Construction of the underlying circRNA-miRNA-mRNA regulatory network and a new diagnostic model in ulcerative colitis by bioinformatics analysis

BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.

Anti-inflammatory Activity of Mollugin on DSS-induced Colitis in Mice

We aimed to explore the anti-infammatory bactivity of mollugin extracted from Rubia cordifolia L,a traditional Chinese medicine,on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice.Thirty C57BL/6 mice were divided into a control group(n=6),a model group(n=6),and three experimental groups(40,20,10 mg/kg of mollugin,n=6 each).DSS solution(3%)was given to mice in the model group and experimental groups from day 4 to day 10 to induce the mouse UC model.Mice in the experimental groups were intragastrically administrated mollugin from day 1 to day 10.Animals were orally given distilled water in the control group for the whole experiment time and in the model group from day 1 to day 3.The changes in colon pathology were detected by hematoxylin and eosin(HE)staining.Interleukin-1β(IL-1β)in the serum,and tumor necrosis factor-α(TNF-α)and interferon-γ(IFN)in the tissues were measured by enzyme linked immunosorbent assay.Expression levels of Toll-like receptor 4(TLR4)and myeloid differentiation factor 88 in the colon tissues were detected by immunohistochemistry.Results showed that mollugin could significantly reduce weight loss and the disease activity index in the DSS-induced UC mouse model.HE examinations demonstrated that mollugin treatment effectively improved the histological damage(P<0.05).The overproduction of IL-Iβand TNF-α was remarkably inhibited by mollugin treatment at doses of 20 and 40 mg/kg(P<0.05).Additionally,the levels of TLR4 in colon tissues were significantly reduced in mollugin-treated groups compared with the DSS group.Our findings demonstrated that mollugin ameliorates DSS-induced UC by inhibiting the production of pro-inflammatory chemocytokines.

Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced colitis in rats

AIM:To investigate the effects of the free radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decandioate(IAC) in the dextran sodium sulphate(DSS) experimental model of ulcerative colitis.METHODS:Colitis was induced in Sprague Dawley male rats by administration of 5% DSS in drinking water.IAC(30 mg/kg,lipophilic or hydrophilic form) was administered daily(orally or ip) for 6 d until sacrifice.Colonic damage was assessed by means of indirect(Disease Activity Index score) and direct measures(macroscopic and microscopic scores) and myeloperoxidase(MPO)activity.Neutrophil infiltration within the tissue and glutathione S-transferase activity were also investigated.RESULTS:DSS-induced colitis impaired body weight gain and markedly increased all inflammatory parameters.Six-day treatment with lipophilic IAC significantly reduced intestinal damage caused by inflammation,induced a down-regulation in MPO activity(0.72 ± 0.12 and 0.45 ± 0.12 with lipophilic IAC po and ip,respectively,vs 1.10 ± 0.27 in untreated DSS colitis animals) and minimized DSS-induced neutrophil infiltration,while hydrophilic IAC administered orally did not ameliorate DSS-induced damage.CONCLUSION:These results support the hypothesis that reactive oxygen metabolites contribute to inflammation and that the radical scavenger IAC has therapeutic potential in inflammatory bowel disease.

A chronic ulcerative colitis model in rats

INTRODUCTIONIn recent years,there have been many reports aboutanimal model to investigate drugs for inflammatorybowel diseases (IBD).The experimental animalmodel often used is acetic acid-induced damage ofcolonic muscosa.In the present study,this animalmodel was investigated by administering variousconcentrations of TNBS.

A new chronic ulcerative colitis model produced by combined methods in rats

INTRODUCTIONThe etiopathogenesis of ulcerative colitis (UC)remains obscure,due to lack of an ideal animalmodel.With thc improvement of theory andmethodology in the last 30 years,people used toadopt chemicals(acetic acid,ethanol,carrageen,etc.),immunotechniques(humoral or cellularimmunity,immune complex) and substance derivedfrom UC patients to set up various kinds of UCanimal model,which mimic the pathologic changesof human UC,so far these remain far

Bifidobacterium lactis attenuates onset of inflammation in a murine model of colitis

AIM: To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis. METHODS: Donor and recipient mice received either B. lactis or bacterial culture medium as control (deMan Rogosa Sharpe) in drinking water for one week prior to transfer of a mix of naive and regulatory T cells until sacrifice. RESULTS: All recipient mice developed signs of colonic inflammation, but a significant reduction of weight loss was observed in B. lactis-fed recipient mice compared to control mice. Moreover, a trend toward a diminution of mucosal thickness and attenuated epithelial damage was revealed. Colonic expression of pro-inflammatory and T cell markers was significantly reduced in B. lactis-fed recipient mice compared to controls. Concomitantly, forkhead box protein 3, a marker of regulatory T cells, was significantly up-regulated by B. lactis. CONCLUSION: Daily oral administration of B. lactis was able to reduce inflammatory and T cells mediators and to promote regulatory T cells specific markers in a mouse model of colitis.

Impact of Probiotics on Toll-like Receptor 4 Expression in an Experimental Model of Ulcerative Colitis

Toll-like receptors （TLRs） are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics （Lactoba- cillus, Bifiidobacterium） on the expression of TLR4 and tumor necrosis factor-alpha （TNF-α in the co- lon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid （TNBS）/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The pro- tein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Westem blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As com- pared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group （P〈0.01 for both）. No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group （P〉0.05）, whereas sig- nificant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group （P〈0.01）. There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.

Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis

AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.

Identification of differentially expressed genes in ulcerative colitis and verification in a colitis mouse model by bioinformatics analyses

BACKGROUND Ulcerative colitis(UC)is an inflammatory bowel disease that is difficult to diagnose and treat.To date,the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators,such as C-reactive protein and the erythrocyte sedimentation rate,but these indicators have an unsatisfactory specificity.In this study,we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus(NCBI-GEO)databases and verified the selected core genes in a mouse model of dextran sulfate sodium(DSS)-induced colitis.AIM To identify UC-related differentially expressed genes(DEGs)using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC.METHODS Two microarray datasets from the NCBI-GEO database were used,and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams.We annotated these genes based on their functions and signaling pathways,and then protein-protein interactions(PPIs)were identified using the Search Tool for the Retrieval of Interacting Genes.The data were further analyzed with Cytoscape software and the Molecular Complex Detection(MCODE)app.The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed.Finally,colitis model mice were established by administering DSS,and the top three core genes were verified in colitis mice using real-time polymerase chain reaction(PCR).RESULTS One hundred and seventy-seven DEGs,118 upregulated and 59 downregulated,were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways.Seven clusters with close interactions in UC formed:Seventeen core genes were upregulated[C-X-C motif chemokine ligand 13(CXCL13),C-X-C motif chemokine receptor 2(CXCR2),CXCL9,CXCL5,C-C motif chemokine ligand 18,interleukin 1 beta,matrix metallopeptidase 9,CXCL3,formyl peptide receptor 1,complement component 3,CXCL8,CXCL1,CXCL10,CXCL2,CXCL6,CXCL11 and hydroxycarboxylic acid receptor 3]and one was downregulated[neuropeptide Y receptor Y1(NYP1R)]in the top cluster according to the PPI and MCODE analyses.These genes were substantially enriched in the cytokinecytokine receptor interaction and chemokine signaling pathways.The top three core genes(CXCL13,NYP1R,and CXCR2)were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice,but only CXCR2 expression was significantly different.CONCLUSION Core DEGs identified in UC are related to inflammation and immunity inflammation,indicating that these reactions are core features of the pathogenesis of UC.CXCR2 may reflect the degree of inflammation in patients with UC.

Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model

AIM: To investigate the possible role of chitinase 3-like-1 (CHI3L1) in the progression of colitis-associated carcinoma (CAC).

Agent-Based Network Modeling Study of Immune Responses in Progression of Ulcerative Colitis

Ulcerative colitis, an inflammatory bowel disease, is a chronic inflammatory disorder that results in ulcers of the colon and rectum without known etiology. Ulcerative colitis causes a huge public health care burden particularly in developed countries. Many studies suggest that ulcerative colitis results from an abnormal immune response against components of cornrnensal rnicrobiota in genetically susceptible individuals. However, understanding of the disease mechanisms at cellular and molecular levels remains largely elusive. In this paper, a network model is developed based on our previous study and computer simulations are perforrned using an agent-based network modeling to elucidate the dynamics of immune response in ulcerative colitis progression. Our modeling study identifies several important positive feedback loops as a driving force for ulcerative colitis initiation and progression. The results demonstrate that although immune response in ulcerative colitis patients is dominated by anti-inflarnrnatory/regulatory cells such as alternatively activated rnacrophages and type II natural killer T cells, proinflarnrnatory cells including classically activated rnacrophages, T helper 1 and T helper 17 cells, and their secreted cytokines tumor necrosis factor-α, interleukin-12, interleukin-23, interleukin-17 and interferon-γ remain at certain levels （lower than those in Crohn＇s disease, another inflammatory bowel disease）. Long-terrn exposure to these proinflarnrnatory components, causes rnucosal tissue damage persistently, leading to ulcerative colitis. Our simulation results are qualitatively in agreement with clinical and laboratory measurements, offering novel insight into the disease mechanisms.

Changes of CD8+CD28-T regulatory cells in rat model of colitis induced by 2,4-dinitrofluorobenzene

AIM:To determine the changes of CD8+ T subsets especially CD8+CD28-T regulatory cells in rat model of experimental colitis induced by 2,4-dinitrofluorobenzene (DNFB). METHODS:The rat model of experimental colitis was induced by enema with DNFB.Ten days later,colonic intraepithelial and splenic lymphooltes were isolated from colitis animals (n=16) and controls (n=8).The proportion of CD8+ T cells,CD8+CD28+ T cells and CD8+CD28-T regulatory cells were determined by flow cytometry. RESULTS:The model of experimental colitis was successfully established by DNFB that was demonstrated by bloody diarrhea,weight loss and colonic histopathology.The proportion of CD8+ T cells in either splenic or colonic intraepithelial lymphocytes was not significantly different between colitis animals and controls (spleen:34.6±7.24 % vs 33.5±9.41%, colon:14.0±8.93 % vs 18.0±4.06 %,P>0.05).But CD8+CD28- T regulatory cells from colitis animals were significantly more than those from controls (spleen:11.3±2.26 % vs 5.64±1.01%, colon:6.50±5.37 % vs 1.07±0.65 %,P<0.05).In contrast, CD8+CD28+ T cells from colitis animals were less than those from controls (spleen:23.3±6.14 % vs 27.8±9.70 %,P=0.06; colon:7.52±4.18 % vs 16.9±4.07 %,P<0.05).The proportion of CD8+CD28-T regulatory cells in splenic and colon intraepithelial CD8+ T cells from colitis animals was higher than that from controls (spleen:33.3±5.49 % vs 18.4±7.26 %, colon:46.0±14.3 % vs6.10±3.72 %,P<0.005). CONCLUSION:Experimental colitis of rats can be induced by DNFB with simplicity and good reproducibility.The proportion of CD8+CD28-T regulatory cells in rats with experimental colitis is increased,which may be associated with the pathogenesis of colitis.

Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model

AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 d.To induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 wk.One group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the vehicle.After rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon.Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated animals.In vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells.Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.

Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis

AIM: To evaluate the effect of pyrrolidine dithio- carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: Mice were divided into a DSS-untreated group (normal group), DSS-treated control group, DSS+PDTC-treated groupⅠ(low-dose group), and DSS+PDTC-treated groupⅡ (high-dose group). In each group, the disease activity index score (DAI score), intestinal length, histological score, and the levels of activated NF-κB and inflammatory cytokines (IL-1β and TNF-α) in tissue were measured. RESULTS: The DSS+PDTC-treated groupⅡ exhibited suppression of shortening of intestinal length and reduction of DAI score. Activated NF-κB level and IL-1β and TNF-α levels were significantly lower in DSS+PDTC- treated groupⅡ. CONCLUSION: These findings suggest that PDTC is useful for the treatment of ulcerative colitis.

Screening of differentially expressed microRNA in ulcerative colitis related colorectal cancer

Objective:To investigate the differential expression of microRNA(miRNA)in colon between ulcerative colitis(UC)and ulcerative colitis related colorectal cancer(UCRCC).Methods:An UC mouse model was built by dextran sodium sulfate,and an UCRCC mouse model by dextran sodium sulfate and 1,2-diformylhydrazine.RNAs were extracted from the colon,purified and hybridized with fluorescence-labeled miRNA oligonucleotide gene chip.Real-time fluorescence quantitative PCR was used to verity the expression variation of miRNA.SAM was employed for the data analysis.Results:The up-regulated miRNA in colon cancer included has-miR-194,hasmiR-215,has-miR-93,has-miR-192,has-miR-92a,has-miR-29b,and has-miR-20a(median false discovery rate<5%),while the down-regulated miRNAs were has-miR-1231,has-miR-195,has-miR-143,and has-miR-145(median false discovery rate<5%).Conclusions:Significant differential expression of miRNA was found between the UC mouse and UCRCC mouse,which may be related to the onset,erosion and transfer of colorectal cancer.

Faecalibacterium prausnitzii supernatant ameliorates dextran sulfate sodium induced colitis by regulating Th17 cell differentiation

AIM: To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii(F. prausnitzii) supernatant on dextran sulfate sodium(DSS) induced colitis in mice.METHODS: Forty C57BL/6J male mice were randomlydivided into four groups: control group, model group, treatment group, and prevention group. Mice were weighed daily. On day 10, the colon length was measured, the colorectal histopathologic damage score(HDS) was assessed, and plasma interleukin(IL)-17 A, IL-6, and IL-4 levels were detected by enzyme-linked immunosorbent assay. The expression of transcription factor retinoic acid-related orphan receptor-γt(RORγt) and IL-17 A in colon inflammatory mucosa tissue were determined by immunohistochemical assay, and the expression levels of RORγt m RNA, IL-17 A m RNA, and IL-6 m RNA were detected by real-time quantitative polymerase chain reaction(PCR). The proportion of Th17 in mononuclear cells in spleen was assayed by fluorescence activated cell sorter. RESULTS: When compared with the model group, the colon length(P < 0.05) and body weight(P < 0.01) in the treatment and prevention groups were significantly increased, and the colon HDS was decreased(P < 0.05 and P < 0.01). There was no statistical difference between the treatment group and prevention group. After treatment with F. prausnitzii supernatant, the plasma levels of IL-17 A and IL-6(P < 0.05), the protein and m RNA expression of IL-17 A and RORγt, and the Th17 cell ratio of spleen cells(P < 0.01) were significantly decreased compared to the model group. Plasma IL-4 level in the prevention group was significantly higher than that in the model group(P < 0.05), but there was no significant difference between these two groups in the expression of IL-6 in both the plasma and colon mucosa tissues.CONCLUSION: F. prausnitzii supernatant exerts protective and therapeutic effects on DSS-induced colitis in mice, probably via inhibition of Th17 differentiation and IL- 17A secretion in the plasma and colon mucosa tissues. It can also improve colitis in mice by downregulating IL-6 and prevent colitis by upregulating IL-4.

Interventional effect of electroacupuncture combined with medicine on monoamine neurotransmitters in hypothalamus of rats with ulcerative colitis

BACKGROUND： Ulcerative colitis （UC） is conventionally treated with sulfasalazine and other aminosalicylic acids. The symptoms of UC can be rapidly controlled, but high recurrence, severe adverse reactions and other shortages exist commonly. Whether electroacupuncture combined with medicine can make up these shortages remains unclear. OBJECTIVE： This study was to observe the regulatory effect of electroacupuncture combined with medicine on monoamine neurotransmitter in hypothalamus of rats with ulcerative colitis, and to analyze the pathogenesis of UC and the action pathway of electroacupuncture combined with medicine. DESIGN： A randomized controlled observation. SETTING： Shanghai Institute of Acupuncture and Meridian. MATERIALS： Thirty involved male SD rats of clean grade, weighing （200±20）g, were provided by the Experimental Animal Center, Shanghai University of Traditional Chinese Medicine. Sulfasalazine was produced in the Shanghai Sanwei Pharmaceutical Co., Ltd [certification No. （1995）002083]. METHODS： This study was carried out in the State Laboratory （grade 3） for Acupuncture and Immunology, Shanghai Institute of Acupuncture and Meridian. The involved 30 rats were randomized into 5 groups： normal group, model group, electroacupuncture group, medicine group and electroacupuncture combined with medicine group, with 6 rats in each group. Rats in the latter 4 groups were prepared into models of UC. In the electroacupuncture group, Zusanli（shuang） point was selected. Electro-acupuncture apparatus （G6805Ⅱ type） was connected to the point and used to stimulate it with continuous wave, frequency of 2 Hz, electrical intensity 4 mA, 20 minutes a day, for 14 days successively. In the medicine group, rats were intragastrically administrated with sulfasalazine, twice a day, 3 mL once, for 14 days successively. In the electroacupuncture combined with medicine group, rats were treated with electroacupuncture and medicine simultaneously as described in the previous two groups. Rats in the model group and normal control group were untouched except for being fixed. MAIN OUTCOME MEASURES： The levels of noradrenaline acid tartrate （NE）, 3-methoxy-4 hydroxyphenylglycol （MHPG）, dopamine hydrochloride （DA）, 3,4-dihydroxyphenylacetic acid （DOPAC）, 5-hydroxytryptamine （5-HT） hydrochloride, homovanillic acid （HVA） and 5-hydroxyindole acetic acid （5-HIAA） of rats in each group were detected by high-performance liquid chromatography （HPLC）-electrochemical method. RESULTS： All the 30 involved rats entered into the stage of final analysis. ①Detection of NE and MHPG levels： After treatment, NE level in the hypothalamus of rats was significantly higher in the electroacupuncture combined with medicine group, electroacupuncture group and medicine group was all significantly higher than that in the model group, respectively （P 〈 0.01）. After treatment, MHPG level in the metabolite of NE was very significantly higher in the electroacupuncture group than in the medicine group （P 〈 0.01）. ②Detection of DA and DOPAC levels： After treatment, DA level in the hypothalamus of rats was very significantly higher in the medicine group than in the model group （P 〈 0.01）. ③Detection of 5-HT, HVA and 5-HIAA levels： After treatment, 5-HIAA level in the hypothalamus of rats was significantly higher in the medicine group than in the model group （P 〈 0.05）. CONCLUSION： The abnormal synthesis and metabolism of monoamine neurotransmitter in the central nervous system is one of pathogenesis of UC. Electroacupuncture combined with medicine might reach its goal of treatment by regulating the monoamine neurotransmitter disorder in the hypothalamus of rats with UC.

Magnetic resonance imaging:A new tool for diagnosis of acute ischemic colitis?

AIM： To define the evolution of ischemic lesions with 7T magnetic resonance imaging （7T-MRI） in an animal model of acute colonic ischemia. METHODS： Adult Sprague-Dawley rats were divided into two groups. Group I underwent inferior mesenteric artery （IMA） ligation followed by macroscopic observa- tions and histological analysis. In group H, 7T-MRI was performed before and after IMA ligation and followed by histological analysis. RESULTS： Morphological alterations started to develop 1 h after IMA ligation, when pale areas became evident in the splenic flexure mesentery and progressively wors-ened up to 8 h thereafter, when the mesentery was less pale, and the splenic flexure loop appeared very dark. The 7T-MRI results reflected these alterations, showing a hyperintense signal in both the intraperitoneal space and the colonic loop wall 1 h after IMA ligation; the lat- ter progressively increased to demonstrate a reduction in the colonic loop lumen at 6 h. Eight hours after IMA ligation, MRI showed a persistent colonic mural hyper- intensity associated with a reduction in peritoneal free fluid. The 7T-MRI findings were correlated with histolog- ical alterations, varying from an attenuated epithelium with glandular apex lesions at 1 h to coagulative necro- sis and loss of the surface epithelium detected 8 h after IMA ligation. CONCLUSION： MRI may be used as a substitute for invasive procedures in diagnosing and grading acute ischemic colitis, allowing for the early identification of pathological findings.

Induction of experimental acute ulcerative colitis in rats by administration of dextran sulfate sodium at low concentration followed by intracolonic administration of 30% ethanol

Several models of experimental ulcerative colitis have been reported previously. However, none of these models showed the optimum characteristics. Although dextran sulfate sodium-induced colitis results in inflammation resembling ulcera-tive colitis, an obvious obstacle is that dextran sulfate sodium is very expensive. The aim of this study was to develop an inex-pensive model of colitis in rats. Sprague-Dawley rats were treated with 2% dextran sulfate sodium in drinking water for 3 d fol-lowed by an intracolonic administration of 30% ethanol. The administration of 2% dextran sulfate sodium followed by 30% ethanol induced significant weight loss, diarrhea and hematochezia in rats. Severe ulceration and inflammation of the distal part of rat colon were developed rapidly. Histological examination showed increased infiltration of polymorphonuclear leukocytes, lymphocytes and existence of cryptic abscesses and dysplasia. The model induced by dextran sulfate sodium at lower concentra-tion followed by 30% ethanol is characterized by a clinical course, localization of the lesions and histopathological features similar to human ulcerative colitis and fulfills the criteria set out at the beginning of this study.

Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice

BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acute colitis,in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.METHODS Colitis was induced by administration of dextran sodium sulfate(DSS),and carcinogenesis was induced by azoxymethane(AOM).Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model.The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.RESULTS IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase.The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization.IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS.No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice.IL-34 was dramatically increased in the active UC patients as previously reported.More importantly,expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.CONCLUSION IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice.It might be served as a potential therapeutic target in UC.