Gastrointestinal organoids have emerged as a model system that authentically recapitulates the in vivo situation. Despite biomedical and technical challenges, self-assembled 3D structures derived from pluripotent stem cells or healthy and diseased tissues have proved to be invaluable tools for cancer drug discovery, disease modeling, and studying infection with carcinogenic pathogens.
View Article and Find Full Text PDFThe human pathogen Helicobacter pylori induces a strong inflammatory response in gastric mucosa manifested by the recruitment of neutrophils and macrophages to the places of infection, and by changes in epithelial integrity and function. At the molecular level, this innate immune response is essentially dependent on the activation of NF-κB transcription factors regulating the expression of chemotactic factors, e.g.
View Article and Find Full Text PDFA hallmark of infection by the pathogen Helicobacter pylori, which colonizes the human gastric epithelium, is the simultaneous activation of the classical and alternative nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, underlying inflammation and cell survival. Here, we report that the classical NF-κB target gene product A20 contributes to the negative regulation of alternative NF-κB signaling in gastric epithelial cells infected by H. pylori.
View Article and Find Full Text PDFNF-κB signaling pathways, induced by a variety of triggers, play a key role in regulating the expression of genes involved in the immune response and cellular responses to stress. The human pathogen Helicobacter pylori induces classical and alternative NF-κB signaling pathways via its effector ADP-L-glycero-β-D-manno-heptose (ADP-heptose). We review H.
View Article and Find Full Text PDFHelicobacter pylori infection constitutes one of the major risk factors for the development of gastric diseases including gastric cancer. The activation of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) via classical and alternative pathways is a hallmark of H. pylori infection leading to inflammation in gastric epithelial cells.
View Article and Find Full Text PDFHelicobacter pylori infection represents a major risk factor for the development of gastric diseases and gastric cancer. The capability of H. pylori to inject the virulence factor cytotoxin-associated gene A (CagA) depends on a type IV secretion system (T4SS) encoded by the cag pathogenicity island (cagPAI).
View Article and Find Full Text PDFDysregulation of the alternative NF-κB signaling has severe developmental consequences that can ultimately lead to oncogenesis. Pivotal for the activation of the alternative NF-κB pathway is the stabilization of the NF-κB-inducing kinase (NIK). The aim of this review is to focus on the emerging role of NIK in cancer.
View Article and Find Full Text PDFHelicobacter pylori infection persists in more than half of the world's population and represents a risk factor for peptic ulcer disease and gastric cancer. Virulent strains of H. pylori carry a cag pathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS) with the capability to inject the effector protein cytotoxin-associated gene A (CagA) into eukaryotic cells.
View Article and Find Full Text PDFThe nuclear factor (NF)-κB essential modulator (NEMO) is a key regulator in NF-κB-mediated signaling. By transmitting extracellular or intracellular signals, NEMO can control NF-κB-regulated genes. NEMO dysfunction is associated with inherited diseases such as incontinentia pigmenti (IP), ectodermal dysplasia, anhidrotic, with immunodeficiency (EDA-ID), and some cancers.
View Article and Find Full Text PDFThe human pathogen Helicobacter pylori infects more than half of the world's population and is a paradigm for persistent yet asymptomatic infection but increases the risk for chronic gastritis and gastric adenocarcinoma. For successful colonization, H. pylori needs to subvert the host cell death response, which serves to confine pathogen infection by killing infected cells and preventing malignant transformation.
View Article and Find Full Text PDFHelicobacter pylori is estimated to infect more than half of the worlds human population and represents a major risk factor for chronic gastritis, peptic ulcer disease, MALT lymphoma, and gastric adenocarcinoma. H. pylori infection and clinical consequences are controlled by highly complex interactions between the host, colonizing bacteria, and environmental parameters.
View Article and Find Full Text PDFBiochim Biophys Acta
April 2014
Helicobacter pylori colonises the gastric epithelial cells of half of the world's population and represents a risk factor for gastric adenocarcinoma. In gastric epithelial cells H. pylori induces the immediate early response transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) and the innate immune response.
View Article and Find Full Text PDFHelicobacter pylori, a class I carcinogen, induces a proinflammatory response by activating the transcription factor nuclear factor-kappa B (NF-κB) in gastric epithelial cells. This inflammatory condition could lead to chronic gastritis, which is epidemiologically and biologically linked to the development of gastric cancer. So far, there exists no clear knowledge on how H.
View Article and Find Full Text PDFWorld J Gastroenterol
June 2011
Aim: To understand which and how different miRNAs are implicated in the process of hepatic stellate cell (HSC) activation.
Methods: We used microarrays to examine the differential expression of miRNAs during in vitro activation of primary HSCs (pHSCs). The transcriptome changes upon stable transfection of rno-miR-146a into an HSC cell line were studied using cDNA microarrays.
Intercellular communication is an important tool used by the cells to effectively regulate concerted responses. Hepatic stellate cells (HSCs) communicate to each other through functional gap junctions composed of connexin 43 (Cx43) proteins. We show that exogenous human TGF-beta1 (hTGF-beta1), a pro-fibrotic stimulus, decreases Cx43 mRNA and protein in a rat HSC cell line and primary HSCs.
View Article and Find Full Text PDFSeveral lysosomal cathepsins have been implicated in a number of diseases, from arthritis to cancer. A recent member of the cathepsin family, cathepsin S (Cat S) has been associated with several types of cancer in humans. However, to date, no report has linked Cat S to human hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFActivation of hepatic stellate cells during liver fibrosis is a major event facilitating an increase in extracellular matrix deposition. The up-regulation of smooth muscle alpha-actin and collagen type I is indicative of the activation process. The involvement of cysteine cathepsins, a class of lysosomal cysteine proteases, has not been studied in conjunction with the activation process of hepatic stellate cells.
View Article and Find Full Text PDFThe glial fibrillary acidic protein (GFAP) is traditionally used as a marker for astrocytes of the brain, and more recently for the hepatic stellate cells (HSCs) of the liver. Several GFAP splice variants have been previously reported in the astrocytes of the CNS and in the non-myelinating Schwann cells of the PNS. In this study, we investigate whether GFAP splice variants are present in the HSCs and their expression as a function of HSCs activation.
View Article and Find Full Text PDFAn optical technique for the parallel manipulation of nanoscale structures with molecular resolution is presented. Bioconjugated metal nanoparticles are thereby positioned at the location of interest, such as, e.g.
View Article and Find Full Text PDF