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Maternal immunity plays a vital role in protecting offspring from pathogen invasion, and it is present in nearly all vertebrates. As the most ancient vertebrates, teleost fish continuously secrete a substantial amount of mucus due to their unique living environment, and often exhibit schooling behavior. Previous studies have highlighted the presence of numerous immune components in the mucus of fish, that plays a crucial role in resisting pathogens. We hypothesize that this represents a distinctive maternal immune response mechanism in fish. In this study, we established a dextran sulfate sodium (DSS)-induced injury model by immersing zebrafish larvae in 0.5% DSS. This elicited robust inflammatory responses and showed DSS-induced alterations in microbial abundance via 16S rRNA sequencing. These changes included the disruption of normal gut structure; an increase in goblet cells; increased expression of inflammatory cytokines; and infiltration of neutrophils and macrophages into the gut, as well as an increase in pathogenic bacteria and a decline in probiotic bacteria. Furthermore, we conducted a mucus protection test by adding adult zebrafish mucus in fish tank water containing 0.5% DSS to test our hypothesis. As suspected, the mucus from adult zebrafish exhibited a protective role in defending zebrafish larvae against DSSinduced enteritis by alleviating excessive inflammatory responses and increasing probiotic abundance. In conclusion, our results confirm a significant role of adult fish mucus in the immune response of teleost fish to DSSinduced inflammation. Collectively, our findings show that the mucus of adult zebrafish may represent a novel form of maternal immunization, playing roles analogous to mammalian milk in immune regulatory functions. [ABSTRACT FROM AUTHOR]

Oxidative stress is implicated in the pathogenesis of various acute disorders including ischemia/reperfusion injury, ultraviolet/radiation burn, as well as chronic disorders such as dyslipidemia, atherosclerosis, diabetes mellitus, chronic renal disease, and inflammatory bowel disease (IBD). However, the precise mechanism involved remains to be clarified. We formerly identified a novel apoptosis-inducing humoral protein, in a hypoxia/reoxygenation-conditioned medium of cardiac myocytes, which proved to be 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A). We named this novel tyrosine-sulfated secreted form of eIF5A Oxidative Stress-Responsive Apoptosis-Inducing Protein (ORAIP). To investigate the role of ORAIP in a dextran sulfate sodium (DSS)-induced murine model of ulcerative colitis (UC), we analyzed the effects of in vivo treatment with anti-ORAIP neutralizing monoclonal antibody (mAb) on the DSS-induced disease exacerbation. The body weight in anti-ORAIP mAb-treated group was significantly heavier than that in a mouse IgG-treated control group on day 8 of DSS-treatment ((85.21 ± 1.03%) vs. (77.38 ± 2.07%); (mean ± SE0, n = 5 each, p < 0.01, t-test). In vivo anti-ORAIP mAb-treatment also significantly suppressed the shortening of colon length as well as Disease Activity Index (DAI) score ((5.00 ± 0.44) vs. (8.20 ± 0.37); (mean ± SE), n = 5 each, p < 0.001, t-test) by suppressing inflammation of the rectal tissue and apoptosis of intestinal mucosal cells. These data reveal the pivotal role of ORAIP in DSS-induced oxidative stress involved in an animal model of UC. [ABSTRACT FROM AUTHOR]

This paper aims to explore the effect and mechanism of water-soluble astaxanthin succinate diester (Asta-SD) on ulcerative colitis (UC) induced by dextran sodium sulfate in zebrafish and C57BL/6J mice. Asta-SD was synthesized with hydrophilic fatty acid succinic anhydride and the hydroxyl groups at the ends of F-Asta were synthesized by esterifying. Through the construction of a zebrafish intestinal inflammation model, it was found that Asta-SD could effectively reduce the levels of ROS and increase the number of healthy intestinal lysosomes in zebrafish. After continuous gavage of Asta-SD for seven days, the body weight, disease activity index, colonic length, colonic histopathology, expression of inflammatory factors, and intestinal flora of the mice were measured. The results showed that Asta-SD could significantly alleviate weight loss and colonic shrinkage, as well as reducing pro-inflammatory cytokines and recess injury in UC mice. The 16S rRNA gene sequencing showed that Asta-SD significantly increased the beneficial bacteria (Lactobacillus, Anaerotruncus) and decreased the relative abundance of pathogenic bacteria, effectively maintaining intestinal microbiota homeostasis in mice. Based on Pearson analysis, Bacteroides, Parabacteroides, and Butyrimionas were expected to be associated with the significant difference in the expression of inflammatory factors between the UC and the corresponding host. Thus, Asta-SD significantly improves UC and maintains intestinal microbiota homeostasis. [ABSTRACT FROM AUTHOR]

Oxidative stress is implicated in the pathogenesis of various acute disorders including ischemia/reperfusion injury, ultraviolet/radiation burn, as well as chronic disorders such as dyslipidemia, atherosclerosis, diabetes mellitus, chronic renal disease, and inflammatory bowel disease (IBD). However, the precise mechanism involved remains to be clarified. We formerly identified a novel apoptosis-inducing humoral protein, in a hypoxia/reoxygenation-conditioned medium of cardiac myocytes, which proved to be 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A). We named this novel tyrosine-sulfated secreted form of eIF5A Oxidative Stress-Responsive Apoptosis-Inducing Protein (ORAIP). To investigate the role of ORAIP in a dextran sulfate sodium (DSS)-induced murine model of ulcerative colitis (UC), we analyzed the effects of in vivo treatment with anti-ORAIP neutralizing monoclonal antibody (mAb) on the DSS-induced disease exacerbation. The body weight in anti-ORAIP mAb-treated group was significantly heavier than that in a mouse IgG-treated control group on day 8 of DSS-treatment ((85.21 ± 1.03%) vs. (77.38 ± 2.07%); (mean ± SE0, n = 5 each, p < 0.01, t-test). In vivo anti-ORAIP mAb-treatment also significantly suppressed the shortening of colon length as well as Disease Activity Index (DAI) score ((5.00 ± 0.44) vs. (8.20 ± 0.37); (mean ± SE), n = 5 each, p < 0.001, t-test) by suppressing inflammation of the rectal tissue and apoptosis of intestinal mucosal cells. These data reveal the pivotal role of ORAIP in DSS-induced oxidative stress involved in an animal model of UC.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disorder. Pharmacotherapy serves as the main treatment strategy for IBD; however, the current medications have certain limitations, such as inefficacy and a tendency to induce tolerance, thereby requiring the development of innovative drugs to fulfill therapeutic requirements. A model of acute colitis induced with a solution of approx. 3% dextran sulfate sodium (DSS) has been widely used in preclinical drug development. Nevertheless, this model has some drawbacks, including rapid disease progression leading to mortality in some mice and disparities between the inflammatory characteristics of mice and the pathological features of human IBD. The current study found that mice freely consuming a lower concentration of a DSS solution (1-1.5%) for 10-15 days exhibited milder colitis symptoms. Continued consumption of the DSS solution for 15-20 days resulted in chronic inflammation in colon tissue, accompanied by a significant increase in the proportion of Th1 cells, indicating the involvement of adaptive immune responses. Subsequently, mice were treated with mesalazine or Centella triterpenes while concurrently consuming the DSS solution for 10 days. The treated mice had significant improvements in body weight and colon length compared to the control group. The advantages of this subacute model include minimal mortality among experimental mice and the fact that intestinal mucosal inflammation in mice resembles the pathological features of human IBD, enabling the assessment of drug efficacy against IBD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Saccharomyces boulardii and its freeze-dried and spray-dried postbiotics on the intervention and potential mechanism of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. [Methods] After the acclimation period of C67BL/6J mice, a colitis model was constructed by applying 2% DSS for 7 d, followed by 7 d of intervention. Subsequently, the disease activity index (DAI), organ index, colon length, colon HE staining of pathological sections, ELISA for blood inflammatory factors (Interleukin (IL)-1β, IL-6, IL-10, Tumor necrosis factor (TNF)-α), Real time quantitative polymerase chain reaction (RT-qPCR) to determine the levels of colonic inflammatory factors (IL-1β, IL-6, IL-10, TNF-α), Occludin gene expression, and intestinal flora were assessed to evaluate the protective effects of S. boulardii and its postbiotics on colitis in mice. Results: Compared with the DSS group, S. boulardii and the postbiotics interventions effectively improved colonic shortening and tissue damage, increased the expression of intestinal tight junction protein, reduced the secretion of pro-inflammatory factors, increased the secretion of anti-inflammatory factors, and maintained the homeostasis of intestinal microorganisms. Postbiotics intervention is better than probiotics. Conclusions: S. boulardii and its postbiotics can effectively alleviate DSS-induced colitis in mice through modulating host immunity and maintaining intestinal homeostasis. Postbiotics are promising next-generation biotherapeutics for ulcerative colitis treatment. [ABSTRACT FROM AUTHOR]

This paper aims to explore the effect and mechanism of water-soluble astaxanthin succinate diester (Asta-SD) on ulcerative colitis (UC) induced by dextran sodium sulfate in zebrafish and C57BL/6J mice. Asta-SD was synthesized with hydrophilic fatty acid succinic anhydride and the hydroxyl groups at the ends of F-Asta were synthesized by esterifying. Through the construction of a zebrafish intestinal inflammation model, it was found that Asta-SD could effectively reduce the levels of ROS and increase the number of healthy intestinal lysosomes in zebrafish. After continuous gavage of Asta-SD for seven days, the body weight, disease activity index, colonic length, colonic histopathology, expression of inflammatory factors, and intestinal flora of the mice were measured. The results showed that Asta-SD could significantly alleviate weight loss and colonic shrinkage, as well as reducing pro-inflammatory cytokines and recess injury in UC mice. The 16S rRNA gene sequencing showed that Asta-SD significantly increased the beneficial bacteria (Lactobacillus, Anaerotruncus) and decreased the relative abundance of pathogenic bacteria, effectively maintaining intestinal microbiota homeostasis in mice. Based on Pearson analysis, Bacteroides, Parabacteroides, and Butyrimionas were expected to be associated with the significant difference in the expression of inflammatory factors between the UC and the corresponding host. Thus, Asta-SD significantly improves UC and maintains intestinal microbiota homeostasis.

Ulcerative colitis is one of the main gastrointestinal diseases that threaten human health. This study investigated the effect of Limosilactobacillus fermentum HFY06 (LF-HFY06) on dextran sulfate sodium (DSS)-induced murine colitis. The protective effect of LF-HFY06 was evaluated by examining the length and histopathological sections of colon, related biochemical indicators, and genes related to inflammation. Direct and microscopic observations showed that LF-HFY06 increased the length of the colon and ameliorated the pathological damage induced by DSS. The biochemical indicators showed that LF-HFY06 enhanced the activities of antioxidant enzymes total superoxide dismutase (T-SOD) and catalase (CAT) in serum, while reducing the level of malondialdehyde (MDA). It was also observed that the serum inflammatory cytokines levels of tumor necrosis factor-a (TNF-a), interferon (IFN)-g, interleukin (IL)-1β, IL-6, and IL-12 were decreased, and the anti-inflammatory cytokine IL-10 level was increased. The qPCR experiment revealed that LF-HFY06 downregulated the mRNA expression levels of nuclear factor-kB-p65 (Rela), Tnf, Il 1b, Il 6, and prostaglandinendoperoxide synthase 2 (Ptgs2) in colon tissues, and upregulated the mRNA expression of NF-kB inhibitor-a (Nfkbia) and Il 10. These data indicated that LFHFY06 inhibited inflammation through the NF-kB signaling pathway to prevent the occurrence and development of colitis. This research demonstrates that probiotics LF-HFY06 have the potential to prevent and treat colitis. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effects of radish sprout ethanol extract (RSE) on inflammatory responses in the macrophages and a mouse model of colitis. RSE administration was found to effectively inhibit the phosphorylation of IκB and, in turn, the production of pro-inflammatory enzymes and cytokines in lipopolysaccharide-stimulated macrophages. In dextran sulfate sodium (DSS)-colitis mice, RSE administration prevented body weight and colon length reduction, while decreasing inflammation and mucosal necrosis. The diversity of the fecal microbiota was significantly increased in the group treated with RSE. In addition, RSE administration decreased the relative abundance of the phylum Proteobacteria, which includes many pathogens, and increased the abundance of the genus Akkermansia. Beta diversity analyses showed that RSE administration restored the gut microbiota composition close to that of healthy mice. For the first time, we identified glycosides of sinapic acid as part of hydroxycinnamic acids in RSE with colitis-alleviating effects. Notably, 1,2-O-disinapoyl glucoside substantially decreased nitric oxide generation in LPS-stimulated macrophages.

Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides. [ABSTRACT FROM AUTHOR]

Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides.

Inflammatory bowel disease, an intestinal relapsing inflammatory disease, not only impairs gastrointestinal function but also increases the chances of developing colon cancer. Currently, the effects of shrimp peptide (SP) in mice model of ulcerative colitis (UC) are still unclear. In particular, it is uncertain whether SP affects the gut flora with UC mice. In this study, we investigated the anti-inflammatory effects of SP on a dextran sulfate sodium (DSS)-induced mouse model of UC. Firstly, the molecular weight of SP was mainly distributed in the range of 180–1,000 Da (61.95% proportion), and the amino acid composition showed that SP contained 17 amino acids, of which, the essential amino acids accounted for 54.50%. In vivo, oral SP significantly attenuated the severity of colitis, such as diarrhea, weight loss, and rectal bleeding. Furthermore, treatment with SP remarkably ameliorated intestinal barrier integrity, thus lowering the levels of the inflammatory cytokines and ameliorating antioxidant indices and intestinal injury indicators in the serum and colon. Lastly, the cecal contents were used to sequence and analyze the 16S rRNA genes of bacteria. Results suggested that treatment with SP could restore the balance of intestinal flora in modeled mice by regulating the abundance of pathogenic and beneficial bacteria. Furthermore, SP could significantly improve intestinal flora dysfunction in mice with UC. In summary, our findings show that SP has a prophylactic and therapeutic effect in UC in vivo, thereby highlighting its broad medicinal applications.

The cell adhesion molecule CHL1, which belongs to the immunoglobulin superfamily, functions in a variety of physiological and pathological processes, including neural development, tissue injury, and repair. We previously found that the loss of CHL1 exacerbated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we further addressed the role of CHL1 in mouse model of DSS-induced colitis and its’ potential mechanism. Colon tissues were collected from CHL1+/+, CHL1+/−, and CHL1−/− mice after DSS induction to investigate the effects of CHL1 on the development of colitis. The data showed that CHL1 was expressed in intestine tissue, and expression of CHL1 was increased by DSS-induced inflammation. CHL1 deficiency induced more pronounced colitis features, exacerbated inflammation, and damage to colonic tissues in DSS-induced mice. Moreover, colonic tissues of CHL1−/− mice showed a marked increase in neutrophil and macrophage infiltration, be accompanied by more severe damage to intestinal epithelial cells and higher fluorescein isothiocyanate (FITC) leakage. Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice.

Ulcerative colitis is an inflammatory bowel disease that affects a large number of people around the world. Galectin-1 is a β-galactoside-binding lectin with a broad range of biological activities. The effects of galectin-1 on dextran sulfate sodium (DSS)-induced ulcerative colitis in vivo is not clear. We investigated the effect of galectin-1 on colon morphology, cell proliferation, oxidative stress, antioxidant system, and proinflammatory/antiinflammatory cytokines in a DSS-induced mouse model of ulcerative colitis. Thirty-two C57BL/6 mice were randomly assigned to one of the four groups: control, acute colitis, galectin-1, and DSS+galectin-1. Controls were treated with phosphate-buffered saline (PBS) for seven days. Acute colitis was induced by 3% DSS in drinking water administered orally for five days. Mice in galectin-1 groups were treated with 1 mg/kg recombinant human galectin-1 in PBS for seven consecutive days. Oral DSS administration resulted in acute colitis by causing histopathological changes; an increase in disease activity index (DAI), lipid peroxidation (malondialdehyde [MDA]), myeloperoxidase (MPO), and tumor necrosis factor (TNF)-α levels; a decrease in body weight, colon length, cell proliferation index, catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and GSH and interleukin (IL)-10 levels. The treatment with galectin-1 attenuated DSS-induced acute colitis by reducing DAI, MDA, MPO, and TNF-α levels and by increasing body weight, colon length, cell proliferation, antioxidant enzyme activity, GSH, and IL-10 levels. These findings suggest that galectin-1 has proliferative, antioxidant, antiinflammatory, and cytoprotective effects against DSS-induced ulcerative colitis in mice. Due to its antiinflammatory and antioxidant activity galectin-1 may be effective in preventing and treating ulcerative colitis.

Flaxseed oil is a type of herbal oil obtained from the ripened seeds of the flax plant (Linum usitatissimum L.) that is widely utilized for baked foods. The aim of present study was to investigate the effect of flaxseed oil on ulcerative colitis. The rats were gavaged daily with flaxseed oil at doses of 400, 800 and 1600 mg/kg b.w. for six weeks, while ulcerative colitis was induced by daily administrating with 3% (w/v) dextran sulfate sodium (DSS) on the sixth week. Results showed that the rats fed with flaxseed oil had less disease activity index, colon weight, colon weight/length ratio and colon cell damage. Flaxseed oil consumption relieved the oxidative condition, reduced colon inflammation and partly restored the microbiota change by DSS. Flaxseed oil (1600 mg/kg b.w.) has a great potential in prevention of ulcerative colitis possibly by regulating the oxidative condition, inflammatory factors and cecal microbiota.

Inflammatory bowel disease (IBD) is a lifelong chronic inflammation of the gastrointestinal tract. Polysaccharides from mushrooms have been extensively used to treat inflammatory diseases including IBD. Dictyophora indusiata polysaccharide (DIP) modulates gut microbiota and alleviate inflammatory reactions; however, its effect on ulcerative colitis (UC) is yet to explore. In this study DIP effect on DSS induced colitis was determined. Our findings revealed that DIP treatment alleviated the severity of colitis, especially at the high dose. The histopathological alterations and gut epithelial integrity were ameliorated. The inflammatory reactions and oxidative stress were improved. Moreover, proinflammatory cytokines were reduced, conversely, anti-inflammatory cytokines and tight junction proteins (TJs) were elevated. Furthermore, Illumina MiSequencing exhibited perturbation of bacterial community upon DSS treatment; however, the bacterial shift was reversed after DIP treatment. Inclusively, our findings suggest mushroom polysaccharides may have a potential therapeutic effect against colitis and inflammatory-related diseases.

The cell adhesion molecule CHL1, which belongs to the immunoglobulin superfamily, functions in a variety of physiological and pathological processes, including neural development, tissue injury, and repair. We previously found that the loss of CHL1 exacerbated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we further addressed the role of CHL1 in mouse model of DSS-induced colitis and its' potential mechanism. Colon tissues were collected from CHL1+/+, CHL1+/−, and CHL1−/− mice after DSS induction to investigate the effects of CHL1 on the development of colitis. The data showed that CHL1 was expressed in intestine tissue, and expression of CHL1 was increased by DSS-induced inflammation. CHL1 deficiency induced more pronounced colitis features, exacerbated inflammation, and damage to colonic tissues in DSS-induced mice. Moreover, colonic tissues of CHL1−/− mice showed a marked increase in neutrophil and macrophage infiltration, be accompanied by more severe damage to intestinal epithelial cells and higher fluorescein isothiocyanate (FITC) leakage. Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) comprises two major illnesses: Crohn's disease (CD) and ulcerative colitis (UC). Dextran sulfate sodium (DSS) mouse colitis model has been used in understanding the mechanism of IBD. This study was conducted to examine selected Lactobacillus spp. as potential IBD treatment in the DSS-induced animal model. Balb/c mice were used and colitis was induced by adding 5% dextran sodium sulfate into the drinking water for 8 days. Colon length, disease activity index (DAI) and histological analysis were measured as markers of inflammation in DSS colitis mice. The majority of the Lactobacillus species significantly prevented the shortening of the colon length compared with the DSS group. The DAI scores of mice were significantly reduced following usage of four Lactobacillus strains included: Lactobacillus plantarum 03 and 06, Lactobacillus brevis 02 and Lactobacillus rhamnosus 01. The histological analysis exhibited that oral administration of Lactobacillus strains had therapeutic effects on mice colitis. L. plantarum and L. brevis showed better therapeutic effect against DSS-induced acute colitis mice. The probiotic activities of these three isolates indicated that the probiotic effects were strain specific and none of these useful bacteria could exhibit all of the valued probiotic properties simultaneously. [ABSTRACT FROM AUTHOR]

Dextran sulfate sodium is used in inflammatory bowel disease (IBD) mice models to trigger chronic intestinal inflammation. In this study, we have analyzed DSS effects in the genetic model and pest beetle, Tribolium castaneum , which can be easily and cost-effectively cultivated and examined in very large quantities compensating for individual variations. We fed the larvae with DSS and uracil, which is known to induce the production of reactive oxygen species by activating DUOX, a member of the NADPH oxidase family. Both chemicals induced IBD-like phenotypes, including impaired growth and development, midgut thickening, epithelial swelling, and a loss of epithelial barrier function. RNAi mediated knockdown of DUOX expression enhanced the effects of DSS and uracil on mortality. Finally, we showed that both treatments result in an altered activity of the intestinal microbiome, similar as observed in IBD patients. Our findings suggest that both chemicals impair the epithelial barrier by increasing the permeability of the peritrophic matrix. The loss of the barrier function may facilitate the entry of midgut bacteria triggering innate immune responses that also affect the intestinal microbiome. As the observed effects resemble those induced by DSS treatment in mice, T. castaneum might be suitable high-throughput invertebrate model for IBD research and preclinical studies. [Display omitted] • Dextran sulfate sodium (DSS) is used in mice models to induce IBD-like colitis. • Uracil is known to trigger the DUOX pathway in insects. • DSS and uracil treatments affect weight, mortality and development of T. castaneum. • Both treatments trigger intestinal inflammation and disrupt PM barrier function. • The activity of the intestinal microbiome is altered in response to both treatments. [ABSTRACT FROM AUTHOR]

Gochujang is a traditional Korean fermented soy-based spicy paste made of meju (fermented soybean), red pepper powder, glutinous rice, and salt. This study investigated the anti-inflammatory effects of Gochujang containing salt in DSS-induced colitis. Sprague–Dawley (SD) rats were partitioned into five groups: normal control, DSS control, DSS + salt, DSS + mesalamine, and DSS + Gochujang groups. They were tested for 14 days. Gochujang improved the disease activity index (DAI), colon weight/length ratio, and colon histomorphology, with outcomes similar to results of mesalamine administration. Moreover, Gochujang decreased the serum levels of IL-1β and IL-6 and inhibited TNF-α, IL-6, and IL-1β mRNA expression in the colon. Gochujang downregulated the expression of iNOS and COX-2 and decreased the activation of NF-κB in the colon. Gochujang induced significant modulation in gut microbiota by significantly increasing the number of Akkermansia muciniphila while decreasing the numbers of Enterococcus faecalis and Staphylococcus sciuri. However, compared with the DSS group, the salt group did not significantly change the symptoms of colitis or cytokine levels in serum and colon. Moreover, the salt group significantly decreased the gut microflora diversity. Gochujang mitigated DSS-induced colitis in rats by modulating inflammatory factors and the composition of gut microflora, unlike the intake of salt alone.

Colitis severely affects the quality of life of patients, and lactic acid bacteria have been reported to be able to improve or treat colitis. In this study, we selected a strain of Lactobacillus fermentum (CQPC04) with good resistance in vitro to evaluate its effect on improvement in mice with dextran sulfate sodium (DSS)–induced colitis. We analyzed the effects of L. fermentum CQPC04 on mice with colitis macroscopically via colon length and histopathology. We also used conventional biochemical and ELISA kits, real-time quantitative PCR (RT-qPCR), and Western blotting to analyze microscopically the effects of L. fermentum CQPC04 on related oxidant indices and pro- and anti-inflammatory cytokines in serum and colon tissue of mice. The results indicated that L. fermentum CQPC04 notably increased colon length and ameliorated pathological damage of colon tissue in colitic mice. Serum indices showed that L. fermentum CQPC04 increased the enzyme activity of total superoxide dismutase (T-SOD) and catalase (CAT) and decreased the content of malondialdehyde (MDA) and the activity of myeloperoxidase (MPO). In addition, it inhibited the release of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IFN-γ, IL-1β, IL-6, and IL-12, and increased the release of the anti-inflammatory cytokine IL-10 in serum. The RT-qPCR experiments confirmed that L. fermentum CQPC04 downregulated the expression of pro-inflammatory cytokine nuclear factor-κB-p65 (NF-κBp65), NF-κB inhibitor-α (IκB-α), TNF-α, IFN-γ, IL-1β, IL-6, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS), and upregulated the expression of IL-10 in colon tissue. Western blot analysis indicated that L. fermentum CQPC04 significantly reduced expression of NF-κBp65, TNF-α, IL-1β, COX-2, and iNOS in mouse colon tissues, and increased expression of IκB-α and superoxide dismutase 2 (SOD2). Thus, L. fermentum CQPC04 could effectively alleviate the symptoms of DSS-induced colitis mice and is a potential probiotic for human experiments. [ABSTRACT FROM AUTHOR]

Isaria cicadae Miquel (IcM) is an edible fungus used in traditional Chinese medicine. In this study, we identified the nutritional components of IcM using classical analytical methods and investigated the protective effects and mechanisms of intestinal mucosal inflammation mitigation and repair capacity in a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. IcM, mesalazine alone, and co-administration significantly reduced colonic pathological damage, downregulated inflammatory factors (anti-tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), high mobility group box 1 (HMGB1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory immunoglobulin A (SIgA)), and improved the severity of UC in a dose-dependent manner by regulating the interaction between glucocoriticoid receptor (GR) and key proteins in the Hippo pathway, remodeling the intestinal mucosal barrier tissue structure by increasing the expression of mucin 2 (MUC2), Occludin, zonula occluden-1 (ZO-1), and E-cadherin, whereas high-dose IcM treatment increased significantly. Moreover, IcM and mesalazine have a synergistic effect, weaken toxicity to the liver and kidney, and contribute to alleviating the disease process in clinical patients.

Background/Aims: Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate dextran sulfate sodium (DSS) -induced colitis through modulation of transforming growth factor β (TGFβ) receptor signaling. However, the exact molecular mechanisms are not known. Methods: Here, we transplanted primary mouse MSCs or injected TGFβ1 into mice with DSS-induced colitis. Cells were purified by flow cytometry. Gene expression was analyzed by RT-qPCR. Results: We found that MSCs significantly alleviated the DSS-induced colitis, and the major sources for TGFβ1 were macrophages that were recruited by MSCs. Specific ablation of macrophages completely abolished the anti-inflammatory effects of MSCs. On the other hand, TGFβ1 administration, without the presence of MSCs, was sufficient to reduce the severity of DSS-induced colitis. Conclusions: Taken together, our data suggest that MSCs transplantation may recruit macrophages to produce TGFβ1, which mitigates the pathology of colitis. Thus, MSCs transplantation appears to be a promising therapy for severe enteritis.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disorder. Pharmacotherapy serves as the main treatment strategy for IBD; however, the current medications have certain limitations, such as inefficacy and a tendency to induce tolerance, thereby requiring the development of innovative drugs to fulfill therapeutic requirements. A model of acute colitis induced with a solution of approx. 3% dextran sulfate sodium (DSS) has been widely used in preclinical drug development. Nevertheless, this model has some drawbacks, including rapid disease progression leading to mortality in some mice and disparities between the inflammatory characteristics of mice and the pathological features of human IBD. The current study found that mice freely consuming a lower concentration of a DSS solution (1-1.5%) for 10-15 days exhibited milder colitis symptoms. Continued consumption of the DSS solution for 15-20 days resulted in chronic inflammation in colon tissue, accompanied by a significant increase in the proportion of Th1 cells, indicating the involvement of adaptive immune responses. Subsequently, mice were treated with mesalazine or Centella triterpenes while concurrently consuming the DSS solution for 10 days. The treated mice had significant improvements in body weight and colon length compared to the control group. The advantages of this subacute model include minimal mortality among experimental mice and the fact that intestinal mucosal inflammation in mice resembles the pathological features of human IBD, enabling the assessment of drug efficacy against IBD.

Background Roflumilast (Rof), a phosphodiesterase 4 (PDE4) inhibitor, has been shown to be an effective agent in inflammatory diseases and marketed for chronic obstructive pulmonary disease. Objective This study was conducted to examine the potential anti-inflammatory effects of Rof in dextran sulphate sodium (DSS)–induced ulcerative colitis (UC) in rats and to investigate the molecular mechanisms underlying these effects. Methods Forty male Wistar rats were divided into four groups: normal control, colitis group (rats received 5% DSS in their drinking water continuously for 7 days), Rof group, and sulfasalazine (SLZ) group. The Rof (5 mg/kg) and SLZ (500 mg/kg) groups underwent pretreatment with DSS one week ahead of DSS challenge and parallel with DSS. Colitis was determined by assessing colon length, weight loss, histologic colon score, quantifying the concentration of tumor necrosis factor alpha (TNF-α), nitric oxide (NO), cyclic adenosine monophosphate (cAMP), myeloperoxidase (MPO) activity and inducible nitric oxide synthase (iNOS) gene expression in colon tissue. Results Rof attenuated the severity of colitis as evidenced by increased colon length, prevention of body weight loss, and improved colon histologic score compared to DSS group. Rof also suppressed the inflammatory response induced in DSS colitis group by decreasing colon concentration of TNF-α, NO and MPO activity and down- regulation of iNOS gene expression. The level of cAMP was increased by Rof compared to DSS group. The obtained results of Rof were comparable to those exerted by SLZ. Conclusion These findings revealed the beneficial effects of Rof in alleviating inflammation in DSS colitis. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment has fueled the search for alternative therapeutic strategies. In recent studies, berberine, a plant alkaloid with a long history of medicinal use in Chinese medicine, has shown beneficial effects against animal models of acute UC. However, UC usually presents as a chronic condition with frequent relapse in patients. How berberine will act on chronic UC remains unclear. In the present study, we adopted dextran sulfate sodium (DSS)-induced chronic relapsing colitis model to assess the ameliorating activity of berberine. Colitis was induced by two cycles of 2.0% DSS for five days followed by 14 days of drinking water plus a third cycle consisting of DSS only for five days. The colitis mice were orally administered 20 mg/kg berberine from day 13 onward for 30 days and monitored daily. The body weight, stool consistency, and stool bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and samples were collected and subjected to histological, RT-qPCR, Western blot, and LC–MS analyses. Lymphocytes were isolated from spleens and mesenteric lymph nodes (MLN) and cultured for flow cytometry analysis of IL-17 secretion from CD 4 + cells and the Th17 cell differentiation. Results showed that berberine significantly ameliorated the DAI, colon shortening, colon tissue injury, and reduction of colonic expression of tight junction (TJ) protein ZO-1 and occludin of colitis mice. Notably, berberine treatment pronouncedly reduced DSS-upregulated Th17-related cytokine (IL-17 and ROR-γt) mRNAs in the colon. Furthermore, the mRNA expression of IL-6 and IL-23, and the phosphorylation of STAT3 in colon tissues from DSS-treated mice were pronouncedly inhibited by berberine. Moreover, the up-regulation of IL-17 secretion from CD 4 + cells of spleens and MLNs caused by DSS were significantly reversed by berberine treatment. Furthermore, Th17 cell differentiation from naive CD 4 + cells isolated from above DSS colitis mice were suppressed by berberine in a concentration-dependent manner. In summary, we demonstrated for the first time that berberine reduced the severity of chronic relapsing DSS-induced colitis by suppressing Th17 responses. The demonstration of activity in this mouse model supports the possibility of clinical efficacy of berberine in treating chronic UC. [ABSTRACT FROM AUTHOR]

Indirubin, an active ingredient of a traditional Chinese medicine prescription named Danggui Longhui Wan, has been reported to exhibit abroad anti-cancer and anti-inflammation activities. However, the effect of indirubin on ulcerative colitis (UC) has not been addressed. Here, we investigated the therapeutic efficacy of indirubin on dextran sulfate sodium (DSS)-induced UC in mice and explored its underlying mechanisms. UC model was induced in BALB/c mice by administrating with 3% DSS in drinking water for 7 days. Subsequently, indirubin treatment (10 mg/kg) for 7 days obviously inhibited the loss of body weight, reversed the elevation of disease activity index (DAI), alleviated crypt distortion and mucosal injury, and reduced inflammatory cell infiltration in the colon mucosa, thereby ameliorating DSS-induced UC. Mechanically, the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-2 as well as myeloperoxidase (MPO) activity in colon tissues were decreased significantly, while the levels of IL-4 and IL-10 were increased remarkably by indirubin treatment. Moreover, indirubin administration effectively suppressed CD4 + T cell infiltration in the colon of DSS-induced UC mice and promoted the generation of Foxp3-expressing regulatory T cells. Additionally, further studies showed that indirubin obviously inhibited DSS-induced activation of nuclear factor (NF)-κB signaling. These results reveal that the significant anti-UC effect of indirubin may be attributable to its inhibition of inflammatory responses and promotion of Foxp3 + T cells. Our studies provide the first evidence for the anti-UC effect of indirubin as well as the related molecular mechanisms and suggest a promising candidate drug for UC therapy. [ABSTRACT FROM AUTHOR]

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Crohn's disease (CD) is associated with increased psychiatric co-morbidities. Nitric oxide (NO) is implicated in inflammation and tissue injury in CD, and it may also play a central role in pathogenesis of the accompanying behavioral despair. This study investigated the role of the NO pathway in behavioral despair associated with a mouse model of CD. Colitis was induced by intrarectal (i.r.) injection of 2,4,6-trinitrobenzenesulfonic acid (10 mg TNBS in 50% ethanol). Forced swimming test (FST), pharmacological studies and tissues collection were performed 72 h following TNBS administration. To address a possible inflammatory origin for the behavioral despair following colitis induction, tumor necrosis factor-alpha (TNF-α) level was measured in both the hippocampal and colonic tissue samples. In parallel, hippocampal inducible nitric oxide synthase (iNOS) and nitrite level were evaluated. Pharmacological studies targeting the NO pathway were performed 30–60 min before behavioral test. Colitis was confirmed by increased colonic TNF-α level and microscopic score. Colitic mice demonstrated a significantly higher immobility time in the FST associated to a significant increase of hippocampal TNF-α, iNOS expression and nitrite content. Acute NOS inhibition using either Nω-nitro- l -arginine methyl ester (a non-specific NOS inhibitor) or aminoguanidine hydrochloride (a specific iNOS inhibitor) decreased the immobility time in colitic groups. Moreover, acute treatment with both NOS inhibitors decreased the TNF-α level and nitrite content in the hippocampal samples. This study suggests that the NO pathway may be involved in the behavioral effects in the mouse TNBS model of CD. These findings endow new insights into the gut-brain communication during the development of colonic inflammation, which may ultimately lead to improved therapeutic strategies to combat behavior changes associated with gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Background: As an intestinal non-specific inflammatory lesion, ulcerative colitis (UC) affects the health of many individuals. This study examined the possible beneficial effects of the chloroform extract of Fomitopsis pinicola (Swartz.: Fr) Karst (FPKc) on UC., Methods: The mice were given free access to drink with 4% dextran sulfate sodium (DSS) for 1 week to establish acute UC model. Next, 35 mg of FPKc or sulfasalazine (SASP) was given to the mice via gavage for 3 weeks. The disease activity index (DAI) and colonic mucosa damage index (CMDI) scores were calculated. The colon tissues of the mice were collected to measure the length and perform hematoxylin and eosin staining. The thymus and spleen indexes were determined. Interleukin (IL)-6, IL-8, tumor necrosis factor-α, aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum were determined., Results: FPKc or SASP treatment alleviated hematochezia and weight loss, ameliorated DAI and CMDI scores, and improved the crypt structure and length of the colon tissues. Relative to the UC model group, the spleen index in the FPKc group was reduced, which was accompanied by decreases of the IL-6 and IL-8 levels in the serum. FPKc also lowered the AST and ALT levels in the serum of the UC mice., Conclusions: FPKc protected the mice from DSS-induced UC injury. It may be that FPKc activates immune regulation and downregulates the expression of pro-inflammatory cytokines., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5143/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn's disease. Serum-derived bovine immunoglobulin/protein isolate (SBI) is comprised primarily of immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins.Aim: To demonstrate that oral administration of SBI may modulate mucosal inflammation following colonization with E. coli, LF82, and exposure to dextran sodium sulfate (DSS).Methods: Defined microbiota mice harboring the altered Schaedler flora (ASF) were administered SBI or hydrolyzed collagen twice daily starting 7 days prior to challenge with E. coli LF82 and continuing for the remainder of the experiment. Mice were treated with DSS for 7 days and then evaluated for evidence of local and peripheral inflammation.Results: Igs within SBI bound multiple antigens from all eight members of the ASF and E. coli LF82 by western blot analysis. Multiple parameters of LF82/DSS-induced colitis were reduced following administration of SBI, including histological lesion scores, secretion of cytokines and chemokines from cecal biopsies, intestinal fatty acid binding protein (I-FABP) and serum amyloid A from plasma.Conclusions: Oral administration of SBI attenuated clinical signs of LF82/DSS-induced colitis in mice. The data are consistent with the hypothesis that SBI immunoglobulin binding of bacterial antigens in the intestinal lumen may inhibit the inflammatory cascades that contribute to IBD, thus attenuating DSS-induced colitis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Inflammatory bowel disease (IBD) is generally associated with a set of debilitating symptoms including abdominal pain, tenesmus, diarrhea and bloody stool. The standard approaches for treating IBD, which are the application of pharmaceuticals, are often unsatisfactory. IBD patients may suffer from repeated relapses and even exacerbation after taking these medications. Thus, patients are increasingly seeking relief through the use of complementary and alternative medicines. Aim of study To provide scientific ground for the mode of actions of a Chinese medicinal formulation—modified ZenWu Decoction (MZWD) in ulcerative colitis. Materials and methods C57BL6 mice were fed with 3 cycles of 2% dextran sulfate sodium (DSS) in drinking water for the induction of chronic colitis and then given MZWD at 17.47 g/kg/day. Effects of MZWD were evaluated by histopathological and biochemical assays. Results When MZWD was given, inflammatory responses namely immune-cell infiltration, elevated serum levels of pro-inflammatory cytokines and mucosal lesions were notably suppressed. Further, MZWD treatment attenuated the activation of nuclear factor-kappaB (NF-κB), the vital regulator of inflammatory cascades, while lessening the degradation of I-kappaB-alpha and reducing the activity of protease-activated receptor 2 in DSS-induced colonic tissues. Consequently, diarrhea, bloody stool and colon shortening were reduced whilst mucosal integrity was improved in MZWD-treated colitis mice. Conclusions Our findings suggest that MZWD is a potential remedy for treating IBD, and the mechanism of its efficacy is an anti-inflammatory effect associated with the suppression of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Diplacone ( 1 ) and mimulone ( 2 ), two geranylated flavanones, have previously shown anti-inflammatory and antiradical activity in vitro . The present study aimed to evaluate their activity in vivo on a model of colitis induced in Wistar rats by an oral administration of dextran sulfate sodium (DSS). Diplacone ( 1 ) and mimulone ( 2 ) were administered at a bolus dose of 25 mg/kg by gastric gavage 48 and 24 h prior to the induction of colitis by DSS and every 24 h on the following days of the experiment. The effect of the treatment was assessed by monitoring the disease activity index (DAI), histopathological examination, evaluation of the weight and length of the colon and by analysis of the levels and activities of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP2), superoxide dismutase-2 (SOD2), and catalase (CAT) in the inflamed tissue. Administration of the test compounds prior and after induction of colitis ameliorated the symptoms of colitis (diarrhea, presence of the blood in the stool) and delayed their onset. The ability of compounds 1 and 2 to reduce the levels of COX-2 and to increase the ratio of pro-MMP2/MMP2 activity correlates with the values of the DAI. The lowering of the levels of the antioxidant enzymes SOD2 and CAT reflects the ability of the test compounds to scavenge reactive oxygen species. [ABSTRACT FROM AUTHOR]

Background/Aims: Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate dextran sulfate sodium (DSS) -induced colitis through modulation of transforming growth factor β (TGFβ) receptor signaling. However, the exact molecular mechanisms are not known. Methods: Here, we transplanted primary mouse MSCs or injected TGFβ1 into mice with DSS-induced colitis. Cells were purified by flow cytometry. Gene expression was analyzed by RT-qPCR. Results: We found that MSCs significantly alleviated the DSS-induced colitis, and the major sources for TGFβ1 were macrophages that were recruited by MSCs. Specific ablation of macrophages completely abolished the anti-inflammatory effects of MSCs. On the other hand, TGFβ1 administration, without the presence of MSCs, was sufficient to reduce the severity of DSS-induced colitis. Conclusions: Taken together, our data suggest that MSCs transplantation may recruit macrophages to produce TGFβ1, which mitigates the pathology of colitis. Thus, MSCs transplantation appears to be a promising therapy for severe enteritis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Bacterial β-(1,3)-glucan has more advantages in terms of cost, yield and efficiency than that derived from mushrooms, plants, yeasts and fungi. We have previously developed a novel and high-yield β-(1,3)-glucan produced by Agrobacterium sp. R259. This study aimed to elucidate the functional mechanism and therapeutic efficacy of bacterial β-(1,3)-glucan in dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD).Mice were orally pretreated with bacterial β-(1,3)-glucan at daily doses of 2.5 or 5 mg/kg for 2 weeks. After 6 days of DSS treatment, clinical assessment of IBD severity and expression of pro-inflammatory cytokines were evaluated. In vivo cell proliferation was examined by immunohistochemistry using Ki-67 and ER-TR7 antibodies. The frequency of regulatory T cells (Tregs) was analyzed by flow cytometry. Natural killer (NK) activity and IgA level were evaluated using NK cytotoxicity assay and ELISA.The deterioration of body weight gain, colonic architecture, disease score and histological score was recovered in DSS-induced IBD mice when pretreated with bacterial β-(1,3)-glucan. The recruitment of macrophages and the gene expression of proinflammatory cytokines, such as IL-1β, IL-6 and IL-17A/F, were markedly decreased in the colon of β-(1,3)-glucan-pretreated mice. β-(1,3)-Glucan induced the recovery of Tregs in terms of their frequency in DSS-induced IBD mice. Intriguingly, β-(1,3)-glucan reversed the functional defects of NK cells and excessive IgA production in DSS-induced IBD mice. We conclude that bacterial β-(1,3)-glucan prevented the progression of DSS-induced IBD by recovering the reduction of Tregs, functional defect of NK cells and excessive IgA production. [ABSTRACT FROM AUTHOR]

Abstract: The incidence of inflammatory and autoimmune disorders is highest in well-developed countries which is directly related to their higher hygienic standards: it is suggested that the lack of exposure to helminths contributes to the susceptibility for immune-related diseases. Epidemiological, experimental and clinical data support the idea that helminths provide protection against immune-mediated diseases such as inflammatory bowel disease (IBD). The most likely mechanism for the suppression of immune responses by helminths is the release of helminth-derived immunomodulatory molecules. This article reviews the experimental and clinical studies investigating the therapeutic potential of helminth-based therapy in IBD and also focuses on the current knowledge of its immunomodulatory mechanisms of action highlighting innate as well as adaptive immune mechanisms. Identifying the mechanisms by which these helminths and helminth-derived molecules modulate the immune system will help in creating novel drugs for the treatment of IBD and other disorders that result from an overactive immune response. [Copyright &y& Elsevier]

Abstract: The TNF-α expression-inhibitory effect of lactic acid bacteria (LAB) isolated from kimchi were measured in lipopolysaccharide (LPS)-stimulated peritoneal macrophages. Among the LAB evaluated, Lactobacillus plantarum CLP-0611 inhibited the IL-1β and IL-6 expression, as well as the NF-κB and AP1 activation in LPS-stimulated peritoneal macrophages. Therefore, we investigated its inhibitory effect on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. TNBS significantly induced colon shortening, as well as myeloperoxidase activity and macroscopic score. Oral administration of CLP-0611 significantly reduced TNBS-induced body weight loss, colon shortening, myeloperoxidase activity, IRAK-1 phosphorylation, NF-κB and MAP kinase (p38, ERK, JNK) activation, and iNOS and COX-2 expression. CLP-0611 also inhibited TNBS-induced expression of TNF-α, IL-1β, and IL-6. However, IL-10 expression was induced. CLP-0611 also induced the production of M2 macrophage markers (IL-10, arginase I and CD206). Based on these findings, CLP-0611 inhibits TLR-4-linked NF-κB and MAPK signaling pathways and polarizes M1 to M2-like macrophages, thus ameliorating colitis. [Copyright &y& Elsevier]

Highlights: [•] In contrast to other models of experimental colitis, treatment with a MCHR1 antagonist did not attenuate disease in IL-10 deficient mice. [•] An underlying mechanism for this observation could be direct interactions between MCH and IL-10. [•] In vitro, MCH inhibits LPS-induced IL-10 expression in monocytes. [•] Treatment of monocytes with IL-10 prevents upregulation of MCH receptor 1. [•] MCH might promote intestinal inflammation via inhibition of anti-inflammatory pathways. [Copyright &y& Elsevier]

Abstract: Colorectal cancer is one of the major causes of death in the western world. Despite increasing knowledge of the molecular signaling pathways implicated in colon cancer, therapeutic outcomes are still only moderately successful. Sphingolipids, a family of N-acyl linked lipids, have not only structural functions but are also implicated in important biological functions. Ceramide, sphingosine and sphingosine-1-phosphate are the most important bioactive lipids, and they regulate several key cellular functions. Accumulating evidence suggests that many cancers present alterations in sphingolipids and their metabolizing enzymes. The aim of this review is to discuss the emerging roles of sphingolipids, both endogenous and dietary, in colon cancer and the interaction of sphingolipids with WNT/β-catenin pathway, one of the most important signaling cascades that regulate development and homeostasis in intestine. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology. [Copyright &y& Elsevier]

Abstract: Several studies have shown the anti-neoplastic effects of non-steroidal anti-inflammatory drugs (NSAIDs) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis, but how these drugs act in case of inflammation-augmented tumorigenesis is still not clear. The present study therefore designs an animal model of colitis-associated colon cancer where 3% Dextran sufate sodium (DSS) is used to develop ulcerative colitis and DMH treatment leads to colon carcinogenesis as early as in six weeks. Clinical symptoms for ulcerative colitis were studied using Disease Activity Index (DAI) while myeloperoxidase assay marked the neutrophil infiltration in DSS and DMH treated groups. The present results indicated the upregulation of the activity of inflammatory marker enzyme, cyclooxygenase-2 (cox-2) and pro-inflammatory cytokines such as TNF-α, IL-1β, IL-4 and IFN-γ with the treatment of DSS as well as DMH. The presence of cytokines in the inflammatory milieu might lead to the transformation of cytoplasmic inactive NF-κB (Nuclear Factor κB) to its active nuclear form, thereby leading to tumorigenesis. The administration of celecoxib along with DSS and DMH, revealed its chemopreventive efficacy in colitis as well as colon cancer. The effect of different doses of DMH on mouse colon was also investigated to obtain a minimum dose of DMH which can induce visible lesions in mice colons at a high incidence. [Copyright &y& Elsevier]

Background & Aims: A dysregulated response of CD4+ T cells against the microbiota contributes to the development of inflammatory bowel disease. Effector CD4+ T cells, generated in response to microbe-derived antigens, can reduce somatic inflammatory pain through the local release of opioids. We investigated whether colitogenic CD4+ T cells that accumulate in the inflamed colon also produce opioids and are able to counteract inflammation-induced visceral pain in mice. Methods: Colitis was induced via transfer of naive CD4+CD45RBhigh T cells to immune-deficient mice or by administration of dextran sulfate sodium. Mice without colitis were used as controls. Samples of colon tissue were collected, and production of opioids by immune cells from inflamed intestine was assessed by quantitative polymerase chain reaction and cytofluorometry analyses. The role of intestinal opioid tone in inflammation-induced visceral hypersensitivity was assessed by colorectal distention. Results: In mice with T cell– or dextran sulfate sodium–induced colitis, colitogenic CD4+ T cells (T-helper 1 and Th17 cells) accumulated in the inflamed intestine and expressed a high level of endogenous opioids. In contrast, macrophages and epithelial cells did not express opioids; opioid synthesis in the myenteric plexus was not altered on induction of inflammation. In mice with colitis, the local release of opioids by colitogenic CD4+ T cells led to significant reduction of inflammation-associated visceral hypersensitivity. Conclusions: In mice, colitogenic Th1 and Th17 cells promote intestinal inflammation and colonic tissue damage but have simultaneous opioid-mediated analgesic activity, thereby reducing abdominal pain. [Copyright &y& Elsevier]

Abstract: Numb is highly expressed throughout the crypt-villus axis of intestinal mucosa and functions as cell fate determinant and integrator of cell-to-cell adhesion. Increased paracellular permeability of intestinal epithelial cells is associated with the epithelial barrier dysfunction of inflammatory bowel diseases (IBDs). The apical junctional complex (AJC) assembly and myosin light chain (MLC) phosphorylation regulate adherens junctions (AJ) and tight junctions (TJ). We determined whether and how Numb modulate the paracellular permeability of intestinal epithelial cells. Caco-2 intestinal epithelial cells and their Numb-interfered counterparts were used in the study for physiological, morphological and biological analyses. Numb, expressed in intestinal epithelial cells and located at the plasma membrane of Caco-2 cells in a basolateral to apical distribution, increased in the intestinal epithelial cells with the formation of the intestinal epithelial barrier. Numb expression decreased and accumulated in the cytoplasm of intestinal epithelial cells in a DSS-induced colitis mouse model. Numb co-localized with E-cadherin, ZO-1 and Par3 at the plasma membrane and interacted with E-cadherin and Par3. Knockdown of Numb in Caco-2 cells altered the F-actin structure during the Ca2+ switch assay, enhanced TNFα-/INF-γ-induced intestinal epithelial barrier dysfunction and TJ destruction, and increased the Claudin-2 protein level. Immunofluorescence experiments revealed that NMIIA and F-actin co-localized at the cell surface of Caco-2 cells. Numb knockdown in Caco-2 cells increased F-actin contraction and the abundance of phosphorylated MLC. Numb modulated the intestinal epithelial barrier in a Notch signaling-independent manner. These findings suggest that Numb modulates the paracellular permeability by affecting AJC assembly and MLC phosphorylation. [Copyright &y& Elsevier]

Ulcerative colitis is one of the main gastrointestinal diseases that threaten human health. This study investigated the effect of Limosilactobacillus fermentum HFY06 (LF-HFY06) on dextran sulfate sodium (DSS)-induced murine colitis. The protective effect of LF-HFY06 was evaluated by examining the length and histopathological sections of colon, related biochemical indicators, and genes related to inflammation. Direct and microscopic observations showed that LF-HFY06 increased the length of the colon and ameliorated the pathological damage induced by DSS. The biochemical indicators showed that LF-HFY06 enhanced the activities of antioxidant enzymes total superoxide dismutase (T-SOD) and catalase (CAT) in serum, while reducing the level of malondialdehyde (MDA). It was also observed that the serum inflammatory cytokines levels of tumor necrosis factor-α (TNF-α), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and IL-12 were decreased, and the anti-inflammatory cytokine IL-10 level was increased. The qPCR experiment revealed that LF-HFY06 downregulated the mRNA expression levels of nuclear factor-κB-p65 ( Rela ), Tnf , Il 1b , Il 6 , and prostaglandin-endoperoxide synthase 2 ( Ptgs2 ) in colon tissues, and upregulated the mRNA expression of NF-κB inhibitor-α ( Nfkbia ) and Il 10 . These data indicated that LF-HFY06 inhibited inflammation through the NF-κB signaling pathway to prevent the occurrence and development of colitis. This research demonstrates that probiotics LF-HFY06 have the potential to prevent and treat colitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yang, Wu and Zhao.)

An impaired intestinal epithelial barrier is thought to be a major factor in the pathogenesis of human inflammatory bowel disease (IBD). IBD is frequently investigated by inducing a damaged barrier in murine models of colitis. This can be done by feeding mice with dextran sulfate sodium (DSS) polymers in their drinking water. Refinement measures should focus on alleviating unnecessary suffering during this probably painful condition. Appropriate parameters are needed to decide when to terminate the experiments. Our aim was to investigate whether a change in burrowing behaviour is a sensitive measure of animal welfare in murine models of colitis. Acute colitis was induced in C57BL/6 mice with 2.0% DSS over nine days. The burrowing test is based on the species-typical behaviour of mice to spontaneously displace items from tubes within their home cage. As a burrowing apparatus, a water bottle (250 mL, 150 mm length, 55 mm diameter) filled with 138–142 g of pellets of the animal’s diet was used. The presence of intestinal inflammation as a result of acute DSS-induced colitis was confirmed by a decrease in body weight, colon length and an increase of murine endoscopic index of colitis severity, histological score and spleen weight in the group receiving DSS as compared with the control group. An onset of intestinal inflammation correlated with a significant decrease in burrowing behaviour (P < 0.05). Altered adrenal gland histology indicated stress as a result of acute colitis. Our findings provide evidence that changes of spontaneous burrowing behaviour correlate with the onset of inflammation in acute DSS-induced colitis. [ABSTRACT FROM AUTHOR]

Background & Aims: Hypoxic inflammation (decreased oxygen tension at sites of inflammation) is a feature of inflammatory bowel disease (IBD). The hypoxia response is mediated by the transcription factors hypoxia-inducible factor (HIF) 1α and endothelial PAS domain protein 1 (EPAS1 or HIF2α), which are induced in intestinal tissues of patients with IBD. HIF1α limits intestinal barrier dysfunction, but the role of EPAS1 has not been assessed under conditions of hypoxic inflammation or in models of IBD. Methods: Acute colitis was induced by administration of Citrobacter rodentium or dextran sulfate sodium (DSS) to transgenic hypoxia reporter mice (oxygen-dependent degradation−luciferase), mice with conditional overexpression of Epas1 (Epas1 LSL/LSL), mice with intestinal epithelium-specific deletion of Epas1 (Epas1 ΔIE ), or wild-type littermates (controls). Colon tissues from these mice and from patients with ulcerative colitis or Crohn's disease were assessed by histologic and immunoblot analyses, immunohistochemistry, and quantitative polymerase chain reaction. Results: Levels of hypoxia and EPAS1 were increased in colon tissues of mice after induction of colitis and patients with ulcerative colitis or Crohn's disease compared with controls. Epas1 ΔIE mice had attenuated colonic inflammation and were protected from DSS-induced colitis. Intestine-specific overexpression of EPAS1, but not HIF-1α, led to spontaneous colitis, increased susceptibility to induction of colitis by C rodentium or DSS, and reduced survival times compared with controls. Disruption of intestinal epithelial EPAS1 attenuated the inflammatory response after administration of DSS or C rodentium, and intestine-specific overexpression of EPAS1 increased this response. We found EPAS1 to be a positive regulator of tumor necrosis factor−α production by the intestinal epithelium. Blocking tumor necrosis factor−α completely reduced hypoxia-induced intestinal inflammation. Conclusions: EPAS1 is a transcription factor that activates mediators of inflammation, such as tumor necrosis factor−α, in the intestinal epithelium and promotes development of colitis in mice. [Copyright &y& Elsevier]

Highlights: [•] α-Lipoic acid (LA) protected against ulcerative colitis (UC) in mice. [•] LA reduced inflammation, oxidative stress, DNA damage and fibrosis in mice with UC. [•] It prevented UC-induced increased gut permeability and reduced plasma LPS level. [•] It further reduced systemic inflammation and genotoxicity in mice with UC. [•] It ameliorated UC-induced local as well as systemic damage in mice. [ABSTRACT FROM AUTHOR]