Publications by authors named "Hamersveld P"

Innervation of the intestinal mucosa by the sympathetic nervous system is well described but the effects of adrenergic receptor stimulation on the intestinal epithelium remain equivocal. We therefore investigated the effect of sympathetic neuronal activation on intestinal cells in mouse models and organoid cultures, to identify the molecular routes involved. Using publicly available single-cell RNA sequencing datasets we show that the α isoform is the most abundant adrenergic receptor in small intestinal epithelial cells.

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  • Vagus nerve stimulation (SpNS) was tested in mice to see if it could reduce inflammation in inflammatory bowel disease (IBD) by targeting the splenic nerve and releasing norepinephrine (NE).
  • Mice received stimulation during an induced colitis experiment, showing improved symptoms and lower inflammation markers compared to those with no stimulation.
  • The results suggest SpNS may lower immune response activation, indicating potential for clinical application in IBD treatment for humans.
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  • * A study analyzed fecal samples from 31 UC patients and 7 donors to determine which fungal species are linked to improved clinical outcomes following FMT.
  • * The findings suggest that certain yeast species in donor feces correlate with successful FMT outcomes, indicating the potential for these fungi to serve as biomarkers for predicting treatment success in UC patients.
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Background: Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.

Methods: The peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array.

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  • Antimicrobial responses are crucial for gut health, and the study focuses on how miR-511 affects TLR4 responses, leading to increased intestinal inflammation.
  • Mice lacking miR-511 showed less severe colitis symptoms and lower inflammatory cytokine levels compared to normal mice when exposed to DSS, indicating a protective role against intestinal inflammation.
  • The research also identified Wdfy1 as a target of miR-511, suggesting that diminished WDFY1 levels in miR-511-deficient macrophages contribute to reduced immune responses from TLR3 and TLR4.
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Background And Aims: Histone deacetylase inhibitors [HDACi] exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif [ESM] technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 [CES1].

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β-glucan consumption is known for its beneficial health effects, but the mode of action is unclear. While humans and mice lack the required enzymes to digest β-glucans, certain intestinal microbes can digest β-glucans, triggering gut microbial changes. Curdlan, a particulate β-glucan isolated from , is used as a food additive.

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  • Recent studies show that SARS-CoV-2 can infect intestinal cells expressing the ACE2 receptor, highlighting the importance of these cells in the virus's entry point.
  • The research examined the relationship between nicotinic receptors, inflammation regulation, and ACE2 expression, particularly focusing on the effects of vagus nerve stimulation (VNS) on intestinal epithelial cells.
  • Results indicated that while ACE2 and nicotinic receptors are co-expressed in certain intestinal cells, VNS did not influence ACE2 expression, suggesting VNS may not help reduce the risk of SARS-CoV-2 infection in the intestines.
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  • * The study found that specific HDAC inhibitors (HDACi) like HDAC3i and pan-HDACi diminished cytokine secretion in monocytes and M1 macrophages but had no effect on M2 macrophages.
  • * HDAC3 was shown not to be essential for macrophage polarization or IFNγ signaling in humans, suggesting that targeting HDAC3 could help manage macrophage responses during inflammation and promote endotoxin tolerance.
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  • TYK2, a key player in the signaling of cytokines, is critical for the development of inflammatory bowel disease (IBD), and a selective inhibitor (TYK2i) was tested for its effectiveness in treating it in a mouse model of colitis.
  • In the study, TYK2i significantly reduced weight loss and disease severity in mice with colitis, while T cells lacking TYK2 activity also showed reduced disease symptoms.
  • The findings suggest that targeting TYK2 could be a promising approach for IBD treatment, as it decreased specific immune responses both in mice and human T cells.
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  • * Research using mice showed that when ChAT T cells were absent in CD4 T cells, the mice experienced less severe acute colitis but struggled more during the recovery phase compared to control mice.
  • * Overall, ChAT T cells can increase inflammation during the early stages of bowel inflammation but are beneficial for the healing process afterward, suggesting a complex role in managing colitis.
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Background: Janus kinases (JAKs) mediate cytokine signaling involved in inflammatory bowel disease. The pan-JAK inhibitor tofacitinib has shown efficacy in the treatment of ulcerative colitis. However, concerns regarding adverse events due to their wide spectrum inhibition fueled efforts to develop selective JAK inhibitors.

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  • The sympathetic nervous system is important for controlling innate immune responses, and its reduction in inflammatory bowel disease affects immune function in the intestines.
  • Researchers examined how activation of adrenergic receptors impacts cytokine production in macrophages and studied the effects of sympathetic nerve damage in mice lacking certain immune cells.
  • Results showed that nerve damage led to increased inflammation and histological damage in the intestines, indicating that the sympathetic nervous system helps regulate immune cell activity in response to microbial threats.
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Objectives: The esophageal mucosal integrity is impaired in eosinophilic esophagitis (EoE) and it has been suggested that the duodenal permeability is increased. The absence of food allergens may restore the integrity. The aims of this study were to assess duodenal permeability in EoE and to evaluate the effect of an elemental diet on the esophageal and duodenal integrity.

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