Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1292352 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:<h4><strong>INTRODUCTION:</strong> Sepsis is intricately linked to intestinal damage and barrier dysfunction. At present times, there is a growing interest in a metabolite-based therapy for multiple diseases.</h4><p><strong>METHODS:</strong> Serum samples from septic patients and healthy individuals were collected and their metabonomics profiling assessed using Ultra-Performance Liquid Chromatography-Time of Flight Mass Spectrometry (UPLC-TOFMS). The eXtreme Gradient Boosting algorithms (XGBOOST) method was used to screen essential metabolites associated with sepsis, and five machine learning models, including Logistic Regression, XGBoost, GaussianNB(GNB), upport vector machines(SVM) and RandomForest were constructed to distinguish sepsis including a training set (75%) and validation set(25%). The area under the receiver-operating characteristic curve (AUROC) and Brier scores were used to compare the prediction performances of different models. Pearson analysis was used to analysis the relationship between the metabolites and the severity of sepsis. Both cellular and animal models were used to HYPERLINK 'javascript:;' assess the function of the metabolites.</p><p><strong>RESULTS:</strong> The occurrence of sepsis involve metabolite dysregulation. The metabolites mannose-6-phosphate and sphinganine as the optimal sepsis-related variables screened by XGBOOST algorithm. The XGBoost model (AUROC=0.956) has the most stable performance to establish diagnostic model among the five machine learning methods. The SHapley Additive exPlanations (SHAP) package was used to interpret the XGBOOST model. Pearson analysis reinforced the expression of Sphinganine, Mannose 6-phosphate were positively associated with the APACHE-II, PCT, WBC, CRP and IL-6. We also demonstrated that sphinganine strongly diminished the LDH content in LPS-treated Caco-2 cells. In addition, using both <em>in vitro</em> and <em>in vivo</em> examination, we revealed that sphinganine strongly protects against sepsis-induced intestinal barrier injury.</p><p><strong>DISCUSSION:</strong> These findings highlighted the potential diagnostic value of the ML, and also provided new insight into enhanced therapy and/or preventative measures against sepsis.</p>
2023-07-28 | MTBLS7878 | MetaboLights
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.
2025-06-18 | GSE295764 | 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:Effective therapeutic strategies for myocardial ischemia/reperfusion (I/R) injury are still lacking. Targeting reactive oxygen species (ROS), the major cause of I/R injury, provides a practical approach to alleviate myocardial damage after reperfusion procedure. Herein, we synthesized an innovative antioxidant nanozyme equipped with single-platinum-atom (PtsaN-C) for protecting against I/R injury. PtsaN-C exhibited potent multiple enzyme-mimicking activities with high-efficiency ROS-scavenging. Mechanistic studies demonstrated that excellent ROS-elimination performance in single platinum atom center was prior to that of platinum cluster center attributing to good synergistic effect and metallic electronic property with nitrogen-doping coordination structure. Systematic in vitro and in vivo studies confirmed that PtsaN-C counteracted ROS efficiently to restore cellular homeostasis and prevented apoptotic progress after I/R injury. PtsaN-C presented excellent biocompatibility and biosafety, making it promising for future clinical application. Current study broadens the horizon of single-atom nanomedicine against ROS-induced damage, offering a promising therapeutic avenue for treatment of I/R injury.
2024-01-16 | PXD048584 |