Royal Jelly Acid in Ulcerative Colitis Treatment: Modulating miR-210-3P/Gbp3 Pathway and Pyroptosis via miRNA Expression and NLRP3 Inflammasome
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE256425 | GEO | 2026/02/01
REPOSITORIES: GEO
Similar Datasets
Project description:This study investigates the therapeutic effects of RJA (purity 99.42%) on DSS-induced colitis in male C57BL/6J mice. Using high-throughput miRNA sequencing, we analyzed the miRNA expression profiles in mouse colon samples. The study revealed significant changes in miRNA expression in response to DSS and RJA treatments, identifying potential molecular mechanisms behind RJA's protective effects against DSS-induced colitis.
2026-02-01 | GSE259315 | GEO
Project description:Royal Jelly Acid in Ulcerative Colitis Treatment: Modulating miR-210-3P/Gbp3 Pathway and Pyroptosis via miRNA Expression and NLRP3 Inflammasome
| PRJNA1079391 | ENA
Project description:Royal Jelly Acid in Ulcerative Colitis Treatment: Modulating miR-210-3P/Gbp3 Pathway and Pyroptosis via miRNA Expression and NLRP3 Inflammasome (miRNA-Seq)
| PRJNA1081051 | ENA
Project description:Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which has been shown to increase the incidence of colorectal cancer. Recent studies have highlighted the role of ubiquitination, a post-translational modification, in the occurrence and development of colonic inflammation. Ovarian tumor deubiquitinase 6A (OTUD6A) is a deubiquitinating enzyme, which regulates cell proliferation and tumorigenesis. In this study, we investigated the expression and role of OTUD6A in IBD. Wide-type or Otud6a-/- mice were used to develop dextran sodium sulfate (DSS)- or 2,6,4-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, as well as azoxymethane (AOM)/DSS-induced colitis-associated cancer model. Bone marrow-derived macrophages (BMDMs) were isolated from wild-type and Otud6a-/- mice to dissect molecular mechanisms. Our data show that OTUD6A deficiency attenuated DSS or TNBS-induced colitis, as well as AOM/DSS-induced colitis-related colon cancer in vivo. Bone marrow transplantation experiments further revealed that OTUD6A in myeloid cells was responsible for exacerbation of DSS-induced colitis. Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation. Taken together, our research identifies a new function of OTUD6A in the pathogenesis of colitis by promoting NLRP3 inflammasome activation, suggesting that OTUD6A could be a potential target for the treatment of IBD.
2023-04-01 | GSE224239 | GEO
Project description:Dextran sulfate sodium (DSS)-induced colitis is a widely used model to study ulcerative colitis (UC). However, the extent to which acute versus repeated DSS exposure mimics human disease remains unclear. Using histopathology, flow cytometry, single-cell RNA sequencing (scRNA-seq) and 16S rRNA profiling we compared disease outcomes, immune infiltrate, transcriptional programs and changes in the microbiome in mice subjected to a single (acute) versus two (repeated) DSS cycles. We found that repeated cycles of DSS-induced colitis in mice result in more severe intestinal inflammation compared to a single exposure, with increased PMN and T cell infiltration, mucosal remodeling, and microbiota normalization. Single-cell transcriptomics revealed that acute vs repeated DSS exposure drives differential programs in immune cell subtypes distinctly overlapping with human UC. Overall, our findings suggest that repeated DSS exposure may more accurately models human disease, highlighting its utility for translational IBD research.
2025-10-31 | GSE306845 | GEO
Project description:Huntington's disease (HD) is a neurodegenerative disease characterized by several symptoms encompassing movement, cognition, and behavior. The mutation of the IT15 gene encoding for the huntingtin protein is the cause of HD. Mutant huntingtin interacts with and impairs the function of several transcription factors involved in neuronal survival. Although many mechanisms determining neuronal death have been described over the years, the significant role of inflammation has gained momentum in the last decade. Drugs targeting the elements that orchestrate inflammation have been considered powerful tools to treat HD. In this review, we will describe the data supporting inflammasome and NLRP3 as a target of therapeutics to fight HD, deepening the possible mechanisms of action underlying these effects.
| S-EPMC9368941 | biostudies-literature
Project description:Ulcerative colitis (UC), a form of inflammatory bowel disease, is characterized by a Q7 recurrent and persistent nonspecific inflammatory response. Polydatin (PD), a natural stilbenoid polyphenol with potent properties, exhibits unexpected beneficial effects beyond its well-documented anti-inflammatory and antioxidant activities. In this study, we presented evidence that PD confers protection against dextran sodium sulfate (DSS)-induced ulcerative colitis. Our findings demonstrated that PD mitigated the DSS-induced increases in proinflammatory cytokines (IL-6, TNF-α, and IL-1β), alleviated colon length shortening, reduced morphological damage to the intestinal mucosa, and preserved tight junction proteins (TJ) occludin and Zonula occludens-1 (ZO-1) in both Caco-2 cells and murine models of colitis. Results from bulk RNA sequencing and differential gene analysis suggested a potential role for ferroptosis in the protective mechanisms of PD against UC. Further investigations revealed that PD modulated the expression levels of several ferroptosis-related proteins and transcription factors within the DSS-induced colitis model. Notably, treatment with PD enhanced nuclear translocation of Nrf2, which inhibits ferroptosis while ameliorating oxidative stress through upregulation of Slc7a11 and Gpx4 expression. Additionally, erastin—a known inducer of ferroptosis—reversed the protective effects conferred by PD in the DSS-induced colitis model by downregulating Slc7a11 expression. These findings underscore that PD protects against DSS-induced ulcerative colitis via the Nrf2/ Slc7a11/Gpx4 signaling axis, highlighting its potential as a novel therapeutic agent for UC.
2025-01-07 | GSE285956 | GEO
Project description:The innate immune system recognizes nucleic acids as a signature of microbial infection and initiates host-protective responses, including the production of type I IFN and proinflammatory cytokines. Z-DNA binding protein 1 (ZBP1, also known as DLM-1 or DAI) was previously identified as a dsDNA binding protein, triggering DNA-mediated activation of innate immune responses. However, mice or cells lacking ZBP1 produce normal levels of type I IFN in response to dsDNA. Therefore, the classification of ZBP1 as a true DNA sensor remains to be resolved. Here, we report that the single stranded RNA virus, influenza A virus (IAV) is a trigger of the cytosolic sensor ZBP1. Sensing of IAV infection by ZBP1 engages a novel NLRP3 inflammasome pathway that is not defined by the conventions of the canonical and non-canonical NLRP3 inflammasome pathways. Surprisingly, IAV-induced cell death was not prevented by the absence of the NLRP3 inflammasome. Instead, we identified parallel contributions from pyroptosis, necroptosis and apoptosis in the execution of ZBP1-dependent cell death, mediated by the kinase RIPK3. Overall, the ability of ZBP1 to sense IAV infection signifies a point of divergence for IAV-induced programmed cell death pathways and inflammasome activation. We used microarrays to explore the gene expression profiles differentially expressed in influenza-infected bone marrow derived macrophages (BMDM) isolated from Ifnar1-/- and wild-type mice.
2016-08-11 | E-GEOD-77611 | biostudies-arrayexpress
Project description:Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin phytohormone present in many herbal medicines and fruits, exibits anti-inflammatory activity. In this study we characterized the therapeutic potential of BeG against bacterial infection and inflammation-related disorders, and elucidated the underlying mechanisms. We showed that pre-treatment with BeG (20 μM) effectively inhibited NLRP3 inflammasome activation in both lipopolysaccharides (LPS)-primed J774A.1 cells and bone marrow-derived macrophages (BMDMs), evidenced by attenuated cleaved caspase-1 and mature IL-1β release, as well as reduced ASC speck formation and subsequent gasdermin D (GSDMD)-mediated pyroptosis. Transcriptome analysis revealed that BeG regulated the expression of genes involved in mitochondrial and reactive oxygen species (ROS) metabolism in BMDMs. Moreover, BeG treatment reversed the diminished mitochondrial activity and ROS production after NLRP3 activation, and elevated the expression of LC3-II and enhanced the co-localization of LC3 with mitochondria. Treatment with 3-methyladenine (3-MA, 5 mM) reversed the inhibitory effects of BeG on IL-1β, cleaved caspase-1 and LDH release, GSDMD-N formation as well as ROS production. In mouse model of Escherichia coli-induced sepsis and mouse model of Citrobacter rodentium-induced intestinal inflammation, pre-treatment with BeG (50 mg/kg) significantly ameliorated tissue inflammation and injury. In conclusion, BeG inhibits NLRP3 inflammasome activation and pyroptosis by promoting mitophagy and maintaining mitochondrial homeostasis. These results suggest BeG as a promising drug candidate for the treatment of bacterial infection and inflammation-related disorders.
| S-EPMC10462717 | biostudies-literature
Project description:BackgroundNeuroinflammation is widely recognized as a key factor in the pathogenesis of Alzheimer's disease (AD), alongside ß-amyloid deposition and the formation of neurofibrillary tangles. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, part of the innate immune system, has been implicated in the neuropathology of both preclinical amyloid and tau transgenic models. Activation of the NLRP3 pathway involves an initial priming step, which increases the expression of Nlrp3 and interleukin (IL)-1β, followed by the assembly of the NLRP3 inflammasome complex, comprising NLRP3, ASC, and caspase-1. This assembly leads to the proteolytic maturation of the pro-inflammatory cytokines IL-1β and IL-18. Additionally, the NLRP3 inflammasome induces Gasdermin D (GSDMD) cleavage, forming membrane pores through which IL-1β and IL-18 are secreted. Inhibition of NLRP3 has been shown to enhance plaque clearance by modulating microglial activation. Furthermore, blocking NLRP3 in tau transgenic mice has been found to reduce tau phosphorylation by affecting the activity of certain tau kinases and phosphatases.MethodsIn this study, organotypic brain slice cultures from P301S transgenic mice were treated with lipopolysaccharide (LPS) plus nigericin as a positive control or exposed to tau seeds (K18) to evaluate NLRP3 inflammasome activation. The effect of tau seeding on NLRP3 activity was further examined using Meso Scale Discovery (MSD) assays to measure IL1β secretion levels in the presence and absence of NLRP3 inhibitors. The role of NLRP3 activity was investigated in full-body Nlrp3 knockout mice crossbred with the tau transgenic P301S model. Additionally, full-body and microglia-selective Gsdmd knockout mice were crossbred with P301S mice, and tau pathology and neurodegeneration were evaluated at early and late stages of the disease using immunohistochemistry and biochemical assays.ResultsActivation of the NLRP3 pathway was observed in the mouse organotypic slice culture (OSC) model following stimulation with LPS and nigericin or exposure to tau seeds. However, Nlrp3 deficiency did not mitigate tauopathy or neurodegeneration in P301S mice in vivo, showing only a minor effect on plasma neurofilament (NF-L) levels. Consistently, Gsdmd deficiency did not alter tau pathology in P301S mice. Furthermore, neither full-body nor microglia-selective Gsdmd deletion had an impact on neuronal pathology or the release of pro-inflammatory cytokines.ConclusionThe absence of key components of the NLRP3 inflammasome pathway did not yield a beneficial effect on tau pathology or neurodegeneration in the preclinical Tau-P301S mouse model of AD. Nonetheless, organotypic slice cultures could serve as a valuable ex vivo mechanistic model for evaluating NLRP3 pathway activation and pharmacological inhibitors.
| S-EPMC11458539 | biostudies-literature