Deoxycholic acid activates epidermal growth factor receptor and promotes intestinal carcinogenesis by ADAM17‐dependent ligand release

High fat diet is implicated in the elevated deoxycholic acid (DCA) in the intestine and correlated with increased colon cancer risk. However, the potential mechanisms of intestinal carcinogenesis by DCA remain unclarified. Here, we investigated the carcinogenic effects and mechanisms of DCA using the intestinal tumour cells and Apc^min/+ mice model. We found that DCA could activate epidermal growth factor receptor (EGFR) and promote the release of EGFR ligand amphiregulin (AREG), but not HB‐EGF or TGF‐α in intestinal tumour cells. Moreover, ADAM‐17 was required in DCA‐induced promotion of shedding of AREG and activation of EGFR/Akt signalling pathway. DCA significantly increased the multiplicity of intestinal tumours and accelerated adenoma‐carcinoma sequence in Apc^min/+ mice. ADAM‐17/EGFR signalling axis was also activated in intestinal tumours of DCA‐treated Apc^min/+ mice, whereas no significant change occurred in tumour adjacent tissues after DCA exposure. Conclusively, DCA activated EGFR and promoted intestinal carcinogenesis by ADAM17‐dependent ligand release.     

Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells

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Mucosal bacterial dissemination in a rhesus macaque model of experimental brucellosis

Animals were experimentally infected with Brucella melitensis via aerosol. B. melitensis was cultured from the saliva and vaginal vault of infected animals, corresponding to bacterial dissemination in other target tissues. This is the first report of bacterial dissemination to these mucosal surfaces in a non‐human primate model of brucellosis.     

几种常用的甜味剂对肠道微生物的调节机制

甜味剂是指能赋予软饮料食品甜味的食品添加剂,它可分为高甜度甜味剂和减热值甜味剂。目前甜味剂对肠道菌群的调节机制已成为研究热点之一,甜味剂可影响肠道微生物群的生态平衡,进而影响宿主的健康。越来越多的数据表明,甜味剂的过度食用可致代谢功能障碍,同时对宿主体重和葡萄糖耐受量产生影响。本文综述了近年来几种常用的甜味剂对肠道微生物调节方面的研究进展,以期为研究者提供借鉴。     

Lithium chloride contributes to blood–spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux

Blood–spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) significantly compromises functional neuronal recovery. Autophagy is a potential therapeutic target when seeking to protect the BSCB. We explored the effects of lithium chloride (LiCl) on BSCB permeability and autophagy-induced SCI both in a rat model of SCI and in endothelial cells subjected to oxygen–glucose deprivation. We evaluated BSCB status using the Evans Blue dye extravasation test and measurement of tight junction (TJ) protein levels; we also assessed functional locomotor recovery. We detected autophagy-associated proteins in vivo and in vitro using both Western blotting and immunofluorescence staining. We found that, in a rat model of SCI, LiCl attenuated the elevation in BSCB permeability, improved locomotor recovery, and inhibited the degradation of TJ proteins including occludin and claudin-5. LiCl significantly induced the extent of autophagic flux after SCI by increasing LC3-II and ATG-5 levels, and abolishing p62 accumulation. In addition, a combination of LiCl and the autophagy inhibitor chloroquine not only partially eliminated the BSCB-protective effect of LiCl, but also exacerbated TJ protein degradation both in vivo and in vitro. Together, these findings suggest that LiCl treatment alleviates BSCB disruption and promotes locomotor recovery after SCI, partly by stimulating autophagic flux.     

Overexpression of the lamina proteins Lamin and Kugelkern induces specific ultrastructural alterations in the morphology of the nuclear envelope of intestinal stem cells and enterocytes

The nuclear envelope has a stereotypic morphology consisting of a flat double layer of the inner and outer nuclear membrane, with interspersed nuclear pores. Underlying and tightly linked to the inner nuclear membrane is the nuclear lamina, a proteinous layer of intermediate filament proteins and associated proteins. Physiological, experimental or pathological alterations in the constitution of the lamina lead to changes in nuclear morphology, such as blebs and lobulations. It has so far remained unclear whether the morphological changes depend on the differentiation state and the specific lamina protein. Here we analysed the ultrastructural morphology of the nuclear envelope in intestinal stem cells and differentiated enterocytes in adult Drosophila flies, in which the proteins Lam, Kugelkern or a farnesylated variant of LamC were overexpressed. Surprisingly, we detected distinct morphological features specific for the respective protein. Lam induced envelopes with multiple layers of membrane and lamina, surrounding the whole nucleus whereas farnesylated LamC induced the formation of a thick fibrillary lamina. In contrast, Kugelkern induced single-layered and double-layered intranuclear membrane structures, which are likely be derived from infoldings of the inner nuclear membrane or of the double layer of the envelope.     

Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain

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Physical control of Eurasian watermilfoil in an oligotrophic lake

The introduction of Eurasian watermilfoil (Myriophyllum spicatum) into oligotrophic waters of high water clarity in temperate zones of North America has produced growth in excess of 6 m depth and yearly biomass approaching 1000 g m^–2 dry weight. From its initial observation in Lake George, New York, USA in 1985, by 1993 milfoil had spread to 106 discrete locations within the lake. A 7-year study of one site having no management showed milfoil to grow expansively, suppressing native plant species from 20 in 1987 to 6 in 1993 with the average number of species m^–2 quadrat declining from 5.5 in 1987 to less than 2 in 1993. Management of milfoil by means of hand harvesting, suction harvesting and benthic barrier has reduced the number of unmanaged sites from 106 in 1993 to 11. One year post-treatment at sites utilizing suction harvesting, showed a greater number of native species at all sites than pretreatment with a substantial reduction in milfoil biomass. At sites where benthic barrier was removed 1–2 years after installation, milfoil had recolonized 44% of grid squares within 30 days. Ninety days after barrier removal 74% of grid squares contained milfoil and one year later 71% of the grids supported milfoil. During the first year following mat removal, the average number of species m^–2 peaked at 4.7 and stabilized at 4.5 during the second year. Hand harvesting by SCUBA in areas of limited milfoil growth (new sites of infestation and sites of former treatment) was found to reduce the number of milfoil plants present in subsequent years. Hand harvesting did not eliminate milfoil at any of the sites and regrowth/colonization necessitated reharvesting every 3 or more years. Results of evaluations of physical plant management techniques indicate that (1) an integrated program utilizing different techniques based on plant density reduced the growth of milfoil and (2) long term commitment to aquatic plant management is necessary since none of the techniques employed singly were found to eliminate milfoil.