Background
Neuroplastic changes in the enteric nervous system (ENS) observed during IBD might participate in physiopathological processes. Vasoactive intestinal polypeptide has been shown to be ...involved in intestinal inflammation and barrier functions. We aimed to investigate the modulation of VIP expression in colonic biopsies of IBD patient, the ability of soluble factors from biopsies to reproduce in vitro these modulations and identify soluble factors responsible.
Methods
VIP and cytokines mRNA expressions were assessed in colonic biopsies of healthy subjects (HS) and IBD patients from inflamed (I) and non‐inflamed areas (NI). Supernatants (SUP) of biopsies were applied to primary culture of ENS and VIP and cytokines mRNA expressions were assessed. The role of cytokines in SUP induced changes in VIP expression was evaluated.
Key Results
VIP mRNA expression was lower in biopsies of patients with Crohn's disease (CD) than Ulcerative Colitis (UC) but unchanged as compared to HS. VIP mRNA and protein expression were lower in primary culture of ENS incubated with SUP‐CD than with SUP‐UC. Furthermore, in CD but not UC, SUP‐I reduced VIP expression in the ENS as compared to SUP‐NI. Next, IL‐6 but not IL‐5, IL‐10, IL‐17, IFN‐γ or TNF‐α reduced VIP expression in the ENS. Finally, in CD, SUP‐I incubated with anti‐IL‐6 antibody increased VIP expression as compared to SUP‐I alone.
Conclusions & Inferences
Mucosal soluble factors from IBD induce VIP neuroplastic changes in the ENS. IL‐6 was identified as a putative soluble factor responsible in part for changes in VIP expression in CD.
Mucosal soluble factors from IBD induce VIP neuroplastic changes in the ENS. IL‐6 is a putative soluble factor responsible in part for changes in VIP expression in CD.
Summary
Background
The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut‐specificity.
Aim
To assess effectiveness of vedolizumab for ...EIM in patients with inflammatory bowel disease (IBD) in a large real‐life experience cohort.
Methods
Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3‐step scale: complete remission, partial response and no response.
Results
At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% 1.05‐3.41, P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% 1.12‐3.52, P = .02). During the follow‐up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation.
Conclusion
Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.
Linked Content
This article is linked to Barclay and Stamp paper. To view this article visit https://doi.org/10.1111/apt.14465.
Cancer stem cells (CSCs) represent a subset of cells within tumours that exhibit self-renewal properties and the capacity to seed tumours. CSCs are typically refractory to conventional treatments and ...have been associated to metastasis and relapse. Salinomycin operates as a selective agent against CSCs through mechanisms that remain elusive. Here, we provide evidence that a synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast CSCs in vitro and in vivo, by accumulating and sequestering iron in lysosomes. In response to the ensuing cytoplasmic depletion of iron, cells triggered the degradation of ferritin in lysosomes, leading to further iron loading in this organelle. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis. These findings reveal the prevalence of iron homeostasis in breast CSCs, pointing towards iron and iron-mediated processes as potential targets against these cells.
A key challenge in nanonetworking is to develop a means of coordinating a large number of nanoscale devices. Molecular communication has emerged as a promising technique to assist in the coordination ...problem. Devices in molecular communication systems- -once information molecules are released--are typically viewed as passive, not reacting chemically with the information molecules. While this is an accurate model in \textit{diffusion-limited links}, it is not the only scenario. In particular, the dynamics of molecular communication systems are more generally governed by reaction- diffusion, where the reaction dynamics can also dominate. This leads to the notion of \textit{reaction-limited molecular communication systems}, where the concentration profiles of information molecules and other chemical species depends largely on reaction kinetics. In this regime, the system can be approximated by a chemical reaction network. In this paper, we exploit this observation to design new protocols for both point-to-point links with feedback and networks for event detection. In particular, using connections between consensus and advection theory and reaction networks lead to simple characterizations of equilibrium concentrations, which yield simple-- but accurate--design rules even for networks with a large number of devices.
PDF
