Development of novel GI-centric prostaglandin E receptor type 4 (EP4) agonist prodrugs as treatment for ulcerative colitis and other intestinal inflammatory diseases.

Prostaglandin E receptor type 4 (EP4) agonists have been shown to be effective in treating experimental ulcerative colitis (UC) in animals and in human clinical trials, but their development has been impeded by unacceptable systemic side effects. In this study, a series of methylene phosphate prodrugs of a highly potent and selective prostaglandin EP4 receptor agonist were designed to target and remain localized in the gastrointestinal (GI) tract after either oral or rectal instillation. The prodrugs were designed to be converted to liberate active EP4 agonist by intestinal alkaline phosphate (IAP), a ubiquitous enzyme found at the luminal of the intestinal wall thus exposing the colon epithelial barrier while reducing systemic exposure to the active agonist.

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.

Public Interest in Online Information on Recurrent Urinary Tract Infections Is Greatest for Information with the Poorest Publication Quality.

: Urinary tract infections (UTIs) are among the most prevalent bacterial infections. With many patients turning to the Internet as a health resource, this study seeks to understand public engagement with online resources concerning recurrent UTIs (rUTIs), assess their reliability, and identify common questions/concerns about rUTIs. : Social media analysis tool BuzzSumo was used to calculate online engagement (likes, shares, comments, views) with information on rUTIs.

Rapid degeneration and neurochemical plasticity of the lateral geniculate nucleus following lesions of the primary visual cortex in marmoset monkeys.

Lesions of the primary visual cortex (V1) cause retrograde neuronal degeneration, volume loss and neurochemical changes in the lateral geniculate nucleus (LGN). Here we characterised the timeline of these processes in adult marmoset monkeys, after various recovery times following unilateral V1 lesions. Observations in NeuN-stained sections obtained from animals with short recovery times (2, 3 or 14 days) showed that the volume and neuronal density in the LGN ipsilateral to the lesions were similar to those in the contralateral hemispheres.