Duodenal Mucosa of Patients With Type 1 Diabetes Shows Distinctive Inflammatory Profile and Microbiota
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Authors: Pellegrini, Silvia; Sordi, Valeria; Bolla, Andrea Mario; Saita, Diego; Ferrarese, Roberto; Canducci, Filippo; Clementi, Massimo; Invernizzi, Francesca; Mariani, Alberto; Bonfanti, Riccardo; Barera, Graziano; Testoni, Pier Alberto; Doglioni, Claudio; Bosi, Emanuele; Piemonti, Lorenzo
Abstract
Context: Increasing evidences suggest a correlation between gut and type 1 diabetes (T1D). Objective: The objective of this study is to evaluate the gut inflammatory profile and microbiota in patients with T1D compared with healthy control (CTRL) subjects and patients with celiac disease (CD) as gut inflammatory disease controls. Design/Setting/Participants: The inflammatory status and microbiome composition were evaluated in biopsies of the duodenal mucosa of patients with T1D (n = 19), in patients with CD (n = 19), and CTRL subjects (n = 16) recruited at San Raffaele Scientific Institute, in Milan, Italy, between 2009 and 2015. Main Outcome Measures: Inflammation was evaluated by gene expression study and immunohistochemistry. Microbiome composition was analyzed by 16S ribosomal RNA gene sequencing. Results: An increased expression of CCL13, CCL19, CCL22, CCR2, COX2, IL4R, CD68, PTX3, TNF alpha, and VEGFA was observed in patients with T1D compared with CTRL subjects and patients with CD. Immunohistochemical analysis confirmed T1D-specific inflammatory status compared with healthy and CD control tissues, mainly characterized by the increase of the monocyte/macrophage lineage infiltration. The T1D duodenal mucosal microbiome results were different from the other groups, with an increase in Firmicutes and Firmicutes/Bacteroidetes ratio and a reduction in Proteobacteria and Bacteroidetes. The expression of genes specific for T1D inflammation was associated with the abundance of specific bacteria in the duodenum. Conclusions: This study shows that duodenal mucosa in T1D presents disease-specific abnormalities in the inflammatory profile and microbiota. Understanding the mechanisms underlying these features is critical to disentangle the complex pathogenesis of T1D and to gain new perspectives for future therapies targeting the intestine.
Interferon-alpha restrains growth and invasive potential of hepatocellular carcinoma induced by hepatitis B virus X protein
WORLD JOURNAL OF GASTROENTEROLOGY
Authors: Yang, Jian-Qing; Pan, Guang-Dong; Chu, Guang-Ping; Liu, Zhen; Liu, Qiang; Xiao, Yi; Yuan, Lin
Abstract
AIM: To investigate the effects of interferon-alpha (IFN-alpha) to restrain the growth and invasive potential of hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV) X protein. METHODS: The pcDNA3.1-HBx plasmid was transfected into Chang cells by Lipofectamine In vitro, and Chang/HBx was co-cultured with IFN-alpha. Cell survival growth curve and clonogenicity assay were used to test the growth potential of Chang/pcDNA3.1, Chang/HBx and IFN-alpha-Chang/HBx in vitro. Growth assay in nude mice was used to detect the growth potential of Chang/pcDNA3.1, Chang/HBx and IFN-a-Chang/HBx In vivo. Wound healing and transwell migration assays were used to detect the invasive ability of Chang/pcDNA3.1, Chang/HBx and IFN-alpha-Chang/HBx. RESULTS: Compared with CCL13 cells transfected with pcDNA3.1, CCL13 with stable expression of hepatitis B virus X protein showed the characteristics of malignant cells with high capability of growth and invasion by detecting their growth curves, colony forming efficiency wound healing, transwell migration assays and growth assays in nude mice. Its capability of growth and invasion could be controlled by IFN-alpha. CONCLUSION: IFN-a can restrain the growth and invasive potential of HCC cells induced by HBx protein, which has provided an experimental basis for IFN-alpha therapy of HCC. (C) 2008 The WJG Press. All rights reserved.