In an analysis of data from real-life clinical practice, we associated infliximab concentrations during the induction therapy with STMH in patients with UC.
The transcription factor NF-kB is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-kB and apoptotic signalling, was identified as a susceptibility gene for multiple inflammatory diseases, including IBD. Despite absence of spontaneous intestinal inflammation in intestinal epithelial cell (IEC) specific A20 knockout mice, we found additional myeloid-specific A20 deletion to synergistically drive intestinal pathology through cell-specific mechanisms. A20 ensures intestinal barrier stability by preventing cytokine-induced IEC apoptosis, while A20 prevents excessive cytokine production in myeloid cells. Combining IEC and myeloid A20 deletion induces ileitis and severe colitis, characterized by IEC apoptosis, Paneth and goblet cell loss, epithelial hyperproliferation and intestinal microbiota dysbiosis. Continuous epithelial cell death and regeneration in an inflammatory environment sensitizes cells for neoplastic transformation and the development of colorectal tumours in aged mice.
TNF antagonists have become indispensable in the management of IBD. Efforts to focus on treatment of inflammatory signs only and on optimization of treatment with therapeutic drug monitoring are underway. The advent of several new compounds and "biosimilars" will further challenge the position of TNF antagonists in the treatment algorithm of IBD.
The synthesis and evaluation of gelatin acrylamide as an alternative to the well-established gelatin methacrylamide are reported. High-resolution magic angle spinning NMR is used for the quantitative determination of the chemical cross-linking density. The gelatin acrylamide precursors reveal enhanced cross-linking in terms of reactivity and double bond conversion, resulting in stronger networks. Remarkably, even at very low double bond conversions, ≈5%, gel fractions of ≈40% are obtained. The cross-linked networks are also reviewed in the framework of the rubber elasticity and thermodynamic swelling theories to estimate important nanostructural properties. Preliminary cell tests revealed that highly viable (>90%) cell-laden constructs are obtained.
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