Post‐translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O‐GlcNAcylation and the expression of O‐GlcNAc transferase (OGT), the enzyme adding the O‐GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical‐induced colitis. Paneth cell‐specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical‐induced colitis. On the other hand, the augmentation of O‐GlcNAc signaling by inhibiting O‐GlcNAcase, the enzyme removing O‐GlcNAcylation, alleviated chemical‐induced colitis. Our data reveal that protein O‐GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.
Hematopoiesis is dynamically regulated by metabolic cues in homeostatic and stressed conditions; however, the cellular and molecular mechanisms mediating the metabolic sensing and regulation remain largely obscure. Bone marrow adipose tissue remodels in various metabolic conditions and has been recently proposed as a niche for hematopoietic stem cells after irradiation. Here, we investigated the role of marrow adipose tissue-derived hematopoietic cytokine stem cell factor in unperturbed hematopoiesis by selectively ablating the
Kitl
gene from adipocytes and bone marrow stroma cells using
Adipoq-Cre
and
Osx1-Cre
, respectively. We found that both
Adipoq-Kitl
knockout (KO) and
Osx1-Kitl
KO mice diminished hematopoietic stem and progenitor cells and myeloid progenitors in the bone marrow and developed macrocytic anemia at the steady-state. The composition and differentiation of hematopoietic progenitor cells in the bone marrow dynamically responded to metabolic challenges including high fat diet, β3-adrenergic activation, thermoneutrality, and aging. However, such responses, particularly within the myeloid compartment, were largely impaired in
Adipoq-Kitl
KO mice. Our data demonstrate that marrow adipose tissue provides stem cell factor essentially for hematopoiesis both at the steady state and upon metabolic stresses.
S. K. (2019). Catestatin regulates vesicular quanta through modulation of cholinergic and peptidergic (PACAPergic) stimulation in PC12 cells. Cell and Tissue Research, 376(1), 51-70.
The Zingiber officinale (ginger) and Tinospora cordifolia (giloy) are rich sources of antioxidant compounds and have been used for several decades to improve human health with relatively low side effects. The present research attempted to carry out the sensory and antioxidant activity evaluation of dried mixed paste powder of Z. officinale and T. cordifolia by establishing fuzzy logic, the newly proposed General Mathematical Formula (GMF) and the radical scavenging assay. Antioxidant activity was higher in the powder obtained in combinatorial process than the powders obtained in the separate processing of ginger or giloy. The sample containing powder, sugar and salt at 5, 5 and 1 % were more acceptable (good) and attributes generally fell under ‘important’ by both methods. Fuzzy logic and GMF results were matched perfectly for the category of samples, and quality attributes in general, and GMF method is simple and accurate for sensory evaluation.
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