Pathogenesis Of Ulcerative Colitis Research Articles

METTL14 regulates inflammation in ulcerative colitis via the lncRNA DHRS4-AS1/miR-206/A3AR axis.

As a chronic inflammatory bowel disease, the pathogenesis of ulcerative colitis (UC) has not been fully elucidated. N6-methyladenosine (m6A) modification, observed in various RNAs, is implicated in inflammatory bowel diseases. Methyltransferase-like 14 (METTL14) is the major subunit of the methyltransferase complex catalyzing m6A modifications. Here, we designated to examine the regulatory effects and mechanisms of METTL14 on long non-coding RNA (lncRNA) during UC progression. METTL14 knockdown decreased cell viability, promoted apoptosis, increased cleaved PARP and cleaved Caspase-3 levels, while reducing Bcl-2 levels. METTL14 knockdown also led to a significant increase in NF-κB pathway activation and inflammatory cytokine production in the Caco-2 cells treated with TNF-α. Moreover, the suppression of METTL14 aggravated colonic damage and inflammation in our dextran sulfate sodium (DSS)-induced murine colitis model. METTL14 silencing suppressed DHRS4-AS1 expression by reducing the m6A modification of DHRS4-AS1 transcripts. Furthermore, DHRS4-AS1 mitigated inflammatory injury by targeting the miR-206/adenosine A3 receptor (A3AR) axis. DHRS4-AS1 overexpression counteracted the enhancing impact of METTL14 knockdown on TNF-α-induced inflammatory injury in Caco-2 cells. In conclusion, our findings suggest that METTL14 protects against colonic inflammatory injury in UC via regulating the DHRS4-AS1/miR-206/A3AR axis, thus representing a potential therapeutic target for UC.

Mucosal cytokine expression associated with deep endoscopic mucosal healing in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of unknown cause for which no curative treatments have been developed. Cytokines play an important role in the pathogenesis of UC, and therapies targeting specific cytokines have been successful in treating refractory UC. The purpose of this study was to measure mucosal cytokines in UC and identify those that contribute to non-relapsing mucosal healing diagnosed by endoscopy. This prospective, observational study included 163 patients with UC. The mucosa was evaluated by Mayo Endoscopic Subscore (MES) and linked color imaging (LCI) at the time of endoscopy, and cytokine mRNA expression in biopsy tissue taken from the same site was quantified by real-time PCR and compared with endoscopic findings. The relationship between cytokine mRNA expression and endoscopic findings was investigated. Cytokines such as IFNγ, IL-1β, IL-8, IL-17A, and IL-23 were significantly elevated in proportion to endoscopic severity of MES and LCI classification.Interestingly, we found differences in the expression of cytokines (e.g., IL-22 and IL-33) between MES and LCI classification according to disease severity. Additionally, pathway analysis based on RNA sequencing compared between LCI-A and LCI-B in the patients diagnosed as MES 0 revealed that IL-5 and IL-6 are involved in the finer differences in endoscopic mucosal redness. This study is the first to report the correlation between mucosal cytokine expression and the pathogenesis of mucosal healing (MH) in UC and supports the contribution of specific cytokines as molecular markers of MH or in the pathogenesis of MH in UC.

Neutrophil extracellular traps induce barrier dysfunction in DSS-induced ulcerative colitis via the cGAS-STING pathway

Peptidyl arginine deiminase 4 (PAD4)-mediated neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of ulcerative colitis (UC). The cGAS-STING intracellular DNA-sensing pathway has been recognized as a pivotal mediator of inflammation. This study aimed to explore how NETs contribute to intestinal inflammation and barrier dysfunction in UC, focusing on the cGAS-STING pathway. We observed a significant increase of STING expression in UC mouse colons, which was mitigated by blocking NET formation through PAD4 genetic knockout. Moreover, NETs were discovered to activate the cGAS-STING pathway in MC38 cells in a dose and time-dependent manner, leading to the secretion of inflammatory cytokines and impaired barrier function. Additionally, STING deficiency ameliorated the clinical colitis index, intestinal inflammation, and barrier dysfunction. These findings underscore the involvement of cGAS-STING in regulating NET-mediated intestinal inflammation, suggesting its potential as a novel therapeutic target for UC.

Evaluating the Therapeutic Efficacy of Lactobacillus Strains in the Management of Ulcerative Colitis: An Overview of Recent Advances.

Ulcerative Colitis (UC) known as a sub-category of Inflammatory Bowel Diseases (IBD) is a longterm condition that causes inflammation, irritation, and ulcers in the colon and rectum. Though the precise pathogenesis of UC is not fully understood yet, impaired immune responses and imbalanced intestinal microbiome composition have been regarded as two main key players in colitis pathobiology. As conventional treatments are challenged with limitations and side effects, finding a new therapeutic approach has gained increasing attention. Probiotic bacteria with multifunctional health-promoting properties have been considered novel therapeutic options. There is strong evidence indicating that probiotics exert their therapeutic effects mostly by regulating immune system responses and restoring gut microbiome homeostasis. These results validate the rationale behind the clinical application of probiotics in UC management whether prescribed alone or in combination with conventional therapy. This article explores the pathogenesis of UC, concentrating on the influence of immune dysregulation and intestinal microbiome imbalances. Also, it reviews recent in vitro, in vivo, and clinical studies that have demonstrated the efficacy of Lactobacillus species in decreasing UC symptoms by modifying immune responses, restoring gut microbiota balance, and promoting intestinal barrier function.

Functional Ginger-Derived Extracellular Vesicles-Coated ZIF-8 Containing TNF-α siRNA for Ulcerative Colitis Therapy by Modulating Gut Microbiota.

Tumor necrosis factor-α (TNF-α) plays a causal role in the pathogenesis of ulcerative colitis (UC), and anti-TNF-α siRNA shows great promise in UC therapy. However, delivering siRNA with site-targeted stability and therapeutic efficacy is still challenging due to the complex and dynamic intestinal microenvironment. Here, based on the functional plant-derived ginger extracellular vesicles (EVs) and porous ZIF-8 nanoparticles, we propose a novel TNF-α siRNA delivery strategy (EVs@ZIF-8@siRNA) for UC targeted therapy. Ginger EVs show strong colon and macrophage targeting, as well as robust resistance to acidic degradation in the stomach. Moreover, 6-shogaol in ginger-derived EVs displays anti-inflammatory effects, which enhance the treatment efficiency by cooperation with TNF-α siRNA. In vitro experiments reveal that ZIF-8 nanoparticles have high TNF-α siRNA loading capacity and promote siRNA escape from cellular lysosomes. In vivo experiments show that the TNF-α level is reduced more significantly in colonic tissue than other nontargeted inflammation related factors, showing a good targeting of this composite nanoparticle. Furthermore, gut microbiota sequencing results demonstrate that the nanoparticles can promote intestinal barrier repair by regulating the intestinal microbial balance and restoring the intestinal health of UC mice. Therefore, the developed EVs@ZIF-8@siRNA nanoparticles may represent a novel colon-targeted oral drug, providing a promising therapeutic strategy for UC therapy.

The Role of Claudins in the Pathogenesis of Dextran Sulfate Sodium-Induced Experimental Colitis: The Effects of Nobiletin.

The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin. Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days. Animals were treated daily with nobiletin [oral, 60 mg/Kg body weight] and studied in four groups, C [non-colitis control], D [DSS-induced colitis], CN [nobiletin-treated non-colitis control], and DN [nobiletin-treated DSS-induced colitis]. On day seven, the animals were sacrificed, and colonic tissues were collected and analyzed. Both macroscopic and microscopic findings suggest the progression of colitis. In the inflamed colon, claudin-1 and -4 proteins were decreased, claudin-2 increased, while the claudin-3 protein remained unchanged. Except for claudin-1, these changes were not paralleled by mRNA expression, indicating a complex regulatory mechanism. Uniform β-actin expression along with consistent quality and yield of total RNA indicated selectivity of these changes. Nobiletin treatment reversed these changes. Altered expression of the claudin isoforms -1, -2, and -4 disrupts tight junctions, exposing the lamina propria to microflora, leading to electrolyte disturbance and the development of ulcerative colitis. Nobiletin with its anti-inflammatory properties may be useful in IBD.

Bacteroides salyersiae Is a Candidate Probiotic Species with Potential Anti-Colitis Properties in the Human Colon: First Evidence from an In Vivo Mouse Model.

Previous studies have indicated a critical role of intestinal bacteria in the pathogenesis of ulcerative colitis (UC). B. salyersiae is a commensal species from the human gut microbiota. However, what effect it has on UC development has not been investigated. In the present study, we explored this issue and demonstrated for the first time that oral administration of B. salyersiae CSP6, a bacterium previously isolated from the fecal sample of a healthy individual, protected against dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. In particular, B. salyersiae CSP6 improved mucosal damage and attenuated gut dysbiosis in the colon of DSS-fed mice. Specifically, B. salyersiae CSP6 decreased the population of pathogenic Escherichia-Shigella spp. and increased the abundance of probiotic Dubosiella spp. and Bifidobacterium pseudolongum. Additionally, by reshaping the colonic microbiota, B. salyersiae CSP6 remarkably increased the fecal concentrations of equol, 8-deoxylactucin, and tiglic acid, three beneficial metabolites that have been well documented to exert strong anti-inflammatory effects. Altogether, our study provides novel evidence that B. salyersiae is a candidate probiotic species with potential anti-colitis properties in the human colon, which has applications for the development of next-generation probiotics.

Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan

BackgroundInterleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between IL23R p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population. MethodsThe study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking. ResultsThe frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44–0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (p for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype. ConclusionIL23R SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC.

Epithelial Piezo1 deletion ameliorates intestinal barrier damage by regulating ferroptosis in ulcerative colitis

Ferroptosis, a recently discovered form of regulated cell death, has been implicated in the development of ulcerative colitis (UC). While Piezo1's role in inducing ferroptosis in chondrocytes and pulmonary endothelial cells is documented, its regulatory function in ferroptosis and intestinal epithelial cells in UC remains unclear. To address this, colonic tissue samples from patients with UC were examined, and specific intestinal epithelial Piezo1-deficient (Piezo1ΔIEC) mice were created to investigate Piezo1's role in UC pathogenesis. Elevated epithelial Piezo1 levels were observed in patients with UC, correlating with increased ferroptosis and tight junction (TJ) disruption. In dextran sulfate sodium (DSS)-induced colitis, Piezo1ΔIEC mice exhibited significantly reduced intestinal inflammation and improved gut barrier function compared to wild-type (WT) mice. Moreover, Piezo1 deficiency in colitis mice and lipopolysaccharide (LPS)-stimulated Caco-2 cells led to higher TJ protein levels, reduced lipid peroxidation, enhanced mitochondrial function, and altered expression of ferroptosis-associated proteins. Additionally, erastin, a ferroptosis activator, reversed the protective effect of Piezo1 silencing against LPS-induced ferroptosis in Caco-2 cells. Mechanistically, Piezo1 was found to regulate ferroptosis via the AMPK/mTOR signaling pathway. These findings highlight a novel role for Piezo1 deletion in mitigating ferroptosis in intestinal epithelial cells, suggesting Piezo1 as a potential therapeutic target for UC treatment.

Identification of a Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis

Introduction: Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy. Methods: Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the “Batch correction” and “Robust rank aggregation” (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by “AddModuleScore” and “AUCell.” Results: Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001). Conclusion: This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.

Spatio-temporally controlled all-in-one hydrogel microspheres for ulcerative colitis treatment based on cocktail strategy

Due to the complex pathogenesis of ulcerative colitis (UC), particularly excessive reactive oxygen species (ROS), gut microbiota dysbiosis, and hyperpolarization of M1 macrophages, the cocktail strategy is urgently needed to obtain a sufficient therapeutic outcome. Meanwhile, the accurate lesion location targeting of these combined therapeutic agents is still crucial. Herein, based on NPs-in-MPs approach, a novel integrated “all-in-one” oral delivery system (BMM/MPs), containing the natural gut microbiota regulator berberine, MnO2 nanoenzymes, and cell penetrating peptides-decorated magnolol liposomes to regulate macrophage polarization, was constructed to address these above issues in sequence. BMM/MPs could non-destructively cross the gastrointestinal tract, enduringly detain, and dissociate in the colon site due to the pH-sensitive properties. Conceivably, the released MnO2 nanoenzymes depleted the excess ROS at the colitis location into O2, sequentially promoting the acceleration of hydrogel microspheres rupture and oxidative damage remission. Accordingly, the oral administration of BMM/MPs exhibited remarkably satisfactory therapeutic effects against DSS-induced UC mice, by ameliorating the representative symptoms, scavenging ROS, relieving inflammation, and inhibiting M1 macrophage polarization at colon sites. Meanwhile, the dysbiosis of microbes was effectively regulated by facilitating SCFAs production. This study provides a feasible strategy for administration in the treatment of UC.

The Potential Role of Plant Polysaccharides in Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) results in inflammation and ulceration of the colon and the rectum's inner lining. The application of herbal therapy in UC is increasing worldwide. As natural macromolecular compounds, polysaccharides have a significant role in the treatment of UC due to advantages of better biodegradation, good biocompatibility, immunomodulatory activity, and low reactogenicity. Therefore, polysaccharide drug formulation is becoming a potential candidate for UC treatment. In this review, we summarize the etiology and pathogenesis of UC and the therapeutic effects of polysaccharides on UC, such as regulating the expression of cytokines and tight junction proteins and modulating the balance of immune cells and intestinal microbiota. Polysaccharides can also serve as drug delivery carriers to enhance drug targeting and reduce side effects. This review provides a theoretical basis for applying natural plant polysaccharides in the prevention and treatment of UC.

Effects of the N-Butanol Extract of Pulsatilla Decoction on Neutrophils in a Mouse Model of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease, the incidence of which is increasing worldwide. However, the etiology and pathogenesis of UC remains unclear. The n-butanol extract of Pulsatilla decoction (BEPD), a traditional Chinese medicine, has been shown to be effective in treating UC. This study aimed to explore the molecular mechanism underlying the effects of BEPD on UC, in particular its effects on neutrophil extracellular trap (NET) formation by neutrophils. High-performance liquid chromatography was used to determine the principal compounds of BEPD. UC was induced in mice using dextran sodium sulfate, and mice were treated with 20, 40, or 80 mg/kg BEPD daily for seven days. Colonic inflammation was determined by assessing the disease activity index, histopathology, colonic mucosal damage index, colonic mucosal permeability, and pro- and anti-inflammatory cytokine levels. The infiltration and activation status of neutrophils in the colon were determined by analyzing the levels of chemokine (C-X-C motif) ligand (CXCL) 1 and CXCL2, reactive oxygen species, Ly6G, and numerous NET proteins. The findings suggest that BEPD improved the disease activity index, histopathology, and colonic mucosal damage index scores of mice with UC, and restored colonic mucosal permeability compared with untreated mice. The expression levels of the pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in colon tissues were significantly decreased, while the expression levels of anti-inflammatory cytokines in colon tissues were significantly increased, exceeding those of control mice. In addition, BEPD reduced the expression of the neutrophil chemokines CXCL1 and CXCL2 in the colon tissue of mice with UC, reduced neutrophil infiltration, reduced reactive oxygen species levels, and significantly reduced the expression of NET proteins. BEPD also significantly reduced NET formation. The results of this study suggest that BEPD exerts therapeutic effects in a murine model of UC by inhibiting neutrophil infiltration and activation in the colon, as well as by inhibiting the expression of key proteins involved in NET formation and reducing NET formation, thereby alleviating local tissue damage and disease manifestations.

Research Progress of Ferroptosis in Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous inflammation and ulcer formation in the intestinal mucosa.Its pathogenesis involves immune dysfunction,dysbiosis of gut microbiota,and mucosal damage caused by inflammation.Ferroptosis is an iron-dependent form of cell death regulated by disturbances in iron metabolism,lipid peroxidation,and depletion of glutathione (GSH).Studies have indicated that ferroptosis plays a crucial role in the pathogenesis of UC,particularly in regulating inflammatory responses and damaging intestinal epithelial cells.This article reviews the regulatory mechanisms and roles of ferroptosis in UC and discusses the potential therapeutic strategies to alleviate UC symptoms by modulating iron metabolism,reducing lipid peroxidation,and maintaining GSH levels,providing new targets and directions for the diagnosis and treatment of UC.

Evaluating the Efficacy of Infliximab in Inflammatory Bowel Disease: A Systematic Review of the Literature.

The introduction of steroid therapy in 1955 markedly decreased the mortality rate of severe ulcerative colitis (UC) from 24% in the placebo group to 7%, and it is currently less than 1% in specialist centers. Despite this advancement, the response of severe UC to steroids has stagnated over the past 50 years, with a high rate of colectomy persisting for severe to moderately severe cases. Infliximab (IFX) (Remicade, CentocorInc., Malvern, PA, United States), an intravenously administered chimeric monoclonal immunoglobulin G1 antibody targeting tumor necrosis factor-alpha (TNF-α), has shown efficacy in numerous randomized controlled trials for treating moderate to severe and fistulizing Crohn's disease, particularly in patients unresponsive to conventional therapies. This led to its approval by the US Food and Drug Administration in 1998 for treating active and fistulizing Crohn's disease. Most clinical research on IFX has focused on Crohn's disease, which is characterized as a Th1-type condition driven by pro-inflammatory cytokines like TNF-α. Conversely, UC has traditionally been viewed as a Th2-type condition where TNF-α plays a lesser role. However, recent studies indicate that TNF-α might also contribute to the pathogenesis of UC. These findings highlight the necessity for larger randomized controlled trials to further investigate the benefits of therapies like IFX, with the ultimate goal of improving treatment outcomes and quality of life for patients with inflammatory bowel disease.

Gut colonization with antibiotic-resistant Escherichia coli pathobionts leads to disease severity in ulcerative colitis

Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored until now. Human gut microbiota composition and meta-gut resistome were evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to gain insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy controls (HC) [518]. The metagenome study revealed a higher prevalence of AMR genes in the rural population (378 in HC; 607 in UC) compared to the urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant (MDR), with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and inflammatory mediator (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. In addition to the conventional culturomics method, a multi-omics strategy provides deeper insights into the disease etiology, emergence of MDR pathobionts, and their roles in the disruption of the healthy gut environment in UC patients.

Exploring the butyrate metabolism-related shared genes in metabolic associated steatohepatitis and ulcerative colitis

Metabolic-associated steatohepatitis (MASH) and ulcerative colitis (UC) exhibit a complex interconnection with immune dysfunction, dysbiosis of the gut microbiota, and activation of inflammatory pathways. This study aims to identify and validate critical butyrate metabolism-related shared genes between both UC and MASH. Clinical information and gene expression profiles were sourced from the Gene Expression Omnibus (GEO) database. Shared butyrate metabolism-related differentially expressed genes (sBM-DEGs) between UC and MASH were identified via various bioinformatics methods. Functional enrichment analysis was performed, and UC patients were categorized into subtypes using the consensus clustering algorithm based on sBM-DEGs. Key genes within sBM-DEGs were screened through Random Forest, Support Vector Machines-Recursive Feature Elimination, and Light Gradient Boosting. The diagnostic efficacy of these genes was evaluated using receiver operating characteristic (ROC) analysis on independent datasets. Additionally, the expression levels of characteristic genes were validated across multiple independent datasets and human specimens. Forty-nine shared DEGs between UC and MASH were identified, with enrichment analysis highlighting significant involvement in immune, inflammatory, and metabolic pathways. The intersection of butyrate metabolism-related genes with these DEGs produced 10 sBM-DEGs. These genes facilitated the identification of molecular subtypes of UC patients using an unsupervised clustering approach. ANXA5, CD44, and SLC16A1 were pinpointed as hub genes through machine learning algorithms and feature importance rankings. ROC analysis confirmed their diagnostic efficacy in UC and MASH across various datasets. Additionally, the expression levels of these three hub genes showed significant correlations with immune cells. These findings were validated across independent datasets and human specimens, corroborating the bioinformatics analysis results. Integrated bioinformatics identified three significant biomarkers, ANXA5, CD44, and SLC16A1, as DEGs linked to butyrate metabolism. These findings offer new insights into the role of butyrate metabolism in the pathogenesis of UC and MASH, suggesting its potential as a valuable diagnostic biomarker.

Comprehensive analysis of disulfidptosis-related genes reveals the effect of disulfidptosis in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract. Various programmed cell death pathways in the intestinal mucosa are crucial to the pathogenesis of UC. Disulfidptosis, a recently identified form of programmed cell death, has not been extensively reported in the context of UC. This study evaluated the expression of disulfidptosis-related genes (DRGs) in UC through public databases and assessed disulfide accumulation in the intestinal mucosal tissues of UC patients and dextran sulfate sodium (DSS)-induced colitis mice via targeted metabolomics. We utilized various bioinformatics techniques to identify UC-specific disulfidptosis signature genes, analyze their potential functions, and investigate their association with immune cell infiltration in UC. The mRNA and protein expression levels of these signature genes were confirmed in the intestinal mucosa of DSS-induced colitis mice and UC patients. A total of 24 DRGs showed differential expression in UC. Our findings underscore the role of disulfide stress in UC. Four UC-related disulfidptosis signature genes—SLC7A11, LRPPRC, NDUFS1, and CD2AP—were identified. Their relationships with immune infiltration in UC were analyzed using CIBERSORT, and their expression levels were validated by quantitative real-time PCR and western blotting. This study provides further insights into their potential functions and explores their links to immune infiltration in UC. In summary, disulfidptosis, as a type of programmed cell death, may significantly influence the pathogenesis of UC by modulating the homeostasis of the intestinal mucosal barrier.

Intestinal epithelial Cldn-7 regulates intestinal inflammation by altering the gut microbiota

Background and aimTight junctions maintain gut homeostasis by forming a physical barrier that protects the gut from invasion by microbiota. Cldn-7 is an important component involved in this protection, but the relationship between Cldn-7, intestinal inflammation, and gut microbiota has not been clarified. Here, we hypothesize that Cldn-7 depletion affects intestinal inflammation by altering the gut microbiota. MethodsBased on the induced intestinal condition of Cldn-7 knockout mice (Cldn7fl/fl;villin-CreaERT2), we established the intestinal flora depletion model and colitis model by antibiotic drinking and feeding with dextran sodium sulfate (DSS). The environment of Cldn-7 gene deletion mice was changed by co-housing experiment. AB-PAS staining and Muc2 were used to detect the effect of co-housing and Cldn-7 deficiency on the mucus layer after flora depletion. qRT-PCR was used to detect the expression of intestinal inflammatory factors and AMPs in mice. Feces were collected and proportions of microbiota were analyzed by 16 S rRNA amplicon sequencing. ResultsMice in the co-housing experiment had altered intestinal microbiota, including diversity, composition, and functional prediction, compared to controls. Intestinal inflammation was restored to some extent following altered intestinal microbiota. The intestinal inflammation caused by Cldn-7 deficiency and susceptibility to DSS could be reduced after antibiotic administration compared to controls, in terms of phenotype, pathological changes, inflammatory factors, mucus barrier, and expression of AMPs. ConclusionsIn analyses of intestinal tissues, colitis induction, and gut microbiota in mice with intestinal disruption of Cldn-7, we found this protein to prevent intestinal inflammation by regulating the gut microbiota. Cldn-7might therefore be an important mediator of host–microbiome interactions. Our research has revealed that Cldn-7 plays an indispensable role in maintaining intestinal homeostasis by regulating the gut microbiota and impacting intestinal inflammation. These findings provide new insights into the pathogenesis of ulcerative colitis.

Curcumin-Encapsulated Co-ZIF-8 for Ulcerative Colitis Therapy: ROS Scavenging and Macrophage Modulation Effects.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by the disruption of the intestinal epithelial barrier. This study described the synthesis and characterization of CCM-Co-ZIF-8, a novel composite material with enzyme-like activities similar to catalase, peroxidase, and superoxide dismutase. CCM-Co-ZIF-8 demonstrated the ability to scavenge reactive oxygen species that play a critical role in UC pathogenesis. In vitro studies using lipopolysaccharide-induced RAW264.7 cells showed that CCM-Co-ZIF-8 exhibited anti-inflammatory activity by promoting the transition of macrophages from an M1 to an M2 phenotype. In vivo experiments using a mouse model of UC demonstrated that CCM-Co-ZIF-8 suppressed the expression of proinflammatory cytokines. These findings suggested that CCM-Co-ZIF-8 might hold promise as a therapeutic strategy for the treatment of UC.