Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1292352 | ENA |
REPOSITORIES: ENA
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Project description:Single-Atom Catalysts Ameliorate Sepsis-Induced Intestinal Barrier Damage
| PRJNA1292362 | ENA
Project description:Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here we construct a single-atom manganese (Mn)-N/C nanozyme. Mn-N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton-like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti-tumor immunity. Moreover, RNA sequencing reveals that Mn-N/C treatment activates type I interferon (IFN) signaling which is critical for Mn-N/C-mediated anti-tumor immune response. Mechanistically, Mn-N/C-triggered releasing of cytosolic DNA from ICD tumor cells activates cGAS-STING pathway, consequently stimulating type I IFN induction. We propose a new promising single-atom nanozyme with extraordinary catalytic activity, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with anti-PD-L1 blockade.
2024-04-24 | GSE249852 | GEO
Project description:<p>The intestinal microflora and metabolites produced by these microbes serve as important regulators of the development of sepsis. Accordingly, this study was designed to systematically explore the relationships between the regulation of septicemia and both the intestinal flora and fecal metabolites by examining the functional roles of metabolites in the protection against sepsis-associated intestinal damage. To that end, fecal and peripheral blood mononuclear cell (PBMC) samples were collected from sepsis patients and healthy controls. A series of longitudinal multi-omics analyses were then used to assess the links between the intestinal flora or associated metabolites and PBMCs in sepsis patients, while animal model studies were further used to probe the protective effects of intestinal flora-derived metabolites on intestinal damage and immunity in the context of sepsis. These analyses revealed that intestinal dysbiosis was a common finding in sepsis patients, which commonly exhibited higher levels of deleterious bacteria and/or reductions in beneficial bacteria. A machine learning approach was used to identify samples from sepsis patients, revealing that at the genus level, sepsis samples could be distinguished by the presence of Bifidobacterium, Bacteroides, Porphyromonas, Prevotell, Enterococcus, Anaerococcus and Veillonella species. Metabolomics analyses indicated that there were significant differences in the levels of intestinal flora-derived metabolites including L-serine, L-valine and L-tyrosine when comparing samples from the sepsis and control groups, while corresponding transcriptomic analyses of PBMC samples using an ImmunecellAI analytical approach revealed a significant sepsis-related increase in the abundance of T cells and Th17 cells. Single-cell sequencing data from sepsis-associated PBMCs was also downloaded from the GEO database, confirming the observation that Th17 cell levels and those of other immune cells rose significantly in the context of septicemia. Animal model experiments revealed that intestinal microbiota-derived L-valine was able to alleviate inflammation and protest against sepsis-induced intestinal damage by inhibiting Th17 cell activation. Overall, these results thus highlight the successful application of machine learning to distinguish between sepsis and control samples based on the composition of the intestinal flora while demonstrating the potential therapeutic benefits of L-valine as an inhibitor of Th17 cell activity that may offer value as a means of alleviating or preventing intestinal damage in treated individuals. </p>
2023-07-28 | MTBLS7866 | MetaboLights
Project description:Paneth cells, critical sentinels of the innate immune system within the intestinal epithelium, play a vital role in maintaining intestinal homeostasis and defending against pathogens. Their dysfunction is implicated in the pathogenesis of sepsis. However, the specific mechanisms by which Paneth cells communicate with and regulate the surrounding intestinal microenvironment, particularly via extracellular vesicles (EVs), remain poorly understood. This study aims to characterize the global miRNA expression profile of intestinal epithelial cell-derived EVs (IEC-EVs) in a mouse model of acute Paneth cell loss, to identify key intercellular signaling molecules that may mediate intestinal barrier response to injury. We employed a well-established model of Paneth cell ablation by a single intraperitoneal injection of dithizone in C57BL/6 mice. Control mice received a vehicle solution. Intestinal epithelial cells were isolated six hours post-injection, and IEC-EVs were subsequently purified from these cells. Small RNA from the purified IEC-EVs was extracted and subjected to next-generation sequencing to comprehensively profile the miRNA cargo. Our comparative analysis reveals a distinct set of miRNAs that are differentially expressed in IEC-EVs following Paneth cell ablation. These candidate miRNAs are predicted to target signaling pathways crucial for epithelial cell proliferation, apoptosis, and inflammatory responses. We hypothesize that the alteration of the miRNA landscape in IEC-EVs represents a novel mechanism of intercellular communication that orchestrates the intestinal epithelial response to damage. This dataset provides the comprehensive resource of miRNA expression in IEC-EVs under conditions of Paneth cell deficiency. The findings are expected to elucidate novel pathways in intestinal pathophysiology and may identify potential miRNA biomarkers or therapeutic targets for conditions involving intestinal barrier dysfunction, such as sepsis.
2025-12-01 | GSE311914 | GEO
Project description:Sepsis, a critical organ dysfunction resulting from an aberrant host response to infection, remains a leading cause of mortality in ICU patients. Recent evidence suggests that angiotensin converting enzyme 2 (ACE2) contributes to intestinal barrier function, the mechanism of which is yet to be explored. The findings of this study indicate that ACE2 shedding significantly weakens the integrity of the intestinal barrier in septic conditions. Mice lacking ACE2 exhibited increased intestinal permeability and higher mortality rates post-sepsis compared to their wild-type counterparts. Notably, ACE2 deficiency was associated with distinct alterations in gut microbiota composition and reductions in protective metabolites, such as 5-methoxytryptophan (5-MTP). 5-MTP was barely detected in ABX mice, while its level was reversed by FMT of WT mice. Supplementing septic mice with 5-MTP ameliorated gut leak through enhanced epithelial cell proliferation and repairment. The relationship between intestinal barrier integrity and the expression of ACE2 in septic mice was explored in both ACE2 knockout and overexpressing mice. Intestinal barrier function was assessed through measurements of intestinal tight junction proteins and permeability tests. The resulting bacteria translocation and multi-organ dysfunction were also evaluated.
2025-06-04 | GSE267002 | GEO
Project description:Emerging evidence suggests that priming intestinal stem cell (ISC) lineages towards secretory progenitor cells is beneficial for maintaining gut homeostasis against inflammatory bowel disease (IBD). However, the mechanism driving such biased lineage commitment remains elusive. Here we show that MG53, also named as TRIM72, plays and important role in maintaining intestinal epithelium integrity against various insults-induced IBD. Specifically, MG53 deficiency leads to exacerbated IBD manifestations caused by various injuries in mice, whereas MG53 overexpression in ISCs is sufficient to ameliorate intestinal damage.
2024-05-21 | GSE267687 | GEO
Project description:Emerging evidence suggests that priming intestinal stem cell (ISC) lineages towards secretory progenitor cells is beneficial for maintaining gut homeostasis against inflammatory bowel disease (IBD). However, the mechanism driving such biased lineage commitment remains elusive. Here we show that MG53, also named as TRIM72, plays and important role in maintaining intestinal epithelium integrity against various insults-induced IBD. Specifically, MG53 deficiency leads to exacerbated IBD manifestations caused by various injuries in mice, whereas MG53 overexpression in ISCs is sufficient to ameliorate intestinal damage.
2025-06-18 | GSE295764 | GEO