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Objective: to conduct a literature review on possible serum markers in patients with UC to identify potential biomarkers. Methods: the descriptors "Colitis Ulcerative", "Biomarkers", and "Diagnosis" were used for the search in the PUBMED, LILACS, SciELO, and SCOPUS databases. After applying the inclusion and exclusion criteria in the databases, the 32 articles were classified as samples. Results: research indicates that biomarkers can play distinct roles in assessing activity and diagnosing UC. For instance, the peptide nesfatin-1 showed elevated serum levels during active periods of the disease, while the peptide trefoil factor 3 showed promise in predicting UC activity. It is worth highlighting that C-reactive protein (CRP) is a commonly used marker in which high values are observed in patients during the active phase of the disease; however, studies suggest the need to redefine CRP cutoff values to better predict endoscopic remission. Other approaches, such as the analysis of proteins, specific fatty acids, and proteins related to the extracellular matrix, have also been explored, highlighting their potential as biomarkers. Conclusion: in summary, there is a diversity of possible clinically important biomarkers that play different roles in the assessment and diagnosis of UC. However, it is essential to conduct further research to validate these biomarkers and achieve greater reliability.

Objetivo: realizar uma revisão da literatura sobre possíveis marcadores séricos em pacientes com RU com o objetivo de identificar potenciais biomarcadores. Métodos: os descritores "Colitis Ulcerative", "Biomarkers" e "Diagnosis" foram utilizados para a busca nas bases de dados PUBMED, LILACS, SciELO e SCOPUS. Após a aplicação dos critérios de inclusão e exclusão nas bases de dados, os 32 artigos foram classificados como amostras. Resultados: a pesquisa indica que os biomarcadores podem desempenhar papéis distintos na avaliação da atividade e no diagnóstico da RU. Por exemplo, o peptídeo nesfatin-1 apresentou níveis séricos elevados durante os períodos ativos da doença, enquanto o peptídeo trefoil factor 3 mostrou-se promissor na predição da atividade da RU. Vale destacar que a proteína C-reativa (PCR) é um marcador comumente utilizado, no qual valores elevados são observados em pacientes durante a fase ativa da doença; no entanto, estudos sugerem a necessidade de redefinir os valores de corte da PCR para melhor predizer a remissão endoscópica. Outras abordagens, como a análise de proteínas, ácidos graxos específicos e proteínas relacionadas à matriz extracelular, também têm sido exploradas, destacando seu potencial como biomarcadores. Conclusão: em resumo, há uma diversidade de possíveis biomarcadores de importância clínica que desempenham diferentes papéis na avaliação e diagnóstico da CU. No entanto, é essencial conduzir mais pesquisas para validar esses biomarcadores para obter maior confiabilidade.

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OBJECTIVE@#To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.@*METHODS@#Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).@*CONCLUSION@#EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

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Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.

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Eosinophilic colitis is a rare and severe form of eosinophilic gastrointestinal disease. This study presents the case of a 69-year-old woman from Anadia, Alagoas, Brazil, who experienced intermittent abdominal pain in the right and left iliac fossae, along with recurrent eructations, flatus, in-creased bowel movements, diarrhea, and loss of appetite for approximately six months. The diagnosis of eosinophilic colitis was confirmed through upper digestive endoscopy, colonoscopy, and histopathology, which revealed eosinophilic pancolitis with about 100 eosinophils per high-power field in most tissue fragments. After three months of a restricted diet and treatment with ketotifen 1 mg (twice daily for 30 days) and esomeprazole 40 mg (once daily on an empty stomach for 56 days), the patient showed clinical improvement. This case highlights the diagnostic challenges of eosinophilic colitis due to its non-specific clinical signs and emphasizes the necessity of supplementary examinations (AU)

A colite eosinofílica é uma doença rara, sendo a forma menos frequente e mais grave entre as doenças eosinofílicas gastrintestinais. Este estudo apresenta o caso de uma mulher de 69 anos, natural de Anadia, Alagoas, Brasil, que apresentou dor abdominal intermitente nas fossas ilíacas direita e esquerda, acompanhada de eructações, flatos, aumento da frequência do trânsito intestinal, diarreia e inapetência por aproximadamente seis meses. O diagnóstico de colite eosinofílica foi confirmado por endoscopia digestiva alta, colonoscopia e histopatologia, que revelaram pancolite eosinofílica com cerca de 100 eosinófilos por campo de grande aumento na maioria dos fragmentos de tecido. Após três meses de dieta restritiva e tratamento com cetotifeno 1 mg (duas vezes ao dia por 30 dias) e esomeprazol 40 mg (uma vez ao dia em jejum por 56 dias), a paciente apresentou melhora clínica. Este caso destaca os desafios diagnósticos da colite eosinofílica devido aos seus sinais clínicos inespecíficos e enfatiza a necessidade de exames complementares (AU)

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A Anexina A1 (AnxA1) é uma proteína de 37 kDa que controla o desenvolvimento da reação inflamatória inata, e favorece a eferocitose e o reparo tecidual. Em doenças inflamatórias intestinais (DIIs), tanto a AnxA1 endógena, como a sintética e o peptídeo sintético mimético ao N-terminal da proteína (Ac2-26) inibem o desenvolvimento de doença e induzem a cicatrização. O presente projeto teve o objetivo de obter novas formulações para carrear a AnxA1 recombinante (rAnxA1) ou o Ac2-26 e testar suas eficácias no modelo de colite experimental induzida pelo dextram sulfato de sódio (DSS, 0-6 dias) em camundongos C57Bl/6 machos. A rAnxA1 foi funcionalizada em nanocápsulas de núcleo lipídico de parede múltipla (MLNC) pela ligação Zn2+, com alta eficência de incorporação (92%) e adminsitrada pelas vias oral, intravenosa ou intraperitoneal durante a fase latente da doença (6º-9º dia). Somente o tratamento intraperitoneal com MLNC-AnxA1 (12,5 µg/mL) reduziu significativamente os sinais clínicos da doença, restaurou a integridade da estrutura colônica e a proliferação celular, bem como aumentou expressão de junções celulares da barreira intestinal. Ainda, MLNC-AnxA1 induziu a polarização de macrófagos para o fenótipo M2 in vivo no tecido inflamado e in vitro após estímulo com lipopolissacarídeos (LPS) bacteriano. Na tentativa de obter uma formulação terapêutica com atividade por vial oral, o peptídeo Ac2-26 foi incorporado em sílica mesoporosa ordenada SBA-15 e revestidos com Eudragit® L30-D55. A incorporação do peptídeo foi efetiva (88%) e a administração oral de Eudragit-SBA15-Ac2-26 (6º-9º dia; 200 µg/camundongo; 8 mg/kg) reduziu significativamente os sintomas clínicos e inflamação. De fato, ensaios de PET-SCAN mostraram que o SBA-15 permaneceu no intestino por até 16 horas após a administração e promoveu a liberação do peptídeo no intestino inflamado. Em cultura celular de epitélio (Caco-2), Eudragit-SBA15-Ac2-26 favoreceu a internalização de Ac2-26. Em conjunto, as duas estratégias expermentais de entrega do rAnxA1 ou Ac2-26 foram eficientes e os resultados obtidos sugerem que mais estudos devem ser realizados para a confirmação das estratégias de tratamento. Com o intuito de buscar ferramentas para ampliar estes estudos, durante estágio BEPE foram realizados estudos em cultura de células epiteliais baseado em células-tronco adultas diferenciadas in vitro. Os resultados mostraram que rAnxA1 ou Ac2-26 protegeram a integridade epitelial após desafio com LPS, pela regulação positiva da expressão das junções oclusivas e aderentes e redução da expressão de claudina-2, responsável pelo aumento da permeabilidade intercelular; pela modulação negativa decitocinas pró-inflamatórias CXCL-1 e MCP-1, e positiva de citocina antiinflamatória IL-10. Desta forma, padronizamos um novo modelo de cultura celular ainda não testada para a AnxA1 ou Ac2-26, que poderá ser empregada para desvendar os mecanismos da MLNC-AnxA1 e do Eudragit-SBA15-Ac2-26

Annexin Al (AnxA1) is a 37 kDa protein that controls the development of the innate inflammatory reaction, and favors efferocytosis and tissue repair. In inflammatory bowel diseases (IBDs), both endogenous and synthetic AnxA1 and the synthetic peptide mimetic to the N-terminal of the protein (Ac2-26) inhibit the development of disease and induce healing. The present project aimed to obtain new formulations to carry recombinant AnxA1 (rAnxA1) or Ac2-26 and test their efficacy in the experimental colitis model induced by dextram sodium sulfate (DSS, 0-6 days) in C57Bl/6 mice. rAnxA1 was functionalized into multiwall lipid core nanocapsules (MLNC) by Zn2+ binding, with high incorporation efficiency (92%) and administered orally, intravenously or intraperitoneally during the latent phase of the disease (6º-9º day). Only intraperitoneal treatment with MLNC-AnxA1 (12.5 µg/mL) significantly reduced the clinical signs of the disease, restored the integrity of the colonic structure and cell proliferation, as well as increased the expression of intestinal barrier cell junctions. Furthermore, MLNC-AnxA1 induced macrophage polarization to the M2 phenotype in vivo in inflamed tissue and in vitro after stimulation with bacterial lipopolysaccharides (LPS). In an attempt to obtain a therapeutic formulation with oral activity, the Ac2-26 peptide was incorporated into ordered mesoporous silica SBA-15 and coated with Eudragit® L30-D55. Peptide incorporation was effective (88%) and oral administration of Eudragit-SBA15-Ac2-26 (6º-9º day; 200 µg/mice; 8 mg/kg) significantly reduced clinical symptoms and inflammation. PET-SCAN assays showed SBA-15 remained in the intestine for up to 16 hours after administration and promoted the release of the peptide in the inflamed intestine. In epithelial cell culture (Caco-2), SBA15-Ac2-26 favored the internalization of Ac2-26. Taken together, the two experimental delivery strategies for rAnxA1 or Ac2-26 were efficient and the results obtained suggest that more studies should be carried out to confirm the treatment strategies. In order to seek tools to expand these studies, during the BEPE internship, studies were carried out in epithelial cell cultures based on adult stem cells differentiated in vitro. The results showed rAnxA1 or Ac2-26 protected epithelial integrity after challenge with LPS, by upregulating the expression of tight and adherens junctions and reducing the expression of claudin-2, responsible for increasing intercellular permeability; by negative modulation of pro-inflammatory cytokines CXCL-1 and MCP-1, and positive modulation of anti-inflammatory cytokine IL-10. In this way, we standardized a new cell culture model that has not yet been tested for AnxA1 or Ac2-26, which could be used to unravel the mechanisms of MLNC-AnxA1 and Eudragit-SBA15-Ac2-26

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Eosinophilic colitis (EoC), a rare immune-mediated disease that is part of the eosinophilic gastrointestinal diseases, is characterized by the presence of an eosinophilic infiltrate in the colonic wall in symptomatic patients. Before considering the diagnosis of EoC, other diseases associated with colonic eosinophilia should be ruled out, such as parasitic infections, drugs, chronic immune-mediated diseases, and neoplasms. The symptoms of EoC are variable and non-specific, being abdominal pain and diarrhea the most common. Although systemic corticosteroids and budesonide have demonstrated their efficacy, these drugs have only been evaluated in case series studies and cli- nical case reports. Herein, we discuss the clinical strategy for diagnosis, therapy selection, and follow-up of EoC

La colitis eosinofílica (CEo), una enfermedad inmunomediada que forma parte de las enfermedades gastrointes- tinales eosinofílicas, se caracteriza por la presencia de infiltrado eosinofílico en la pared del colon en pacientes sintomáticos. Antes de plantear el diagnóstico de una CEo, otras enfermedades asociadas a una eosinofilia coló- nica, incluyendo infecciones parasitarias, fármacos, enfermedades crónicas inmunomediadas y neoplasias, deben ser descartadas. Los síntomas de la CEo son variables e inespecíficos, siendo el dolor abdominal y la diarrea los más frecuentes. Aunque los corticoides sistémicos y la budesonida han demostrado su eficacia, estos fármacos han sido evaluados solo en estudios de serie de casos y reportes de casos clínicos. En este artículo, discutimos la estrategia clínica para el diagnóstico, selección del tratamiento y el seguimiento de la CEo.

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OBJECTIVE@#To investigate the effect of pachymic acid (PA) against TNBS-induced Crohn's disease (CD)-like colitis in mice and explore the possible mechanism.@*METHODS@#Twenty-four C57BL/6J mice were randomized equally into control group, TNBS-induced colitis model group and PA treatment group. PA treatment was administered via intraperitoneal injection at the daily dose of 5 mg/kg for 7 days, and the mice in the control and model groups were treated with saline. After the treatments, the mice were euthanized for examination of the disease activity index (DAI) of colitis, body weight changes, colon length, intestinal inflammation, intestinal barrier function and apoptosis of intestinal epithelial cells, and the expressions of TNF-α, IL-6 and IL-1β in the colonic mucosa were detected using ELISA. The possible treatment targets of PA in CD were predicted by network pharmacology. String platform and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network. David database was used to analyze the GO function and KEGG pathway; The phosphorylation of PI3K/AKT in the colonic mucosal was detected with Western blotting.@*RESULTS@#PA significantly alleviated colitis in TNBS-treated mice as shown by improvements in the DAI, body weight loss, colon length, and histological inflammation score and lowered levels of TNF-α, IL-6 and IL-1β. PA treatment also significantly improved FITC-dextran permeability, serum I-FABP level and colonic transepithelial electrical resistance, and inhibited apoptosis of the intestinal epithelial cells in TNBS-treated mice. A total of 248 intersection targets were identified between PA and CD, and the core targets included EGFR, HRAS, SRC, MMP9, STAT3, AKT1, CASP3, ALB, HSP90AA1 and HIF1A. GO and KEGG analysis showed that PA negatively regulated apoptosis in close relation with PI3K/AKT signaling. Molecular docking showed that PA had a strong binding ability with AKT1, ALB, EGFR, HSP90AA1, SRC and STAT3. In TNBS-treated mice, PA significantly decreased p-PI3K and p-AKT expressions in the colonic mucosa.@*CONCLUSION@#PA ameliorates TNBS-induced intestinal barrier injury in mice by antagonizing apoptosis of intestinal epithelial cells possibly by inhibiting PI3K/AKT signaling.

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Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

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Ulcerative colitis (UC) is a chronic, non-specific intestinal disease that not only affects the quality of life of patients and their families but also increases the risk of colorectal cancer. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of inflammatory response system, and its activation induces an inflammatory cascade response that is involved in the development and progression of UC by releasing inflammatory cytokines, damaging intestinal epithelial cells, and disrupting the intestinal mucosal barrier. Chinese medicine (CM) plays a vital role in the prevention and treatment of UC and is able to regulate NLRP3 inflammasome. Many experimental studies on the regulation of NLRP3 inflammasome mediated by CM have been carried out, demonstrating that CM formulae with main effects of clearing heat, detoxifying toxicity, drying dampness, and activating blood circulation. Flavonoids and phenylpropanoids can effectively regulate NLRP3 inflammasome. Other active components of CM can interfere with the process of NLRP3 inflammasome assembly and activation, leading to a reduction in inflammation and UC symptoms. However, the reports are relatively scattered and lack systematic reviews. This paper reviews the latest findings regarding the NLRP3 inflammasome activation-related pathways associated with UC and the potential of CM in treating UC through modulation of NLRP3 inflammasome. The purpose of this review is to explore the possible pathological mechanisms of UC and suggest new directions for development of therapeutic tools.

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OBJECTIVE@#This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR).@*METHODS@#Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.@*RESULTS@#Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.@*CONCLUSION@#Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.

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This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.

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OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

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OBJECTIVE@#To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD).@*METHODS@#The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction.@*RESULTS@#Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01).@*CONCLUSION@#RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.

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Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H2S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

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The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

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Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms. The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice, increased colon length, and reduced DAI, spleen index, and pathological damage within the colon. PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity. Meanwhile, PGP restored the levels of Th1, Th2, Th17, and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity. Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation. Taken together, PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.

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Purpose: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. Methods: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. Results: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. Conclusions: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

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INTRODUCCIÓN: La colitis eosinofílica y la colitis de la enfermedad inflamatoria intestinal, son dos entidades que pueden compartir similares características clínicas, endoscópicas y terapéuticas pero diferentes criterios diagnósticos. OBJETIVOS: Describir el caso clínico de un niño preescolar con antecedente de alergia alimentaria, de hospitalizaciones y uso de antibióticos por varias ocasiones, que evoluciona con diarrea crónica intermitente. CASO CLÍNICO: Se trata de un paciente masculino, de 3 años 5 meses, con antecedente de alergia alimentaria con cuadro crónico de dolor abdominal, diarrea y retraso en el crecimiento. Se realiza abordaje de diarrea crónica. RESULTADOS: Con hallazgos clínicos de enfermedad inflamatoria intestinal y descripción histopatológica de colitis eosinofílica, se considera la asociación entre estas dos patologías sin dejar la posibilidad de que esta última se trate de una fase inicial de enfermedad inflamatoria intestinal. CONCLUSIONES: El tratamiento de pacientes con colitis eosinofílica complicada es similar a la enfermedad inflamatoria intestinal, se requiere seguimiento clínico, endoscópico e histopatológico de pacientes con colitis eosinofílica a largo plazo.

INTRODUCTION: Eosinophilic colitis and inflammatory bowel disease colitis are two entities that may share similar clinical, endoscopic and therapeutic features but different diagnostic criteria. OBJECTIVES: To describe the clinical case of a preschool child with a history of food allergy, hospitalizations and use of antibiotics for several occasions, who evolves with chronic intermittent diarrhea. CLINICAL CASE: This is a male patient, 3 years 5 months old, with a history of food allergy with chronic abdominal pain, diarrhea and growth retardation. Chronic diarrhea was approached. RESULTS: With clinical findings of inflammatory bowel disease and histopathological description of eosinophilic colitis, the association between these two pathologies is considered without leaving the possibility that the latter is an initial phase of inflammatory bowel disease. CONCLUSIONS: The treatment of patients with complicated eosinophilic colitis is similar to inflammatory bowel disease, clinical, endoscopic and histopathological follow-up of patients with eosinophilic colitis is required in the long term.

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Abstract Introduction: Microscopic colitis is a benign and multifactorial disease characterized by watery diarrhea and histological alterations in the colonic mucosa. The incidence of this disease is increasing, being diagnosed more frequently. Materials and methods: In this retrospective study, patients were examined employing colonoscopy and biopsy due to a diagnosis of chronic diarrhea in a gastroenterology unit throughout 22 months. Their diagnosis of colitis was confirmed by clinical picture and microscopic analysis. Results: In the study period, a total of 2849 colonoscopies were performed, 116 in patients with chronic diarrhea. We identified 15 patients with microscopic colitis, 12 were men (80 %), and only three were older than 60 (20 %). Conclusion: Unlike the world literature, this study found that microscopic colitis in our patients affects the male sex primarily (male/female ratio: 4/1) and occurs in young people, with an average age of 47.5 years (range: 21-82 years).

Resumen Introducción: la colitis microscópica es una enfermedad benigna y multifactorial caracterizada por la presencia de diarrea acuosa y alteraciones histológicas en la mucosa colónica. La incidencia de esta enfermedad viene en aumento y su diagnóstico se realiza cada vez con mayor frecuencia. Métodos: estudio retrospectivo en el que se revisaron los pacientes por medio de colonoscopia y biopsias por diagnóstico de diarrea crónica en un período de 22 meses en una unidad de gastroenterología, y en quienes mediante la clínica y el análisis histológico se confirmó el diagnóstico de colitis microscópica. Resultados: en el período de estudio se realizó un total de 2849 colonoscopias, 116 en pacientes con diarrea crónica. Se identificaron 15 pacientes con colitis microscópica, 12 fueron hombres (80 %) y solo hubo 3 mayores de 60 años (20 %). Conclusión: a diferencia de lo informado en la literatura mundial, en este estudio se encontró que la colitis microscópica en nuestros pacientes compromete especialmente al sexo masculino (relación hombre/mujer: 4/1) y se presenta en personas jóvenes, con un promedio de edad de 47,5 años (rango de 21 a 82 años).

ABSTRACT

Malignant neoplasms are increasingly prevalent in the daily clinical practice. Up to 61% of patients with pelvic malignancies undergo pelvic radiotherapy in different doses, which may cause intestinal damage, and the rectum is the segment most frequently affected due to its fixed position in the pelvis. Currently, there are several strategies to minimize the effects of radiation on the tissues surrounding the neoplastic site; despite those strategies, radiotherapy can still result in serious damage to organs and structures, and these injuries accompany patients throughout their lives. One of the most common damages resulting from pelvic radiotherapy is acute proctitis.The diagnosis is confirmed by visualizing the rectal mucosa through rigid or flexible rectosigmoidoscopy and colonoscopy. The objective of the present study was to review the forms of radiation-induced proctopathytherapy, and to evaluate the results of each method to propose a standardization for the treatment of this pathology. Despite the prevalence of radiation-induced proctopathy, there is no definitive standardized treatment strategy so far. The first approach can be tried with local agents, such as mesalazine and formalin. For refractory cases, control can usually be achieved with argon plasma coagulation, hyperbaric oxygen, and radiofrequency ablation therapies. Regarding the study of radiation-induced proctopathy, there is a lack of robust studies with large samples and standardized therapies to be compared. There is a lack of double-blinded, randomized controlled studies to determine a definitive standard treatment algorithm. (AU)