Receptor Signaling Pathway Research Articles

In Silico Identification of MicroRNAs Targeting Epidermal Growth Factor Receptor in the Initiation and Progression of Hepatocellular Carcinoma

Objectives Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. The epidermal growth factor receptor (EGFR) signalling pathway plays a vital role in the progression of HCC by influencing cell proliferation, survival, and resistance to apoptosis. This study aimed to identify the microRNAs (miRNAs) that regulate EGFR signalling in HCC using in silico approaches. Material and Methods The differential expression of EGFR and its correlation with patient survival in HCC were first established by analysing relative gene expression and overall survival using the University of Alabama at Birmingham Cancer (UALCAN) data analysis portal. Further, EGFR-associated genes and the regulatory transcription factors (TFs) were identified through STRING and Network Analyst tools, respectively. The protein–protein interaction (PPI) network of EGFR-associated genes was then constructed using Cytoscape. The differentially expressed miRNAs (DE-miRNAs) in HCC were identified by analysing the GSE dataset GSE147889 using the GEO2R tool. The miRWalk database was extensively mined to predict miRNAs targeting EGFR and its associated genes. Finally, a regulatory network was built to map the interactions between the miRNAs, TFs, and EGFR-associated genes. Results The UALCAN analysis revealed that EGFR is downregulated in liver carcinoma, but there is no significant correlation with patient survival. The PPI network analysis identified 21 critical genes and 30 TFs involved in EGFR regulation. Among the 18 differentially expressed miRNAs, hsa-miR-216 b-5p, hsa-miR-214-3p, hsa-miR-325, hsa- miR-199a/b-3p, and hsa-miR-200a-3p were identified as key regulators of EGFR expression. Furthermore, the regulatory network analysis revealed that 15 DE-miRNAs regulate EGFR by targeting 14 EGFR-associated genes and interacting with 23 TFs. Conclusion This in silico study identifies hsa-miR-216b-5p, hsa-miR-214–3p, hsa-miR-325, hsa-miR-199a-3p, hsa-miR-200a-3p, and hsa-miR-199b-3p as hub miRNAs regulating EGFR in HCC. Although further experimental validation is required, these miRNAs may have the potential to develop as diagnostic or prognostic markers, as well as therapeutic targets, in the management of liver carcinomas.

Comparative transcriptomic and genomic analysis of tumor cells in the marginal and center regions of tumor nests in human hepatocellular carcinoma

BackgroundThe tumor nests in solid tumors, including hepatocellular carcinoma (HCC), possess tumor-initiating potential, with the capacity to metastasize and form new metastatic lesions. However, the biological characteristics and heterogeneity of tumor cells at the central and marginal regions of these tumor nests remain poorly understood.MethodBased on pathological tissue sections, data integration and dimensionality reduction, we defined the boundaries and centers of tumor nests and fibrous nodules within 19 spatial transcriptomics (ST) samples from 8 HCC patients. Differential gene expression was analyzed at the single-unit, sample, patient, and pseudobulk levels, followed by Gene Ontology (GO) enrichment analysis. Additionally, spatial copy number variation (CNV) was inferred using inferCNV, and comparisons were made at the single-unit, sample, patient, and pseudobulk levels.ResultsUltimately, 24 tumor nests and 15 liver fibrosis nodules were analyzed. The spatial gene expression patterns of the tumor nests exhibited significant heterogeneity, with gene enrichment analysis revealing upregulation of immune-related pathways (e.g., humoral immune response mediated by circulating immunoglobulin; B cell receptor signaling pathway, etc.) at the tumor nest margins and growth/metabolism-related pathways (e.g., sulfur amino acid metabolic process; proteinogenic amino acid metabolic process, etc.) within the tumor nest center. Similar expression patterns were also observed in liver fibrous nodule samples. CNV and clustering analyses demonstrated transcriptional differences between tumor nests within individual patients, suggesting the evolutionary diversity, or heterogeneity, of tumor nests within the same tumor.ConclusionTumor nests exhibit significant transcriptional differentiation along spatial axes: the central regions show high expression of metabolism-related genes, while the marginal regions are enriched in immune-regulatory genes. This pattern is also observed in liver fibrotic nodules. This center-margin functional division may inform rational design of therapeutics that simultaneously modulate metabolism and immune responses.

Therapeutic potency of a developed optimized polyherbal formulation in ameliorating obesity induced inflammation and oxidative stress in Swiss albino mice by targeting PPARγ, insulin receptor and AMPK signalling pathway.

High fat diet (HFD) induced obesity plays a key role in onset of inflammation, a chronic response of the body to elevated expression of proinflammatory cytokines. Our work emphasized on assessing the therapeutic potency of the polyherbal formulations (PHF), composed of Phyllanthus urinaria and Adhatoda vascia nees by studying the expression pattern of iNOS, pro, anti-inflammatory cytokines, chemokine along with identification of potent anti-inflammatory compounds in HFD induced inflammation in four weeks old (23-25g bw, n = 6 in triplcates) Swiss albino mice. The findings demonstrated high percentage of free radical scavenging property of PHF, downregulation of expression level of proinflammatory cytokines and chemokines, profound elevation of anti-inflammatory cytokines, anti-oxidant enzymes in both PHF treated groups signifying protection against oxidative stress. In silico study revealed binding energy of Okanin, Vomicine, Granisetron and Pisdic acid -9.31kcal/mol, -8.34kcal/mol, -8.10kcal/mol, -7.93kcal/mol respectively with strong protein ligand interaction with inflammatory, lipid marker PPARγ and insulin resistance marker protein receptor INSR. Among other four ligands, Peganine, Coralyne, Soraphen O and 2-hydroxyhexadecanoic acid; Soraphen O and Coralyne showed best binding affinity with INSR (-6.8kcal/mol) and PPARγ (-6.9kcal/mol) respectively. The evaluation based on network pharmacology, the active ingredients of the PHF for AMPK signalling pathway and protein analysis identified 121 targets. A network of interaction between the eight ligands and known therapeutic targets of INSR and AMPK depicted pharmacological mechanisms of the PHF in inhibition of insulin resistance by activating INSR and AMPK-pathway thus establishing itself as potent alternative drug in treating ailments associated with obesity induced inflammation.

Identifying pyroptosis- and inflammation-related genes in spinal cord injury based on bioinformatics analysis.

Spinal cord injury (SCI) is a common traumatic central nervous system disorder characterized by a complex microenvironment after injury, leading to severe neurological dysfunction. Increasing attention has been paid to the role of inflammatory cells in SCI. Pyroptosis, a form of programmed inflammatory cell death, plays a significant role in SCI; however, its underlying mechanisms remain unclear. This study utilized bioinformatics methods to identify pyroptosis-related genes (PRGs) and investigate their roles in inflammatory responses. Additionally, we explored the potential interactions between differentially expressed PRGs (DEPRGs) and miRNAs(microRNAs), lncRNAs(Long non-coding RNAs), and circRNAs(Circular RNAs). RNA expression profiles, including mRNA(Messenger RNA), miRNA, lncRNA, and circRNA, were obtained from the Gene Expression Omnibus (GEO) database. A total of 78 PRGs were identified through a literature search in PubMed. DEPRGs, miRNAs, lncRNAs, and circRNAs were screened using R software. Functional enrichment analyses of DEPRGs were performed, and a protein-protein interaction (PPI) network was constructed. Weighted Gene Co-expression Network Analysis (WGCNA) was conducted, and external validation was performed using an independent dataset to identify hub genes and their correlations with immune cells. Western blotting was used to validate hub gene expression. Finally, a competing endogenous RNA (ceRNA) network was constructed based on differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and circRNAs (DEcircRNAs). Eleven DEPRGs were identified in SCI, including ten upregulated and one downregulated gene. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEPRGs were mainly enriched in processes such as the regulation of interleukin-1 beta production, NLRP3 inflammasome complex, and NOD-like receptor signaling pathway. Two hub genes, IL18 and GSDMD, were identified using Cytoscape and WGCNA. External dataset validation revealed significant differences in hub gene expression between SCI and control groups (P < 0.05), with AUC(Area Under Curve) values > 0.75. Immune infiltration analysis indicated significant positive correlations between hub genes and M1 macrophages, CD8 + T cells, and resting dendritic cells. Four downregulated DEmiRNAs were identified as potential regulators of hub genes. Additionally, 29 DEmiRNAs, 55 upregulated DElncRNAs, and 2 upregulated DEcircRNAs were identified and used to construct the ceRNA network. Bioinformatics analyses revealed a strong association between pyroptosis and SCI, identifying two potential hub genes, IL18 and GSDMD, linked to pyroptosis and immune cell infiltration. These findings provide insights into the potential mechanisms of pyroptosis in SCI and offer a basis for further studies.

Improved mRNA-based RSV vaccine with PreF forming enveloped virus-like particles

Respiratory syncytial virus (RSV) causes severe respiratory disease in infants and the elderly. However, natural infection fails to induce durable immune protection, and existing mRNA vaccines for older adults exhibit limited long-term efficacy. We developed an antigen engineering strategy inserting ESCRT/ALIX-binding region (EABR) into truncated RSV prefusion F (PreF) cytoplasmic tails to form enveloped virus-like particles (eVLPs). In murine models, PreF-EABR mRNA vaccines elicited higher, more persistent neutralizing antibodies than conventional PreF mRNA, correlating with enhanced germinal center B cell and memory B cell responses. A lower dose of PreF-EABR mRNA (1 μg) suppressed viral load and pathology comparable to higher-dose PreF mRNA (2.5 μg). Transcriptomic analysis showed PreF-EABR mRNA activated toll-like receptor and chemokine signaling pathways, enhancing antibody longevity via platelet-associated signatures. This study explores the development and possible mechanism of long-lasting RSV mRNA vaccines by eVLPs technology, which also suggest its potential application in other vaccines.

Expression and Function of Vasopressin Receptors in the HT-29 Cell Line.

Vasopressin receptors can have different effects on tumorigenesis. The in vitro usage of agonists and antagonists of these receptors can also have a potential impact on developing adjuvant treatment options. Therefore, we aimed to demonstrate the expression and function of vasopressin receptors in the HT- 29 cell line, which is one of the cell lines frequently used in colorectal cancer studies. Colorectal cancer is one of the most prevalent cancer types worldwide. There are many risk factors for colorectal cancer, including unhealthy lifestyle and social environment, and early diagnosis can enhance the survival of patients. Main treatment strategies aim to slow down the progression of cancer, increase survival, and enhance the quality of life. Investigating the relationship between colorectal cancer and vasopressin receptors has been an interesting research area in terms of developing new treatment strategies lately. For receptor expression and functional analysis, RT-PCR experiments and cAMP accumulation assay were performed. The expression of V2R and V1aR was observed in HT-29 cells, and V2Rs demonstrated their function as cAMP responders after treatment with agonists and antagonists. This is the first study to report that V2R and V1aR expressions were detected by RT-PCR, and the functionality of V2R was analyzed by cAMP accumulation assay after treating HT-29 cells with agonists and antagonists. We hope that these results may contribute to colorectal cancer research and the development of novel therapeutic strategies targeting vasopressin receptor signaling pathways.

Investigating the molecular mechanisms of the “Astragalus-Codonopsis” herb pair in treating diabetes: a network pharmacology and bioinformatics approach with molecular docking validation

Astragalus membranaceus and Codonopsis pilosula are widely used in traditional chinese medicine for the treatment of diabetes because of their notable hypoglycemic pharmacological effects. Studies have indicatedthat the active compounds in the Astragalus-Codonopsis herb pair may exert their hypoglycemic effects through the modulation of the insulin receptor (IRSP) signaling pathway. In this study, the rhamnolitrin and folic acid were confirmed as the key active components in the Astragalus-Codonopsis herb pair that regulate the IRSP, with their synergistic mechanisms in Type 2 Diabetes Mellitus (T2DM) being further systematically explored by network pharmacology combined with DFT theoretical calculation, molecular docking, molecular dynamics simulation and alanine scanning mutation technology. The results suggest that GSK3β is a critical target through which rhamnolitrin and folic acid exert their anti-diabetic effects. Subsequent molecular docking and molecular dynamics simulations confirmed that both active compounds selected in this study can bind stably with the GSK3β protein. Further alanine scanning mutagenesis experiments validated the importance of key amino acid residues in ligand-receptor interactions. Finally, DFT theoretical calculations provided a detailed elucidation of the binding mechanism between the core components (rhamnolitrin and folic acid) and the target protein GSK3β. This study not only revealed the molecular mechanism of Astragalus-Codonopsis for the treatment of type 2 diabetes, provided a theoretical basis for its clinical application, but also provided a potential molecular target for the development of new anti-diabetes drugs.

LYN and CYBB are pivotal immune and inflammatory genes as diagnostic biomarkers in recurrent spontaneous abortion

Recurrent spontaneous abortion (RSA) seriously affects women’s reproductive health, and its pathogenesis is complex and varied. The aim of this study is to identify key molecular markers closely associated with RSA to rapidly and effectively predict the RSA, and to provide simple and practical indicators for clinical diagnosis and treatment.MethodWe obtained mRNA expression profiles from the GSE26787 and GSE165004 datasets of the Gene Expression Omnibus (GEO) database, immune-related genes (IRGs) from the ImmPort database (https://www.immport.org), and genes related to inflammatory response from the Molecular Signatures database. Different Inflammation- and immunity-related genes (DIIRGs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein-protein interaction (PPI) networks were utilized to explore the connections between various DIIRGs. The candidate DIIRGs were analyzed by the least absolute shrinkage and selection operator (LASSO) and the multiple support vector machine recursive feature elimination (mSVM-RFE). The diagnostic ability of the candidate genes was verified using receiver operating characteristic (ROC) curves. The performance of the predictive model was evaluated using a Nomo plot. We further confirmed the expression levels and diagnostic value of key genes by performing immunohistochemistry (IHC) in clinical tissue samples. The compositional patterns of the infiltration of 22 immune cell types in RSA were analyzed via the CIBERSORT algorithm.ResultWe identified 403 differentially expressed genes (DEGs) and 7 DIIRGs between RSA endometrium and Non-RSA endometrium. GO analysis showed that DIIRGs were significantly enriched in positive regulation of cell-cell adhesion, inflammatory response to antigenic stimulus, and protein tyrosine kinase activity. KEGG enrichment analyses were performed mainly on Epithelial cell signaling in Helicobacter pylori infection, NOD-like receptor signaling pathway, and Ras signaling pathway. A predictive and diagnostic model composed of three genes (CYBB, LYN, and MET). The CYBB, LYN, and MET genes were identified as diagnostic biomarkers of RSA (AUC = 0.747, AUC = 0.751, AUC=0.703), and reduced levels of CYBB and LYN expression were found to correlate with RSA in clinical samples. In addition, immune microenvironment analysis showed that CYBB and MET were positively correlated with naïve B cells and negatively correlated with CD8 T cells, LYN and MET were positively correlated with M2 macrophages and negatively correlated with eosinophils, respectively (P &amp;lt; 0.05).ConclusionInflammation-immunity is a key factor in the pathogenesis of RSA. CYBB and LYN are regarded as the crucial genes that constitute a model and contribute to inflammation-immunity throughout the occurrence and progression of RSA. These findings provide a new perspective on the diagnosis and pathogenesis of RSA.

Faecalibacterium prausnitzii Ameliorates DSS-Induced Colitis via Modulating Bile Acid Metabolism and Regulating FXR Signaling.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with a globally increasing incidence. Faecalibacterium prausnitzii (F. prausnitzii) is known for its anti-inflammatory and immunomodulatory properties. However, the mechanisms by which gut microbiota and bile acid metabolism contribute to the therapeutic effects of F. prausnitzii in colitis remain unclear. This study aims to investigate the effects of F. prausnitzii on colitis and elucidate its potential mechanism through modulation of gut microbiota and bile acid metabolism. Mice were treated with dextran sulfate sodium (DSS), followed by administration of F. prausnitzii and its supernatant. Colitis symptoms, inflammatory responses, and intestinal barrier integrity were then evaluated. 16S rRNA sequencing and targeted bile acid metabolomics analysis were performed. F. prausnitzii and its supernatant reshaped dysbiotic gut microbiota in DSS-induced colitis mouse models, increasing the ratio of unconjugated to conjugated bile acids and secondary to primary bile acids, thereby activating the farnesoid X receptor (FXR) signaling pathway. Experiments in FXR-/- mice confirmed that FXR is a critical target for the protective effects of F. prausnitzii, promoting intestinal mucosal repair and inhibiting NLRP3 inflammasome activation, which in turn alleviates colitis. Additionally, the differential bile acid isoLCA, enriched by F. prausnitzii and its supernatant, effectively suppressed inflammation and enhanced intestinal barrier function. This study demonstrates that F. prausnitzii alleviates colitis by modulating bile acid composition and regulating FXR signaling, suggesting that targeting the microbiota-bile acid-FXR pathway may represent a promising therapeutic strategy for inflammatory bowel disease.

Neuroimaging and biological markers of different paretic hand outcomes after stroke

BackgroundHand dysfunction significantly affects independence after stroke, with outcomes varying across individuals. Exploring biomarkers associated with the paretic hand can improve the prognosis and guide personalized rehabilitation. However, whether biomarkers derived from resting-state fMRI (rs-fMRI) can effectively classify and predict different hand outcomes and their biological mechanisms remain unclear.MethodsThis study analyzed 65 patients with chronic subcortical stroke, including 32 patients with partially paretic hand (PPH) and 33 patients with completely paretic hand (CPH). For patients with PPH and CPH respectively, the age was 56.19 ± 10.53 and 55.60 ± 9.00 years, disease duration was 15.31 ± 14.87 and 14.12 ± 17.36 months, lesion volume was 9.45 ± 5.57 and 16.00 ± 11.33 ml, Fugl-Meyer Assessment for Hand and Wrist (FMA-HW) was 11.25 ± 6.15 and 1.24 ± 1.22. Four rs-fMRI metrics were analyzed, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and voxel-mirrored homotopic connectivity (VMHC). Multivariate pattern analysis was used to classify and predict paretic hand performance. To explore the biological mechanisms of neuroimaging biomarkers, partial least squares regression was conducted to associate gene expression data (from Allen Human Brain Atlas), neurotransmitter maps, neuron types and developmental stages with the classification weight maps of rs-fMRI metrics.ResultsALFF achieved a higher classification accuracy of 0.88 in differentiating PPH from CPH, outperforming the other three rs-fMRI metrics. Machine learning further identified the top contributing regions from the ALFF classification weight maps, such as the ipsilesional precentral gyrus, contralesional cerebellum posterior lobe, and ipsilesional parietal lobule. Neuroimaging-transcriptome analysis revealed that macroscopic biomarkers from the ALFF were associated with the G protein-coupled receptor signaling pathway and the detection of chemical stimuli involved in sensory perception. Additionally, these neuroimaging biomarkers from ALFF showed prominent expression in astrocytes and early fetal stages. Most importantly, the neurotransmitter noradrenaline positively correlated with the distribution of ALFF biomarkers.ConclusionsThe ALFF is an effective macroscopic biomarker for classifying and predicting paretic hand outcomes in individuals following chronic stroke. These neuroimaging biomarkers correspond to molecular transcriptional profiles and neurotransmitter distributions, offering insights into the potential of personalized stroke rehabilitation.

An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis

BackgroundNucleoside and nucleotide analogs are one of the mainstays of treatment for chronic hepatitis B, but their effects on bone density are highly controversial.MethodsIn this study, four pharmacovigilance analysis methods and Bonferroni-corrected p-values were used to analyze the FDA Adverse Event Reporting System database to investigate the relationship between adefovir and tenofovir and osteoporosine-related adverse events. In addition, the biological pathways and target proteins were studied by network toxicology and molecular docking techniques.ResultsAdefovir showed signs of adverse skeletal events at the two PT levels of OSTEOPOROSIS and BONE DENSITY DECREASED, while tenofovir showed signs of adverse skeletal events at the five PT levels of BONE DENSITY DECREASED, BONE LOSS, OSTEOPENIA, OSTEOPOROSIS and OSTEOPOROTIC FRACTURE. Furthermore, at the overall SMQ level, positive signals of adverse skeletal events were also valid. Subgroup analysis showed that adefovir was more likely to cause osteoporosis in the elderly and women, while tenofovir exhibited the opposite trend. Furthermore, GO and KEGG analyses indicated that both drugs may jointly promote osteoporosis through pathways such as cell migration, G protein-coupled receptor and Toll-like receptor signaling pathways. Molecular docking technology further reveals that the two drugs can produce pathological effects by binding to osteoporosis-related genes such as ADORA1 and JAK1.ConclusionThis study comprehensively reported the risk and mechanisms of osteoporosis caused by the clinical use of NAs drugs, and provided more detailed recommendations for clinical improvement and prevention of adverse events.

Clarifying the mechanism of astaxanthin in the treatment of inflammation in ischemic stroke using integrated network analysis.

Clarifying the mechanism of astaxanthin in the treatment of inflammation in ischemic stroke using integrated network analysis.

Root hair: An important guest-meeting avenue for rhizobia in legume-Rhizobium symbiosis.

Root hair: An important guest-meeting avenue for rhizobia in legume-Rhizobium symbiosis.

Sulforaphanin ameliorates the damage of the Cyprinus carpio liver induced by Aeromonas hydrophila via activating AMPK pathway.

Sulforaphanin ameliorates the damage of the Cyprinus carpio liver induced by Aeromonas hydrophila via activating AMPK pathway.

Lanthanum oxide nanoparticles induce AHR-mediated hepatotoxicity in zebrafish via oxidative stress and metabolic dysregulation.

Lanthanum oxide nanoparticles induce AHR-mediated hepatotoxicity in zebrafish via oxidative stress and metabolic dysregulation.

Verbenalin protects against coronavirus pneumonia by promoting host immune homeostasis: Evidences for its mechanism of action.

Verbenalin protects against coronavirus pneumonia by promoting host immune homeostasis: Evidences for its mechanism of action.

Joint effects of rice straw-derived biochar and microcystin-LR on splenic histopathological injuries, inflammation, and innate immune responses in male zebrafish.

Joint effects of rice straw-derived biochar and microcystin-LR on splenic histopathological injuries, inflammation, and innate immune responses in male zebrafish.

Investigating acupuncture therapy in depression: mechanisms of synaptic plasticity regulation.

Investigating acupuncture therapy in depression: mechanisms of synaptic plasticity regulation.

Synbiotics of Lactobacillus suilingensis and inulin alleviates cognitive impairment via regulating gut microbiota indole-3-lactic acid metabolism in female AD mice.

Recent studies have found that gut microbial tryptophan metabolism is altered in Alzheimer's disease (AD) patients. However, the functional consequences of these changes and their therapeutic potential remain unclear. The metagenomic data of 49 preclinical AD patients and 115 healthy controls were analyzed. A synbiotic with targeted metabolic functions was formulated based on in vitro testing, and its effect on AD was evaluated using female 5×FAD mice. Indole lactic acid (ILA) synthesis was downregulated in AD patients. Synbiotic treatment combining Lactobacillus suilingensis and inulin outperformed probiotic treatment alone in enhancing tryptophan metabolism, and increasing ILA biosynthesis. Increased ILA could reduce Aβ accumulation and significantly alleviate cognitive impairment in female AD mice by inhibiting neuroinflammation through activation of the aryl hydrocarbon receptor (AhR) signaling pathway. This study highlights the therapeutic potential of targeting gut microbial tryptophan metabolism in AD and provides a rationale for future precision strategies aimed at modulating microbiota-derived metabolic pathways. Gut metagenomic analysis reveals reduced indole lactic acid (ILA) biosynthesis genes in preclinical AD patients. Screening and formulating ILA-producing synbiotic by using whole-genome analysis. Synbiotic treatment alleviates cognitive impairment and promotes ILA synthesis in female 5×FAD mice. ILA alleviates neuroinflammation in female 5×FAD mice by activating aryl hydrocarbon receptor (AhR) in the brain. Synbiotic targeting tryptophan metabolism provides a novel approach for Alzheimer's intervention.

Dahuang Huanglian Decoction alleviates dysbiosis by inhibiting GBP5/NLRP3 signaling pathway-mediated pyroptosis of colonic epithelial cells.

Dahuang Huanglian Decoction alleviates dysbiosis by inhibiting GBP5/NLRP3 signaling pathway-mediated pyroptosis of colonic epithelial cells.