Selenium and Selenoproteins in Gut Inflammation—A Review

Inflammatory bowel disease (IBD), characterized by severe flares and remissions, is a debilitating condition. While the etiology is unknown, many immune cells, such as macrophages, T cells and innate lymphoid cells, are implicated in the pathogenesis of the disease. Previous studies have shown the ability of micronutrient selenium (Se) and selenoproteins to impact inflammatory signaling pathways implicated in the pathogenesis of the disease. In particular, two transcription factors, nuclear factor-κB (NF-κB), and peroxisome proliferator activated receptor (PPAR)γ, which are involved in the activation of immune cells, and are also implicated in various stages of inflammation and resolution, respectively, are impacted by Se status. Available therapies for IBD produce detrimental side effects, resulting in the need for alternative therapies. Here, we review the current understanding of the role of NF-κB and PPARγ in the activation of immune cells during IBD, and how Se and selenoproteins modulate effective resolution of inflammation to be considered as a promising alternative to treat IBD

Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair

Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. SELENOW expression in the human GI tract using ScRNAseq Gut Cell Atlas and Gene Expression Omnibus (GEO) databases revealed its expression in the small intestine and colonic epithelial, endothelial, mesenchymal, and stem cells and correlated with a protective effect in ulcerative colitis patients. Selenow KO mice treated with 4% dextran sodium sulfate (DSS) showed exacerbated acute colitis, with greater weight loss, shorter colons, and increased fecal occult blood compared to the WT counterparts. Selenow KO mice expressed higher colonic Tnfα, increased Tnfα+ macrophages in the colonic lamina propria, and exhibited loss in epithelial barrier integrity and decreased zonula occludens 1 (Zo-1) expression following DSS treatment. Expression of epithelial cellular adhesion marker (EpCam), yes-associated protein 1 (Yap1), and epidermal growth factor receptor (Egfr) were decreased along with CD24lo cycling epithelial cells in Selenow KO mice. Colonic lysates and organoids confirmed a crosstalk between Egfr and Yap1 that was regulated by Selenow. Overall, our findings suggest Selenow expression is key for efficient resolution of inflammation in experimental colitis that is mediated through the regulation of Egfr and Yap1

The role of Selenoprotein N in the differentiation of erythroid progenitors during stress erythropoiesis

Posebni programi u turističkoj ponudi zauzimaju posebno mjesto, prije svega jer istovremeno ispunjavaju svoju svrhu kroz dva cilja, a to je primarno povećanje turističke potrošnje, odnosno efikasno i efektivno poboljšanje poslovanja, na kvantitativnoj bazi, te sekundarno zadovoljenje raznih potreba, motiva i zahtjeva turista, kao sudionika, odnosno korisnika posebnog programa, na kvalitativnoj bazi.Posebni programi imaju dugu prošlost, ali kratku povijest. To je splet usluga i proizvoda, koji se na nov i jedinstven način plasiraju kao ekskluzivni dio turističke ponude na turističkom tržištu, sa ciljem zadovoljenja potreba i zahtjeva turista, ali isto tako i multipliciranje dobiti poduzeća.Svrha ovog rada je prikazati utjecaj i ulogu posebnih programa u turističkoj ponudi, te istražiti i definirati ulogu i značaj posebnih gradskih programa, koji se nude na turističkom tržištu, u ovom slučaju u okviru turističke ponude grada Splita.Cilj rada je otkriti stupanj utjecaja posebnih gradskih programa na cjelokupnu ponudu Splita, te prikazati važnost i ulogu komuniciranja menadžera posebnih programa sa tržištem, ali isto tako i uvidjeti stupanj očekivanja, zadovoljstva i percepciju posebnih gradskih programa sa aspekta turista i lokalnog stanovništva, te s treće strane sa aspekta Turističke zajednice grada

Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells

Summary: Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ12-PGJ2, and 15d-PGJ2, which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic analysis of GPR44−/− LICs indicated that GPR44 activation by CyPGs suppressed KRAS-mediated MAPK and PI3K/AKT/mTOR signaling pathways, to enhance apoptosis. Our studies show the role of GPR44, providing mechanistic underpinnings of the chemopreventive and chemotherapeutic properties of selenium and CyPGs in AML

IGF2BP1/IMP1 Deletion Enhances a Facultative Stem Cell State via Regulation of MAP1LC3BSummary

Background & Aims: The intestinal epithelium interfaces with a diverse milieu of luminal contents while maintaining robust digestive and barrier functions. Facultative intestinal stem cells are cells that survive tissue injury and divide to re-establish the epithelium. Prior studies have shown autophagic state as functional marker of facultative intestinal stem cells, but regulatory mechanisms are not known. The current study evaluated a post-transcriptional regulation of autophagy as an important factor for facultative stem cell state and tissue regeneration. Methods: We evaluated stem cell composition, autophagic vesicle content, organoid formation, and in vivo regeneration in mice with intestinal epithelial deletion of the RNA binding protein IGF2 messenger RNA binding protein 1 (IMP1). The contribution of autophagy to resulting in vitro and in vivo phenotypes was evaluated via genetic inactivation of Atg7. Molecular analyses of IMP1 modulation of autophagy at the protein and transcript localization levels were performed using IMP1 mutant studies and single-molecule fluorescent in situ hybridization. Results: Epithelial Imp1 deletion reduced leucine rich repeat containing G protein coupled receptor 5 cell frequency but enhanced both organoid formation efficiency and in vivo regeneration after irradiation. We confirmed prior studies showing increased autophagy with IMP1 deletion. Deletion of Atg7 reversed the enhanced regeneration observed with Imp1 deletion. IMP1 deletion or mutation of IMP1 phosphorylation sites enhanced expression of essential autophagy protein microtubule-associated protein 1 light chain 3β. Furthermore, immunofluorescence imaging coupled with single-molecule fluorescent in situ hybridization showed IMP1 colocalization with MAP1LC3B transcripts at homeostasis. Stress induction led to decreased colocalization. Conclusions: Depletion of IMP1 enhances autophagy, which promotes intestinal regeneration via expansion of facultative intestinal stem cells