Colorectal cancer (CRC) is highly prevalent in Western society, and increasing evidence indicates strong contributions of environmental factors and the intestinal microbiota to CRC initiation, progression and even metastasis. We have identified a synergistic inflammatory tumor-promoting mechanism through which the resident intestinal microbiota boosts invasive CRC development in an epithelial-to-mesenchymal transition-prone tissue environment. Intestinal epithelial cell (IEC)-specific transgenic expression of the epithelial-to-mesenchymal transition regulator Zeb2 in mice (Zeb2) leads to increased intestinal permeability, myeloid cell-driven inflammation and spontaneous invasive CRC development. Zeb2 mice develop a dysplastic colonic epithelium, which progresses to severely inflamed neoplastic lesions while the small intestinal epithelium remains normal. Zeb2 mice are characterized by intestinal dysbiosis, and microbiota depletion with broad-spectrum antibiotics or germ-free rederivation completely prevents cancer development. Zeb2 mice represent the first mouse model of spontaneous microbiota-dependent invasive CRC and will help us to better understand host-microbiome interactions driving CRC development in humans.
As a common digestive disease, acute pancreatitis (AP) often threatens the life of patients. Bone marrow mesenchymal stem cells (BMSCs) derived exosomes have exhibited some benefits for AP. However, the mechanism remains unclear and deserves to be further investigated.
Background: Pre-eclampsia (PE) is a pregnancy specific disease characterized by hypertension and proteinuria. The aim of this study was to investigate the effects of Zinc finger E-box binding homologous box 2 (ZEB2) on PE mice and on placental trophoblast cells, as well as to elucidate its role in Wnt/β-Catenin pathway.
Methods: The PE mice models were established through L-NAME administration.
Various bacteria are suggested to contribute to colorectal cancer (CRC) development, including pks Escherichia coli, which produces the genotoxin colibactin that induces characteristic mutational signatures in host epithelial cells. However, it remains unclear how the highly unstable colibactin molecule is able to access host epithelial cells to cause harm. Here, using the microbiota-dependent ZEB2-transgenic mouse model of invasive CRC, we demonstrate that the oncogenic potential of pks E.
The study investigates the role of circular RNA circTMCO3 in sepsis-induced acute kidney injury (S-AKI), finding that circTMCO3 expression is reduced in S-AKI models, which negatively impacts kidney health.*
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Introducing circTMCO3 into cell models enhances kidney cell survival and reduces injury by counteracting inflammation and oxidative stress, while its downregulation worsens these conditions.*
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The protective mechanism of circTMCO3 involves its interaction with miR-218-5p and ZEB2, suggesting that boosting circTMCO3 levels may provide a new therapeutic approach for treating S-AKI.*
Experimental and Molecular Pathology, Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, D-80337, Munich, Germany.
We have previously shown that general deletion of the gene encoding the p53-inducible Mir34a microRNA enhances the number and invasion of colitis-associated colorectal cancers (CACs) in mice. Since the p53-pathway has been implicated in tumor-suppression mediated by cells in the tumor microenvironment (TME) we deleted Mir34a in myeloid cells and characterized CACs in these with scRNA-Seq (single cell RNA sequencing). This revealed an increase in specific macrophage subtypes, such as Cdk8 macrophages and Mrc1, M2-like macrophages.
