China
Africa
Explore chapters and articles related to this topic
The Role of Nonspecific Injury in Colon Carcinogenesis *
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Initiation following a single DMH exposure can remain in a cryptic state until promoted by hyperplasia. When DMH is given at the same time or 1 month prior to C. freundii, a high incidence of atypia emerges following promotion by hyperplasia.62 This is analogous to carcinogenesis in other tissues, particularly skin and liver, in which tumors emerge, even after long intervals, once stimulated by proliferation.21,69 However, the colonic mucosa may also be able to repair some initiating damage over the course of time. If initiation occurs 2, 4, or 6 months prior to promotion by TMCH, a smaller yield of atypia evolves compared to 1 month.16 This may indicate that although initiation may be irreversible, some initiated cells may be purged by cell extrusion over the course of time if they are not promoted into emergence.
Mechanisms of bacillary dysentery: lessons learnt from infant rabbits
Published in Gut Microbes, 2020
In animals infected with the bacterial mutant ΔicsA, the colon did not undergo the massive epithelial fenestration observed in animals infected with wild type bacteria (compare Figure 2(a) top and bottom, and Figure 2(b,c), bottom). These results point to the essential role of bacterial spread from cell to cell in the fenestration process. In animals infected with the ΔicsA mutant, the epithelium recovered completely within a few days and infected cells had been removed, perhaps through single-cell extrusion, leaving the rest of the epithelial structure intact. In cells infected with wild type S. flexneri, however, bacteria promptly spread from cell to cell, perhaps augmenting the shear magnitude of extrusion events, ultimately leading to total fenestration of the epithelium. In addition, we often observed clusters of cells sloughing off together in animals infected with wild type bacteria. This observation suggests that in addition to single-cell extrusion events, cell-to-cell spread may lead to dramatic exfoliation of the epithelium en masse. We have previously shown that S. flexneri utilizes its T3SS to manipulate tyrosine kinase and phosphoinositide signaling in order to successfully form and resolve membrane protrusions upon cell-to-cell spread.16,17 Moreover, the activity of various T3SS effector proteins interferes with vesicular trafficking,33,34 which may affect the composition of proteins inserted in the plasma membrane and challenge the integrity of cell-cell contacts. Thus, the infant rabbit model offers a new platform to decipher the host/pathogen interface supporting the cell-to-cell spread and the mechanisms leading to epithelial fenestration.
Modification of late human embryo development after blastomere removal on day 3 for preimplantation genetic testing
Published in Systems Biology in Reproductive Medicine, 2021
Jenna Lammers, Arnaud Reignier, Sophie Loubersac, Sana Chtourou, Tiphaine Lefebvre, Paul Barrière, Thomas Fréour
Embryo biopsy was performed on day 3 for all embryos with at least 6 blastomeres, <25% fragmentation and fair evenness. Briefly, embryos were first placed in Ca/Mg-free medium (G-PGD, Vitrolife®) for a few minutes, before laser-assisted zona pellucida hatching (ZilosTK, Hamilton Thorn®). One to 2 cells were then extracted for subsequent genetic analysis depending on the number of blastomeres (1 cell in 6 to 7-cell embryos, 2 cells in ≥8-cell embryos). Cell extrusion was obtained by gently pressing on the zona pellucida with the biopsy pipette close to the breach. In our experience, this allows faster procedure and less cell damage than with conventional blastomere aspiration.
Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
Published in Gut Microbes, 2021
Alyssa C. Fasciano, Gaya S. Dasanayake, Mary K. Estes, Nicholas C. Zachos, David T. Breault, Ralph R. Isberg, Shumin Tan, Joan Mecsas
How does the loss of RhoA activity promote M cell extrusion? RhoA stimulates contractility and promotes actin stress fiber formation by regulating actomyosin complexes that control tension and forces between cells, which helps to maintain epithelial monolayer integrity.64,76,77 Widespread inactivation of RhoA, using the Rho specific inhibitor C3 transferase, prevents apical extrusion of apoptotic cells.78 During Yptb infection, targeted injection of Yops into only M cells limits the inhibitory effects of YopE on RhoA to within infected M cells. Therefore, localized M cell extrusion may be similar to a cell non-autonomous extrusion process whereby neighboring cells actively participate by recognizing local changes in tension.79 Two recent reports have shown that contractile tension that occurs in response to a perturbation, such as apoptosis or inducible expression of the epithelial morphogenesis transcription factor Snail6SA in some cells, activates RhoA in neighboring cells resulting in apical extrusion of affected cells.80,81 Based on these findings, it is plausible that YopE inhibition of RhoA activity in M cells results in the generation of contractile tension that is sensed by neighboring cells that respond by activating RhoA to contract and squeeze the infected M cell out of the monolayer. The idea that neighboring cells respond to infected M cells is supported by our findings that the TEER did not decrease after infection and that monolayers stained for F-actin appeared to be closing up beneath extruding M cells (unpublished data). Therefore, unlike Salmonella induced destruction of M cells,74 it is not likely that Yptb-induced M cell extrusion creates holes in the FAE as additional access points for Yptb.