Adaptive cellular responses are often required during wound repair. Following disruption of the intestinal epithelium, wound‐associated epithelial (WAE) cells form the initial barrier over the wound. ...Our goal was to determine the critical factor that promotes WAE cell differentiation. Using an adaptation of our in vitro primary epithelial cell culture system, we found that prostaglandin E2 (PGE2) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to in vivo WAE cells. WAE cell differentiation was a permanent state and dominant over enterocyte differentiation in plasticity experiments. WAE cell differentiation was triggered by nuclear β‐catenin signaling independent of canonical Wnt signaling. Creation of WAE cells via the PGE2‐Ptger4 pathway was required in vivo, as mice with loss of Ptger4 in the intestinal epithelium did not produce WAE cells and exhibited impaired wound repair. Our results demonstrate a mechanism by which WAE cells are formed by PGE2 and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury.
Synopsis
Intestinal wound‐associated epithelial (WAE) cells are a transient class of repair cells critical for repair initiation. Prostaglandin PGE2 triggers WAE cell generation in response to injury, acting through its epithelial receptor EP4.
The prostaglandin PGE2 stimulates wound‐associated epithelial cell formation in mouse and human cells.
PGE2 acts through the receptor Ptger4 (EP4) on intestinal epithelial cells.
WAE cell differentiation suppresses enterocyte differentiation of epithelial progenitors.
Intestinal wound‐associated epithelial (WAE) cells are a transient class of repair cells critical for repair initiation. Prostaglandin PGE2 triggers WAE cell generation in response to injury, acting through its epithelial receptor EP4.
Intestinal Paneth cells modulate innate immunity and infection. In Crohn’s disease, genetic mutations together with environmental triggers can disable Paneth cell function. Here, we find that a ...western diet (WD) similarly leads to Paneth cell dysfunction through mechanisms dependent on the microbiome and farnesoid X receptor (FXR) and type I interferon (IFN) signaling. Analysis of multiple human cohorts suggests that obesity is associated with Paneth cell dysfunction. In mouse models, consumption of a WD for as little as 4 weeks led to Paneth cell dysfunction. WD consumption in conjunction with Clostridium spp. increased the secondary bile acid deoxycholic acid levels in the ileum, which in turn inhibited Paneth cell function. The process required excess signaling of both FXR and IFN within intestinal epithelial cells. Our findings provide a mechanistic link between poor diet and inhibition of gut innate immunity and uncover an effect of FXR activation in gut inflammation.
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•Diet-induced obesity results in Paneth cell dysfunction in humans and mice•Consumption of western diet leads to Clostridium-mediated deoxycholic acid conversion•Deoxycholic acid activates both FXR and type I IFN pathways•Both FXR and type I IFN pathways are essential in triggering Paneth cell defects
Small intestinal Paneth cells are gatekeepers of gut innate immunity. Liu et al. identified a link between consumption of high fat, high sugar diet (western diet; WD) and Paneth cell dysfunction. The mechanisms involve WD-associated microbiota conversion of bile acids, which activate both FXR and type I interferon pathways.
Prostate cancer is for many men a chronic disease with a long life expectancy after treatment. The impact of prostate cancer therapy on men has been well defined, however, explanation of the ...consequences of cancer treatment has not been modelled against the wider variables of long-term health-care provision. The aim of this study was to explore the parameters of unmet supportive care needs in men with prostate cancer in relation to the experience of nursing care.
A survey was conducted among a volunteer sample of 1001 men with prostate cancer living in seven European countries.
At the time of the survey, 81% of the men had some unmet supportive care needs including psychological, sexual and health system and information needs. Logistic regression indicated that lack of post-treatment nursing care significantly predicted unmet need. Critically, men's contact with nurses and/or receipt of advice and support from nurses, for several different aspects of nursing care significantly had an impact on men's outcomes.
Unmet need is related not only to disease and treatment factors but is also associated with the supportive care men received. Imperative to improving men's treatment outcomes is to also consider the access to nursing and the components of supportive care provided, especially after therapy.
Labile non-bridging ligands modify coordination polymer structure and provide a route to the preparation of materials with vacant metal coordination sites.
•New 1D chain coordination polymers ...prepared with porous structure.•Labile aqua ligands lead to materials with open metal sites.•Faster water binding by Co-bpy 1D chains than 2D bilayer due to open metal sites.
The inclusion of labile non-bridging ligands in coordination polymers can be used to modify their topology and provide a route to the preparation of materials with vacant metal coordination sites. The reaction of Co(NO3)2 and 4,4′-bipyridine (bpy) in ethanol is known to produce a 2D coordination polymer Co2(bpy)3(NO3)4n, 1. The inclusion of non-bridging aqua ligands produces new coordination polymer structures, 1D chains of Co(bpy)(H2O)2(NO3)2n, 2, and Ni(bpy)(H2O)2(NO3)2n, 3. The structures of the 2 and 3 were determined by single-crystal X-ray diffraction, which showed that they had the same packing motif, layers of parallel chains stacked in an ABAB pattern along the c axis. The crystals had 4Å channels running parallel to the c axis. The disordered guest molecules in the channels of 2 were removed by heating at 90°C, along with the two aqua ligands. This produced a coordination polymer with vacant metal coordination sites that had a high selectivity for the adsorption of water and its coordination to the Co. Aqua ligands also bound to the Co when 1 adsorbed water and, but the process was much slower due to the larger structural changes this required in the 2D framework and the lack of vacant coordination sites.
We report the case of a 97 year old woman suffering from a voluminous diverticle of the cervical esophagus with important comorbidities and a very poor quality of life. A diverticulectomy under ...general anesthesia implied a high level of risk. Regional anesthesia was chosen, i.e. an intermediate cervical plexus block, with mild sedation allowing to maintain contact with the patient. The procedure was carried out without complications and the patient's and surgical staff satisfaction were optimal.
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