostaff, Maureen J.; Saigenji, Katunori; Ott, German; Schaller, Martin; Stange, Eduard F.; Wehkamp, Jan
Abstract
Background: Although antimicrobial peptides protect mucus and mucosa from bacteria, Helicobacter pylori is able to colonize the gastric mucus. To clarify in which extend Helicobacter escapes the antimicrobial defense, we systematically assessed susceptibility and expression levels of different antimicrobial host factors in gastric mucosa with and without H. pylori infection. Materials and Methods: We investigated the expression levels of HBD1 (gene name DEFB1), HBD2 (DEFB4A), HBD3 (DEFB103A), HBD4 (DEFB104A), LL37 (CAMP) and elafin (PI3) by real time PCR in gastric biopsy samples in a total of 20 controls versus 12 patients colonized with H. pylori. Immunostaining was performed for HBD2 and HBD3. We assessed antimicrobial susceptibility by flow cytometry, growth on blood agar, radial diffusion assay and electron microscopy. Results: H. pylori infection was associated with increased gastric levels of the inducible defensin HBD2 and of the antiprotease elafin, whereas the expression levels of the constitutive defensin HBD1, inducible HBD3 and LL37 remained unchanged. HBD4 was not expressed in significant levels in gastric mucosa. H. pylori strains were resistant to the defensins HBD1 as well as to elafin, and strain specific minimally susceptible to HBD2, whereas HBD3 and LL37 killed all H. pylori strains effectively. We demonstrated the binding of HBD2 and LL37 on the surface of H. pylori cells. Comparing the antibacterial activity of extracts from H. pylori negative and positive biopsies, we found only a minimal killing against H. pylori that was not increased by the induction of HBD2 in H. pylori positive samples. Conclusion: These data support the hypothesis that gastric H. pylori evades the host defense shield to allow colonization.
Identification of Biomarker for Cutaneous Squamous Cell Carcinoma Using Microarray Data Analysis
JOURNAL OF CANCER
Authors: Wei, Wei; Chen, Yan; Xu, Jie; Zhou, Yu; Bai, Xinping; Yang, Ming; Zhu, Ju
Abstract
Cutaneous squamous cell carcinoma (CSCC) is one of the most malignant tumors worldwide. We aimed to explore the molecular mechanism of this CSCC and screen feature genes that can function as the biomarker of CSCC and thus provide a theoretical basis for the pathogenesis research and development of medicine. The method of microarray data analysis was used in this study to explore the differentially expressed genes between tissues of normal specimens and tissues of patients with CSCC. Besides, functional enrichment analysis and signal pathway were performed on these genes to screen the feature genes that are closely associated with CSCC can function as the potential biomarkers of CSCC. A total of 53 samples from two datasets, GSE45216 and GSE45164, were used in the differentially expressed analysis. And as a result, a total of 833 genes were screened out, including 465 up-regulated genes and 215 down-regulated genes. Candidate genes, including up-regulated genes like S100A12, MMP1, DEFB4B/DEFB4A, KRT16 and PI3, and down-regulated genes like EGR3, LRP4, C14orf132, PAMR1, CCL27, and KRT2 were screened out. All these genes were testified in the dataset of GSE66359. The result showed that only three genes, KRT16, PI3 and EGR3, were mostly differentially expressed and only EGR3 had the same expression pattern with both datasets, GSE45216 and GSE45164. Of note, EGR3 gene was found to be the most differentially expressed gene in cutaneous squamous cell carcinoma, which had the potential to function as the candidate genes and help in the diagnosis and prognostic treatments of CSCC.