Colon Shortening Research Articles

Type 5 Resistant Starch Can Effectively Alleviate Experimentally Induced Colitis in Mice by Modulating Gut Microbiota.

Resistant starch (RS) has been shown to modulate intestinal microbiota in animal models in ways that could reduce the effects of dysbiosis-related diseases. However, the mechanism of how this is achieved is not understood. The present study aimed to reveal the mechanism of how RS mitigates dextran sulfate sodium (DSS)-induced colitis in mice by using a starch-lipid complex (RS type 5), with an RS type 2 from high-amylose maize starch as a comparison. Both RS5 and RS2 induced changes in the diversity and composition of the gut bacteria, leading to the alleviation of the induced colitis symptoms including decreasing the loss in body weight, disease activity index score, and colonic shortening. The levels of inflammatory cytokines were modulated and accompanied by an increase in goblet cell numbers and thickening of the intestinal mucus layer. RS5 was more effective, compared to RS2, in alleviating all of the colitis symptoms, mainly through improving the gut microflora dysbiosis and stimulating the generation of short-chain fatty acids (SCFAs). Our study shows that RS5 could effectively alleviate the symptoms of colitis, highlighting a potential use for RS5, particularly in relieving inflammatory bowel disease.

Pickled radish alleviates the progression of colitis in mice by reducing inflammation and repairing intestinal barrier

Scope: Pickled radish is a traditional fermented food known for its health benefits, however, evidence supporting its role in regulating gastrointestinal function is limited. This study aimed to investigate the beneficial effect of pickled radish on DSS-induced colitis in mice. Method and Results: Divide the mice into four groups: control, DSS model, low-dose (DSS+ 5 % pickled radish powder), and high-dose (DSS+ 10 % pickled radish powder). Colitis was induced by 3 % DSS administration in drinking water for eight days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory markers were measured to evaluate the effects of pickled radish on colitis. The results indicate that pickled radish significantly eased symptoms of colitis in mice induced by DSS, dose-dependently reducing DAI, reversed colon shortening, alleviating pathological damage to colon tissue and inflammatory response. Mechanistic investigation revealed that pickled radish upregulated the expression of tight junction-related genes (Zo-1, E-cadherin) and down-regulated inflammation-related genes (Il-1β, Il-6, TNF-α). Moreover, low-dose pickled radish significantly reversed the imbalance of gut microbiota and increased SCFAs. Conclusion: These findings suggest the potential of pickled radish in functional foods targeting the improvement of gastrointestinal health.

Costunolide and dehydrocostus lactone alleviate ulcerative colitis via regulating TLR4, NF-κB and PI3K expression

In this study, we aimed to study the mechanism of costunolide (COS) and dehydrocostus lactone (DEH) in the treatment of ulcerative colitis (UC) based on network pharmacology, molecular docking and animal experiments. Firstly, network pharmacology was used to predict the target proteins of compounds and diseases. Subsequently, the network analysis was performed, and the key target proteins were screened out. Finally, molecular docking and animal experiments were conducted to validate the network pharmacology analysis results. A total of 39 common target proteins of compounds and diseases were collected. The target proteins TLR4, PIK3R1, PTGS2, RELA, NOS3, MPO and CHUK were obtained from PPI network analysis, GO analysis, KEGG enrichment analysis, and the compound-target-pathway network. Molecular docking results showed that COS and DEH could bind to these target proteins. The results of animal experiments showed that dextran sulfate sodium (DSS) induced UC in mice, resulting in weight loss, colon shortening, and significantly upregulated expression of TLR4, PIK3R1 and RELA in colon tissue. COS and DEH could reduce these pathological changes in UC mice. And they could alleviate UC by downregulating TLR4, PIK3R1 and RELA. Our findings suggested that COS and DEH could exert protective effects on UC by downregulating TLR4, PIK3R1, and RELA.

Lactobacillus johnsonii GLJ001 prevents DSS-induced colitis in mice by inhibiting M1 macrophage polarization via gut microbiota-SCFAs axis

Inflammatory Bowel Disease (IBD) is increasing worldwide and has become a global emergent disease. Probiotics have been reported to be effective in relieving colitis. Previous studies found ripened Pu-erh tea (RPT) promoted gut microbiota resilience against dextran sulfate sodium (DSS)-induced colitis in mice by increasing relative abundance of Lactobacillus. However, whether and how it alleviated DSS-induced colitis in mice need to be explored. Here, we screened a probiotic Lactobacillus johnsonii GLJ001 from feces of ripened Pu-erh tea (RPT)-administrated mice. In this study, L. johnsonii GLJ001 attenuated symptoms of DSS-induced colitis in mice, including weight loss, increased disease activity index (DAI), colon shortening and colon tissue damage, as well as high expression of inflammatory cytokines and disturbances of intestine barrier function. Furthermore, abundances of short-chain fatty acids (SCFAs)-producing bacteria (i.e. Clostridium cluster IV and XIVa, Lachnospiracea_incertae_sedis and Ruminococcus) were enhanced in the cecum of mice treated with L. johnsonii GLJ001, accompanying by an increase of SCFAs. It was also found that SCFAs inhibited mRNA expression of M1 macrophage markers (Inos and CD86), inflammatory cytokines (TNF-α and Il-1β) and SCFAs receptors (Gpr41 and Gpr43) induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in THP-1 cell line. Collectively, L. johnsonii GLJ001 prevented DSS-induced colitis in mice by inhibiting M1 macrophage polarization via gut microbiota-SCFAs axis, and can be administered for management of colitis.

The probiotic Lactobacillus plantarum alleviates colitis by modulating gut microflora to activate PPARγ and inhibit MAPKs/NF-κB.

In order to address the global public health concern of colitis, this study was conducted to investigate the beneficial effect of Lactobacillus plantarum LR002 (LR) on the remission of ulcerative colitis (UC) in mice and to explore the possible underlying mechanisms. The effect of LR on UC was analyzed by using dextran sodium sulfate (DSS)-induced UC model in mice (n = 9). To assess the therapeutic effect of LR on UC in mice, the disease activity index (DAI) of mice, histopathological alterations, intestinal epithelial barrier integrity, and intestinal microflora were determined. The results demonstrated a reduction in the DSS-induced DAI in UC mice. Additionally, it mitigated colon shortening, minimized intestinal tissue damage, and preserved intestinal tight junction proteins (Claudin-3, Occludin, and ZO-1). LR reduced the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and oxidative mediators (MPO, SOD and MDA) in the colon of UC mice, which could also alleviate the imbalance of intestinal flora in UC mice, increase the abundance of Prevotellaceae, and Ligilactobacillus, and decrease the abundance of Bacteroidaceae and Eubacteriumrum. LR can also increase the levels of PPARγ in the nucleus and inhibit the MAPK/NF-ĸB signaling pathway in UC mice. Besides, the reduction of the content of short-chain fatty acid (SCFAs) in the colon of UC mice was relieved. The above results forge a scientific basis for LR as natural anti-inflammatory food to improve the imbalance of inflammatory intestinal flora and promote intestinal health.

The resolvin D2 and omega-3 polyunsaturated fatty acid as a new possible therapeutic approach for inflammatory bowel diseases

Inflammatory bowel diseases (IBD) are idiopathic disorders characterized by chronic gastrointestinal inflammation. Given conventional therapies’ adverse effects and clinical failures, novel approaches are being investigated. Recent studies have highlighted the role of specialized pro-resolving lipid mediators (SPMs) in the active resolution of chronic inflammation. In this regard, omega-3 fatty acid-derived Resolvin D2 (RvD2) appears to play a protective role in the pathophysiology of IBD. Therefore, we characterized the RvD2 pathway and its receptor expression in the intestinal mucosa of experimental colitis induced by dextran sulfate sodium. We also evaluated the preventive impact of an omega-3-enriched diet and the therapeutic efficacy of RvD2 compared with anti-TNF-α treatment. We found an increase in TNFα and IL22 expression and decreased levels of enzymes involved in RvD2 biosynthesis, such as PLA2, 15-LOX, 5-LOX, and its receptor GPR18 in experimental colitis. Omega-3 supplementation reduced the Disease Activity Index (DAI), weight loss, colonic shortening, and inflammation. These results and the increased IL-10 transcriptional levels after RvD2 treatment suggest that this mediator attenuated experimental colitis. These results enhance our understanding of the molecular mechanisms involved in the exacerbated inflammatory response present in experimental colitis and suggest that RvD2 and its omega-3 precursor offer a promising therapeutic approach for IBD.

Panduratin A mitigates inflammation and oxidative stress in DSS-induced colitis mice model.

This study explored Panduratin A's protective effects against DSS-induced colitis in mice, focusing on reducing inflammation and oxidative stress in the colon. Mice were treated with dextran sodium sulfate (DSS) and Panduratin A (3, 6, 18 mg/kg), and changes in body weight, colon length, Disease Activity Index (DAI), histopathology, inflammation markers including tumor necrosis factor- α (TNF-α), Interleukin-1 β (IL-1β), Myeloperoxidase (MPO), and oxidative stress, Malondialdehyde (MDA) were evaluated. Panduratin A significantly reversed DSS-induced symptoms, including body weight loss, colonic length shortening, and DAI increase, while reducing histopathological damage. It lowered inflammatory markers and oxidative stress, suppressed NF-κB activation, and enhanced Nrf2 and HO-1 expression. Panduratin A shows promise as a colitis treatment, warranting further research for broader clinical application.

Epimedium polysaccharides ameliorate ulcerative colitis by inhibiting oxidative stress and regulating autophagy.

Epimedium polysaccharide (EPS) is a bioactive compound derived from the traditional Chinese herb Epimedium brevicornum. The objective of this study was to investigate the protective effects of EPS on ulcerative colitis (UC) and to elucidate the underlying mechanisms involved. The findings showed that EPS treatment mitigated UC symptoms, including weight loss, anal bleeding, elevated disease activity index (DAI), and colon shortening. Hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining demonstrated that EPS alleviated histopathological damage and improved the integrity of the colonic mucosa. Mechanistically, EPS was found to substantially decrease inflammation by inhibiting the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and to alleviate oxidative stress through modulation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (Keap1/Nrf2) pathway. Notably, EPS failed to exert protective effects against dextran sulfate sodium (DSS)-induced UC in Nrf2-knockout (Nrf2-/-) mice. Additionally, Western blotting and immunohistochemical analysis demonstrated that EPS facilitated autophagy via the adenosine monophosphate-dependent protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway. In vitro experiments revealed that EPS effectively suppressed lipopolysaccharide (LPS)-mediated cellular damage and oxidative stress by regulating Keap1/Nrf2 pathway. Transcriptomic analysis of LPS-treated Caco-2 cells following EPS treatment revealed a significant up-regulation of Nrf2 expression. In conclusion, the findings of this study suggest that EPS exerts protective effects against DSS-induced UC through the inhibition of the TLR4/NF-κB signaling pathway, regulation of the Keap1/Nrf2 pathway, and promotion of autophagy via the AMPK/mTOR pathway. Consequently, EPS may represent a potential therapeutic target for the treatment of UC. © 2024 Society of Chemical Industry.

MnNi@PVP Nanoenzyme Based on Regulating Inflammation and Immune Homeostasis for the Therapy of Inflammatory Bowel Disease.

Nanozymes exhibiting remarkable antioxidant capabilities represent an effective therapeutic approach for ulcerative colitis (UC). This study synthesized the MnNi@PVP nanoenzyme through high-temperature pyrolysis and the NaCl template method, which exhibited multienzyme activity comprising glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). This study investigated the therapeutic effect of MnNi@PVP on colitis caused by sodium dextran sulfate (DSS). The findings indicated that MnNi@PVP notably decreased the disease activity index (DAI) score, which encompasses weight loss, colon shortening, and histopathological changes. MnNi@PVP showed effectiveness in addressing oxidative damage and suppressing the levels of proinflammatory markers, such as tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin (IL)-6, by inactivating the TLR4 pathway and macrophages. In addition, MnNi@PVP demonstrated the ability to repair tight junction proteins (occludin and ZO-1) and restore the intestinal barrier. The transcriptome sequencing demonstrated that MnNi@PVP could regulate inflammatory factor expression pathways and immune processes. Additionally, negatively charged MnNi@PVP can selectively bind to inflamed colonic tissues through electrostatic interactions, endowing it with targeted reparative capabilities at the location of intestinal inflammation. The MnNi@PVP, which possesses the reactive oxygen and nitrogen species (RONS) clearance capability examined in this section, is expected to provide the basis for the targeted repair of intestinal function.

The Hydrophobic Amino Acid-Rich Fish Collagen Peptide Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice via Repairing the Intestinal Barrier, Regulating Intestinal Flora and AA Metabolism.

The incidence of ulcerative colitis (UC) is increasing annually, but treatment option is limited. Fish collagen peptide (FCP) is a food source collagen peptide that has shown promise in alleviating UC symptoms. However, its impact on the intestinal barrier and intestinal metabolic homeostasis in UC remains unclear. This study aimed to analyze the peptide sequences and absolute amino acid (AA) content of FCP, assessing its effects on UC in mice induced by dextran sulfate sodium (DSS). FCP was examined by liquid chromatography and tandem mass spectrometry (LC-MS/MS) analysis. The 3% DSS was utilized to induce UC in murine models, followed by the assessment of the therapeutic efficacy of FCP. Clinical manifestations of UC mice were meticulously evaluated and scored. Subsequently, samples were procured for histological examination and intestinal epithelial barrier integrity analysis as well as macrogenomic and metabolomic profiling. Here, it shows that abundant peptide sequences and AAs were in FCP, particularly enriched in hydrophobic AAs (HAAs). Furthermore, it was observed that FCP effectively reversed colon shortening and reduced the extent of histological damage. Additionally, FCP suppressed the abnormal expression of inflammatory factors and intestinal barrier proteins and modulated the dysbiosis of gut microbiota toward a balanced state. These alterations led to the activation of intestinal alkaline AA and various AA metabolisms, ultimately contributing to the mitigation of UC symptoms. In summary, the diverse peptide sequences and high AAs in FCP, particularly rich in HAAs, can alleviate DSS-induced UC via preserving intestinal barrier integrity, regulating gut microbiota, and modulating AA metabolism.

A Novel Synbiotic Protects Against DSS-Induced Colitis in Mice via Anti-inflammatory and Microbiota-Balancing Properties.

Inflammatory bowel disease (IBD) is a chronic immune-inflammatory disease. Gut microbes, intestinal immunity, and gut barrier function play a critical role in IBD. Growing evidence suggests that synbiotic may offer therapeutic benefits for individuals with colitis, suggesting an alternative therapy against colitis. With this in mind, we creatively prepared a new synbiotic combination consisting of a probiotic strain (Limosilactobacillus reuteri) along with one prebiotic chitooligosaccharides (COS). The protective effects of the synbiotic on DSS-induced colitis and the underlying mechanisms were investigated. We demonstrated that the synbiotic ameliorated colitis in mice, as evidenced by a significant remission in body weight loss and colon shortening, and a decreased disease activity index (DAI). Notably, synbiotic reduced the intestinal inflammation and injury by synergistically decreasing inflammatory factors, inhibiting TLR4/Myd88/NF-κB/NLRP3 signaling, preventing macrophage infiltration, and enhancing the integrity of the intestinal barrier. Moreover, synbiotic selectively promoted the growth of beneficial bacteria (e.g., Akkermansia, Lactobacillus) but decreased the pathogenic bacteria (e.g., Helicobacter). BugBase's analysis supported its ameliorated role in reducing pathogenic bacteria. Collectively, our findings revealed the novel synbiotic had a potential to treat colitis, which was associated with its anti-inflammatory and microbiota-balancing properties. This study will contribute to the development of functional synbiotic products for IBD therapy and will provide valuable insights into their mechanisms.

Exploring the mechanism of Phyllanthus urinaria L. against ulcerative colitis based on network pharmacology and in vivo experiments

ObjectiveThis study aims to explore the therapeutic effect and molecular mechanism of the aqueous extract of Phyllanthus urinaria L. (PUL) on ulcerative colitis (UC). MethodPUL was administered to UC mice induced by 2.25% DSS. The changes of body weight, DAI score and colon length were recorded during the experiment. HE staining was conducted for pathology analysis of the mice in each group. The contents of inflammatory cytokines in colon tissues were detected by Elisa. Additionally, UPLC-TOF-MS/MS method was employed to identify the main components of PUL. Then, the TCMSP database was utilized to explore the potential active ingredients and drug targets of PUL. The matching of drug targets and disease targets yielded cross targets, which were used to construct a PPI network in String. Key targets underwent GO and KEGG enrichment analysis. Finally, Western blotting was performed to verify the key proteins expressions in the predicted pathway of network pharmacology and the expressions of tight junction proteins in the colon tissue. ResultPUL has been found to effectively alleviate the symptoms such as weight loss, bloody stools, and colon shortening in mice with UC. Administration of PUL led to an increase in tight junction protein in the colonic tissue of mice, as compared to the model group. Elisa results revealed that PUL reduced the expression of pro-inflammatory factors in mice with UC. HE staining results show that PUL can alleviate colon tissue damage caused by UC. A total of 773 components were detected in the water extract of PUL, among which 26 components, including quercetin, epigallocatechin gallate and kaempferol, may possess anti-UC activity. Network pharmacology analysis suggested that PUL may play an anti-ulcerative colitis role by inhibiting TNF pathway. Finally, Western blotting results confirmed that the PUL inhibited the TNF pathway and effectively treated ulcerative colitis. ConclusionThese preliminary research results indicate that PUL has the potential to exhibit anti-inflammatory activity by inhibiting the TNF pathway, thereby alleviating symptoms associated with UC. Substances such as quercetin, epigallocatechin gallate and kaempferol in PUL are believed to play an important role in this process.

Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

Anti-inflammatory effects of para-quinone methide derivatives on ulcerative colitis.

A series of para-quinone methide derivatives were evaluated their anti-inflammatory activity. Through the screening of the lipopolysaccharide (LPS)-induced inflammatory cell model in Raw264.7 cells, it was found that the inhibitory activity of meta-substituted derivatives on NO production was superior to that of ortho- and para-substituted derivatives. Among them, in the inflammatory cell model, the meta-trifluoromethyl substituted para-quinone methide derivative 1i had the best activity in inhibiting LPS-induced excess generation of NO. And 1i could effectively inhibit the increase of ROS in inflammatory cells, the expression of iNOS related to the production of NO, and the expressions of inflammation related initiating protein TLR4, pro-inflammatory cytokines IL-6 and TNF-α, inflammasome NLRP3 and Caspase1. In the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model, the active derivative 1i could inhibit DSS-induced colon shortening, and reverse DSS-induced pathological changes in colon tissue, such as inflammatory infiltration, structural destruction and crypt disappearance. 1i could effectively inhibit oxidative stress, inflammation and apoptosis in UC mice. Moreover, through the determination of serum biochemical indicators, tissue pathologies and tissue organ indexes, 1i could effectively reverse the damage to mouse liver and kidney caused by DSS, playing a protective role in liver and kidney of mice. In summary, 1i was an effective anti-inflammatory reagent and could be developed as a potential drug for anti-UC.

Lactiplantibacillus plantarum NMGL2 exopolysaccharide ameliorates DSS-induced IBD in mice mainly by regulation of intestinal tight junction and NF-κB p65 protein expression.

Treatment of inflammatory bowel disease (IBD), a common chronic intestinal disease, by exopolysaccharides (EPSs) produced by lactic acid bacteria has raised increasing concerns. Here, the EPS produced by Lactiplantibacillus plantarum NMGL2 was evaluated for its ameliorating effect on dextran sodium sulfate (DSS)-induced IBD in mice. Administration of the EPS was shown to decrease the body weight loss and the values of disease activity index (DAI) and alleviate the colon damage as evidenced by an improvement in colonic length shortening, a reduction in colonic coefficient, and a reduction in colonic mucosal architecture and inflammatory infiltration. Cytokine assay of the blood and colon tissue samples showed that the EPS could decrease the levels of pro-inflammatory TNF-α and IL-1β, and increase anti-inflammatory IL-10. Oxidative stress assay of the colon tissue showed that the nitric oxide (NO) and malondialdehyde (MDA) levels decreased significantly (p < 0.05), while superoxide dismutase (SOD) and glutathione (GSH) levels increased significantly (p < 0.05) after the EPS intervention. These results were further confirmed by the significantly (p < 0.05) down-regulated levels of NF-κB p65, p-IKKβ, and p-IκBα, and significantly (p < 0.05) enhanced expression of ZO-1 and occludin, as evaluated by Western-blot analysis of these proteins expressed in colonic tissue. The EPS produced by L. plantarum NMGL2 alleviated IBD by suppressing the NF-κB signaling pathway, suggesting its potential as a functional food agent in the prevention of IBD.

Staphylea bumalda Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Regulating Inflammatory Cytokines, Oxidative Stress, and Maintaining Gut Homeostasis.

Staphylea bumalda is a rare medicine and edible shrub native to the temperate regions of Asia, possessing significant medicinal potential. In this study, the components of S. bumalda tender leaves and buds extract (SBE) were analyzed and identified by HPLC and LC/MS method, and the safety of SBE was evaluated through mouse acute toxicity models. The protective effects of SBE on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated in terms of inflammatory factor levels, oxidative stress, and gut microorganisms. Results showed that hyperoside, kaempferol-3-O-rutinoside, isorhoifolin, and rutin were the main components of the extract, and SBE demonstrated good safety in experimental mice. SBE could alleviate weight losing, disease activity index (DAI) raising, and colon shortening in mice. Pathological section results showed that the inflammatory cell infiltration decreased significantly, and the number of goblet cells increased significantly in the SBE group. After SBE treatment, interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in serum were significantly decreased, and the levels of myeloperoxidase (MPO) and nitric oxide (NO) in colon tissues were significantly decreased. SBE inhibited gut inflammation by increasing Lactobacillus. In summary, SBE played a therapeutic role in UC mice by relieving colon injury, reducing inflammatory factor levels, and maintaining gut flora homeostasis. SBE is expected to become an auxiliary means to participate in the prevention and treatment of UC.

Scutellarein ameliorates dextran sulfate sodium-induced ulcerative colitis by inhibiting colonic epithelial cell proinflammation and barrier disruption.

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. 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. 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. 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.

Phage cocktail inhibits inflammation and protects the integrity of the intestinal barrier in dextran sulfate sodium-induced colitis mice model

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by abdominal pain, diarrhea, and rectal bleeding. This study aims to explore the protective effects of a phage cocktail (108 PFU/mL of Clostridium perfringens phage, 108 PFU/mL of Escherichia coli phage, and 108 PFU/mL of Salmonella phage) on a mouse colitis model induced by dextran sulfate sodium (DSS) and its potential toxic effects on normal mice. The results demonstrate that the phage cocktail significantly alleviates clinical symptoms in mice, reduces colon shortening, weight loss, and colonic pathological damage. Furthermore, the phage cocktail markedly suppresses the inflammatory response and safeguards intestinal barrier integrity in the colonic tissues of the mouse colitis model. Preliminary investigation of the toxic effects of the phage cocktail in mice indicates that continuous administration for 14 days does not yield statistically significant differences in hematological and blood biochemical parameters, and specific pathological changes are absent in histopathological examination results. The aforementioned findings suggest that the phage cocktail exhibits anti-inflammatory and intestinal barrier protective effects in the mouse colitis model, and it does not exert significant toxic side effects on mice.

Ninjurin1 deficiency differentially mitigates colorectal cancer induced by azoxymethane and dextran sulfate sodium in male and female mice.

This study investigated the role of Ninjurin1 (Ninj1), encoding a small transmembrane protein, in colitis-associated colon tumorigenesis in relation to sex hormones. Male and female wild-type (WT) and Ninj1 knockout (KO) mice were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), with or without testosterone propionate (TP). At week 2 (acute colitis stage), Ninj1 KO exhibited an alleviation in the colitis symptoms in both male and female mice. The M2 macrophage population increased and CD8+ T cell population decreased only in the female Ninj1 KO than in the female WT AOM/DSS group. In the female AOM/DSS group, TP treatment exacerbated colon shortening in the Ninj1 KO than in the WT. At week 13 (tumorigenesis stage), male Ninj1 KO mice had fewer tumors, but females showed similar tumors. In the WT AOM/DSS group, females had more M2 macrophages and fewer M1 macrophages than males, but this difference was absent in Ninj1 KO mice. In the Ninj1 KO versus WT group, the expression of pro-inflammatory mediators and Ho-1 and CD8+ T cell populations decreased in both female and male Ninj1 KO mice. In the WT group, M2 macrophage populations were increased by AOM/DSS treatment and decreased by TP treatment. However, neither treatment changed the cell populations in the Ninj1 KO group. These results suggest that Ninj1 is involved in colorectal cancer development in a testosterone-dependent manner, which was different in male and female. This highlights the importance of considering sex disparities in understanding Ninj1's role in cancer pathogenesis.

Preparation and structural characterization of selenium nanoparticles from Lactobacillus reuteri and their protective effects on DSS-induced ulcerative colitis in mice

In this study, selenium nanoparticles (SeNPs) with protection against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were prepared extracellularly by co-culturing a sodium selenite solution with Lactobacillus reuteri. Multiple analytical techniques have shown that SeNPs are mainly composed of C, N, O, and Se elements and are spherical structures encapsulated by polysaccharides or proteins, with a diameter distribution of 70∼130 nm and a potential of approximately −25 mV. The results of cell experiments showed that the prepared SeNPs could significantly reduce the production of nitric oxide (NO) induced by lipopolysaccharide (LPS) in Raw264.7 cells and exert an anti-inflammatory effect by decreasing the levels of TNF-α and IL-1β and increasing the level of IL-10. Animal experiments demonstrated that the SeNPs could effectively alleviate symptoms, such as diarrhea, weight loss, bloody stool, colon shortening, and histopathological changes induced by DSS in mice. They could also reduce mucus damage, goblet cell depletion, and intestinal permeability. In addition, the prepared SeNPs could alleviate colitis by promoting the expression of tight junction proteins, occludin-1 and zonula occluden 1 (ZO-1) and inhibiting oxidative enzymes and pro-inflammatory factors, thereby protecting the barrier function. Analysis of intestinal microbiota revealed that the SeNPs could greatly modulate the gut microbiota in colitis, restore the normal levels of gut microbiota, and enhance immune regulation in mice, thereby inhibiting the further occurrence and development of UC.