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1.
J Ethnopharmacol ; 300: 115690, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075274

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear. AIM OF THE STUDY: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice. MATERIALS AND METHODS: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1ß, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4-/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms. RESULTS: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1ß, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4-/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis. CONCLUSIONS: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway.


Assuntos
Colite Ulcerativa , Fator 88 de Diferenciação Mieloide , Animais , Caspases/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Interleucina-18/uso terapêutico , Interleucina-6/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
J Ethnopharmacol ; 300: 115741, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162543

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD), is an herbal formula commonly used for the treatment of ulcerative colitis (UC) in clinical practice, but the mechanism of PD alters the colitis remains elusive. AIM OF THE STUDY: To evaluate the intervention effect of PD on Dextran Sodium Sulfate (DSS)-induced UC based on gut microbiota and intestinal short-chain fatty acid (SCFAs) metabolism, and to investigate the mechanism of action of PD in treating UC. MATERIALS AND METHODS: A 3% (wt/vol) DSS-induced ulcerative colitis model in C57BL/6 male mice was used to evaluate the effect of oral PD in treating UC. The changes in gut microbiota in mice were analyzed by 16SrDNA gene sequencing, and the content of SCFAs in the intestinal contents of mice was determined by gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze the expression of inflammatory cytokines in serum and colonic tissues, and western blotting (WB) was applied to analyze the expression of tight junction proteins in colonic tissues. RESULTS: PD can alleviate the symptoms of UC mice, Pulsatilla Decoction high dose treatment group (PDHT) shows the best effect. Compared with the DSS group, the PDHT had significantly lower body mass, disease activity index (DAI) score, colonic macroscopic damage index (CMDI) score, and pathological damage score, at the phylum level, the relative abundance of Bacteroidetes increased while that of Firmicutes and Proteobacteria decreased, at the Genus level, the abundance of Bacteroides and Lachnospiraceae.NK4A136.group increased while that of Clostridium. sensu.stricto。, Escherichia. shigella and Turicibacter decreased. Compared with the DSS group, acetate, propionate, and total SCFAs in the PDHT with significantly higher levels. The concentrations of interleukin-1ß (L-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) decreased whereby the concentration of interleukin-10 (IL-10) increased in the PDHT group. The expression levels of Occludin, zonula occludens-1 (ZO-1), Claudin1, Claudin5, G protein-coupled receptor43 (GPR43) protein, and the relative expression of ZO-1 and Occludin mRNA were significantly increased PDHT group. CONCLUSIONS: PD has a good therapeutic effect on UC mice. The pharmacological mechanism is probably maintaining the homeostasis and diversity of gut microbiota, increasing the content of SCFAs, and repairing the colonic mucosal barrier.


Assuntos
Colite Ulcerativa , Colite , Pulsatilla , Animais , Bactérias/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Propionatos , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Food Chem ; 404(Pt B): 134707, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36327509

RESUMO

The effects of bamboo (Phyllostachys edulis) shoot dietary fiber (BSDF-1) on ulcerative colitis (UC) are unclear. Therefore, we performed an in vitro glycolysis study of intestinal microbiota samples, based on 16S rDNA sequencing and determining the metabolites in non-targeted colonic fecal fermentation broth. After a 48 h fermentation, the pH of the fermentation broth decreased significantly (p < 0.05) with the dextran sulfate sodium group (referred to here as the Mod group). The carbohydrate utilization rate was 26.59 %, and the total short-chain fatty acid content was 16.46 ± 0.71 mmol/L. The abundances of Alistipes and Lactobacillus increased after BDSF-1 fermentation, whereas those of Escherichia-Shigella, Enterococcus, and Proteus significantly decreased. BSDF-1 altered the levels of 17 metabolites in the Mod group after fermentation for 48 h, which reduced the cadaverine increasing induced by DSS. These results indicate that BSDF-1 can regulate the metabolism of the intestinal microbiota and the host, suggesting its use as a promising therapeutic strategy.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Camundongos , Sulfato de Dextrana , Fermentação , Fibras na Dieta/metabolismo , Colite Ulcerativa/tratamento farmacológico , Colo/metabolismo , Poaceae , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
4.
J Ethnopharmacol ; 301: 115800, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36228890

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lagotis integra W. W. Smith (L. integra W. W. Smith) is an important origin plant of the famous Tibetan medicine HERBA LAGOTIS. It was documented to treat "Chi Ba" disease clinically, the symptoms of which are similar to ulcerative colitis (UC). AIMS OF THIS STUDY: To screen out the active components and study the mechanisms of L. integra W. W. Smith treating UC. MATERIALS AND METHODS: The components of L. integra W. W. Smith were comprehensively analyzed using UHPLC-Q-TOF/MS method. The mechanisms were investigated using network pharmacology method including target prediction, protein-protein interaction network analysis and gene enrichment analysis. Then, the mechanisms were verified using Dextran Sulfate Sodium (DSS)-induced UC model. Finally, the core active components were further screened out through molecular docking. RESULTS: The results showed that 32 major components were identified including 8 flavonoids, 9 phenylpropanoid glycosides, 13 iridoid glycosides and 1 phenolic acid. 76 potential core therapeutic targets and top 5 key targets, which were AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor (VEGFA), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), were screened out according to network pharmacology analysis. Animal experiments confirmed that those compounds could downregulate the expression levels of the 5 key target proteins in colonic tissue of mice to exert excellent anti-UC effect. Molecular docking results showed that the main active components were echinacoside, hemiphroside B, plantamajoside, plantainoside D, 10-O-trans-isoferuloyl catalpol and scutellarioside II. CONCLUSIONS: For the first time, our study provides insights into the effective materials and molecular mechanisms of L. integra W. W. Smith treating UC, which contributes to the understanding of its pharmacodynamics.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Plantas Medicinais , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Simulação de Acoplamento Molecular , Medicina Tradicional Tibetana , Medicina Herbária , Medicamentos de Ervas Chinesas/farmacologia , Fator A de Crescimento do Endotélio Vascular , Farmacologia em Rede , Tibet
5.
J Ethnopharmacol ; 301: 115765, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36195303

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mesua Assamica (King & prain) Kosterm. (MA) is an evergreen endemic medicinal tree available in Assam in India and other parts of south Asia. The bark of the plant is traditionally used for ant-malarial activity and treating fevers. It was reported to have anti-oxidant, anti-inflammatory, anti-diabetic, anti-cancer and anti-malarial properties, but no research findings have been reported about its protective activity on intestinal inflammatory disorders like ulcerative colitis (UC) yet. AIM OF THE STUDY: The aim of the current study is to evaluate the anti-ulcerative property of ethanolic extract of MA (MAE) in-vitro on GloResponse™ NF-кB-RE-luc2P HEK 293 cells for its anti-oxidant and anti-inflammatory activities and in-vivo chronic restraint stress aggravated dextran sodium sulfate (DSS)-induced UC model. MATERIALS AND METHODS: The chemical constituents of MAE were identified by LC-MS/MS. The in-vitro effects of MAE on GloResponse™ NF-кB-RE-luc2P HEK 293 cells stimulated with TNF-α 30 ng/ml were investigated for its potential therapeutic effects. Parameters such as body weights, behavioural, colonoscopy, colon lengths and spleen weights were measured and recorded in chronic restraint stress aggravated DSS-induced UC model in C57BL/6 mice. Histological, cytokines and immunoblotting analysis in the colon tissues were determined to prove its anti-inflammatory and anti-oxidant activities. RESULTS: MAE poses significant anti-oxidant and anti-inflammatory activity in-vitro in GloResponse™ NF-кB-RE-luc2P HEK 293 cells evidenced by DCFDA and immunoflourescence assay. MAE treatment at 100 mg/kg and 200 mg/kg for 14 consecutive days has reduced Disease activity Index (DAI), splenomegaly and improved the shortened colon length and sucrose preference in mice. MAE treatment has increased the levels of anti-oxidants like GSH and reduced the levels of MDA, MPO and nitrite levels in colon tissues. Moreover, MAE has ameliorated neutrophil accumulation, mucosal and submucosal inflammation and crypt density evidenced by histopathology. Furthermore, MAE treatment significantly reduced the increased pro-inflammatory cytokines like IL-6, IL-1ß and TNF-α. we found from immunoblotting that there is a concomitant decrease in protein expression of NF-κB, STAT3 signalling cascades and phosphorylation of IKBα with an increase in Nrf2, SOD2, HO-1 and SIRT1 in colon tissues. In addition, we have performed molecular docking studies confirming that phytochemicals present in the MAE have a stronger binding ability and druggability to the NF-κB, Nrf2 and SIRT1 proteins. CONCLUSIONS: MAE exhibited significant anti-colitis activity on chronic restraint stress aggravated DSS-induced ulcerative colitis via regulating NF-κB/STAT3 and HO-1/Nrf2/SIRT1 signaling pathways.


Assuntos
Colite Ulcerativa , NF-kappa B , Animais , Humanos , Camundongos , Anti-Inflamatórios , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Cromatografia Líquida , Colite Ulcerativa/induzido quimicamente , Colo , Citocinas/metabolismo , Sulfato de Dextrana , Células HEK293 , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Casca de Planta/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismo
6.
Eur J Gastroenterol Hepatol ; 35(1): 15-20, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36165073

RESUMO

INTRODUCTION: Smoking has been associated with lower levels of anti-TNF agents, higher antibodies and a reduced response to anti-TNF in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate the possible association between smoking and adverse events (AEs) of biologics in patients with IBD. MATERIAL AND METHODS: Consecutive IBD patients under biologics from a prospective, longitudinal registry of a tertiary center were included. A specially designed questionnaire including a wide range of AEs associated with biologics was also used. RESULTS: A total of 147 patients with IBD under biologics [median age (IQR) 46 (32.5-56) years, Crohn's disease (CD) 109 (74%), female 51 (35%), under combination with immunosuppressants 60 (41 %), under intensified biologic therapy 50 (34%), under anti-TNF 132 (89%), vedolizumab 11 (7.5%), ustekinumab 3 (2%)] who had completed the questionnaire forms for AEs were included. There were 52 (35%) active smokers and 33 (22.5%) ex-smokers. The prevalence of all AEs was 88% in smokers, 87% in ex-smokers and 79% in nonsmokers. Active smoking was significantly associated with the presence of arthralgias and skin rashes ( P = 0.01 and 0.002, respectively). These correlations were the same for the CD and ulcerative colitis (UC), except for arthralgias where there was a significant correlation only with CD ( P = 0.001). There were no significant associations between smoking and other AEs ( P > 0.05). CONCLUSION: Active smoking is associated with the development of dermatological manifestations (both in UC and CD) and arthralgias (in CD) in IBD patients under biologics.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Fator de Necrose Tumoral , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/terapia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Terapia Biológica , Doença Crônica , Produtos Biológicos/efeitos adversos , Artralgia
7.
Phytomedicine ; 108: 154490, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36332386

RESUMO

BACKGROUND: Ulcerative colitis (UC) progression is driven by the activation of immune cells that release pro-inflammatory mediators to disrupt intestinal epithelial barrier integrity. This study aimed to investigate the potential protective effects of Angelica oil (AO) on the intestinal epithelial barrier in mice with UC and the underlying mechanisms. METHODS: Improvement of the disease state and protective effect of AO on the intestinal epithelial barrier were observed in mice with dextran sulphate sodium salt (DSS)-induced UC. Protein microarrays were used to screen AO-affected cytokine pools and their recruited immune cells for accumulation in the tissues. Furthermore, quantitative proteomics was applied to search for AO-acting molecules and to verify in vitro the functions of key molecules between inflammation and the intestinal mucosal barrier. RESULTS: AO significantly alleviated intestinal inflammation, reduced intestinal permeability, and retained barrier function in mice with UC. Furthermore, cytokines inhibited by AO mainly promoted monocyte and neutrophil activation or chemotaxis. Moreover, proteomic screening revealed that S100A8/A9 was a key molecule significantly regulated by AO, and its mediated TLR4/NF-κB pathway was also inhibited. Finally, we verified that AO inhibited the activation of the S100A8/A9/TLR4 signalling pathway and enhanced the expression of tight junctions (TJs) proteins using a cellular model of intestinal barrier damage induced by S100A8/A9 or macrophage-derived medium. And the enhancement of TJs in intestinal epithelial cells and the inhibition of inflammatory signalling by AO were significantly attenuated due to the application of S100A8/A9 monoclonal antibody. CONCLUSION: These results demonstrated that AO improves intestinal mucosal barrier damage in the inflammatory environment of mice with UC by inhibiting the expression of S100A8/A9 and the activation of its downstream TLR4/NF-κB signalling pathway.


Assuntos
Angelica , Colite Ulcerativa , Colite , Animais , Camundongos , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteômica , Receptor 4 Toll-Like/metabolismo
8.
J Ethnopharmacol ; 302(Pt B): 115919, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36356716

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gegen Qinlian decoction (GQD) is a traditional Chinese medicine derived from Treatise on febrile diseases and is clinically used for the treatment of acute ulcerative colitis (UC). However, the potential mechanism of GQD treatment for UC remains elusive. AIM OF STUDY: In this study, we aimed to explore the involvement of gut microbiota-related tryptophan metabolism in mediating protective effects of GQD against intestinal barrier damage. MATERIALS AND METHODS: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 6 days. The therapeutic effects of GQD in UC mice were examined based on body weight, disease activity index (DAI), organ index, length and pathological changes in the colon. The distribution of fluorescein isothiocyanate dextran (FITC-dextran) in the intestinal tract was observed using small animal imaging, while concentration of FITC-dextran in serum was detected using a fluorescein microplate analyser. Bacterial infiltration in colon tissues was observed by fluorescence in situ hybridisation (FISH), and the bacterial load in mesenteric lymph nodes (MLNs) was further examined through bacterial culture. Subsequently, colonic goblet cells were detected using Alcian blue staining. The tight junctions of the colonic epithelium were observed using transmission electron microscopy, and the expression of tight junction proteins was detected by immunofluorescence (IF) and western blot. In addition, flow cytometry was used to analyse the proportion of interleukin-22-positive (IL-22+) ILC3 cells in lamina propria lymphocytes, and the content of IL-22 in colon homogenates was determined using an ELISA kit. In addition, targeted tryptophan metabolomics was used to detect the concentration of indole derivatives produced by tryptophan metabolism in faeces, and 16S rDNA was used to investigate the composition and abundance of gut microbiota-related tryptophan metabolism. RESULTS: Administration of GQD significantly alleviated the pathological symptoms, including weight loss, increased DAI score, changes in organ index, colon shortening, and colon pathological injury in UC mice. In addition, GQD reduced the diffusion of FITC-dextran in the intestinal tract, the content of FITC-dextran in serum, and bacterial infiltration in MLNs and colon tissues. Additionally, GQD significantly increased the number of colonic goblet cells, repaired the structure of epithelial tight junctions and increased the expression of tight junction proteins. Furthermore, GQD significantly increased the proportion of IL-22+ ILC3 in the lamina propria, the expression of CYP1A1 protein in colon tissue, and the level of IL-22 in colon homogenates. However, the above protective effects of GQD were inhibited by co-administration of GQD and aryl hydrocarbon receptor (AhR) antagonist. Additionally, GQD restored the content of indole derivatives generated by tryptophan metabolism, regulated the diversity of the gut microbiota, and significantly increased the abundance of genes related to tryptophan metabolism. CONCLUSION: Our results confirmed that GQD repaired the damaged intestinal barrier in UC mice by regulating gut microbiota-related tryptophan metabolism and restoring the generation of indole derivatives to activate AhR-mediated IL-22 production.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Sulfato de Dextrana/toxicidade , Triptofano/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Camundongos Endogâmicos C57BL , Colite/tratamento farmacológico , Colo , Proteínas de Junções Íntimas/metabolismo , Indóis/farmacologia , Modelos Animais de Doenças
9.
Int J Cancer ; 152(2): 172-182, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36059225

RESUMO

Pancreatic cancer (PC) is highly fatal, and its incidence is increasing in the United States. Population-based registry studies suggest associations between a few autoimmune conditions and PC risk, albeit based on a relatively small number of cases. We conducted a population-based, nested case-control study to examine the associations between autoimmune conditions and PC risk within the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare population. Incident primary malignant PC cases (n = 80 074) were adults ≥66 years and diagnosed between 1992 and 2015. Controls (n = 320 296) were alive at the time cases were diagnosed and frequency-matched to cases (4:1 ratio) by age, sex, and year of diagnosis. We used multivariable-adjusted, unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 45 autoimmune conditions identified from Medicare claims. Eight autoimmune conditions including ankylosing spondylitis (OR = 1.45; 95% CI: 1.14-1.84), Graves' disease (OR = 1.18; 95% CI: 1.03-1.34), localized scleroderma (OR = 1.27; 95% CI: 1.06-1.52), pernicious anemia (OR = 1.08; 95% CI: 1.02-1.14), primary sclerosing cholangitis (OR = 1.37; 95% CI: 1.18-1.59), pure red cell aplasia (OR = 1.31; 95% CI: 1.16-1.47), type 1 diabetes (OR = 1.11; 95% CI: 1.07-1.15), and ulcerative colitis (OR = 1.18; 95% CI: 1.07-1.31) were associated with increased PC risk (false discovery rate-adjusted P values <.10). In subtype analyses, these conditions were associated with pancreatic ductal adenocarcinoma, whereas only ulcerative colitis was associated with pancreatic neuroendocrine tumors. Our results support the hypothesis that autoimmune conditions may play a role in PC development.


Assuntos
Doenças Autoimunes , Colite Ulcerativa , Neoplasias Pancreáticas , Humanos , Idoso , Adulto , Estados Unidos/epidemiologia , Estudos de Casos e Controles , Medicare , Pâncreas , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia
10.
J Exp Med ; 220(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36413219

RESUMO

Intelectin-1 (ITLN1) is a lectin secreted by intestinal epithelial cells (IECs) and upregulated in human ulcerative colitis (UC). We investigated how ITLN1 production is regulated in IECs and the biological effects of ITLN1 at the host-microbiota interface using mouse models. Our data show that ITLN1 upregulation in IECs from UC patients is a consequence of activating the unfolded protein response. Analysis of microbes coated by ITLN1 in vivo revealed a restricted subset of microorganisms, including the mucolytic bacterium Akkermansia muciniphila. Mice overexpressing intestinal ITLN1 exhibited decreased inner colonic mucus layer thickness and closer apposition of A. muciniphila to the epithelial cell surface, similar to alterations reported in UC. The changes in the inner mucus layer were microbiota and A. muciniphila dependent and associated with enhanced sensitivity to chemically induced and T cell-mediated colitis. We conclude that by determining the localization of a select group of bacteria to the mucus layer, ITLN1 modifies this critical barrier. Together, these findings may explain the impact of ITLN1 dysregulation on UC pathogenesis.


Assuntos
Colite Ulcerativa , Verrucomicrobia , Humanos , Camundongos , Animais , Verrucomicrobia/metabolismo , Muco/metabolismo , Lectinas , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia
11.
Talanta ; 252: 123834, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35985193

RESUMO

Ulcerative colitis, a kind of inflammatory bowel disease (IBD), is caused by dysregulated immune response of intestinal bacteria. This chronic disorder can lead to a deficiency of O2 (hypoxia) in the colon microenvironment. Nitroreductase (NTR) is a highly expressed endogenous enzyme under hypoxia, so the detection of NTR can provide diagnostic information about ulcerative colitis. Herein, an ultrasensitive NTR-triggered fluorescence probe (WS-1-NO2) is developed for hypoxia imaging in ulcerative colitis. The probe shows a significant fluorescence enhancement (45-fold) after reacting with NTR, with an extremely low detection limit of 0.096 ng/mL. Furthermore, we apply it for fluorescence imaging of hypoxia in living cells, tumors and dextran sulphate sodium (DSS)-induced ulcerative colitis mouse models. We believe that the probe may be investigated as an effective potential tool for gaining insight into the hypoxia-relevant diseases, such as cancer and ulcerative colitis.


Assuntos
Colite Ulcerativa , Corantes Fluorescentes , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/diagnóstico por imagem , Nitrorredutases , Imagem Óptica/métodos , Hipóxia/diagnóstico por imagem , Sulfato de Dextrana
12.
J Nutr Biochem ; 111: 109190, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36272692

RESUMO

Auricularia polytricha and Flammulina velutipes are two dietary mushrooms mostly consumed in China and known for their traditional use on gastric ulceration and to boost bowel movement. Considering the gut-liver axis, which has been recognized for its role in the autoimmune modulation, and the implications of the intestinal barrier in the pathogenesis of liver diseases that remain unclear, the therapeutic effects of A. polytricha (APE) and F. velutipes (FVE) on inflammatory bowel disease (IBD)-induced liver injury in mice was investigated as well as their potential mechanism via the signaling pathways they could involve. 3% DSS was administered to the mice in drinking water, to induce ulcerative colitis, followed by oral administration of APE and FVE. The biochemical, oxidative stress and inflammatory parameters, mRNA and protein expressions were assessed. The results revealed that DSS-induced liver histopathological changes were ameliorated by APE and FVE treatment. APE and FVE administration also improved the ALT and AST activity as well as the pro-inflammatory cytokines and oxidative factors. Data also showed that, in addition to their regulation of tight junctions' disruption, APE and FVE attenuated genes and proteins expression involved in apoptosis, lipid metabolism, and bile acid homeostasis via inhibiting TLR4/NF-κB and caspase signaling pathways and stimulating Keap1/Nrf2 signaling pathways. In conclusion, APE and FVE regulated liver injury on DSS-induced ulcerative colitis by alleviating inflammation, oxidative stress, and apoptosis, suggesting that they could be used as therapeutic alternatives against liver diseases in addition to their functions as dietary supplements.


Assuntos
Colite Ulcerativa , Flammulina , Hominidae , Doenças Inflamatórias Intestinais , Camundongos , Animais , Flammulina/metabolismo , NF-kappa B/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Colite Ulcerativa/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Inflamação/metabolismo , Transdução de Sinais , Estresse Oxidativo , Apoptose , Fígado/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Hominidae/metabolismo , Sulfato de Dextrana
13.
J Ethnopharmacol ; 291: 115145, 2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35219821

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SBS) is commonly employed to improve gastrointestinal dysfunction in patients with ulcerative colitis (UC) in China. SBS combined with mesalamine has been demonstrated to result in improve its curative effects without increasing any adverse reactions, but the underlying mechanism remains unclarified. AIM OF THE STUDY: Our study aimed to illuminate the potential therapeutic effects and mechanisms of SBS, which is a medicine complementary to mesalamine, in the treatment of UC. MATERIALS AND METHODS: A prospective cohort study was conducted to evaluate the efficacy of SBS as a complementary medicine to mesalamine for patients with UC (n = 48). The patients in the control group (n = 24) were given mesalamine alone, whereas those in the experimental group were administered mesalamine combined with SBS. The therapeutic outcome was assessed at 8 weeks. The structures of the gut microbiota (GMB) were characterized by 16S rRNA sequencing, and the microbial tryptophan metabolites were analyzed by UPLC-MS/MS to investigate the mechanism through which SBS achieves its effects. RESULTS: Our results showed that the combination of SBS and mesalamine could significantly improve the clinical signs of UC by achieving mucosal healing and relieving colon damage. Interestingly, the combination of SBS and mesalamine could alter the GMB structures and increase the microbial levels of tryptophan metabolites, including indole-3-propionic acid and indole-3-acetic acid. CONCLUSION: SBS combined with mesalamine is effective in improving the clinical and endoscopic outcomes of patients with UC. SBS, as a complementary therapy to conventional treatment, alleviates UC via the GMB-tryptophan metabolite axis.


Assuntos
Colite Ulcerativa , Terapias Complementares , Microbioma Gastrointestinal , Cromatografia Líquida , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Medicamentos de Ervas Chinesas , Humanos , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Estudos Prospectivos , RNA Ribossômico 16S , Espectrometria de Massas em Tandem , Triptofano
15.
Gastroenterol. hepatol. (Ed. impr.) ; 45(10): 789-798, dic. 2022. mapas, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-VR-407

RESUMO

Introducción: En nuestra opinión existe un desequilibrio entre la relevancia del síndrome del intestino irritable (SII) y los medios que se le proporcionan. Objetivo: Revisar los diferentes factores que determinan (o deberían determinar) el interés de los gastroenterólogos por el SII, comparándolo con la enfermedad inflamatoria intestinal (EII). Para ello se han analizado 7 áreas diferentes: 1.Impacto médico; 2.Impacto social; 3.Importancia académica; 4.Relevancia clínica; 5.Relevancia científica; 6.Relevancia pública, y 7.Aspectos personales del médico. Resultados: La prevalencia es 10 veces superior en el SII, suponiendo hasta el 25% de las visitas del gastroenterólogo. Ambas patologías alteran la calidad de vida, en muchos casos de forma semejante. El coste social es muy importante en ambos casos (p.ej., absentismo del 21 y del 18%), así como el económico, aunque muy superior en medicación para la EII. La dedicación académica es más del doble para la EII, tanto en la universidad como en la formación MIR. La relevancia científica es mayor en la EII, con un número de publicaciones cuatro veces superior. La relevancia pública no es muy diferente entre las dos entidades, aunque los pacientes con EII son más asociativos. Los médicos prefieren la EII y tienden a estigmatizar el SII. Conclusión: En nuestra opinión, para disminuir este desequilibrio entre necesidades y recursos, humanos y materiales, en el SII es imprescindible realizar cambios drásticos tanto en los aspectos educativos, de habilidades de comunicación, de priorización de acuerdo con las demandas de los pacientes, y de recompensa (personal y social) de los médicos.(AU)


Introduction: In our opinion there is an imbalance between the relevance of irritable bowel syndrome (IBS), and the resources that are provided. Objective: To review the different factors that determine (or should determine) the interest of gastroenterologists in IBS, comparing it with inflammatory bowel disease (IBD). For this, 7 different areas have been analyzed: (1)Medical impact; (2)Social impact; (3)Academic importance; (4)Clinical relevance; (5)Scientific relevance; (6)Public relevance, and (7)Personal aspects of the doctor. Results: The prevalence is 10 times higher in IBS, which represents up to 25% of gastroenterologist visits. Both pathologies alter the quality of life, in many cases in a similar way. The social cost is very important in both cases (e.g.: absenteeism of 21% and 18%) as well as the economic cost, although much higher in medication for IBD. Academic dedication is more than double for IBD, both in university and in MIR training. Scientific relevance is greater in IBD, with a number of publications four times higher. Public relevance is not very different between the two entities, although IBD patients are more associative. Doctors prefer IBD and tend to stigmatize IBS. Conclusion: In our opinion, to reduce this imbalance between needs and resources, human and material, in IBS it is essential to make drastic changes both in educational aspects, communication skills, prioritization according to the demands of patients, and reward (personal and social) of physicians.(AU)


Assuntos
Humanos , Doenças Inflamatórias Intestinais , Síndrome do Intestino Irritável , Prevalência , Mudança Social , Doença de Crohn , Estereotipagem , Colite Ulcerativa , Gastroenterologia , Gastroenteropatias , Custos e Análise de Custo
16.
Gastroenterol. hepatol. (Ed. impr.) ; 45(10): 805-818, dic. 2022. tab
Artigo em Espanhol, Português | IBECS | ID: ibc-VR-410

RESUMO

Los pacientes con enfermedad inflamatoria intestinal (EII) pueden requerir diferentes tratamientos inmunosupresores a lo largo del curso de su enfermedad. Por ello, es fundamental evaluar el estado de inmunización en el momento del diagnóstico o, si no es posible, siempre antes de iniciar un tratamiento inmunosupresor, y administrar las vacunas apropiadas. El objetivo del presente documento es establecer unas recomendaciones claras y concisas sobre la vacunación en pacientes con EII en diferentes escenarios de práctica clínica, incluyendo situaciones especiales como la vacunación en la edad pediátrica, el embarazo, la lactancia o en viajes al extranjero. Se presentan las diferencias entre vacunas inactivadas y atenuadas, los diferentes grados de inmunosupresión y su relación con las pautas de administración de las diferentes vacunas (tanto obligatorias como opcionales) recomendadas a los pacientes con EII. En el documento, se establecen 17 recomendaciones basadas en la evidencia científica disponible y opinión de expertos. En la elaboración de estas recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa ha participado un equipo multidisciplinar con amplia experiencia en EII y vacunación formado por especialistas de gastroenterología, pediatría, enfermería y farmacia.(AU)


Patients with inflammatory bowel disease (IBD) may require different immunosuppressive treatments throughout their illness. It is essential to assess the immunization status of patients at diagnosis or, if this is not possible, at least before the beginning of immunosuppressive therapy and, subsequently, administering the appropriate vaccines. Therefore, the aim of this work is to establish clear and concise recommendations on vaccination in patients with IBD in the different settings of our clinical practice including vaccination in children, during pregnancy, breastfeeding or on trips. This consensus document emphasises the differences between inactivated and attenuated vaccines and the different degrees of immunosuppression and correlates them with the administration of both mandatory and optional vaccines recommended to our patients with IBD. Finally, as a summary, 17 recommendations are established based on the available scientific evidence and expert opinion. A multidisciplinary team with extensive experience in IBD and vaccination, made up of specialists in gastroenterology, paediatrics, nursing and pharmacy, has participated in the preparation of these recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis.


Assuntos
Humanos , Doença de Crohn , Colite Ulcerativa , Pacientes , Programas de Rastreamento , Prevenção de Doenças , Infecções , Doenças Inflamatórias Intestinais , Gastroenterologia , Gastroenteropatias
17.
Medicine (Baltimore) ; 101(47): e30945, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451450

RESUMO

BACKGROUND: Although anti-inflammatory and immunomodulatory measures have delayed the progression of ulcerative colitis (UC) to a certain extent, the adverse drug reactions and recurrence after recovery still trouble clinicians. Acupoint catgut embedding is a possible alternative strategy for the treatment of UC, but its clinical efficacy remains controversial. Therefore, this study systematically evaluated the clinical efficacy and safety of acupoint catgut embedding compared with conventional western medicine in the treatment of UC. METHODS: VIP, Wanfang, China National Knowledge Infrastructure, China Biology Medicine, PubMed, Embase, Web of Science, the Cochrane Library databases were searched. And the publication time of the literature was limited from the time that the database was established to February 2022. Two researchers independently screened the literature, extracted data, and assessed risk of bias as required. Meta-analysis was performed with Revman 5.3. Trial sequential analysis (TSA) was performed with TSA 0.9.5.10 Beta. Publication bias was assessed by Stata 15.0. And evidence quality was appraised with GRADEpro3.6. RESULTS: A total of 10 studies were listed, with a total sample size of 782 cases. Meta-analysis showed that compared with conventional western medicine, acupoint catgut embedding can effectively improve the total effective rate of clinical symptoms (relative risk [RR] = 1.16, 95% confidence interval [CI] = [1.09,1.24], P < .00001), endoscopic total effective rate (RR = 1.16, 95%CI = [1.08,1.25], P < .0001), clinical symptom cure rate (RR = 1.80, 95%CI = [1.37,2.38], P < .0001), and endoscopic cure rate (RR = 1.97, 95%CI = [1.36,2.86], P = .0004) of UC, but the adverse event rate (RR = 0.20, 95%CI = [0.01,4.00], P = .29) was similar. Trial sequential analysis indicated that the efficacy endpoint was conclusive. Harbord test confirmed no significant publication bias. The quality of evidence for these outcomes ranges from low to medium. CONCLUSION: The clinical efficacy of acupoint catgut embedding in the treatment of UC is superior to that of conventional western medicine, and the safety may be equivalent to that of conventional western medicine, which has the value of further research and exploration.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Humanos , Categute , Pontos de Acupuntura , Colite Ulcerativa/terapia
18.
J Investig Med ; 70(8): 1771-1776, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36455956

RESUMO

Prescriptions for biologic therapy for treatment of Crohn's disease (CD) and ulcerative colitis (UC) have increased during the past two decades; however, trends are less clear regarding corticosteroid prescriptions in this context. We designed a cross-sectional study using the IQVIA Ambulatory Electronic Medical Records databases. Weighted linear regressions by age group were used to estimate annual percentage change from 2011 to 2020 in prescriptions for biologics and for corticosteroids among patients with or without biologic prescriptions within the same calendar year. Using 2019 data, we compared patient demographic and lifestyle risk factors using χ2 test for biologic prescriptions and corticosteroids with or without biologics prescriptions. There was an 11% (CD) and 16% (UC) annual increase in the percentage of patients prescribed biologics during the study period. The percentage of patients with biologics prescriptions prescribed corticosteroids decreased by 2% (CD) and 3% (UC) annually after 2015, while the percentage remained unchanged for corticosteroid prescriptions among patients without biologics. In 2019, differences in medication prescriptions existed by patient's demographic and lifestyle factors for patients with CD (n=52,892) and UC (n=52,280), including a higher percentage prescribed biologics among younger patients, men, those with fewer comorbidities, and current alcohol drinkers, and a higher percentage prescribed corticosteroids without biologics among women, those with more comorbidities, and a history of smoking. While medications continue to evolve during the biologic era, it is important to continue to monitor trends and differences in prescription patterns to assess progress toward optimizing treatment for patients with CD or UC.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Masculino , Humanos , Feminino , Registros Eletrônicos de Saúde , Estudos Transversais , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Corticosteroides/uso terapêutico , Doença Crônica , Prescrições de Medicamentos , Demografia , Produtos Biológicos/uso terapêutico
19.
Pol Przegl Chir ; 94(6): 54-60, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36468508

RESUMO

<b> Introduction: </b> Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is a procedure which enables reconstruction of the continuity of the gastrointestinal track after resection of the large intestine and rectum. The most common diseases that require this type of resection include: ulcerative colitis and familial adenomatous polyposis. </br></br> <b>Aim:</b> The study aimed to determine the effectiveness of IPAA in the surgical treatment of the paediatric age group. </br></br> <b>Material and methods:</b> The research material was collected based on medical records of 21 patients who underwent proctocolectomy at the Department of Pediatric Surgery, Traumatology, and Urology of the Medical University of Poznan in 2000-2021. </br></br> <b>Results: </b> In a group of 21 patients, 11 children were qualified for proctocolectomy due to ulcerative colitis (UC), 6 due to familial adenomatous polyposis (FAP), 3 due to Hirschsprung's disease (HD), and one child due to Crohn's disease (CD). Early complications in treated patients included dehiscence of the postoperative wound, bleeding from the lower gastrointestinal tract and anastomotic leakage. Late complications included pouchitis, stenosis of the ileostomy, narrowing of the anastomotic site and soiling. Quality of life was rated at an average of 9-10 by 16 patients on a scale of 1-10. </br></br> <b>Conclusions:</b> IPAA is a proven method of reconstruction for the paediatric age group requiring proctocolectomy. Complications are common, most often related to the underlying disease and the clinical condition of the patients. Despite possible complications, patients rate their quality of life high on the scale. Each qualification for surgery should be carried out in a multidisciplinary team.


Assuntos
Polipose Adenomatosa do Colo , Colite Ulcerativa , Proctocolectomia Restauradora , Criança , Humanos , Satisfação do Paciente , Colite Ulcerativa/cirurgia , Qualidade de Vida , Período Perioperatório , Polipose Adenomatosa do Colo/cirurgia , Anastomose Cirúrgica
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