notch gut

Chinese liquor distillers' grain (CLDG) is a valuable and abundant by-product from traditional Chinese baijiu production, containing a diverse array of bioactive components that have attracted significant interest. Herein, a water-soluble polysaccharide, DGPS-2B, with a weight-average molecular weight of 37.3 kDa, was isolated from the alkali-extract fraction of CLDG. Methylation and NMR analysis identified that the primary constituents of DGPS-2B are arabinoxylans, with an arabinose-to-xylose ratio of 0...

Inside the finger-like intestinal projections called villi, strands of smooth muscle cells contract to propel absorbed dietary fats through the adjacent lymphatic capillary, the lacteal, sending fats into the systemic blood circulation for energy production. Despite this vital function, mechanisms of formation, assembly alongside lacteals, and maintenance of villus smooth muscle are unknown. By combining single-cell RNA sequencing and quantitative lineage tracing of the mouse intestine, we identified a local hierarchy of subepithelial fibroblast progenitors that differentiate into mature smooth muscle fibers via intermediate contractile myofibroblasts...

Interleukin-(IL) 22 production by intestinal group 3 innate lymphoid cells (ILC3) is critical to maintain gut homeostasis. However, IL-22 needs to be tightly controlled; reduced IL-22 expression is associated with intestinal epithelial barrier defect while its overexpression promotes tumor development. Here, using a single cell RNAseq approach, we identified a core set of genes associated with increased IL-22 production by ILC3. Among these genes, Programmed cell death 1 (PD-1), extensively studied in the context of cancer and chronic infection, was constitutively expressed on a subset of ILC3...

To maintain the integrity of the adult gut, the proliferation and differentiation of stem cells must be strictly controlled. Several signaling pathways control the proliferation and differentiation of Drosophila intestinal epithelial cells. Although the modulatory effects of insulin pathway components on cell proliferation have been characterized, their specific role in which cell type and how these components interact with other regulatory signaling pathways remain largely unclear. In this study, we found that InR/Pi3K has major functions in enteroblasts (EBs) that were not previously described...

Gut hormones are produced by enteroendocrine cells (EECs) found along the intestinal epithelium, and these cells play a crucial role in regulating intestinal function, nutrient absorption and food intake. A hydrolyzed casein diet has been reported to promote the secretion of gut hormones through the regulation of EEC development, but the underlying mechanism remains unclear. Therefore, this study was conducted to investigate whether the hydrolyzed casein diet can regulate EEC differentiation by employing mouse and organoid models...

Escherichia coli LF82 (LF82) is associated with Crohn's disease. The simplicity and genetic maneuverability of honeybees' gut microbiota make them suitable for studying host-microbe interactions. To understand the interaction between LF82 and host gut, LF82 was used to infect germ-free honeybees (Apis mellifera) orally. We found that LF82 successfully colonized the gut and shortened the lifespan of germ-free bees. LF82 altered the gut structure and significantly increased gut permeability. RT-qPCR showed that LF82 infection activated anti-infective immune pathways and upregulated the mRNAs levels of antimicrobial peptides in the gut of germ-free bees...

Stem cells are a keystone of intestinal homeostasis, but their function could be shifted during energy imbalance or by crosstalk with microbial metabolites in the stem cell niche. This study reports the effect of obesity and microbiota-derived short-chain fatty acids (SCFAs) on intestinal stem cell (ISC) fate in human crypt-derived intestinal organoids (enteroids). ISC fate decision was impaired in obesity, resulting in smaller enteroids with less outward protruding crypts. Our key finding is that SCFAs switch ISC commitment to the absorptive enterocytes, resulting in reduced intestinal permeability in obese enteroids...

The alleviating effects of Lactobacillus plantarum in microencapsulation (LPM) on lipopolysaccharide (LPS)-induced intestinal inflammatory injury were investigated in layer chicks. A total of 252 healthy Hy-Line Brown layer chicks were randomly divided into six groups. Birds were injected with saline or LPS except for the control, and the diets of birds subjected to LPS were supplemented with nothing, L. plantarum , LPM, and wall material of LPM, respectively. The viable counts of LPM reached 109  CFU/g, and the supplemental levels of L...

OBJECTIVE: Metastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered. DESIGN: We performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). We also conducted immunofluorescence staining and functional experiments to examine the mechanism...

The intestinal epithelium is the first line of host defense, and its homeostasis is dependent on soluble factors that comprise the crypt niche. Antimicrobial proteins are one of the mediators to maintain gut homeostasis. Angiogenin-4 (Ang4) is a member of the ribonuclease A superfamily and plays a pivotal role in antimicrobial activity against gut microbiota. However, the functions of Ang4 within the intestinal crypt niche, particularly its involvement in the development of intestinal epithelial cells (IECs), remain unknown...

Gap junctions mediate intercellular communications across cellular networks in the nervous and immune systems. Yet their roles in intestinal innate immunity are poorly understood. Here, we show that the gap junction/innexin subunit inx-14 acts in the C. elegans gonad to attenuate intestinal defenses to Pseudomonas aeruginosa PA14 infection through the PMK-1/p38 pathway. RNA-Seq analyses revealed that germline-specific inx-14 RNAi downregulated Notch/GLP-1 signaling, while lysosome and PMK-1/p38 pathways were upregulated...

Traditional drug-based treatments for inflammatory bowel disease (IBD) have significant limitations due to their potential off-target systemic side-effects. Currently, there is a lack of understanding on how to effectively address excessive oxidative stress, dysregulated immune homeostasis, and microbiota dysbiosis within the IBD microenvironment. Herein, we introduce a nanotherapeutic approach, named LBL-CO@MPDA, for IBD treatment. LBL-CO@MPDA is an orally administered formulation that supplies carbon monoxide (CO) for therapeutic purposes...

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid‑β (Aβ) in the brain. The gut/brain axis may serve a role in AD pathogenesis. The present study investigated deposition of Aβ in the intestinal epithelium and its potential effects on intestinal barrier function in a transgenic mouse model of AD. To investigate alterations in the structure and functionality of the intestinal mucosal barrier in AD model mice, hematoxylin and eosin staining for Paneth cell count, Alcian blue‑periodic acid Schiff staining for goblet cells, immunohistochemistry and immunofluorescence for mucin (MUC)2 and wheat germ agglutin expression, transmission electron microscopy for mucosal ultrastructure, FITC‑labeled dextran assay for intestinal permeability, quantitative PCR for goblet cell precursor expression and western blot analysis for tight junction proteins, MUC2 and inflammatory cytokine detection were performed...

DNA methylation functions as a repressive epigenetic mark that can be reversed by the Ten-eleven translocation (TET) family of DNA dioxygenases that sequentially oxidize 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be excised by DNA base-excision repair factors leading to unmodified cytosines. TET enzymes were recently implicated as potential risk factors for inflammatory bowel disease (IBD), but the contribution of TET-mediated DNA oxidation to intestinal homeostasis and response to environmental stressors are unknown...

Gastrointestinal epithelial cells respond to milk-born molecules throughout breastfeeding, influencing growth, and development. The rapid renewal of the small intestine depends on the proliferation in the crypt that drives cell fates. We used early weaning model to investigate immediate and late effects of breastfeeding on proliferation, differentiation of jejunal epithelial cells. Wistar rats were either allowed to suckle (S) until 21 postnatal days or submitted to early weaning (EW) at 15 days. By comparing ages (18, 60, and 120 days), we found that EW decreased Ki67 indices and villi height at 18 and 60 days (p < 0...

Cancer is a multi-step process that can be viewed as a cellular and immunological shift away from homeostasis in response to selected infectious agents, mutations, diet, and environmental carcinogens. Homeostasis, which contributes importantly to the definition of "health," is maintained, in part by the production of short-chain fatty acids (SCFAs), which are metabolites of specific gut bacteria. Alteration in the composition of gut bacteria, or dysbiosis, is often a major risk factor for some two dozen tumor types...

Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch's effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT. Short-term DLL4 blockade improved posttransplant survival with durable protection from gastrointestinal GVHD in particular...

Ultraviolet (UV) is a common and abundant environmental factor that affects daily life. Although the effects of UV radiation on the skin have been extensively reported, studies on the influence of UV radiation on internal organs are still limited. This study aimed to evaluate the influence of UVB exposure on the kidney of mice and to investigate the possible mechanism. In the present study, histopathology changes, oxidative stress, and inflammatory response were used to evaluate the kidney and colon injury induced by UVB exposure...

Type 2 diabetes (T2DM) clinically exhibits a higher incidence of hepatocellular carcinoma (HCC), contributing to a lousy prognosis in patients harboring both diseases. Microflora-based therapy draws attention with low side effects. Accumulating evidence shows that Lactobacillus brevis can improve blood glucose and body weight of the T2DM mice model and reduce several cancer incidences. However, the therapeutic effect of Lactobacillus brevis in affecting the prognosis of T2DM+HCC remains unknown. In this study, we aim to explore this question via an established T2DM+HCC mice model...

MiRNAs, as a kind of key regulators in gene expression, play vital roles in numerous life activities from cellular proliferation and differentiation to development and immunity. However, little is known about the regulatory manner of miRNAs in the development of Asian honey bee ( Apis cerana ) guts. Here, on basis of our previously gained high-quality transcriptome data, transcriptome-wide identification of miRNAs in the larval guts of Apis cerana cerana was conducted, followed by investigation of the miRNAs' differential expression profile during the gut development...