BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t m...We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.展开更多
AIM: To study the interplay between butyrate concentration and butyrate-producing bacteria in fecal samples of ulcerative colitis (UC) patients vs control individuals. METHODS: Fecal samples were collected from 14 con...AIM: To study the interplay between butyrate concentration and butyrate-producing bacteria in fecal samples of ulcerative colitis (UC) patients vs control individuals. METHODS: Fecal samples were collected from 14 control individuals (hemorrhoid patients only) and 26 UC patients (severe: n = 12, moderate: n = 6, remission: n = 8), recruited by the gastroenterologist at the Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India. Disease activity in UC patients was determined by clinical colitis activity index. We employed fluorescent in situ hybridization in combination with flow cytometry to enumerate the clostridium cluster population targeted by 16S rRNA gene probe. Major butyrate-producing species within this cluster were quantified to see if any change existed in control vs UC patients with different disease activity. This observed change was further validated by quantitative polymerase chain reaction. In addition to this,we carried out gas chromatography to evaluate the changes in concentration of major short chain fatty acids (SCFAs), namely acetate, n -butyrate, iso -butyrate, in the above samples. Student t test and Graph pad prism-6 were used to compare the data statistically. RESULTS: There was a significant decrease of Clostridium coccoides (control, 25.69% ± 1.62% vs severe, 9.8% ± 2.4%, P = 0.0001) and Clostridium leptum clusters (control, 13.74% ± 1.05% vs severe, 6.2% ± 1.8%, P = 0.0001) in fecal samples of UC patients. Furthermore, we demonstrated that some butyrateproducing members of the clostridial cluster, like Fecalibacterium prausnitzii (control, 11.66% ± 1.55% vs severe, 6.01% ± 1.6%, P = 0.0001) and Roseburia intestinalis (control, 14.48% ± 1.52% vs severe, 9% ± 1.83%, P = 0.02) were differentially present in patients with different disease activity. In addition, we also demonstrated decreased concentrations of fecal SCFAs, especially of n -butyrate (control, 24.32 ± 1.86 mmol/μL vs severe, 12.74 ± 2.75 mmol/μL, P = 0.003), iso -butyrate (control, 1.70 ± 0.41 mmol/μL vs severe, 0.68 ± 0.24 mmol/μL, P = 0.0441) and acetate (control, 39.51 ± 1.76 mmol/μL vs severe, 32.12 ± 2.95 mmol/ μL,P = 0.047), in the fecal samples of UC patients. The observed decrease of predominant butyrate producers of clostridial clusters correlated with the reduced SCFA levels in active UC patients. This was further confirmed by the restoration in the population of some butyrate producers with simultaneous increase in the level of SCFA in remission samples. CONCLUSION: Our observations indicate that decreases in members of the clostridial cluster resulting in reduced butyrate levels contribute to the etiology of UC.展开更多
Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed ...Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.展开更多
Acute and chronic colitis affect a huge proportion of the population world-wide.The etiology of colitis cases can be manifold,and diet can significantly affect onset and outcome of colitis.While many forms of acute co...Acute and chronic colitis affect a huge proportion of the population world-wide.The etiology of colitis cases can be manifold,and diet can significantly affect onset and outcome of colitis.While many forms of acute colitis are easily treatable,chronic forms of colitis such as ulcerative colitis and Crohn’s disease(summarized as inflammatory bowel diseases)are multifactorial with poorly understood pathogenesis.Inflammatory bowel diseases are characterized by exacerbated immune responses causing epithelial dysfunction and bacterial translocation.There is no cure and therapies aim at reducing inflammation and restoring intestinal barrier function.Unfortunately,most drugs can have severe side effects.Changes in diet and inclusion of nutritional supplements have been extensively studied in cell culture and animal models,and some supplements have shown promising results in clinical studies.Most of these nutritional supplements including vitamins,fatty acids and phytochemicals reduce oxidative stress and inflammation and have shown beneficial effects during experimental colitis in rodents induced by dextran sulphate sodium or 2,4,6-trinitrobenzene sulfonic acid,which remain the gold standard in pre-clinical colitis research.Here,we summarize the mechanisms through which such nutritional supplements contribute to epithelial barrier stabilization.展开更多
The link between cytomegalovirus(CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis(UC) and has been shown to be potentially harmful....The link between cytomegalovirus(CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis(UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools(numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flareups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.展开更多
BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many c...BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many complications.AIM To explore the protective effects of panax notoginseng saponin(PNS) against dextran sulfate sodium(DSS)-induced intestinal inflammatory injury through phosphoinositide-3-kinase protein kinase B(PI3K/AKT) signaling pathway inhibition in rats.METHODS Colitis rat models were generated via DSS induction, and rats were divided into control(no modeling), DSS, DSS + PNS 50 mg/k, and DSS + PNS 100 mg/kg groups. Then, the intestinal injury, oxidative stress parameters, inflammatory indices, tight junction proteins, apoptosis, macrophage polarization, and TLR4/AKT signaling pathway in colon tissues from rats in each of the groups were detected. The PI3 K/AKT signaling pathway in the colon tissue of rats was blocked using the PI3K/AKT signaling pathway inhibitor, LY294002.RESULTS Compared with rats in the control group, rats in the DSS group showed significantly shortened colon lengths, and significantly increased disease activity indices, oxidative stress reactions and inflammatory indices, as well as significantly decreased expression of tight junction-associated proteins. In addition, the DSS group showed significantly increased apoptotic cell numbers,and showed significantly increased M1 macrophages in spleen and colon tissues.They also showed significantly decreased M2 macrophages in colon tissues, as well as activation of the PI3K/AKT signaling pathway(all P < 0.05). Compared with rats in the DSS group, rats in the DSS + PNS group showed significantly lengthened colon lengths, decreased disease activity indices, and significantly alleviated oxidative stress reactions and inflammatory responses. In addition, this group showed significantly increased expression of tight junction-associated proteins, significantly decreased apoptotic cell numbers, and significantly decreased M1 macrophages in spleen and colon tissues. This group further showed significantly increased M2 macrophages in colon tissues, and significantly suppressed activation of the PI3K/AKT signaling pathway, as well as a dose dependency(all P < 0.05). When the PI3K/AKT signaling pathway was inhibited, the apoptosis rate of colon tissue cells in the DSS + LY294002 group was significantly lower than that of the DSS group(P < 0.05).CONCLUSION PNS can protect rats against DSS-induced intestinal inflammatory injury by inhibiting the PI3K/AKT signaling pathway, and therefore may be potentially used in the future as a drug for colitis.展开更多
AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood...AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.展开更多
Inflammatory bowel diseases(IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeu...Inflammatory bowel diseases(IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary noninvasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography,discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed t...Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.展开更多
Objective The aim of the study was to investigate the expression of proteins in colonic tissues of mice with ulcerative colitis(UC) by using isobaric tags for relative and absolute quantitation(iTRAQ), probe into the ...Objective The aim of the study was to investigate the expression of proteins in colonic tissues of mice with ulcerative colitis(UC) by using isobaric tags for relative and absolute quantitation(iTRAQ), probe into the pathogenesis of UC, and find potential biomarkers of UC. Methods Forty C57 mice were randomly divided into the control and model groups(20 mice in each group). The mice in the model group were administered dextran sulphate sodium(DSS) for 7 consecutive days ad libitum to induce acute colitis, and the colon tissue was extracted on the 8 th day after the successful establishment of the UC model. Proteins were identified by the i TRAQ and tandem mass spectrometry techniques,and the identified proteins were analyzed by bioinformatics. Results A total of 4019 proteins were identified among the two groups. Among them, 317 significant differentially expressed proteins(DEPs) were detected according to the screening criteria for selecting DEPs, i.e. fold change ratios ≥ 1.5 or ≤ 0.67 and P-values < 0.05, of which 156 were upregulated and 161 were downregulated. In the Gene Ontology(GO) analysis, the DEPs were classified into 48 functional categories, which contained biological process, cellular component, and molecular function. Based on the 317 DEPs, the KEGG pathway analysis identified 160 vital pathways.Conclusion DEPs in colonic tissues of mice with UC were screened using the iTRAQ technique, which laid a foundation for further studies regarding the pathogenesis of UC.展开更多
Objective:To elucidate the ameliorative effect of liydrualcuholic extract of leaves of Hibiscus rosa sinensis(HRS) in acetic acid induced experimental colitis in male wistar rats.Methods: The animals were administered...Objective:To elucidate the ameliorative effect of liydrualcuholic extract of leaves of Hibiscus rosa sinensis(HRS) in acetic acid induced experimental colitis in male wistar rats.Methods: The animals were administered with 2 mL acetic acid(4%) via intra rectal.The animals were divided into various treatment groups(n=6).Prednisolone was used as standard drug and HRS was administered at a dose of 50,100 and 200 mg/kg p.o.The control group of animals received 1 mL of vehicle(distilled water).Ulcer area,ulcer index,spleen weight,colon weight to length ratio, macroscopic score,haemalological parameters,colonic superoxide dismutase(SOD),glutathione(GSH),myeloperoxidase(MPO),malondialdchyde(MDA),tumor necrosis factor-α(TNK- α), nitric oxide(NO) and histological changes were recorded after the treatment regimen of 11 days. Results:Intrarectal instillation of acetic acid caused enhanced ulcer area,ulcer index,spleen weight,colon weight to length ratio,colonic MPO,MDA,NO and TNF-α It caused significant decreased level of SOD and GSH.Pretreatment with HRS for 7 days exhibited significant effect in lowering of oxidative stress,colonic NO,TNF- α and elevation of SOD and GSH at a dose of 100 and 200 mg/kg in acetic acid induced colilis.Conclusions:The present investigation demonstrates HRS is of potent therapeutic value in the amelioration of expcrimenlal colilis in laboralory animals by inhibiting the proinflammatory mediator like NO and TNK-α.展开更多
AIM To investigate the current state of research output from Chinese studies into severe ulcerative colitis(SUC) using a bibliometric analysis of publications. METHODS The contents of the Chinese periodical databases ...AIM To investigate the current state of research output from Chinese studies into severe ulcerative colitis(SUC) using a bibliometric analysis of publications. METHODS The contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015). The number of publications in each year was recorded to assess the temporal trends of research output. All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously. The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers. RESULTS There were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC. The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period. There was a significant increase in analyticalstudies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating. Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management. About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38. The number of patients reported in each 5-year period significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis.CONCLUSION The output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.展开更多
AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobe...AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.展开更多
Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extr...Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.展开更多
Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Lite...Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.展开更多
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of U...Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.展开更多
Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are tradition...Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.展开更多
AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and...AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length(9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability(0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation(90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis(149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2 B group and Ast2 B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups.CONCLUSION CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitisinduced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.展开更多
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
文摘We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.
基金Supported by Council of Scientific and Industrial Research,New Delhi Government of India
文摘AIM: To study the interplay between butyrate concentration and butyrate-producing bacteria in fecal samples of ulcerative colitis (UC) patients vs control individuals. METHODS: Fecal samples were collected from 14 control individuals (hemorrhoid patients only) and 26 UC patients (severe: n = 12, moderate: n = 6, remission: n = 8), recruited by the gastroenterologist at the Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India. Disease activity in UC patients was determined by clinical colitis activity index. We employed fluorescent in situ hybridization in combination with flow cytometry to enumerate the clostridium cluster population targeted by 16S rRNA gene probe. Major butyrate-producing species within this cluster were quantified to see if any change existed in control vs UC patients with different disease activity. This observed change was further validated by quantitative polymerase chain reaction. In addition to this,we carried out gas chromatography to evaluate the changes in concentration of major short chain fatty acids (SCFAs), namely acetate, n -butyrate, iso -butyrate, in the above samples. Student t test and Graph pad prism-6 were used to compare the data statistically. RESULTS: There was a significant decrease of Clostridium coccoides (control, 25.69% ± 1.62% vs severe, 9.8% ± 2.4%, P = 0.0001) and Clostridium leptum clusters (control, 13.74% ± 1.05% vs severe, 6.2% ± 1.8%, P = 0.0001) in fecal samples of UC patients. Furthermore, we demonstrated that some butyrateproducing members of the clostridial cluster, like Fecalibacterium prausnitzii (control, 11.66% ± 1.55% vs severe, 6.01% ± 1.6%, P = 0.0001) and Roseburia intestinalis (control, 14.48% ± 1.52% vs severe, 9% ± 1.83%, P = 0.02) were differentially present in patients with different disease activity. In addition, we also demonstrated decreased concentrations of fecal SCFAs, especially of n -butyrate (control, 24.32 ± 1.86 mmol/μL vs severe, 12.74 ± 2.75 mmol/μL, P = 0.003), iso -butyrate (control, 1.70 ± 0.41 mmol/μL vs severe, 0.68 ± 0.24 mmol/μL, P = 0.0441) and acetate (control, 39.51 ± 1.76 mmol/μL vs severe, 32.12 ± 2.95 mmol/ μL,P = 0.047), in the fecal samples of UC patients. The observed decrease of predominant butyrate producers of clostridial clusters correlated with the reduced SCFA levels in active UC patients. This was further confirmed by the restoration in the population of some butyrate producers with simultaneous increase in the level of SCFA in remission samples. CONCLUSION: Our observations indicate that decreases in members of the clostridial cluster resulting in reduced butyrate levels contribute to the etiology of UC.
文摘Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.
基金funded by the fund SEP-Cinvestav (Project 108)by Conacyt (284292)the Royal Society (NAF/R1/180017)
文摘Acute and chronic colitis affect a huge proportion of the population world-wide.The etiology of colitis cases can be manifold,and diet can significantly affect onset and outcome of colitis.While many forms of acute colitis are easily treatable,chronic forms of colitis such as ulcerative colitis and Crohn’s disease(summarized as inflammatory bowel diseases)are multifactorial with poorly understood pathogenesis.Inflammatory bowel diseases are characterized by exacerbated immune responses causing epithelial dysfunction and bacterial translocation.There is no cure and therapies aim at reducing inflammation and restoring intestinal barrier function.Unfortunately,most drugs can have severe side effects.Changes in diet and inclusion of nutritional supplements have been extensively studied in cell culture and animal models,and some supplements have shown promising results in clinical studies.Most of these nutritional supplements including vitamins,fatty acids and phytochemicals reduce oxidative stress and inflammation and have shown beneficial effects during experimental colitis in rodents induced by dextran sulphate sodium or 2,4,6-trinitrobenzene sulfonic acid,which remain the gold standard in pre-clinical colitis research.Here,we summarize the mechanisms through which such nutritional supplements contribute to epithelial barrier stabilization.
文摘The link between cytomegalovirus(CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis(UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools(numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flareups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.
基金National Natural Science Foundation of China,No.81704059Scientific Research Project of Hebei Province Traditional Chinese Medicine Administration,No.2017130。
文摘BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many complications.AIM To explore the protective effects of panax notoginseng saponin(PNS) against dextran sulfate sodium(DSS)-induced intestinal inflammatory injury through phosphoinositide-3-kinase protein kinase B(PI3K/AKT) signaling pathway inhibition in rats.METHODS Colitis rat models were generated via DSS induction, and rats were divided into control(no modeling), DSS, DSS + PNS 50 mg/k, and DSS + PNS 100 mg/kg groups. Then, the intestinal injury, oxidative stress parameters, inflammatory indices, tight junction proteins, apoptosis, macrophage polarization, and TLR4/AKT signaling pathway in colon tissues from rats in each of the groups were detected. The PI3 K/AKT signaling pathway in the colon tissue of rats was blocked using the PI3K/AKT signaling pathway inhibitor, LY294002.RESULTS Compared with rats in the control group, rats in the DSS group showed significantly shortened colon lengths, and significantly increased disease activity indices, oxidative stress reactions and inflammatory indices, as well as significantly decreased expression of tight junction-associated proteins. In addition, the DSS group showed significantly increased apoptotic cell numbers,and showed significantly increased M1 macrophages in spleen and colon tissues.They also showed significantly decreased M2 macrophages in colon tissues, as well as activation of the PI3K/AKT signaling pathway(all P < 0.05). Compared with rats in the DSS group, rats in the DSS + PNS group showed significantly lengthened colon lengths, decreased disease activity indices, and significantly alleviated oxidative stress reactions and inflammatory responses. In addition, this group showed significantly increased expression of tight junction-associated proteins, significantly decreased apoptotic cell numbers, and significantly decreased M1 macrophages in spleen and colon tissues. This group further showed significantly increased M2 macrophages in colon tissues, and significantly suppressed activation of the PI3K/AKT signaling pathway, as well as a dose dependency(all P < 0.05). When the PI3K/AKT signaling pathway was inhibited, the apoptosis rate of colon tissue cells in the DSS + LY294002 group was significantly lower than that of the DSS group(P < 0.05).CONCLUSION PNS can protect rats against DSS-induced intestinal inflammatory injury by inhibiting the PI3K/AKT signaling pathway, and therefore may be potentially used in the future as a drug for colitis.
基金Cell Analysis Laboratory, 2nd Department of Internal Medicine, and the 1st Department of Pathology and Experimental Oncology, Semmelweis University for their technical support
文摘AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.
基金Supported by The European Union Seventh Framework Programme for Research and Technological Development(FP 7)grant EUTRAIN(European Translational Training for Autoimmunity and Immune Manipulation NetworkNo.289903 to Gohar F
文摘Inflammatory bowel diseases(IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary noninvasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography,discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金financially supported by the Major Science and Technology Special Projects in Henan Province(231100310200)the Key R&D Projects in Henan Province(241111314200)+1 种基金the National Natural Science Foundation of China(32302172)the Natural Science Foundation of Henan Province(252300423038).
文摘Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.
基金Supported by a grant from the Natural Science Foundation of Hubei Province(No.2011CHB025)
文摘Objective The aim of the study was to investigate the expression of proteins in colonic tissues of mice with ulcerative colitis(UC) by using isobaric tags for relative and absolute quantitation(iTRAQ), probe into the pathogenesis of UC, and find potential biomarkers of UC. Methods Forty C57 mice were randomly divided into the control and model groups(20 mice in each group). The mice in the model group were administered dextran sulphate sodium(DSS) for 7 consecutive days ad libitum to induce acute colitis, and the colon tissue was extracted on the 8 th day after the successful establishment of the UC model. Proteins were identified by the i TRAQ and tandem mass spectrometry techniques,and the identified proteins were analyzed by bioinformatics. Results A total of 4019 proteins were identified among the two groups. Among them, 317 significant differentially expressed proteins(DEPs) were detected according to the screening criteria for selecting DEPs, i.e. fold change ratios ≥ 1.5 or ≤ 0.67 and P-values < 0.05, of which 156 were upregulated and 161 were downregulated. In the Gene Ontology(GO) analysis, the DEPs were classified into 48 functional categories, which contained biological process, cellular component, and molecular function. Based on the 317 DEPs, the KEGG pathway analysis identified 160 vital pathways.Conclusion DEPs in colonic tissues of mice with UC were screened using the iTRAQ technique, which laid a foundation for further studies regarding the pathogenesis of UC.
基金Supported by the All India Council of Technical and Education(AICTE),India(Grant No.PG/GATE-SCM/2004-2005/G-39,Dated:11/02/2011)
文摘Objective:To elucidate the ameliorative effect of liydrualcuholic extract of leaves of Hibiscus rosa sinensis(HRS) in acetic acid induced experimental colitis in male wistar rats.Methods: The animals were administered with 2 mL acetic acid(4%) via intra rectal.The animals were divided into various treatment groups(n=6).Prednisolone was used as standard drug and HRS was administered at a dose of 50,100 and 200 mg/kg p.o.The control group of animals received 1 mL of vehicle(distilled water).Ulcer area,ulcer index,spleen weight,colon weight to length ratio, macroscopic score,haemalological parameters,colonic superoxide dismutase(SOD),glutathione(GSH),myeloperoxidase(MPO),malondialdchyde(MDA),tumor necrosis factor-α(TNK- α), nitric oxide(NO) and histological changes were recorded after the treatment regimen of 11 days. Results:Intrarectal instillation of acetic acid caused enhanced ulcer area,ulcer index,spleen weight,colon weight to length ratio,colonic MPO,MDA,NO and TNF-α It caused significant decreased level of SOD and GSH.Pretreatment with HRS for 7 days exhibited significant effect in lowering of oxidative stress,colonic NO,TNF- α and elevation of SOD and GSH at a dose of 100 and 200 mg/kg in acetic acid induced colilis.Conclusions:The present investigation demonstrates HRS is of potent therapeutic value in the amelioration of expcrimenlal colilis in laboralory animals by inhibiting the proinflammatory mediator like NO and TNK-α.
基金Supported by Doctoral Fund of Ministry of Education of China,No.20130181120041
文摘AIM To investigate the current state of research output from Chinese studies into severe ulcerative colitis(SUC) using a bibliometric analysis of publications. METHODS The contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015). The number of publications in each year was recorded to assess the temporal trends of research output. All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously. The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers. RESULTS There were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC. The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period. There was a significant increase in analyticalstudies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating. Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management. About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38. The number of patients reported in each 5-year period significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis.CONCLUSION The output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.
基金Supported by The National Natural Science Foundation of China, No. 81050027
文摘AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.
基金financially supported by the Natural Science Foundation of Zhejiang Province(LY22C010002)China Postdoctoral Science Foundation(2022M721732)+1 种基金the project of sending sci-tech experts to rural areas in Ningbo city(2022S205)the K.C.Wong Magna Fund of Ningbo University.
文摘Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.
基金financial support from the Postdoctoral Fund of Hebei Medical University(30705010038)the Chunyu Project Initial Funding of Hebei Medical University(CYQD2023012)+3 种基金the Science Research Project of Hebei Education Department(QN2025145)the Hebei Yanzhao Golden Platform Talent Gathering Plan Backbone Talent Project(B2024003013)the Natural Science Foundation of Hebei Province(H2024206375,C2022206018,H2023206068)the Traditional Chinese Medicine Administration Project of Hebei Province(2025427).
文摘Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.
基金Supported by National Natural Science Foundation of China,No.82374200Construction of Traditional Chinese Medicine Inheritance and Innovation Development Demonstration Pilot Projects in Pudong New Area-High-Level Research-Oriented Traditional Chinese Medicine Hospital Construction,No.YC-2023-0901.
文摘Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.
基金supported by the Key Scientific Research Project of Hubei Provincial Department of Education (No.D20232001)。
文摘Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.
基金Supported by National Natural Science Foundation of China,No.81473506Natural Science Foundation of Zhejiang Province,No.LY13H030011 and No.LY17H290009+2 种基金State Administration of Traditional Chinese Medicine of Zhejiang Province,No.2013ZB050Department of Zhejiang Province to Build Funded Project,No.WKJ-ZJ-1531Zhejiang TCM Science and Technology Project,No.2016ZB047,No.2017ZA056 and No.2018ZB046
文摘AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length(9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability(0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation(90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis(149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2 B group and Ast2 B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups.CONCLUSION CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitisinduced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.
