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The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Introduction: Scutellarein (Scu) is a natural occurring flavonoid found in multiple traditional Chinese medicines such as Oroxylum indicum (L.) Kurz and Scutellaria baicalensis , with various pharmacological activities including anti-inflammation, anti-oxidation and myocardial protection. Here, we investigated the therapeutic efficacy of Scu on ulcerative colitis (UC) and the underlying mechanism. Methods: Efficacy of Scu on UC was evaluated in dextran sulfate sodium (DSS) induced colitis mouse model. Inflammation in colonic tissues was assessed by myeloperoxidase activity assay and RT-qPCR. Barrier proteins expression was examined using immunostaining and Western blot. IL-1β-treated HT-29 cells was used for mechanical investigation. Results: Gavage of Scu significantly decreased the DAI score, improved colon shortening, ameliorated the pathological score in DSS-treated mice with better efficacy than the positive drug, 5-aminosalicylic acid. Scu also inhibited the expression levels of cytokines (Il-1β , Tnf-α , Il-1α , Il-6 , and Cxcl1) as well as barrier proteins (E-cadherin, Occludin, and ZO-1) in colon tissues of DSS mice. In intestinal epithelial HT-29 cells, Scu attenuated the IL-1β-downregulated expression levels of E-cadherin, occludin, and ZO-1, while reduced IL-1β-upregulated IL-6 and IL-8 mRNA levels. Moreover, Scu inhibited the phosphorylation and nuclear translocation of NF-κB and suppression of NF-κB phosphorylation abolished IL-1β-disrupted epithelial barrier integrity and IL-1β-upregulated proinflammatory mediators expression in HT-29 cells. Conclusion: These data demonstrate that Scu is an efficacious therapeutic agent to treat UC. Inhibition of inflammatory responses and maintenance of epithelial barrier integrity through NF-κB signaling pathway underlines Scu therapeutic effect on UC. [ABSTRACT FROM AUTHOR]

Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined. A better understanding of this phenomenon could improve the identification of high-risk populations. In this study, we characterized these relationships with experiments using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and DSS/azoxymethane (AOM)-induced CRC (DSS/AOM-CRC) in wild-type and conditional transgenic mice of PCa. We showed that DSS-induced UC was more severe in mice with PCa and resulted in the development of CRC in the absence of AOM. We further showed that PCa-free mice that developed DSS-induced UC also showed histological changes in the normal prostate that resembled proliferative inflammatory atrophy. Finally, we used immunohistochemical immune profiling to show that mice with PCa-induced chronic systemic inflammation accumulated Gr1+ myeloid cells in the normal colon and exposure to DSS further enriched these cells in active colitis regions and colon tumors. Our study provides evidence to support a link between systemic chronic inflammation and cancer. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the effects of low-dose dextran sulfate sodium (DSS) on the induction of chronic mild inflammation in mice and to evaluate the therapeutic potential of Lacticaseibacillus rhamnosus LRa05 (LRa05) to ameliorate the associated effects. The focus was on investigating changes in inflammatory, gut microbiota, serum lipopolysaccharide (LPS) and inflammatory cytokines Methods: Mice were exposed to a low-dose of DSS to induce chronic mild inflammation and LRa05 was administered as a probiotic intervention. The experiment included determination of body weight, colon length, histological examinations, and analysis of LPS and inflammatory cytokines in serum over 12 weeks. In addition, liver function, oxidative stress and intestinal microbiota were examined to understand the comprehensive effects of DSS and LRa05. Results: Low-dose DSS did not lead to significant changes in body weight, colon length or histologic signs of inflammation. However, it led to a significant increase in serum levels of LPS, tumor necrosis factor-alpha (TNFa) and interleukin-6 (IL6). Intervention with LRa05 effectively attenuated these changes, particularly by lowering LPS levels and normalizing inflammatory cytokines. In addition, LRa05 protected against DSS-induced liver function damage and attenuated oxidative stress in the liver. Analysis of the gut microbiota demonstrated dynamic regulatory effects, where LRa05 intervention led to significant shifts in microbial populations, promoting a balanced microbiota profile. These changes are indicative of dynamic regulation by LRa05 in response to chronic mild inflammation, highlighting the probiotic's role in modulating the gut environment. Conclusion: The LRa05 intervention showed multi-layered regulation in the chronic mild inflammation model by reducing inflammatory cytokines, maintaining liver function and restoring the balance of the gut microbiota. This provides experimental support for the potential use of LRa05 in chronic inflammation-related diseases and emphasizes the importance of probiotics for overall health. The study suggests that LRa05 is a potential therapeutic agent for the treatment of chronic inflammation associated with gut dysbiosis. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) significantly diminishes an individual's quality of life and increases the risk of colorectal cancer. Recent clinical and experimental findings suggest that infection with parasitic helminths may suppress the development of certain inflammatory conditions. The objective of this study was to evaluate the immunoregulatory effects of Dicrocoelium eggs on experimentally induced colitis in C57BL/6 mice using dextran sulfate sodium (DSS). C57BL/6 mice received 3.5% DSS orally for 7 days to induce colitis, during which they were treated intraperitoneally with Dicrocoelium eggs. The severity of colitis was assessed through parameters such as body weight, stool consistency or bleeding, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, colon gene expression levels, and serum cytokine levels. Our results indicated that Dicrocoelium eggs administration significantly reduced the severity of colitis and disease activity. Histopathological scores improved, correlating with downregulation of IFN-γ and upregulation of IL-4 expression. This findings suggest the therapeutic potential of Dicrocoelium eggs in treating colitis. Immunotherapy involving Dicrocoelium eggs primarily induces a Th2 response and modulates IFN-γ, contributing to reduced inflammation in colitis. Thus, this approach could be a promising therapeutic strategy for alleviating inflammation in IBD. [ABSTRACT FROM AUTHOR]

Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth–/– mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth–/– mice compared to both WT and Slc7a11–/– mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota. [ABSTRACT FROM AUTHOR]

Experimental evidence suggests that, in the inflamed gut of inflammatory bowel disease (IBD) patients, interleukin-34 (IL-34) triggers detrimental signaling pathways. Factors/mechanisms regulating IL-34 production in IBD remain poorly characterized. Bromodomain-containing 4 (BRD4), a transcriptional and epigenetic regulator, is over-expressed in IBD, and studies in cancer cells suggest that BRD4 might positively control IL-34 expression. This study aimed to assess whether, in IBD, BRD4 regulates IL-34 expression. In IBD, there was an up-regulation of both IL-34 and BRD4 compared to the controls, and the two proteins co-localized in both lamina propria mononuclear cells (LPMCs) and epithelial cells. Flow cytometry analysis of CD45+ LPMCs confirmed that the percentages of IL-34- and BRD4-co-expressing cells were significantly higher in IBD than in the controls and showed that more than 80% of the IL-34-positive CD45-LPMCs expressed BRD4. IL-34 and BRD4 were mainly expressed by T cells and macrophages. IL-34 expression was reduced in IBD LPMCs transfected with BRD4 antisense oligonucleotide and in the colons of mice with dextran sulfate sodium-induced colitis treated with JQ1, a pharmacological inhibitor of BRD4. These data indicate that BRD4 is a positive regulator of IL-34 in IBD, further supporting the pathogenic role of BRD4 in IBD-associated mucosal inflammation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) arises from aberrant mutations in colorectal cells, frequently linked to chronic inflammation. This study integrated human gut metagenome analysis with an azoxymethane and dextran sulfate sodium-induced CRC mouse model to investigate the dynamics of inflammation, gut microbiota, and metabolomic profiles throughout tumorigenesis. The analysis of stool metagenome data from 30 healthy individuals and 40 CRC patients disclosed a significant escalation in both gut microbiota diversity and abundance in CRC patients compared to healthy individuals (p < 0.05). Marked structural disparities were identified between the gut microbiota of healthy individuals and those with CRC (p < 0.05), characterized by elevated levels of clostridia and diminished bifidobacteria in CRC patients (p < 0.05). In the mouse model, CRC mice exhibited distinct gut microbiota structures and metabolite signatures at early and advanced tumor stages, with subtle variations noted during the intermediate phase. Additionally, inflammatory marker levels increased progressively during tumor development in CRC mice, in contrast to their stable levels in healthy counterparts. These findings suggest that persistent inflammation might precipitate gut dysbiosis and altered microbial metabolism. Collectively, this study provides insights into the interplay between inflammation, gut microbiota, and metabolite changes during CRC progression, offering potential biomarkers for diagnosis. While further validation with larger cohorts is warranted, the data obtained support the development of CRC prevention and diagnosis strategies. [ABSTRACT FROM AUTHOR]

Spinel LiMn2O4 (LMO) has several beneficial properties for utilization as a cathode material for lithium‐ion batteries, including a high operating voltage, thermal stability, low cost, and eco‐friendliness. However, its application is limited by capacity fading due to structural transformation and manganese dissolution upon cycling. A method is proposed to resolve these two issues, using dextran sulfate sodium (DSS) as an aqueous binder to coat the LMO surface. DSS stabilizes the surface/interface structure of LMO by incorporating Na into the interstitial 16c sites, creating a uniform surface coating layer and promoting the formation of a homogeneous and stable cathode‐electrolyte interphase derived from the sulfate groups in DSS and enriched with LiF/LiSOxF. The aqueous DSS binder effectively suppresses the surface degradation and Mn dissolution of spinel LMO. The LMO electrode based on DSS exhibits superior cycling stability and rate performance compared with those of electrodes using the conventional poly(vinylidene difluoride) binder. These findings demonstrate the potential value of DSS as a multifunctional aqueous binder in stabilizing spinel LMO for lithium‐ion batteries. [ABSTRACT FROM AUTHOR]

Introduction: Ulcerative colitis, a subtype of chronic inflammatory bowel disease (IBD), is characterized by relapsing colonic inflammation and ulcers. The traditional Chinese herbal formulation Huang Lian Jie Du (HLJD) decoction is used clinically to treat diarrhea and colitis. However, the mechanisms associated with the effects of treatment remain unclear. This study aims to elucidate the molecular mechanistic effects of HLJD formulation on colitis. Methods: Chronic colitis in mice was induced by adding 1% dextran sulfate sodium (DSS) to their drinking water continuously for 8 weeks, and HLJD decoction at the doses of 2 and 4 g/kg was administered orally to mice daily from the second week until experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon tissues were collected for biochemical analyses. In addition, the fecal microbiome of treated mice was characterized using 16S rRNA amplicon sequencing. Results: HLJD decoction at doses of 2 and 4 g/kg relieved DSS-induced chronic colitis in mice by suppressing inflammation through compromised macrophage activity in colonic tissues associated with the colony-stimulating factor 1 receptor (Csf1r)/Src pathway. Furthermore, the HLJD formula could modify the gut microbiota profile by decreasing the abundance of Bacteroides, Odoribacter, Clostridium_sensu_stricto_1, and Parasutterella. In addition, close correlations between DAI, colon length, spleen weight, and gut microbiota were identified. Discussion: Our findings revealed that the HLJD formula attenuated DSSinduced chronic colitis by reducing inflammation via Csf1r/Src-mediated macrophage infiltration, as well as modulating the gut microbiota profile. [ABSTRACT FROM AUTHOR]

Legumain is a cysteine protease broadly associated with inflammation. It has been reported to cleave and activate protease‐activated receptor 2 to provoke pain associated with oral cancer. Outside of gastric and colon cancer, little has been reported on the roles of legumain within the gastrointestinal tract. Using a legumain‐selective activity‐based probe, LE28, we report that legumain is activated within colonocytes and macrophages of the murine colon, and that it is upregulated in models of acute experimental colitis. We demonstrated that loss of legumain activity in colonocytes, either through pharmacological inhibition or gene deletion, had no impact on epithelial permeability in vitro. Moreover, legumain inhibition or deletion had no obvious impacts on symptoms or histological features associated with dextran sulfate sodium‐induced colitis, suggesting its proteolytic activity is dispensable for colitis initiation. To gain insight into potential functions of legumain within the colon, we performed field asymmetric waveform ion mobility spectrometry‐facilitated quantitative proteomics and N‐terminomics analyses on naïve and inflamed colon tissue from wild‐type and legumain‐deficient mice. We identified 16 altered cleavage sites with an asparaginyl endopeptidase signature that may be direct substrates of legumain and a further 16 cleavage sites that may be indirectly mediated by legumain. We also analyzed changes in protein abundance and proteolytic events broadly associated with colitis in the gut, which permitted comparison to recent analyses on mucosal biopsies from patients with inflammatory bowel disease. Collectively, these results shed light on potential functions of legumain and highlight its potential roles in the transition from inflammation to colorectal cancer. [ABSTRACT FROM AUTHOR]

A high‐fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to investigate the potential mechanism by which HFD affects IBD using 16S rRNA‐sequencing and RNA‐seq technology. Results indicated that HFD‐treated mice exhibited notable alternations in the structure and composition of the gut microbiota, with some of these alternations being associated with the pathogenesis of IBD. Analysis of the colon transcriptome revealed 11 hub genes and 7 hub pathways among control, DSS‐induced colitis, and HFD + DSS‐treated groups. Further analysis explores the relationship between the hub pathways and genes, as well as the hub genes and gut microbiota. Overall, the findings indicate that the impact of HFD on DSS‐induced colitis may be linked to intestinal dysbiosis and specific genes such as Abca8b, Ace2, Apoa1, Apoa4, Apoc3, Aspa, Dpp4, Maob, Slc34a2, Slc7a9, and Trpm6. These results provide valuable insights for determining potential therapeutic targets for addressing HFD‐induced IBD. [ABSTRACT FROM AUTHOR]

Background: The combination of multiple polymers is anticipated to serve as a means to diversify the physical properties and functionalities of dissolving microneedles. The mixing state of components is considered as a crucial factor in determining their suitability. Objectives: The purpose of this study was to elucidate whether thermal analysis of frozen aqueous solutions can appropriately predict the miscibility of hyaluronic acid (HA) and other polymers used for dissolving microneedles prepared by a micromolding method. Methods: Aliquots of aqueous polymer solutions were applied for thermal analysis by heating the samples from −70 °C at 5 °C/min to obtain the transition temperature of amorphous polymers and/or the crystallization/melting peaks of polymers (e.g., polyethylene glycol (PEG)). Films and dissolving microneedles were prepared by air-drying of the aqueous polymer solutions to assess the polymer miscibility in the solids. Results: The frozen aqueous single-solute HA solutions exhibited a clear Tg′ (the glass transition temperature of maximally freeze-concentrated solutes) at approximately −20 °C. The combination of HA with several polymers (e.g., dextran FP40, DEAE-dextran, dextran sulfate, and gelatin) showed a single Tg′ transition at temperatures that shifted according to their mass ratio, which strongly suggested the mixing of the freeze-concentrated solutes. By contrast, the observation of two Tg′ transitions in a scan strongly suggested the separation of HA and polyvinylpyrrolidone (PVP) or HA and polyacrylic acid (PAA) into different freeze-concentrated phases, each of which was rich in an amorphous polymer. The combination of HA and PEG exhibited the individual physical changes of the polymers. The polymer combinations that showed phase separation in the frozen solution formed opaque films and microneedles upon their preparation by air-drying. Coacervation occurring in certain polymer combinations was also suggested as a factor contributing to the formation of cloudy films. Conclusions: Freezing aqueous polymer solutions creates a highly concentrated polymer environment that mimics the matrix of dissolving microneedles prepared through air drying. This study demonstrated that thermal analysis of the frozen solution offers insights into the mixing state of condensed polymers, which can be useful for predicting the physical properties of microneedles. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. Methods: To study the function of OTUB2 in IBD, we generated Otub2–/– mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. Results: OTUB2 was highly expressed in colon‐infiltrating macrophages in both humans with IBD and mice with DSS‐induced experimental colitis. Colitis was significantly aggravated in Otub2–/– mice and bone marrow chimeric mice receiving Otub2–/– bone marrow. OTUB2‐deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48‐linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. Conclusion: This study identified OTUB2 as a novel regulator of intestinal inflammation. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, with a global incidence that is rising. Despite the increasing prevalence, effective treatment options for UC remain limited. Methods: We utilized an NF-κB promoter dual fluorescence reporter system to screen for compounds that could inhibit p65 and IκBα phosphorylation. The anti-hypertension drug lacidipine was identified as a candidate. Its efficacy was further evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. The analysis included the assessment of colon lesions, inflammation markers, and signal pathway activation, with a focus on NF-κB and Notch signaling. Results: Lacidipine effectively inhibited p65 and IκBα phosphorylation in the reporter system. In the DSS-induced colitis murine model, lacidipine treatment led to a reduction in colon lesions and inflammatory markers. Target analysis showed significant enrichment of the Notch signaling pathway. Additionally, lacidipine inhibited both NF-κB and Notch activation in DSS-stimulated colons. Conclusion: Lacidipine demonstrated a protective effect in UC, reducing inflammation and modulating key signaling pathways. These findings suggest that lacidipine could be a promising candidate for the treatment of UC. [ABSTRACT FROM AUTHOR]

Chemokines are integral components of the immune system and deeply involved in the pathogenesis and progression of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although a considerable amount of transcriptome data has been accumulated on these diseases, most of them are limited to a specific stage of the disease. The purpose of this study is to visually demonstrate the dynamic changes in chemokines across various stages of bowel diseases by integrating relevant datasets. Integrating the existing datasets for IBD and CRC, we compare the expression changes of chemokines across different pathological stages. This study collected 11 clinical databases from various medical centers around the world. Patients: Data of patient tissue types were classified into IBD, colorectal adenoma, primary carcinoma, metastasis, and healthy control according to the publisher's annotation. The expression changes in chemokines in various pathological stages are statistically analyzed. The chemokines were clustered by different expression patterns. The chemokine family was clustered into four distinct expression patterns, which correspond to varying expression changes in different stages of colitis and tumor development. Certain chemokines and receptors associated with inflammation and tumorigenesis have been identified. Furthermore, it was confirmed that the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model and the azoxymethane (AOM)/ dextran sulfate sodium (DSS)-induced colon cancer model shows stronger correlations with the clinical data in terms of chemokine expression levels. This study paints a panoramic picture of the expression profiles of chemokine families at multiple stages from IBD to advanced colon cancer, facilitating a comprehensive understanding of the regulation patterns of chemokines and guiding the direction of drug development. This study provides researchers with a clear atlas of chemokine expression in the pathological processes of inflammatory bowel disease and colon cancer. [ABSTRACT FROM AUTHOR]

Background: Human interleukin-22 (IL-22) is known as a "dual function" cytokine that acts as a master regulator to maintain homeostasis, structural integrity of the intestinal epithelial barrier, and shielding against bacterial pathogens. On the other hand, the overexpression of IL-22 is associated with hyper-proliferation and recruitment of pathologic effector cells, leading to tissue damage and chronic inflammation in specific diseases including inflammatory bowel disease (IBD). To study a role of IL-22-mediated signaling axis during intestinal inflammation, we generated a set of small protein blockers of IL-22R1 and verified their inhibitory potential on murine model of colitis. Methods: We used directed evolution of proteins to identify binders of human IL-22 receptor alpha (IL-22R1), designated as ABR ligands. This approach combines the assembly of a highly complex combinatorial protein library derived from small albumin-binding domain scaffold and selection of promising protein variants using ribosome display followed by large-scale ELISA screening. The binding affinity and specificity of ABR variants were analyzed on transfected HEK293T cells by flow cytometry and LigandTracer. Inhibitory function was further verified by competition ELISA, HEK-Blue IL-22 reporter cells, and murine dextran sulfate sodium (DSS)-induced colitis. Results: We demonstrate that ABR specifically recognizes transgenic IL-22R1 expressed on HEK293T cells and IL-22R1 on TNFα/IFNγ-activated HaCaT cells. Moreover, some ABR binders compete with the IL-22 cytokine and function as IL-22R1 antagonists in HEK-Blue IL22 reporter cells. In a murine model of DSS-induced acute intestinal inflammation, daily intraperitoneal administration of the best IL-22R1 antagonist, ABR167, suppressed the development of clinical and histological markers of colitis including prevention of mucosal inflammation and architecture deterioration. In addition, ABR167 reduces the DSS-induced increase in mRNA transcript levels of inflammatory cytokines such as IL-1β, IL-6, IL-10, and IL-17A. Conclusions: We developed small anti-human IL-22R1 blockers with antagonistic properties that ascertain a substantial role of IL-22-mediated signaling in the development of intestinal inflammation. The developed ABR blockers can be useful as a molecular clue for further IBD drug development. [ABSTRACT FROM AUTHOR]

Background: The intake of high-fructose corn syrup (HFCS) may increase the risk of colorectal cancer (CRC). This study aimed to explore the potential effects and mechanisms of resistant starch (RS) in HFCS-induced colon tumorigenesis. Methods: The azoxymethane/dextran sodium sulfate (AOM/DSS) and ApcMin/+ mice models were used to investigate the roles of HFCS and RS in CRC in vivo. An immunohistochemistry (IHC) staining analysis was used to detect the expression of proliferation-related proteins in tissues. 16S rRNA sequencing for microbial community, gas chromatography for short-chain fatty acids (SCFAs), and mass spectrometry analysis for glycolysis products in the intestines were performed. Furthermore, lactic acid assay kit was used to detect the glycolysis levels in vitro. Results: RS suppressed HFCS-induced colon tumorigenesis through reshaping the microbial community. Mechanistically, the alteration of the microbial community after RS supplement increased the levels of intestinal SCFAs, especially butyrate, leading to the suppression of glycolysis and CRC cell proliferation by downregulating HK2. Conclusions: Our study identified RS as a candidate of protective factors in CRC and may provide a potential target for HFCS-related CRC treatment. [ABSTRACT FROM AUTHOR]

Delivering therapeutic agents efficiently to inflamed regions remains an intractable challenge following myocardial ischemia-reperfusion injury (MI/RI) due to the transient nature of the enhanced permeability and retention effect, which disappears after 24 h. Leveraging the inflammation-homing and plasticity properties of circulating monocytes (MN) as hitchhiking carriers and further inducing their polarization into anti-inflammatory phenotype macrophages upon reaching the inflamed sites is beneficial for MI/RI therapy. Herein, DSS/PB@BSP nanoparticles capable of clearing reactive oxygen species and inhibiting inflammation were developed by employing hollow Prussian blue nanoparticles (PB) as carriers to encapsulate betamethasone sodium phosphate (BSP) and further modified with dextran sulfate sodium (DSS), a targeting ligand for the scavenger receptor on MN. This formulation was internalized into MN as living cell drug depots, reprogramming them into anti-inflammation type macrophages to inhibit inflammation. In vitro assessments revealed the successful construction of the nanoparticle. In a murine MI/RI model, circulating MN laden with these nanoparticles significantly enhanced drug delivery and accumulation at the cardiac injury site, exhibiting favorable therapeutic ability and promoting M2-biased differentiation. Our study provides an effective approach with minimally invasion and biosecurity that makes this nanoplatform as a promising candidate for immunotherapy and clinical translation in the treatment of MI/RI. [Display omitted] [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H 2 S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H 2 S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases. We present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H 2 S) scavenging for synergistic alleviation of IBD. [Display omitted] • Montmorillonite coating enhanced on-site mucus-depleted intestinal colonization of probiotics. • Fe3+-modified Montmorillonite can scavenge elevated H 2 S and alleviate inflammatory factors, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. • Improved probiotic colonization and intestinal microenvironment regulation exhibited synergistic alleviation of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

As one of the most representative natural products among flavonoids, quercetin (QUE) has been reported to exhibit beneficial effects on gut health in recent years. In this study, we utilized a dextran sulfate sodium (DSS)-induced colitis mice model to explore the protective effects and underlying mechanisms of QUE on colitis. Our data demonstrated that QUE oral gavage administration significantly ameliorates the symptoms and histopathological changes associated with colitis. Additionally, the concentration of mucin-2, the number of goblet cells, and the expression of tight junction proteins (such as ZO-1, Occludin, and Claudin-1) were all found to be increased. Furthermore, QUE treatment regulated the levels of inflammatory cytokines and macrophage polarization, as well as the oxidative stress-related pathway (Nrf2/HO-1) and associated enzymes. Additionally, 16S rDNA sequencing revealed that QUE treatment rebalances the alterations in colon microbiota composition (inlcuding Bacteroidaceae, Bacteroides, and Odoribacter) in DSS-induced colitis mice. The analysis of network dynamics reveals a significant correlation between gut microbial communities and microenvironmental factors associated with inflammation and oxidative stress, in conjunction with the previously mentioned findings. Collectively, our results suggest that QUE has the potential to treat colitis by maintaining the mucosal barrier, modulating inflammation, and reducing oxidation stress, which may depend on the reversal of gut microbiota dysbiosis. [ABSTRACT FROM AUTHOR]

The objectives of this study were to design multilayer oil-in-water nanoemulsions using a layer-by-layer technique to enhance the stability of β-carotene and evaluate its effect on in vitro release and antioxidant activity. To prepare β-carotene-loaded multilayer nanoemulsions (NEs), a primary NE (PRI-NE) using Tween 20 was coated with chitosan (CS) for the secondary NE (SEC-CS), and with dextran sulfate (DS) and sodium alginate (SA) for the two types of tertiary NEs (TER-DS, TER-SA). The multilayer NEs ranged in particle size from 92 to 110 nm and exhibited high entrapment efficiency (92–99%). After incubation in a simulated gastrointestinal tract model, the release rate of free fatty acids decreased slightly after coating with CS, DS, and SA. The bioaccessibility of β-carotene was 7.02% for the PRI-NE, 7.96% for the SEC-CS, 10.88% for the TER-DS, and 10.25% for the TER-SA. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging abilities increased by 1.2 times for the multilayer NEs compared to the PRI-NE. In addition, the cellular antioxidant abilities improved by 1.8 times for the TER-DS (87.24%) compared to the PRI-NE (48.36%). Therefore, multilayer nanoemulsions are potentially valuable techniques to improve the stability, in vitro digestion, and antioxidant activity of β-carotene. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a debilitating chronic disease marked by persistent inflammation and intestinal fibrosis. Despite the availability of various treatments, many patients fail to achieve long-term remission, underscoring a significant unmet therapeutic need. BMS-477118, a reversible inhibitor of dipeptidyl peptidase 4 (DPP4), has demonstrated anti-inflammatory properties in preclinical and clinical studies with minimal adverse effects compared to other antidiabetic agents. However, the potential benefits of BMS-477118 in chronic UC have not yet been explored. In this study, we aimed to investigate the effects of BMS-477118 in rats subjected to chronic dextran sodium sulfate (DSS) administration. Our findings indicate that BMS-477118 activates the interconnected positive feedback loop involving AMPK, SIRT1, and FOXO3a, improving histological appearance in injured rat colons. BMS-477118 also reduced fibrotic changes associated with the chronic nature of the animal model, alleviated macroscopic damage and disease severity, and improved the colon weight-to-length ratio. Additionally, BMS-477118 prevented DSS-induced weight loss and enhanced tight junction proteins. These effects, in conjunction with reduced oxidative stress and its potential anti-inflammatory, antiapoptotic, and autophagy-inducing properties, fostered prolonged survival in rats with chronic UC. To conclude, BMS-477118 has the potential to activate the AMPK/SIRT1/FOXO3a signaling pathway in inflamed colons. These results suggest that the AMPK/SIRT1/FOXO3a pathway could be a new therapeutic target for UC. Further research is mandatory to explore the therapeutic possibilities of this pathway. Additionally, continued studies on the therapeutic potential of BMS-477118 and other DPP4 inhibitors are promising for creating new treatments for various conditions, including UC in diabetic patients. [ABSTRACT FROM AUTHOR]

In this study, the anticancer effect of doenjang according to the type of salt was investigated. Three samples were prepared: doenjang made with purified salt, doenjang made with generally manufactured solar salt, and doenjang made with washed and dehydrated solar salt (WDSD). In mice in which colon cancer was induced with azoxymethane/dextran sodium sulfate, doenjang made with solar salt, especially doenjang made with washed and dehydrated solar salt, was found to have a much higher colon cancer inhibition effect. WDSD significantly promoted the mRNA expression of apoptosis-related factors such as Bcl-2–associated X protein (Bax) and caspase 9 and the cell cycle arrest-related factors p53 and p21, and conversely significantly reduced the mRNA expression of apoptosis inhibitors such as B-cell lymphoma-2 (Bcl-2) (p < 0.05). Additionally, metabolites were investigated to determine which substances in WDSD exhibit this anticancer effect. As a result, the contents of isoflavone and soyasaponin B in the form of aglycons such as genistein, daidzein, and glycitein, which are known to have anticancer and anti-inflammatory properties, were found to be significantly high. Therefore, the results confirmed that doenjang prepared with washed and dehydrated solar salt has superior anticancer potential against colon cancer, and that various active ingredients contribute to the improvement of this functionality. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC), characterized by disrupted intestinal barrier integrity and chronic inflammation, was modeled in mice via dextran sulfate sodium (DSS) induction. This study explored the therapeutic potential of berberineevodiamine (BBR-EVO), bioactive components of the traditional Chinese medicine Yulian decoction, in DSS colitis. BBR-EVO intervention ameliorated weight loss, diarrhea, colonic shortening, and histopathological damage in colitic mice. The substance increased antioxidant activity while reducing high levels of pro-inflammatory cytokines in the colon, including as TNF-α, IL-1β, and IL-6. BBR-EVO inhibited the DSS-induced decrease in the tight junction proteins ZO-1 and occludin, according to immunohistochemistry. 16S rRNA sequencing demonstrated BBR-EVO partially attenuated DSS-elicited intestinal dysbiosis, reducing opportunistic pathogens and restoring diminished beneficial taxa. Critically, BBR-EVO alleviated secondary hepatic injury in colitic mice, mitigating immune cell infiltration, oxidative stress, cytokine production, and ultrastructural damage, likely by beneficially modulating gut-liver crosstalk. This study reveals BBR-EVO, derived from a traditional Chinese medicine, confers multi-target protective effects in experimental colitis and associated hepatic pathology, warranting further evaluation as a potential therapy for inflammatory bowel diseases like UC. The mechanisms may involve simultaneous augmentation of intestinal barrier integrity, inhibition of inflammation, microbiota regulation, and gut-liver axis optimization. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Selenium, an essential micronutrient for humans, has been shown to be protective against ulcerative colitis (UC), but the exact mechanism remains unclear. The role of selenium, protecting against ferroptosis of intestinal epithelial cells (IECs) in colitis, was investigated in this current study.Serum selenium level and ferroptosis‐related gene expression in the colonic mucosa were measured in UC patients and healthy controls. The effects of sodium selenite supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)‐treated mice. The influence of sodium selenite on IEC ferroptosis was evaluated through assessing cell death rate, intracellular ferrous iron content, lipid reactive oxygen species level, and mitochondrial membrane damage of DSS‐treated Caco‐2 cells. Moreover, glutathione peroxidase 4 (GPX4) and acyl‐CoA synthetase long‐chain family member 4, ferroptosis‐related genes, were detected in Caco‐2 cells and mouse intestines.Serum selenium was decreased in UC patients in comparison with healthy individuals. Additionally, serum selenium level was negatively correlated with disease activity and was associated with clinical inflammation and nutrition indicators. The expression of GPX4 in the mucosa of UC was positively correlated with serum selenium level. The in vivo experiments showed that selenium treatment ameliorated DSS‐induced colitis and inhibited ferroptosis in IECs. The in vitro results suggested that selenium supplementation inhibited DSS‐induced ferroptosis in Caco‐2 cells. GPX4 was upregulated after selenium supplementation both in vivo and in vitro.Serum selenium level was associated with IEC ferroptosis in UC patients. Selenium supplementation alleviates DSS‐induced colitis and inhibits ferroptosis in IECs by upregulating the expression of GPX4. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Curcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites. Methods: Forty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites. Results: Curcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5'-deoxy-5'-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4'-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05). Conclusions: The gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups. [ABSTRACT FROM AUTHOR]

Abstract\nPLAIN LANGUAGE SUMMARYInflammation induces tumor formation and plays a crucial role in tumor progression and prognosis. KCNK6, by regulating K(+) efflux to reduce NLRP3 Inflammasome-induced lung injury, relaxes the aorta. This study aims to elucidate the effects and biological mechanism of KCNK6 in inflammation-associated carcinogenesis, which may be essential for colon homeostasis and the defense system. To induce colitis, mice were given 3.0% Dextran Sodium Sulfate (DSS) in their drinking water for 7 days. The Azoxymethane (AOM) +DSS method was used to induce colon cancer in the mice model. Bone marrow-derived macrophages (BMDM) from Kcnk6-/- mice, AW264.7 cells, and human colon cancer HCT116 and Caco2 cells were used as in vitro models. The loss of Kcnk6 prevented spontaneous colitis and restored mucosal integrity and homeostatic molecules. Additionally, the loss of Kcnk6 reduced the severity of AOM/DSS-induced carcinogenesis. Kcnk6 promoted cell viability and proliferation in HCT-116 or Caco-2 cells. The loss of Kcnk6 inhibited the levels of inflammatory factors in BMDM cells. Kcnk6 accelerated potassium channel activity, inducing NLRP3 inflammasome activation. METTL3-mediated m6A modification increased Kcnk6 stability in a YTHDF2-dependent manner. Histone lactylation activated the transcription of YTHDF2/Kcnk6. Our study revealed the important role of Kcnk6 in inflammation-associated carcinogenesis progression. The m6A methyltransferase METTL3 and histone lactylation increased Kcnk6 stability in a YTHDF2-dependent manner, providing a potential strategy for inflammation-associated carcinogenesis or colorectal cancer therapy.Our study revealed the important role of Kcnk6 senescence in inflammation associated carcinogenesis progression. The m6A methyltransferase METTL3 and histone lactylation increased Kcnk6 stability in YTHDF2- dependent manner, providing a potential strategy for inflammation associated carcinogenesis or colorectal cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Worldwide, ulcerative colitis (UC) is becoming increasingly fast growing. Ginsenoside Rh2 has been reported to alleviate UC. However, the latent biological mechanism of Rh2 in the treatment of UC remains uncertain. In this study, the goal was to determine the therapeutic effect of Rh2 on dextran sulfate sodium (DSS)-induced UC. Methods: A DSS-induced UC mouse model was established and divided into 7 groups for Rh2 gavage and/or miR-125a-5p lentivirus injection (n = 10 per group). Colonic specimens were collected for phenotypic and pathological analysis. miR-125a-5p and specific protein 1 (SP1) expression, inflammation-related factors IL-6 and IL-10, and apoptosis were detected in mice. Human normal colon epithelial cell line NCM460 was treated with H2O2 and ferric chloride hexahydrate to construct an in vitro cell model of colitis and induce ferroptosis. Independent sample t-test was used to compare cell proliferation, cell entry, apoptosis, and oxidative stress between the two groups. One way analysis of variance combined with the least significant difference t test was used for comparison between groups. Multiple time points were compared by repeated measurement analysis of variance. Results: DSS-induced UC mice had significantly decreased body weight, increased disease activity index, decreased colon length, and decreased miR-125a-5p expression (all P < 0.05). In the DSS-induced mouse model, the expression of miR-125a-5p rebounded and ferroptosis was inhibited after Rh2 treatment (all P < 0.05). Inhibition of miR-125a-5p or upregulation of SP1 expression counteracted the protective effects of Rh2 on UC mice and ferroptosis cell models (all P < 0.05). Conclusions: Rh2 mitigated DSS-induced colitis in mice and restrained ferroptosis by targeting miR-125a-5p. Downregulating miR-125a-5p or elevating SP1 could counteract the protective impacts of Rh2 on ferroptotic cells. The findings convey that Rh2 has a latent application value in the treatment of UC. Highlights: Rh2 mitigates DSS-induced ferroptosis in mice; MiR-125a-5p represses DSS-induced ferroptosis in mice. Rh2 has protective impacts on ferroptotic cells. MiR-125a-5p targets SP1; Repression of miR-125a-5p or elevation of SP1 can counteract the protective effects of Rh2 on ferroptotic cells. [ABSTRACT FROM AUTHOR]

Exorbitant sustained inflammation is closely linked to inflammation-associated disorders, including cancer. The initiation of gastrointestinal cancers such as colorectal cancer is frequently accelerated by uncontrollable chronic inflammation which is triggered by excessive activation of nuclear factor kappa-B (NF-κB) signaling. Linear ubiquitin chains play an important role in activating canonical NF-κB pathway. The only known E3 complex, linear ubiquitin chain assembly complex is responsible for the synthesis of linear ubiquitin chains, thus leading to the activation of NF-κB axis and promoting the development of inflammation and inflammationassociated cancers. We report here cyclophilin J (CYPJ) which is a negative regulator of the linear ubiquitin chain assembly complex. The N terminus of CYPJ binds to the second Npl4 zinc finger (NZF) domain of HOIL-1-interacting protein and the ubiquitin-like domain of Shank-associated RH domain-interacting protein to disrupt the interaction between HOIL-1-interacting protein and Shank-associated RH domaininteracting protein and thus restrains linear ubiquitin chain synthesis and NF-κB activation. Cypj-deficient mice are highly susceptible to dextran sulfate sodium-induced colitis and dextran sulfate sodium plus azoxymethane-induced colon cancer. Moreover, CYPJ expression is induced by hypoxia. Patients with high expression of both CYPJ and hypoxiainducible factor-1a have longer overall survival and progression-free survival. These results implicate CYPJ as an unexpected robust attenuator of inflammation-driven tumorigenesis that exerts its effects by controlling linear ubiquitin chain synthesis in NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

The anti-inflammatory properties of Bacteroides fragilis vesicles were studied in a rat model of dextran sodium sulfate-induced colitis. According to the histology results, addition of B. fragilis vesicles to the therapy promoted colon repair. Evaluation of the disease activity index confirms the high rate of colon recovery: against the background of vesicle administration, the absence of blood in stool, normal stool consistency, and body weight normalization were observed. [ABSTRACT FROM AUTHOR]

Objective：Berberine hydrochloride (BBR) is commonly used for the treatment of ulcerative colitis (UC), but its molecular mechanism, especially the mechanism of rescue of inflammatory-induced pyroptosis, needs to be further analyzed. Methods：SD male rats were randomly divided into four groups：control group (Ctrl), DSS model group, BBR treatment group (DSS+BBR) and BBR+NLRP3 agonist group (DSS+BBR+BMS-986299) . The UC rat model was established by the dextran sulfate sodium method (DSS) . At the same time, BBR was intragastrically administered to BBR treatment group and BBR+NLRP3 agonist group twice per- day for 7 consecutive days. BMS-986299 was intraperitoneally injected to BBR+NLRP3 group twice a day. During the experiment, the body weights were weighed, the general condition was observed, and the disease activity index (DAI) was evaluated every day. After the experiment, the gross morphology and length of colon were observed and evaluated. HE staining was used to observe the pathologi‑ cal changes of colon tissue and evaluate the tissue injury index (TDI) . ELISA was employed for detecting the contents of TNF-α and IL-1β in colon tissue, and Western blot was employed for detecting NLRP3, ASC, GSDMD-N, Cleaved-caspase 1 and IL-1β expres‑ sions. Results：BBR could effectively improve the UC-induced weight loss, colon tissue integrity and cell pyroptosis, reduce the expression levels of inflammatory factors such as TNF-ɑ and IL-1β, the proportion of pyroptosis, and the levels of proteins NLRP3, IL-1β, GSDMD-N, and Cleaved-caspase 1 which play crucial roles in pyroptosis pathway. The therapeutic effect and the regulated pro‑ tein expression through BBR were reversed by NLRP3 activation. Conclusion：BBR exerts a therapeutic effect by reducing the proteins levels of mature NLRP3, IL-1β, GSDMD-N, Cleaved-caspase 1, which are responsible for pyroptosis pathway. This result provides a molecular basis for BBR in treatment of UC [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC). [ABSTRACT FROM AUTHOR]

It is believed that short-chain fatty acids (SCFAs)—the bacterial metabolites produced by the digestion of dietary fiber—potentially contribute to the prevention of colitis. However, this beneficial effect has not been conclusively proven. We thus attempted to verify this beneficial effect by examining whether colitis can be caused or worsened by the deficiency in dietary fiber in mice. We found that dextran sodium sulfate (DSS)-induced colitis was accelerated under a fiber-deficient condition, but the fiber deficiency itself did not provoke colitis. Moreover, episodes of diarrhea and epithelium damage in the large intestine were found upon analysis 24 h after the intervention. Unfortunately, these symptoms and tissue damage could not be ameliorated by administering SCFAs. On the other hand, a fiber-deficient condition increased the population of Desulfovibrio spp. and decreased the population of Lactobaccillus spp. regardless of the presence or absence of DSS upon analysis 24 h after the intervention. These results suggest that a deficiency in dietary fiber makes the intestinal environment irritable to colitis-inducing stimuli within the short term. This change does not appear to be related to the presence of SCFAs, but to the alteration of microbiota. Hence, a regular intake of dietary fiber is strongly recommended to avoid colitis and preserve intestinal health. [ABSTRACT FROM AUTHOR]

Background: Unbalanced gut microbiota is considered to cause dysfunction of the gut barrier function. Lactobacillus johnsonii MG, isolated from mouse feces as gut associating lactobacilli, enhanced gut barrier function in Caco‐2 cells via interaction with JAM‐2 in tight junctions. In this study, the anti‐inflammatory effects of L. johnsonii MG were investigated in a colitis mouse model developed by treating mice with 3% dextran sulfate sodium (DSS) for 9 days. Results: MG treatment of colitis mice resulted in fast recovery of the body weight and showed significant improvement in the disease activity index and histopathological scores. The histomorphological score increased by DSS treatment was significantly improved in the MG‐treated group. In the intestine, the expression of Ocln, Zo1, Itga6, Lama3, and Jam2 genes, which are involved in tight junction functions, were significantly upregulated in MG‐treated colitis mice. In the microflora analysis, the abundance of Ruminococcaceae, Bacteroides, and Lachnospiraceae were reduced in DSS‐treated mice and recovered by MG treatment. Conclusion: We reported the potential of L. johnsonii MG in the regeneration of crypts and integrity of matrix proteins in the gut of mice with colitis through its association with tight junctions. The experimental results provide new insights into the probiotic effect of tight junction associating L. johnsonii MG. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Milk contains abundant polar lipids, which are vital constituents of biological membranes. These polar lipids are present in the human diet as phospholipids and sphingolipids. Nevertheless, the limited focus has been on the attributes and role of camel milk polar lipids (MPL). In this study, camel MPL were isolated, and the composition of their lipidome was determined using ultra-high-performance liquid chromatography-tandem MS. This study characterized a total of 333 polar lipids, which encompassed glycerophospholipids and sphingolipids. Camel milk is rich in polar lipids, mainly phosphatidylethanolamine, sphingomyelin, and phosphatidylcholine. The results indicated that MPL intervention relieved the clinical symptoms and colon tissue damage in mice with dextran sulfate sodium-induced colitis, along with suppressing the expression of proinflammatory cytokines. Moreover, the administration of MPL partially alleviated mouse gut microbiota dysbiosis by increasing the abundance of probiotics (such as Lachnospiraceae_NK4A136_group and Muribaculaceae) and decreasing the number of harmful bacteria (such as Bacteroides and Parabacteroides). This study was conducted to investigate the potent protective effects of MPL in camel milk treatments on a mouse model of colitis and provided new ideas for the application of camel milk. [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND: Ulcerative colitis (UC) refers to an idiopathic chronic inflammatory bowel disease that starts with inflammation of the intestinal mucosa. Dietary fiber plays a crucial role in maintaining the normal architecture of the intestinal mucosa. In this study, the protective effect and potential mechanism of soluble dietary fiber from Rosa roxburghii Tratt residue (SDFR) on dextran sulfate sodium (DSS)‐induced UC mice were explored. RESULTS: The results revealed that SDFR could ameliorate body weight loss and pathological injury, improve the structure and crypt destruction in colon in DSS‐induced mice. Moreover, the levels of NO, IL‐1β, TNF‐α, MPO and protein expression of iNOS and COX‐2 were decreased after administration of SDFR. Notably, nontargeted metabolomics analysis indicated that there were significant differences in 51 potential metabolites in serum between the DSS and control groups. SDFR intervention could regulate aberrant alterations of these metabolites and mitigate UC via regulating metabolic pathways, including arachidonic acid and glycerophospholipid metabolism. CONCLUSION: This study provides novel evidence that SDFR could be used as a potential modulator to relieve UC. Also, the results provide a theoretical basis for the utilization of byproducts in Rosa roxburghii Tratt fruit processing. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Our newly developed menthyl esters of valine and isoleucine exhibit anti‐inflammatory properties beyond those of the well‐known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold‐sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS‐stimulated tumour necrosis factor‐alpha (Tnf) expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non‐competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti‐inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3‐L1 adipocytes at the mitotic clonal expansion stage in an LXR‐independent manner as well as in mice subjected to diet‐induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Yellow tea (YT), a slightly fermented tea with a unique yellowing process and mellow taste, is becoming widely popular. Currently, the YT includes bud yellow tea (BYT), small-leaf yellow tea (SYT), and large-leaf yellow tea (LYT) based on maturity of raw materials. Previous studies have shown that YT has outstanding potential in preventing metabolic syndrome. However, the distinct effects and mechanisms of different types of YT on ulcerative colitis (UC) are still unclear. This study investigated the effects and mechanisms of continuous or intermittent intervention of three yellow tea water extracts (YTEs) on dextran sulfate sodium (DSS)-induced ulcerative colitis in CD-1 mice. The results showed that YTE intervention significantly improves the syndrome of DSS-induced UC in mice. Mechanistic studies reveal that YTEs increase the expression levels of tight junction (TJ) proteins and reduce the levels of pro-inflammatory cytokines in the colon by inactivating TLR4/NF-κB/NLRP3. YTE treatment protected intestinal barrier integrity and reduced serum lipopolysaccharide (LPS) levels. Interestingly, our results indicate that large-leaf yellow tea (LYT) has a better alleviating effect than BYT and SYT. YTE intervention before DSS administration has a certain degree of preventive effect on ulcerative colitis, while continuous YTE intervention after DSS induction has a significant reversing effect on the damage caused by DSS. Our results indicated that drinking YT may have preventive and therapeutic effect on UC, especially drinking LYT. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated.The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short‐chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT.Supplementation of ULP combined with FMT could significantly ameliorate DSS‐induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the antiinflammatory effects of Kumujan B using both the TNF-α-induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease with a relapsing–remitting course. Although its etiology remains unknown, excessive oxidative stress in colon is a major intermediate factor that can promote the progression of UC. In the present study, we investigated the effect and the underlying mechanisms of 4-Octyl itaconate (OI) on dextran sulfate sodium (DSS)-induced UC in mice. Our work identified that OI alleviated the colitis by reducing the oxidative stress and the apoptosis in colon tissue, then increasing the tight junction proteins expression and in turn enhancing the intestinal barrier function, thereby creating less severe inflammatory responses. Moreover, our results demonstrated that OI reduced the Kelch-like ECH-associated protein 1 (KEAP1) expression and subsequent upregulated nuclear factor E2-related factor (NRF2) expression and its nuclear translocation which in turn induced the expression of glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). In addition, ML385, a NRF2 antagonist, can inhibit the protective effects of OI on UC, indicating that the role of OI in this colitis model could be dependent on the activation of KEAP1-NRF2 pathway. Notably, OI co-administration significantly enhanced the therapeutic effects of mesalazine or 1400W on UC. Collectively, itaconate may have a great potential for use in the treatment of IBD. [ABSTRACT FROM AUTHOR]

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium‐induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200‐fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo‐oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation. [ABSTRACT FROM AUTHOR]

In this study, we investigated the role of hypoxia in the development of chronic inflammatory bowel disease (IBD), focusing on its impact on the HIF-1α signaling pathway through the upregulation of lipocalin 2 (LCN2). Using a murine model of colitis induced by sodium dextran sulfate (DSS) under hypoxic conditions, transcriptome sequencing revealed LCN2 as a key gene involved in hypoxia-mediated exacerbation of colitis. Bioinformatics analysis highlighted the involvement of crucial pathways, including HIF-1α and glycolysis, in the inflammatory process. Immune infiltration analysis demonstrated the polarization of M1 macrophages in response to hypoxic stimulation. In vitro studies using RAW264.7 cells further elucidated the exacerbation of inflammation and its impact on M1 macrophage polarization under hypoxic conditions. LCN2 knockout cells reversed hypoxia-induced inflammatory responses, and the HIF-1α pathway activator dimethyloxaloylglycine (DMOG) confirmed LCN2's role in mediating inflammation via the HIF-1α-induced glycolysis pathway. In a DSS-induced colitis mouse model, oral administration of LCN2-silencing lentivirus and DMOG under hypoxic conditions validated the exacerbation of colitis. Evaluation of colonic tissues revealed altered macrophage polarization, increased levels of inflammatory factors, and activation of the HIF-1α and glycolysis pathways. In conclusion, our findings suggest that hypoxia exacerbates colitis by modulating the HIF-1α pathway through LCN2, influencing M1 macrophage polarization in glycolysis. This study contributes to a better understanding of the mechanisms underlying IBD, providing potential therapeutic targets for intervention. [ABSTRACT FROM AUTHOR]

Xanthine oxidoreductase (XOR) serves as the primary source of hydrogen peroxide and superoxide anions in the intestinal mucosa. However, its specific contribution to the progression of colonic disease remains unclear. In this study, we investigated the role of XOR in ulcerative colitis (UC) and attempted to identify the underlying mechanisms. We used the dextran sulfate sodium (DSS)–induced mouse model to mimic UC and observed that XOR inhibitors, allopurinol and diphenyleneiodonium sulfate (DPI), significantly alleviated UC in mice. In addition, treatment with cobalt chloride (CoCl2) and 1% O2 increased the expression of XOR and induced DNA oxidative damage in colonic epithelial cells. Furthermore, we identified that XOR accumulation in the nucleus may directly cause DNA oxidative damage and regulates HIF1α protein levels. In addition, allopurinol effectively protected colon epithelial cells from CoCl2-induced DNA damage. Altogether, our data provided evidence that XOR could induce DNA damage under hypoxic conditions, indicating a significant role of XOR in the initiation and early development of colitis-associated colorectal cancer (CAC). [ABSTRACT FROM AUTHOR]