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- Bosmans, J W A M, et al.
(författare)
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Functional mucous layer and healing of proximal colonic anastomoses in an experimental model.
- 2017
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 104:5, s. 619-630
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Tidskriftsartikel (refereegranskat)abstract
- Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model.Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein.Of 22 Muc2-deficient (Muc2(-/-) ) mice, 20 developed AL, compared with seven of 22 control animals (P <0·001). Control mice showed normal healing, whereas Muc2(-/-) mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2(-/-) mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2(-/-) mice compared with controls (P = 0·011).A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.
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| 2. |
- Bosmans, Laura A., et al.
(författare)
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Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages’ transition into a pro-inflammatory state
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:5, s. 1146-1160
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Tidskriftsartikel (refereegranskat)abstract
- Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. Method and Cd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe−/− background were generated (CD40wt and CD40mac−/− , respect-Results ively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac−/− compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac−/− atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b− macrophages in the atherosclerotic aorta of CD40mac−/− compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac−/− mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1). Conclusions We here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.
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| 3. |
- Matilla-Santander, N., et al.
(författare)
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COVID-19 and Precarious Employment : Consequences of the Evolving Crisis
- 2021
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Ingår i: International Journal of Health Services. - : Sage Publications. - 0020-7314 .- 1541-4469. ; 5:2, s. 226-228
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Tidskriftsartikel (refereegranskat)abstract
- The world of work is facing an ongoing pandemic and an economic downturn with severe effects worldwide. Workers trapped in precarious employment (PE), both formal and informal, are among those most affected by the COVID-19 pandemic. Here we call attention to at least 5 critical ways that the consequences of the crisis among workers in PE will be felt globally: (a) PE will increase, (b) workers in PE will become more precarious, (c) workers in PE will face unemployment without being officially laid off, (d) workers in PE will be exposed to serious stressors and dramatic life changes that may lead to a rise in diseases of despair, and (e) PE might be a factor in deterring the control of or in generating new COVID-19 outbreaks. We conclude that what we really need is a new social contract, where the work of all workers is recognized and protected with adequate job contracts, employment security, and social protection in a new economy, both during and after the COVID-19 crisis.
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