RESUMO
BACKGROUND: Intestinal fibrosis is the most common complication of inflammatory bowel disease; nevertheless, specific therapies are still unavailable. Resolvin D1 (RvD1), a typical endogenous ω-3 fatty acid-derived lipid mediator, has attracted wide attention due to its remarkable anti-fibrosis effects. However, the efficacy and mechanisms of RvD1 in intestinal fibrosis remain unclear. AIM: To investigate the protective effect of RvD1 in a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and explore the molecular mechanisms underlying its anti-fibrotic effect. METHODS: A DSS-induced intestinal fibrosis model and intestinal epithelial-to-mesenchymal transition (EMT) model were used to observe the efficacy of RvD1, and fibroblasts were stimulated with conditioned medium with or without TGF-ß1 to investigate the probable mechanisms of RvD1 in intestinal fibrosis disease. RESULTS: Intestinal fibrosis was effectively alleviated by RvD1 in a DSS-induced model, both preventively and therapeutically, and autophagy inhibition-induced EMT in intestinal epithelial cells was significantly suppressed in vivo and in vitro. Furthermore, RvD1 reduced epithelial cell EMT paracrine signaling, which promoted the differentiation of local fibroblasts into myofibroblasts. CONCLUSIONS: Our results suggested that RvD1 reduces autophagy-induced EMT in intestinal epithelial cells and ameliorates intestinal fibrosis by disrupting epithelial-fibroblast crosstalk.
Assuntos
Transição Epitelial-Mesenquimal , Fator de Crescimento Transformador beta1 , Autofagia , Colágeno , Meios de Cultivo Condicionados/farmacologia , Sulfato de Dextrana/toxicidade , Ácidos Docosa-Hexaenoicos/farmacologia , Fibrose , Humanos , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
BACKGROUND: Cytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients. METHODS: A total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses. RESULTS: A total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49-73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05-119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively. CONCLUSIONS: High-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.
Assuntos
Colite Ulcerativa , Infecções por Citomegalovirus , Albuminas , China/epidemiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Citomegalovirus , Infecções por Citomegalovirus/complicações , DNA Viral , Humanos , Imunoglobulina A , MasculinoRESUMO
BACKGROUND: Mesalamine is a first-line drug in the treatment of inflammatory bowel diseases, while its intolerance occasionally occurs in clinical practice. Most of adverse reactions are due to the active components, which may lead to step-up treatment, but excipients are sometimes regarded as the chief culprit and can be resolved by transferring to other preparations. Thus, distinguishing different kinds of intolerance is extremely important for clinical decision. CASE PRESENTATION: Here we reported two cases with mesalamine intolerance. One patient with 5-aminosalicylic acid intolerance had similar adverse reactions to the treatment of different preparations, while another patient with excipients intolerance failed to tolerate Salofalk but could take Pentasa with no symptoms. Meanwhile, clinical manifestations were analysed and the previous reports referring to excipients intolerance were summarized. It is interesting to found that the patients with excipients intolerance mainly presented with acute skin symptoms, such as skin rash, urticaria and angioedema. But the adverse effects of 5-ASA in previous reports include fever, headache, rash, nausea, vomiting, dyspepsia, hepatotoxicity, pancreatitis, interstitial nephritis, pneumonitis, pericarditis and so on. CONCLUSIONS: 5-aminosalicylic acid and excipients should be taken into consideration together when mesalamine-related adverse events occur. Of note, a diagnosis of excipient intolerance should be paid more attention in the patients with the presentation of acute skin symptoms.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Mesalamina/efeitos adversos , Dor Abdominal/induzido quimicamente , Anti-Inflamatórios não Esteroides/administração & dosagem , Diarreia/induzido quimicamente , Toxidermias/etiologia , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Mesalamina/administração & dosagem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Cronkhite-Canada Syndrome (CCS) is a rare non-inherited disease characterized by gastrointestinal polyposis and ectodermal abnormalities, the estimated incidence is about one per million. Recognizing and curing the disorder face great challenge. CASE PRESENTATION: This report refers to a Chinese 52 year old man with gastrointestinal symptoms and ectodermal abnormalities. Gastrointestinal symptoms occurred without obvious cause, followed by ectodermal abnormalities after two months. In several hospitals, endoscopy examinations found numerous polypoid lesions in various sizes spreading over the stomach and the entire colon and rectum, histopathological examinations showed inflammatory and adenomatous polyp. In our hospital, both endoscopy and the contrast-enhanced computed tomography (CT) of small intestine showed gastrointestinal polyposis. Gastric antrum and the colon biopsy samples suggested hyperplastic and inflammatory polyp respectively. Endoscopic ultrasonography (EUS) suggested gastric wall thickening. Fujinnon intelligent color enhancement (FICE) revealed that the size of gastric glands pit varied, and vessels were visible. Confocal endoscope showed increased glandular epithelium layers. Magnifying narrow-band imaging endoscopy (ME-NBI) detected that pit pattern in the mucous of the polyp were regular and type III-IV of microvessels were seen. Biochemical investigations showed anemia, hypoalbuminemia and electrolyte disturbance. IgG, IgA and C3 decreased. Anti-ribosomal phosphoprotein is weak positive. The patient was given nutritional support treatment. Gstrointestinal symptoms and hyperpigmentation improved gradually. CONCLUSION: The patient was ever hospitalized in four hospitals and was diagnosed with CCS after 8 months of gastrointestinal symptoms. So when encountering the patient with gastrointestinal polyposis and ectodermal abnormalities, try to take CCS into consideration. Due to its low incidence, no standard therapy regimen has been established so far. However, nutritional support treatment is of great significance.
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Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Pólipos do Colo/patologia , Polipose Intestinal/diagnóstico , Neoplasias Gástricas/diagnóstico , Colo/patologia , Colonoscopia , Endossonografia , Gastroscopia , Humanos , Intestino Delgado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pólipos/patologia , Estômago/diagnóstico por imagem , Estômago/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: B cell-activating factor (BAFF) has been proposed to be a regulator of B cell and T cell immune responses and be associated with inflammatory processes in autoimmunity and B cell malignancies. No study has reported the role of BAFF in inflammatory bowel disease (IBD). AIMS: The purpose of this study was to investigate expression and concentrations of BAFF in IBD and determine its value to discriminate patients with IBD. METHODS: Seventy-eight ulcerative colitis (UC) patients, 37 Crohn's disease (CD) patients, 12 irritable bowel syndrome (IBS) patients and 44 healthy controls were recruited. We examined serum and faecal BAFF levels using enzyme-linked immunosorbent assay. Intestinal BAFF expression was analysed in biopsies obtained from IBD patients. Intestinal mucosa localization of BAFF was conducted by immunofluorescence. RESULTS: The median (25th-75th percentile) serum BAFF concentration (pg/ml) was 1430 (1105-1624) in CD patients, 1472 (1018-1772) in UC patients and 977 (482-1345) in healthy controls. Serum BAFF was 64 % sensitive and 93 % specific for identifying active IBD from healthy controls. The BAFF expression was significantly increased in biopsy specimens from IBD patients. Fecal BAFF concentration was 369 (326-493) pg/ml in CD patients, 542 (358-1758) pg/ml in UC patients, 294 (287-299) pg/ml in IBS patients and 295 (284-309) pg/ml in healthy controls. Fecal BAFF was 90 % sensitive and 96 % specific for identifying active IBD from healthy controls and IBS patients. CONCLUSION: The novel association between BAFF and IBD seems to identify that BAFF might regulate the inflammatory process in these diseases and it appears to be a potential marker of IBD.
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Fator Ativador de Células B/metabolismo , Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Mucosa Intestinal/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Ensaio de Imunoadsorção Enzimática , Fezes/química , Feminino , Imunofluorescência , Humanos , Síndrome do Intestino Irritável/metabolismo , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto JovemRESUMO
Toll-like receptors (TLRs) family may play important roles in inflammatory bowel disease. This study examined the expression of TLR2, TLR4 and TLR9 in the colonic tissues of patients with ulcerative colitis (UC) and explored their roles in the pathogenesis of UC. Colonic biopsies were taken from the colon of 30 patients with mild or moderate UC (at active phase) and 10 healthy controls during colonoscopy. TLR2, TLR4 and TLR9 protein expression levels were immunohistochemically detected. The mRNA expression levels of TLR2, TLR4 and TLR9 were assessed by reverse transcription polymerase chain reaction (RT-PCR). The disease activity index (DAI), colonoscopic and histologic grades and fecal microbial flora were determined. Histological examination showed that the intestinal mucous membrane of UC patients underwent acute inflammation changes. Immunohistochemistry exhibited that the expression levels of TLR2, TLR4 and TLR9 in colon epithelia and inflammatory cells were higher in UC patients than in control group (P<0.01). The mRNA expression levels of TLR2, TLR4 and TLR9 were increased in UC patients but were not detected in the normal controls. Expression levels of TLR2, TLR4 and TLR9 were positively correlated, and bore close correlation with DAI, colonoscopic and histologic grades and fecal microbial flora. An important mechanism of UC might be that abnormal activation of mucosal immunity by intestinal dysbacteriosis caused dysregulation of TLRS that mediates innate immunity.
Assuntos
Colite Ulcerativa/metabolismo , Colo/metabolismo , Mucosa Intestinal/metabolismo , Receptor 2 Toll-Like/biossíntese , Receptor 4 Toll-Like/biossíntese , Receptor Toll-Like 9/biossíntese , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colo/microbiologia , Colonoscopia , Fezes/microbiologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Mucosa Intestinal/microbiologia , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor Toll-Like 9/genéticaRESUMO
OBJECTIVE: Interactions between phthalic acid esters (PAEs) exposure and Crohn's disease (CD) were unknown. This study aims to examine the association between exposure to PAEs and CD activity and to explore the roles of oxidative stress and microbiota. METHODS: A cross-sectional study with 127 CD patients was conducted. The disease activity was evaluated based on symptoms (Harvey-Bradshaw index, HBI), endoscopy findings (Simple Endoscopic Score for CD, SES-CD), and computed tomography enterography (CTE-scores). Ten urinary PAEs metabolites (mPAEs), two urinary oxidative stress biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α), as well as 16S rRNA sequencing of stool samples were determined. Multiple linear regression models and Hayes's PROCESS macro for SPSS were used to evaluate the interplays between urinary PAEs metabolites, CD activities, oxidative stress, and microbiota diversity. RESULTS: There were positive associations between most mPAEs and HBI. Oxidative stress mediated 20.69-89.29% of the indirect associations between low molecular weight (LMW) mPAEs and HBI, while the majority of the high molecular weight (HMW) mPAEs were directly associated with HBI. In addition, microbiota diversity moderated the indirect associations of LMW mPAEs on HBI. CONCLUSIONS: PAEs exposure was related to CD activity, and the association could be mediated by oxidative stress and reversed or alleviated by rich gut microbiota.
Assuntos
Doença de Crohn , Microbioma Gastrointestinal , Humanos , Doença de Crohn/genética , Doença de Crohn/diagnóstico , Estudos Transversais , RNA Ribossômico 16S/genética , 8-Hidroxi-2'-Desoxiguanosina , Estresse OxidativoRESUMO
BACKGROUND AND PURPOSE: The maintenance of intestinalmucosalbarrier function plays an important role in hepatic steatosis. Increasing evidence has shown that resolvin D1 (RVD1) exerts a potential effect on hepatic steatosis. The aims of this study were to explore the mechanisms of RVD1 on hepatic steatosis based on the gut-liver axis and intestinal barrier function. EXPERIMENTAL APPROACH: We established a DSS-induced chronic colitis model to evaluate hepatic steatosis. RVD1 was administered i.p. during the last 4 weeks. The colon and liver samples were stained with hematoxylin and eosin for histopathological analysis. The expression levels of intestinal tight junction genes and inflammatory genes were determined by quantitative PCR. The serum levels of glucose, cholesterol, triglycerides and LPS were measured, and the gut microbiota was analyzed by 16S rRNA gene sequencing. KEY RESULTS: RVD1 prevented weight loss, histopathological changes, and elevated levels of inflammatory cytokines. Moreover, RVD1 administration attenuated DSS-induced hepatic steatosis and inflammatory responses in mice. In addition, RVD1 improved intestinal barrier function by increasing levels of tight junction molecules and decreasing the plasma LPS levels. The RVD1-treated mice also showed a different gut microbiota composition compared with found in the mice belonging to the DSS group but similar to that in normal chow diet-fed mice. CONCLUSIONS AND IMPLICATIONS: RVD1 treatment ameliorates DSS-induced hepatic steatosis by ameliorating gut inflammation, improving intestinal barrier function and modulating intestinal dysbiosis.
Assuntos
Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Sulfato de Dextrana/farmacologia , Ácidos Docosa-Hexaenoicos , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND AND AIM: The aim of the present study was to evaluate the contribution of the dimorphism (MICA-129 val and met) to the genetic susceptibility and functions of ulcerative colitis (UC) in patients in central China. METHODS: Genotyping of MICA-129 was performed in 272 consecutive UC patients and 560 age- and sex-matched healthy individuals by using a polymerase chain reaction-sequencing based typing (PCR-SBT) method. A total of 93 patients and 98 healthy individuals serum soluble MICA (sMICA) concentrations were detected by enzyme-linked immunosorbent assay. RESULTS: Both the frequencies of the variant allele (val) and genotype (val/val) in the MICA-129 gene were significantly higher in UC patients than in the controls (77.4% vs 71.7%, P = 0.015, 95% confidence interval [CI]: 1.064-1.716; 56.9% vs 46.4%, P = 0.005, 95% CI: 1.142-2.047). Serum sMICA levels were significantly higher in UC patients than in the controls (560 ± 140 pg/mL vs 157 ± 67 pg/mL, P < 0.0001). The genotype also affected the extent and the activity of UC. Furthermore, patients with the MICA-129 val/val genotype had higher serum sMICA levels than those with the val/met + met/met genotype (661 ± 352 SD pg/mL vs 523 ± 245 SD pg/mL, 95% CI: 13.47-265.35, P = 0.03). In addition, patients with severe colitis were more susceptible to higher levels of sMICA than those with mild colitis. CONCLUSIONS: Our findings showed that the MICA-129 gene polymorphism as a functionally relevant gene was associated with UC and seems to play a potential role in the development of UC in patients in central China.
Assuntos
Povo Asiático/genética , Colite Ulcerativa/genética , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Sequência de Bases , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Colite Ulcerativa/sangue , Colite Ulcerativa/etnologia , Ensaio de Imunoadsorção Enzimática , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , Análise de Sequência de DNA , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: To investigate the association of the major histocompatibility complex class I chain-related antigens A (MICA)-129 gene polymorphism and soluble MICA (sMICA) levels with ulcerative colitis (UC) in Hubei Han nationality. METHODS: The genetic polymorphism of MICA-129 was examined using a polymerase chain reaction-sequence based test (PCR-SBT) in 256 UC patients and 460 healthy controls. From the above subjects, 80 patients and 90 healthy individuals were randomly selected for determining serum sMICA concentrations by ELISA. RESULTS: The frequencies of variant allele (G) and genotype (GG) in MICA-129 gene were significantly higher in the UC patients than in the controls (76.8% vs 72.2%, P = 0.060; 55.9% vs 46.3%, P = 0.016). Serum sMICA levels were significantly elevated in the patients compared to the controls [(576.47 ± 279.02) ng/L vs (182.17 ± 73.11) ng/L, P < 0.001]. In addition, the sMICA levels were higher in the patients carrying MICA-129 GG genotypes than in those carrying (GA + AA) genotypes [(638.87 ± 347.15) ng/L vs (507.51 ± 152.87) ng/L, P = 0.035]. CONCLUSIONS: The genetic polymorphism of MICA-129 and sMICA levels are correlated with the UC patients in Hubei Han nationality. Our findings demonstrate that MICA-129 gene may contribute to the pathogenesis of UC.
Assuntos
Colite Ulcerativa/sangue , Colite Ulcerativa/genética , Antígenos de Histocompatibilidade Classe I/sangue , Antígenos de Histocompatibilidade Classe I/genética , Adulto , Alelos , Estudos de Casos e Controles , Colite Ulcerativa/imunologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
BACKGROUND: Psychosocial factors are seemed as important causes of functional gastrointestinal disorders (FGIDs). However, the role of stress in FGIDs in high school students under the pressure of college entrance examination is largely unknown. The aim of this study is to investigate the association between the stress and FGIDs in high school graduates. METHODS: A cross-sectional survey was conducted in randomly selected high school fresh graduates. Questionnaires concerned health condition, living habits, gastrointestinal symptoms and life stress were given out and be finished voluntarily. Participants were diagnosed as FGIDs based on the Rome IV criteria. RESULTS: Stress level of FGIDs population was higher than control group and stress was independent predicted factor of high risk of FGIDs. The stressor "changes" was significantly correlated with functional gastroduodenal disorders (OR1.118(1.011-1.238)). Stressor "frustration" was significantly correlated with functional bowel disorders (OR1.038(1.006-1.071)). "Physiological reaction" was correlated with functional bowel disease and functional gastroduodenal disorders + functional bowel disorders (OR1.027(1.007-1.046) and OR1.055(1.000-1.113)). Students with more than one gastrointestinal symptom exhibited higher stress level. Moreover, there was mediation effect of stress in the association between gender, sleep quality, allergies and FGIDs. LIMITATIONS: This was a cross-section study and the sample included in the study were only from Wuhan, China. CONCLUSIONS: Our findings illustrated the predicted and mediated role of stress in FGIDs in high school fresh graduates. Different stressors and reactions to stressors contributed to different FGIDs. Intervening measures aimed at stress coping strategies were warranted for students in daily school life.
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Gastroenteropatias , China , Estudos Transversais , Gastroenteropatias/epidemiologia , Humanos , Prevalência , Instituições Acadêmicas , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the effect of (AT)n repeat polymorphism of the 3'untranslated region in cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene on CTLA-4 mRNA stability and full length (flCTLA-4) and soluble CTLA4 (sCTLA-4) expression in ulcerative colitis (UC). METHODS: flCTLA-4 mRNA in colonic biopsies and sCTLA-4 mRNA stability in peripheral blood mononuclear cells of UC patients were measured by quantitative PCR and half-life, respectively. The protein expression of flCTLA-4 in colonic biopsies and sCTLA-4 in sera of UC patients were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The polymorphism of CTLA-4 (AT)n repeats in 300 UC and 700 age and sex matched healthy controls was genotyped by fluorescent PCR. RESULTS: Among the UC patients, sCTLA-4 mRNA expression levels were decreased in active disease compared to non-active disease (P= 0.004). Carriers of the longer alleles of the (AT)n repeats expressed lower levels of flCTLA-4 and sCTLA-4 mRNA and sCTLA-4 protein than those of the shorter alleles in UC (all P< 0.01), and mRNA with long (AT)n repeat alleles has shorter half-life than mRNA with short alleles and, hence, are unstable. The frequency of long allele carriers of CTLA-4 (AT)n repeats was significantly higher in UC patients than in the healthy controls (22.0% vs. 6.3%, P< 0.01, OR= 4.21, 95% CI: 2.79-6.33), and associated with extensive colitis (P= 0.008). CONCLUSION: CTLA-4 gene expression levels were associated with (AT)n repeat polymorphisms in UC patients. The expression of CTLA-4 mRNA and protein were decreased in carriers of the longer alleles of the (AT)n repeats of CTLA-4 gene. This study suggests that CTLA-4 plays an important role in genetic risk and pathophysiology for UC in central China.
Assuntos
Antígenos CD/genética , Antígenos CD/metabolismo , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Polimorfismo Genético , Estabilidade de RNA/genética , Adulto , Antígenos CD/química , Antígeno CTLA-4 , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Genótipo , Humanos , Masculino , Fenótipo , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , SolubilidadeRESUMO
BACKGROUND: Clinical data suggest that enteral nutrition (EN) effectively decreases disease activity and maintains remission in patients with inflammatory bowel disease (IBD). However, the modulatory effects of EN on the intestinal mucosal immune system remain unclear. AIMS: This study first aimed at comparing the therapeutic effects of three EN formulas on ameliorating dextran sulfate sodium- (DSS-) induced chronic colitis; with the most effective formula, we then examined its influence on the mucosal inflammatory response and epithelial barrier function. METHODS: The effect of EN formulas on colitis in mice was assessed by body weight, disease activity index scores, colon length, and H&E staining for pathological examination. Colonic and circulating cytokine expression levels and the frequencies of immune cells were also analyzed. Intestinal epithelial barrier function was evaluated by detecting tight junction proteins. RESULTS: We found that among the three EN formulas, an elemental diet (ED) containing enriched amino acids restored the colitis-related reduction in body weight better than the other two EN formulas. ED amino acids suppressed the release of colonic proinflammatory mediators and maintained the expression of tight junction proteins in these mice. ED amino acid treatment mitigated the colitis-induced increase in CD103+CD11b+ dendritic cells and CD4+ and CD8+ T cells and inhibited the predominant Th1/Th17 responses particularly in the colonic mucosal lamina propria of mice with colitis. CONCLUSIONS: We showed that ED amino acids can be an effective immunomodulatory agent to reduce colitis-related inflammation by inhibiting proinflammatory mediators and Th1/Th17 cell responses and by repairing the disrupted epithelial barrier.
Assuntos
Aminoácidos/administração & dosagem , Ração Animal , Colite/etiologia , Colite/metabolismo , Alimentos Formulados , Mucosa Intestinal/metabolismo , Animais , Biomarcadores , Colite/dietoterapia , Colite/patologia , Colo/imunologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Camundongos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Proteínas de Junções Íntimas , Junções Íntimas/metabolismoRESUMO
OBJECTIVES: The COVID-19 epidemic triggered by coronavirus SARS-CoV-2 is rapidly spreading around the globe. This study is aimed at finding out the suspected or confirmed SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD) in Hubei province, China. We also investigated symptoms, medications, life quality, and psychological issues of IBD patients under the ongoing pandemic. METHODS: We conducted a self-reported questionnaire survey via an online survey platform. SARS-CoV-2 infection-related data was collected from IBD patients. The status quo of medications and symptoms of the subjects were investigated. Life quality, depression, and anxiety were measured by clinical questionnaires and rated on scoring systems. RESULTS: A total of 204 IBD patients from Hubei province were included in this study. No suspected or confirmed SARS-CoV-2 infection case was found in this study. As a result of city shutdown, two-thirds of the patients (138/204) in our series reported difficulty in accessing medicines and nearly half of them (73/138) had to discontinue medications. Apart from gastrointestinal symptoms, systemic symptoms were common while respiratory symptoms were rare in the cohort. Though their quality of life was not significantly lowered, depression and anxiety were problems that seriously affected them during the COVID-19 epidemic. CONCLUSIONS: Inaccessibility to medications is a serious problem for IBD patients after city shutdown. Efforts have to be made to address the problems of drug withdrawal and psychological issues that IBD patients suffer from during the COVID-19 outbreak.
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Infecções por Coronavirus/epidemiologia , Acessibilidade aos Serviços de Saúde , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Ansiedade/psicologia , Betacoronavirus/efeitos dos fármacos , COVID-19 , China/epidemiologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pandemias , Qualidade de Vida/psicologia , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
UNLABELLED: OBJECTIVE; To analyze the change of Th1/Th2/Th17 in colonic mucosa and peripheral blood in diarrhea-predominant IBS (D-IBS) to uncover the underlying mechanism for the activation of mucosal immune system. METHODS: Colonic biopsy specimens and peripheral blood were obtained from patients with D-IBS (n = 27) and controls (n = 16). Two different groups were classified on the basis of histological assessment of biopsy specimens from D-IBS patients. One group (14 of 27) had normal conventional histology (IBS), while another group (13 of 27) had nonspecific microscopic inflammation (IBS-A). Flow cytometric detection of intracellular IFN-gamma/IL-4/IL-17 cytokine production was employed to investigate Th1, Th2 and Th17 cells in colonic lamina propria and peripheral blood. Western blot was used to determine the expressions of IL-12, IL-4 and IL-17 in colonic mucosa. The levels of IL-12, IL-4 and IL-17 in peripheral blood were detected by ELISA. RESULTS: In colonic mucosa, the proportion of Th17 increased in IBS-A group as compared with controls [3.60 (4.05) vs 1.25 (3.70), P = 0.045], but not in IBS group. No difference could be observed in the frequencies of Th1 and Th2 in colonic mucosa and peripheral blood. The levels of IL-12, IL4 and IL-17 in IBS and IBS-A showed no difference in either colonic mucosa or peripheral blood. CONCLUSION: Subgroup of D-IBS showed abnormal conventional histology, implicating the activation of mucosal immune system in pathogenesis. The shift of Th1/Th2/Th17 balance in colonic mucosa showed the enhanced Th17 activity.
Assuntos
Colo/imunologia , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/imunologia , Células Th1/imunologia , Adolescente , Adulto , Colo/patologia , Feminino , Humanos , Mucosa Intestinal/imunologia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Adulto JovemRESUMO
Clinical trials have shown beneficial effects of probiotics on inflammatory bowel diseases (IBD), although the exact mechanism remains unknown. VSL#3, a mixture of 8 probiotic bacteria, has been confirmed to have adjunctive therapeutic effects on colitis. T follicular helper (Tfh) cells, a new separate subset of CD4+ T helper cells, have been proved to play a vital role in autoimmunity. The present study aimed to identify the beneficial effect of the probiotic mixture VSL#3 on the mouse model of colitis by regulating Tfh cells. Dextran sulfate sodium (DSS) was used to induce chronic colitis in C57BL/6 mice. VSL#3 (3×109 live bacteria) was given to C57BL/6 mice every other day for 60 days by gavage. The disease activity index (DAI), histological activity index (HAI), colon length and myeloperoxidase (MPO) activity were detected. Immunofluorescence was used to visualize the location of Tfh cells. Immunoglobulins, Tfh cells and plasma cells were quantified by enzyme-linked immunosorbent assay (ELISA), flow cytometry, real-time PCR or Western blotting. The results showed that after DSS treatment, the humoral immunity was disordered in C57BL/6 mice, with increased IgM, IgG and IgA levels in colonic mucus and increased Tfh cells in mesenteric lymph nodes (MLN). VSL#3 treatment showed anti-inflammatory effects as evidenced by reduced DAI score, HAI score and MPO activity. IgM, IgG and IgA levels were significantly reduced in colon mucus, and the number of Tfh cells was markedly decreased in MLN after VSL#3 treatment. It was concluded that VSL#3 alleviates DSS-induced colitis by downregulating Tfh cells, and Tfh cells may become a potential therapeutic target for IBD.
Assuntos
Colite/dietoterapia , Colo/imunologia , Linfonodos/imunologia , Probióticos/farmacologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Doença Crônica , Colite/genética , Colite/imunologia , Colite/patologia , Colo/patologia , Sulfato de Dextrana , Expressão Gênica , Imunidade Humoral , Imunoglobulina A/genética , Imunoglobulina G/genética , Imunoglobulina M/genética , Linfonodos/patologia , Contagem de Linfócitos , Masculino , Mesentério/imunologia , Mesentério/patologia , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/genética , Peroxidase/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Resultado do TratamentoRESUMO
Estrogen receptor (ER) ß activation has anti-inflammatory activity. However, its effect on the development of inflammatory bowel disease (IBD) and the underlying mechanism have not been clarified. This study aimed to assess the clinical value of ERß+CD4+ T cells in IBD patients and examine the anti-inflammatory role of ERß activation in dextran sulfate sodium (DSS)-induced chronic colitis in mice. We investigated the effects of ERB041 (an ERß-specific agonist) on inflammatory cytokines and pro-inflammatory T-cell and regulatory T-cell (Treg) responses in murine colitis. We tested the role of ERß activation on Treg differentiation and its activity to suppress T-cell proliferation in vitro. We found that reduced frequency of circulating ERß+CD4+ T cells in IBD patients was negatively correlated with inflammation and disease severity. ERß and FoxP3 expression co-localized in the intestinal tissues of IBD patients. Treatment with ERB041 significantly mitigated colitis-induced weight loss, inflammation, and disease severity. It also restored the ERß+CD4+ T cell population in the spleen and colon lamina propria of these mice. ERB041 treatment inhibited CD4+CD25- and CD8+ T cell infiltration and restored Tregs and activated T-cell immunoreceptor with Ig and ITIM domains (TIGIT)+ Tregs in the colon lamina propria. In vitro, we found that ERß activation enhanced Treg differentiation, immunosuppression, and TGF-ß1/Smad signaling in CD4+ T cells. Our data suggest that ERß+CD4+ T cells represent a potential biomarker for evaluating IBD disease severity, and ERß activation may be valuable for the treatment of IBD by enhancing the Treg response.
Assuntos
Colite/induzido quimicamente , Colite/metabolismo , Sulfato de Dextrana/farmacologia , Receptor beta de Estrogênio/metabolismo , Inflamação/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Animais , Anti-Inflamatórios , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Estudos de Casos e Controles , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Colo/efeitos dos fármacos , Colo/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Ativação Linfocitária/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/fisiologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: This study sought to evaluate the risk factors for the development of colitis-associated neoplasia (CAN) in Chinese patients with inflammatory bowel disease (IBD). METHODS: IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers. In addition to initial pathology evaluation, a CAN diagnosis was confirmed by two expert pathologists. Patients with CAN (n = 29) were compared with non-CAN controls (n = 87). Matching was performed for gender and IBD type with a ratio of three controls to one subject. RESULTS: Of the 29 patients with CAN, 8 (27.6%) had colorectal cancer (CRC), 20 (69.0%) had a final diagnosis of low-grade dysplasia and 1 (3.4%) had high-grade dysplasia. Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN, with odds ratios of 1.09 [95% confidence interval (CI): 1.04-1.14, P < 0.001] and 1.14 (95% CI: 1.03-1.27, P = 0.013), respectively. Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis (P = 0.012) and had longer IBD durations (P = 0.019). CONCLUSIONS: Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.
RESUMO
BACKGROUND: Tight crosstalk between the circadian and immune systems has been reported in several inflammatory diseases. We hypothesized that circadian timekeeping was perturbed in inflammatory bowel disease (IBD), and that the bidirectional regulation of circadian disturbance and inflammation may be involved in the pathogenesis of IBD. METHODS: Patients with ulcerative colitis (51) and Crohn's disease (39) and 42 healthy controls were recruited and their circadian gene expression levels evaluated. Dextran sodium sulfate/2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse models, and lipopolysaccharide-stimulated macrophages, were examined to detect the influence of inflammation on circadian gene expression, both in vivo and in vitro. Light/dark shift and time-restricted feeding models were also used to evaluate the influence of circadian disturbance on a mouse colitis model. RESULTS: We found that (1) almost all circadian genes were reduced in both intestinal biopsies and the peripheral blood mononuclear cells of patients with IBD, especially in patients with ulcerative colitis. Nearly all circadian genes of biopsy tissues showed negative correlations with a Mayo score or a simplified endoscopic activity score for Crohn's disease. Circadian genes of peripheral blood mononuclear cells correlated well with erythrocyte sedimentation rate and C-reactive protein levels in IBD. (2) Exposure to dextran sodium sulfate/2,4,6-trinitrobenzene sulfonic acid and lipopolysaccharide-induced marked changes in circadian gene expression profiles. (3) A phase shift exacerbated colitis in mice, with the increased secretion of proinflammatory cytokines and activation of inflammatory-related signaling pathways. CONCLUSIONS: Our results suggested that inflammation and circadian genes showed complex bidirectional regulations that were relevant to IBD. Consequently, the circadian clock seems to be a potential target for IBD therapy.
Assuntos
Ritmo Circadiano/genética , Citocinas/metabolismo , Doenças Inflamatórias Intestinais/patologia , Adolescente , Adulto , Idoso , Animais , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Colite/induzido quimicamente , Colo/patologia , Sulfato de Dextrana/administração & dosagem , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Inflamação/patologia , Doenças Inflamatórias Intestinais/genética , Mucosa Intestinal/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Adulto JovemRESUMO
Faecal calprotectin and faecal occult blood test (FOBT) were widely used in the diagnosis and assessment of intestinal inflammation in inflammatory bowel disease (IBD). Recently we identified an excellent new biomarker B cell-activating factor (BAFF) for IBD. Here in this study we compared the efficacy of faecal BAFF, calprotectin and FOBT to find the "best non-invasive marker". Results showed that for discriminating IBD from IBS, BAFF ≥227.3 pg/ml yield 84% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 64% negative predictive value (NPV) while calprotectin ≥50 µg/g yield 76% sensitivity, 93% specificity, 97% PPV and 53% NPV. FOBT yield 65% sensitivity, 93% specificity, 97% PPV and 43% NPV. Combining BAFF with calprotectin tests yield 94% sensitivity, 93% specificity, 98% PPV, 81% NPV. Faecal BAFF level showed the stronger correlation with endoscopic inflammatory score as compared to calprotectin not only in UC (correlation coefficient [r] = 0.69, p < 0.0001 vs. r = 0.58, p < 0.0001), but also in CD (r = 0.58, p < 0.0001 vs. r = 0.52, p = 0.0003). Our results indicating that faecal BAFF is a promising non-invasive biomarker in IBD differential diagnosis and monitoring of intestinal inflammation.