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1.
Food Funct ; 15(4): 2314-2326, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38323473

RESUMO

Certain types of soluble dietary fibre, such as pectin and pectic oligosaccharides from different sources, have demonstrated protective effects against inflammation in DSS-induced colitis mouse models. In this work, we have evaluated the impact of a diet enriched in apple pomace (AP-diet), an agricultural by-product with a significant content of pectin and that previously demonstrated prebiotic properties in human fecal batch fermentation models, on the gut microbiota composition, intestinal damage and inflammation markers in a DSS-induced colitis model. We found that the apple pomace enriched diet (AP-diet), providing a significant amount of pectin with demonstrated prebiotic properties, was associated with a slower increase in the disease activity index, translating into better clinical symptomatology of the animals. Histological damage scoring confirmed less severe damage in those animals receiving an AP-diet before and during the DSS administration period. Some serum inflammatory markers, such as TNFα, also demonstrated lower levels in the group receiving the AP-diet, compared to the control diet. AP-diet administration is also associated with the modulation of key taxa in the colonic microbiota of animals, such as some Lachnospiraceae genera and Ruminococcus species, including commensal short chain fatty acid producers that could play a role in attenuating inflammation at the intestinal level.


Assuntos
Colite , Microbioma Gastrointestinal , Malus , Camundongos , Animais , Humanos , Colite/induzido quimicamente , Colite/patologia , Inflamação/patologia , Dieta , Colo/patologia , Pectinas/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
2.
Sci Rep ; 14(1): 3472, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342939

RESUMO

MicroRNAs play a crucial role in regulating the epithelial barrier and immune response, which are implicated in the pathogenesis of ulcerative colitis (UC). This study aimed to investigate the role and molecular mechanism of miR-30c in the pathogenesis of UC using a dextran sulfate sodium salt (DSS)-induced colitis model, which is similar to ulcerative colitis. Wild-type (WT) and miR-30c knockout (KO) mice were assigned to either control or DSS-treated groups to evaluate the influence of aberrant miR-30c expression on UC pathogenesis. The disease activity index, inflammatory factors, and the extent of pathological and histological damage in colon tissues were analyzed. The effect of miR-30c on vasoactive intestinal peptide (VIP) gene expression was validated through luciferase reporter assay, qRT-PCR, Western blotting, and immunohistochemistry. The results showed that miR-30c KO mice with DSS-induced colitis model showed more severe phenotypes: significantly higher disease activity indices, significant body weight loss, reduced length of the colon of mice, increased number of aberrant crypt structures, reduced mucus secretion, and significant differences in inflammatory factors. These findings suggested that the absence of miR-30c might promote DSS-induced colitis, and the targe-regulatory effect of miR-30c on VIP might play an important role in the development of colitis.


Assuntos
Colite Ulcerativa , Colite , MicroRNAs , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Colite/induzido quimicamente , Camundongos Knockout , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colo/patologia
3.
Sci Rep ; 14(1): 3479, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347087

RESUMO

Reduced butyrate-production capacity has been reported in fecal microbial communities in patients with active ulcerative colitis. However, the butyrate-production capacity of the mucosal microbiome from active vs quiescent mucosa in ulcerative colitis has been unexplored. We sought to determine the diversity and relative abundance of mucosal bacterial and fungal communities from endoscopically active vs quiescent mucosa in patients with UC, and aimed to predict contributions of mucosal microbial communities to butyrate synthesis. Systematic, segmental right- and left-sided biopsies were obtained from endoscopically active (n = 13) or quiescent (n = 17) colonic mucosa, among 15 patients with pan-colonic ulcerative colitis. Dietary fiber intake of patients was performed using the validated five-item FiberScreen questionnaire. Amplicon sequencing of mucosal bacteria and fungi was performed. The diversity and relative abundance of mucosal bacterial and fungal taxa were quantified, and predicted contributions to butyrate synthesis were ascertained. Bacterial alpha and beta diversity were similar between active vs quiescent mucosa. Butyrogenic taxa were significantly increased in quiescence, including Butyricimonas, Subdoligranulum, and Alistipes. Predicted butyrate kinase activity was significantly and concomitantly increased in quiescent mucosa. Fiber intake was positively correlated with butyrogenic microbes. Compared to mucosal bacterial prevalence, mucosal fungi were detected in low prevalence. Butyrogenic microbes are relatively increased in quiescent mucosa in ulcerative colitis, and may be related to increased fiber intake during quiescence. Manipulation of the mucosal microbiome towards butyrate-producing bacteria may be associated with endoscopic quiescence.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/patologia , Butiratos , Colo/patologia , Biópsia , Mucosa Intestinal/patologia , Bactérias/genética
4.
Clin Lab ; 70(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345994

RESUMO

BACKGROUND: Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. METHODS: Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1ß, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). RESULTS: The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1ß, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. CONCLUSIONS: Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.


Assuntos
Colite , Labetalol , Ratos , Animais , Labetalol/efeitos adversos , Molécula 1 de Adesão Intercelular/metabolismo , Sulfassalazina/efeitos adversos , Ratos Wistar , Colo/patologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Ácido Acético/efeitos adversos , Ácido Acético/metabolismo
5.
Int Immunopharmacol ; 128: 111499, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38232535

RESUMO

BACKGROUND AND AIMS: S100a10 is a member of the S100 family of proteins, which plays a key role in the depression and tumor metastasis. However, the role of S100a10 is unclear in ulcerative colitis. METHODS: The effect of S100a10 was assessed using a murine ulcerative colitis model which was accompanied by parameters including body weight loss, disease activity index, histological score, colon weight and length. The quantity and role of immune cells was determined by flow cytometry and bone marrow chimeric mice. Neutrophils depletion, adoptive cell transfer and conditional knockout mice were used to ascertain which cells played the key role in ulcerative colitis. The function of neutrophils was evaluated by migration assay, phagocytosis assay, multiplex immunoassay and real-time PCR. RESULTS: In this study, our data showed that S100a10-/- mice were prone to ulcerative colitis induced by dextran sodium sulfate. Neutrophils number increased in colon of S100a10-/- mice after dextran sodium sulfate treatment significantly. Meanwhile, adoptive transfer of neutrophils from wild type mice partially decreased the susceptibility of S100a10-/- mice to dextran sodium sulfate. There was no difference in ulcerative colitis between the groups of S100a10-/- mice without neutrophils and wild type mice. Finally, we found that S100a10-/- neutrophils had stronger function in secretion and synthesis of inflammatory factor. CONCLUSIONS: In one word, these results suggest that S100a10 has a role in inhibiting the pathogenesis of ulcerative colitis through regulation of neutrophils function.


Assuntos
Colite Ulcerativa , Colite , Sulfatos , Animais , Camundongos , Colite/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana/farmacologia , Dextranos/efeitos adversos , Dextranos/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/metabolismo
6.
Int Immunopharmacol ; 128: 111490, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38218008

RESUMO

BACKGROUND AND OBJECTIVES: Ulcerative colitis (UC) is a recurrent intestinal inflammatory disease which poses a serious threat to the life of patients. However, there are no specific drugs for UC yet. Hypericum sampsonii Hance (HS) is a Chinese herbal medicine traditionally used to treat enteritis and dysentery. Our previous studies have demonstrated that HS holds potential anti-UC effects, and a novel compound named Hypersampsonone H (HS-1) isolated from HS possesses significant anti-inflammatory activity. However, the beneficial effects of HS-1 on UC remain unclear. This study aimed to investigate the therapeutic effects of HS-1 on UC and its potential mechanisms, both in vitro and in vivo. METHODS: The in vitro model was employed using LPS-induced RAW264.7 cells to investigate the anti-inflammatory effects of HS-1 and its possible mechanisms. Furthermore, the therapeutic efficacy and potential mechanisms of HS-1 against dextran sulfate sodium (DSS)-induced acute colitis were assessed through histopathological examination, biochemical analysis, and molecular docking. RESULTS: In vitro, HS-1 significantly reduced LPS-induced inflammatory responses, as indicated by inhibiting NO production, down-regulating the overexpression of COX-2 and iNOS, as well as regulating the imbalanced levels of IL-6, TNF-α, and IL-10. Moreover, HS-1 also inhibited the expression of PDE4, elevated the intracellular cAMP level, and promoted the phosphorylation of CREB, thereby activating the PKA/CREB pathway in RAW264.7 cells. In vivo, HS-1 demonstrated therapeutic capacity against DSS-induced colitis by alleviating the symptoms of colitis mice, regulating the abnormal expression of inflammatory mediators, protecting the integrity of intestinal epithelial barrier, and reducing tissue fibrosis. Consistently, HS-1 was found to decrease the expression of PDE4 isoforms, subsequently activating the cAMP/PKA/CREB signaling pathway. Furthermore, the molecular docking results indicated that HS-1 exhibited a high affinity for PDE4, particularly PDE4D. Further mechanistic validation in vitro demonstrated that HS-1 possessed a synergistic effect on forskolin and an antagonistic effect on H-89 dihydrochloride, thereby exerting anti-inflammatory effects through the cAMP/PKA/CREB signaling pathway. CONCLUSION: We disclose that HS-1 serves as a promising candidate drug for the treatment of UC by virtue of its ability to reduce DSS-induced colitis via the inhibition of PDE4 and the activation of cAMP/PKA/CREB signaling pathway.


Assuntos
Colite Ulcerativa , Colite , Humanos , Camundongos , Animais , Colite Ulcerativa/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Transdução de Sinais , Colite/induzido quimicamente , Anti-Inflamatórios/uso terapêutico , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colo/patologia
7.
Int Immunopharmacol ; 128: 111587, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38286073

RESUMO

BACKGROUND: Ulcerative colitis (UC), an ongoing inflammatory disorder of the colon, is marked by persistent mucosal surface irritation extending from the rectum to the near-proximal colon. Tiron is a synthetic analogue of vitamin E which is known to have antioxidant and anti-inflammatory effects in various animal models, so the goal of this study was to find out whether Tiron had any preventive impacts on UC inflicted by acetic acid (A.A) exposure in rats. METHOD: Tiron (235 and 470 mg/kg) was administered intra-peritoneally for 2 weeks, and A.A (2 ml, 3 % v/v) was injected intra-rectally to cause colitis. Colon tissues and blood samples were then collected for measurement of various inflammatory and oxidative stress biomarkers. RESULTS: Tiron administration significantly diminished lactate dehydrogenase (LDH), C-reactive protein (CRP), colon weight, and the weight/length ratio of the colon as compared to A.A-injected rats. Additionally, Tiron attenuated oxidative stress biomarkers. Tiron also enforced the levels of Glucagon-like peptide-1 (GLP-1) and trefoil factor-3 (TFF-3), while it greatly lowered the expression of nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interferon-γ (IFN-γ), and transforming growth factor-1(TGF-ß1), phosphorylated epidermal growth factor receptor (P-EGFR), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) expression in colonic cellular structures. Furthermore, colonichistopathologic damages, revealed by hematoxylin and eosin (H&E) and Alcian Blue stain, were significantly decreased upon Tiron administration. CONCLUSION: Tiron prevented A.A-induced colitis in rats via modulating inflammatory pathway TGF-ß1/P-EGFR/PI3K/AKT/NF-κB, alongside managing the oxidant/antioxidant equilibrium, and boosting the reliability of the intestinal barrier.


Assuntos
Colite Ulcerativa , Colite , Ratos , Animais , NF-kappa B/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/metabolismo , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Antioxidantes/farmacologia , Ácido Acético/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Reprodutibilidade dos Testes , Colo/patologia , Transdução de Sinais , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Receptores ErbB/metabolismo , Biomarcadores/metabolismo
8.
Phytomedicine ; 124: 155292, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190784

RESUMO

BACKGROUND: (-)-Syringaresinol (SYR), a natural lignan with significant antioxidant and anti-inflammatory activities, possesses various pharmacological benefits including cardio-protective, antibacterial, anticancer, and anti-aging effects. It was shown that the effectiveness of (+)-syringaresinol diglucoside on the ulcerative colitis (UC) was attributed to the active metabolite (+)-syringaresinol (the enantiomor of SYR). However, the efficacy of SYR against UC remains unclear, and the associated molecular mechanism has not been revealed yet PURPOSE: This study aimed to assess the protective effect of SYR in UC and its underlying mechanism STUDY DESIGN AND METHODS: We examined SYR's protective impact on the intestinal epithelial barrier and its ability to inhibit inflammatory responses in both a lipopolysaccharide (LPS)-induced Caco-2 cell model and a dextran sodium sulfate (DSS)-induced UC mouse model. We also explored the potential signaling pathways regulated by SYR using transcriptome analysis and western blot assay RESULTS: In Caco-2 cells, SYR significantly increased trans-epithelial electrical resistance, reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), and cyclooxygenase-2 (COX-2) levels, and enhanced cellular tight junction protein expression and distribution. In mice with UC, oral treatment with SYR (10, 20, 40 mg·kg-1) dose-dependently increased body weight, colon length, and expression of tight junction proteins, decreased disease activity index score, spleen coefficient, cytokine serum levels, bacterial translocation, and intestinal damage, and also preserved the ultrastructure of colonic mucosal cells. Transcriptomics indicated that the anti-UC effect of SYR is mediated via the PI3K-Akt/MAPK/Wnt signaling pathway. CONCLUSION: In summary, SYR effectively mitigated the development of UC by enhancing the intestinal epithelial barrier function and attenuating the inflammatory response. The plant-derived product SYR might be a potentially effective therapeutical agent against UC.


Assuntos
Colite Ulcerativa , Colite , Furanos , Lignanas , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Células CACO-2 , Fosfatidilinositol 3-Quinases/metabolismo , Colo/patologia , Lignanas/farmacologia , Lignanas/uso terapêutico , Mucosa Intestinal/metabolismo , Modelos Animais de Doenças , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente
9.
Medicine (Baltimore) ; 103(4): e37026, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277569

RESUMO

BACKGROUND: This study aims to investigate the safety and feasibility of preserving left colonic artery (LCA) in radical sigmoid and rectal cancer surgery. METHODS: Relevant articles were systematically searched on the PubMed, Embase, and Cochrane Library. The quality of included studies was evaluated using the Cochrane Handbook. A meta-analysis was conducted to assess the surgical outcomes and oncological outcomes by RevMan 5.4 software. RESULTS: Fifteen studies with a total of 5054 patients, including 2432 patients with LCA preservation and 2622 patients without LCA preservation, were included and analyzed in this study. The meta-analysis revealed that preserving LCA in radical surgery of sigmoid and rectal cancer has lower anastomotic leakage incidence (OR = 1.03, 95% confidence interval = 0.83-1.27, P < .0001). There were no significant differences in the operative time, intraoperative blood loss, number of dissected lymph nodes, postoperative complications as well as the oncological outcomes including systemic recurrence, local recurrence, 5-year overall survival rate, and 5-year disease-free survival rate. CONCLUSION SUBSECTIONS: This pooled analysis showed that preserving the LCA is safe and feasible in radical sigmoid and rectal cancer surgery.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Artéria Mesentérica Inferior/cirurgia , Colo/patologia , Colo Sigmoide/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Artérias/cirurgia
10.
J Pediatr Gastroenterol Nutr ; 78(1): 68-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38291695

RESUMO

OBJECTIVES: Necrotizing enterocolitis (NEC) is a severe neonatal surgical condition, associated with a prolonged pro-inflammatory state, leading to high mortality and morbidity rates. Carbon dioxide (CO2 ) insufflation during laparoscopy may have an anti-inflammatory effect. We aimed to evaluate the effects of CO2 -insufflation on experimental colitis. METHODS: Acute colitis was induced in 6-week-old Balb/c mice by the administration of 2%-dextran sulfate-sodium (DSS) during 7 days (n = 45). On Day 4, two groups received intraperitoneal insufflation (duration: 30 mn, pressure: 5 mmHg) of CO2 ("DSS+CO2 ") or air ("DSS+air"). A group received no insufflation ("DSS"). Groups were compared for clinical severity using the disease activity index (DAI-body weight loss, stool consistency, and bleeding), histological severity (histopathological activity index, colon length, and ulcerations), colonic mucosecretion, and inflammation. RESULTS: DAI was significantly decreased in DSS+CO2 group, compared to DSS (p < 0.0001) or DSS+air (p < 0.0001) groups. Colon length was increased in DSS+CO2 treated mice compared to DSS (p = 0.0002). The histopathological activity index was lower in DSS+CO2 (vs. DSS, p = 0.0059/vs. DSS+air, p = 0.0389), with decreased ulcerations (3.77 vs. 10.7, p = 0.0306), and persistent mucosecretion with increased mucin-secreting cells. CONCLUSIONS: CO2 -insufflation attenuates DSS-induced colitis and improves both clinical and histological scores. Laparoscopy with CO2 insufflation represents a therapeutic anti-inflammatory strategy for NEC.


Assuntos
Colite , Insuflação , Animais , Camundongos , Dióxido de Carbono/efeitos adversos , Colo/patologia , Modelos Animais de Doenças , Colite/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Úlcera/patologia , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL
11.
PLoS One ; 19(1): e0296311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38165858

RESUMO

Recent magnetic resonance imaging (MRI) studies showed that colonic volumes in children are different between health and functional constipation. The length of the colon has however been rarely measured and principally using unphysiological colon preparations or cadaver studies. The main objective of this study was to measure the length of the undisturbed colon in children with functional constipation (FC) and healthy controls. Here, the colon of 19 healthy controls (10-18 years old) and 16 children with FC (7-18 years old) was imaged using MRI. Different regions of the colon (ascending, transverse, descending, and sigmoid-rectum) were first segmented manually on the MRI images. Three-dimensional skeletonization image analysis methods were then used to reduce the regions of interest to a central, measurable line. Total colon length (corrected for body surface area) in healthy controls was 56±2 cm/m2 (mean±SEM). Total colon length was significantly longer in children with FC 69±3 cm/m2 compared to controls (p = 0.0037). The colon regions showing the largest differences between groups were the ascending colon (p = 0.0479) and the sigmoid-rectum (p = 0.0003). In a linear regression model, there was a positive significant correlation between total colon length and age (R = 0.45, p = 0.0064), height (R = 0.49, p = 0.0031), weight (R = 0.46, p = 0.0059) and colon volume (R = 0.4543, p = 0.0061). Our findings showed significant differences in colon lengths between healthy controls and children with constipation. A new objective diagnostic imaging endpoint such as colon length may help to improve knowledge of colon morphology and function and, in turn, understanding of colon functional pathology.


Assuntos
Colo , Constipação Intestinal , Humanos , Criança , Adolescente , Colo/patologia , Colo Sigmoide , Reto , Imageamento por Ressonância Magnética/métodos
12.
J Med Food ; 27(2): 110-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181190

RESUMO

The objective of this study was to examine the impact and underlying mechanisms of pelargonidin-3-galactoside (Pg3gal) produced from purple sweet potatoes on colonic inflammation induced by dextran sulfate sodium (DSS) in a murine model of ulcerative colitis (UC). C57BL/6J mice were categorized into four groups (n = 6 per group): DSS+Pg3gal, control, control+Pg3gal, and DSS. Colitis was induced by providing free access to 3% DSS for 10 days. The DSS+Pg3gal model mice received DSS concurrently with intragastric Pg3gal (25 mg/kg). The health of the mice was carefully monitored on a regular basis, and scores for the Disease Activity Index (DAI) were documented. A histological assessment was conducted using hematoxylin and eosin staining to evaluate the extent of mucosal injury present. The expression levels of IL-6, NLRP3, ASC, cleaved-Caspase-1, TNF-α, N-GSDMS, and cleaved-IL-1ß proteins were evaluated by Western blot analysis. The process of 16S rRNA sequencing was carried out to examine the composition and relative abundance of gut microbiotas within the intestines of the mice. The DAI results revealed that Pg3gal significantly attenuated the DSS-induced UC in mice. In addition, it successfully alleviated the decline in colon size, improved the condition of colonic tissue, and significantly inhibited the production of proinflammatory cytokines, such as IL-6, IL-1ß, and TNF-α, in the colon tissues. Additionally, Pg3gal modulated the DSS-induced imbalanced gut microbiota, as evidenced by decreased Proteobacteria and Deferribacteres and simultaneous elevation in Firmicutes, Bacteroidetes, and Verrucomicrobia. In summary, Pg3gal alleviated DSS-induced UC by inhibiting pyroptosis in intestinal epithelial cells and enhancing the structural integrity of the gut microbiota.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Ipomoea batatas , Animais , Camundongos , Sulfato de Dextrana/efeitos adversos , Colo/patologia , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Antocianinas/metabolismo , RNA Ribossômico 16S , Piroptose , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Intestinos/patologia , Modelos Animais de Doenças
13.
Phytomedicine ; 123: 155223, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38134862

RESUMO

BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism. METHODS: CD animal models were created using Il-10-/- mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed. RESULTS: The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10-/- mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10-/- mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10-/- mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10-/- mice, and transplantation of feces from AA-treated mice improved CD-like colitis. CONCLUSIONS: The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota.


Assuntos
Colite , Doença de Crohn , Microbioma Gastrointestinal , Triterpenos , Camundongos , Animais , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Interleucina-10/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Inflamação/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Sulfato de Dextrana/efeitos adversos , Colo/patologia
14.
Biochem Biophys Res Commun ; 694: 149410, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38134478

RESUMO

Klebsiella aerogenes (K. aerogenes, KA) is a gram-negative opportunistic pathogen from the Klebsiella species and the Enterobacteriaceae family. However, the impact of K. aerogenes on colorectal cancer (CRC) remains uncertain. A colitis-associated tumorigenesis animal model was established by administering azoxymethane (AOM) and dextran sulfate sodium (DSS) to C57BL/6J mice. The concentration of K. aerogenes gavage in mice was 109 cfu. The study measured the following parameters: tumor formation (number and size), intestinal permeability (MUC2, ZO-1, and Occludin), colonic inflammation (TNF-α, IL-1ß, IL-6, and IL-10), proliferation and the fluctuation of the intestinal flora. Under the AOM/DSS-treated setting, K. aerogenes colonization worsened colitis by exacerbating intestinal inflammatory reaction and destroying the mucosal barrier. The intervention markedly augmented the quantity and dimensions of neoplasm in the AOM/DSS mice, stimulated cellular growth, and impeded cellular programmed cell death. In addition, K. aerogenes exacerbated the imbalance of the intestinal microbiota by elevating the abundance of Pseudomonas, Erysipelatoclostridium, Turicibacter, Rikenella, and Muribaculum and leading to a reduction in the abundance of Odoribacter, Alloprevotella, Roseburia, and Lachnospiraceae_NK4A136_group. The presence of K. aerogenes in AOM/DSS-treated mice promoted tumorigenesis, worsened intestinal inflammation, disrupted the intestinal barrier, and caused disturbance to the gut microbiota.


Assuntos
Colite , Enterobacter aerogenes , Animais , Camundongos , Azoximetano/toxicidade , Azoximetano/metabolismo , Camundongos Endogâmicos C57BL , Colite/patologia , Colo/patologia , Inflamação/patologia , Carcinogênese/patologia , Transformação Celular Neoplásica/patologia , Bacteroidetes , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
15.
Biochem Biophys Res Commun ; 695: 149358, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38159410

RESUMO

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that significantly affected quality of life for patients. In this study, carbon dots based on Bletilla striata (BS-CDs) were synthesized by hydrothermal method and characterized by optical property analysis. In addition, the study measured the potential effect of BS-CDs on colonic histopathology and inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis. The results suggested that BS-CDs significantly increased colon length, improved colonic histopathology, and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in colitis mice. Taken together, BS-CDs alleviate clinical inflammation by blocking pro-inflammatory cytokines which were expected to be a potential agent for the treatment of colitis.


Assuntos
Colite Ulcerativa , Colite , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Qualidade de Vida , Colite/induzido quimicamente , Citocinas/efeitos adversos , Inflamação/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
16.
Clin Res Hepatol Gastroenterol ; 48(2): 102276, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38158154

RESUMO

BACKGROUND: Studies have demonstrated that Bacteroides thetaiotaomicron (BT) has protective effect against colon inflammation in murine models. Macrophages play an important role in gut immunity. However, the specific mechanisms of BT on macrophage are still unelucidated. Thus, our study investigates the anti-inflammatory effect of BT and its heat-treated inactivated bacteria on experimental colitis and macrophages. METHODS: A dextran sulfate sodium (DSS)-induced acute colitis model with male C57BL/6 mice, BT (ATCC29148) strain, THP1 cell lines were used in this study. Live and heat-treated inactivated BT (IBT) solution (1 × 10^9cfu/ml) were intragastrically gavaged daily for 14 days. Colonic inflammation was determined by the disease activity index (DAI) score, colon length, histological score, and inflammatory factors. THP1 cells were induced towards M1, then treated with different concentrations of inactivated BT solution and p38 inhibitor. Western blotting, immunohistochemistry, immunofluorescence and qRT-PCR were performed to assess the levels of inflammatory cytokines and molecules of MAPK pathway including IL-6, TNF-α, IL-1ß, IL-22, p38 and phosphor-p38 expressions. Moreover, 16S rRNA sequencing of colitis murine fecal samples was applied to investigate the influence of supplementation of BT to the gut microbiota homeostasis. RESULTS: Both live and heat-treated inactivated BT decreased the DAI and histological scores as well as levels of inflammatory factors, particularly IL-6 while increasing IL-22 of DSS-induced colitis murine models. The cell experiments showed that inactivated BT downregulates IL-6 expression in THP1 via inhibiting p38 phosphorylation and affecting M1 polarization. Moreover, the 16S rRNA sequencing results showed that BT and IBT gavage could increase beta-diversity of gut flora in DSS-induced colitis mice. Furthermore, the significance test for differences between the groups showed that BT could increase Faecalebaculum, Lactobacillus and Bacteroides, while decreasing Akkermansia. CONCLUSION: In summary, our findings imply that BT and its heat-treated inactivated bacteria exert a protective effect by suppressing macrophage-induced IL-6 through the inhibition of p38 MAPK pathway and ameliorating intestinal gut dysbiosis in experimental colitis.


Assuntos
Bacteroides thetaiotaomicron , Colite , Masculino , Animais , Camundongos , RNA Ribossômico 16S/metabolismo , Interleucina-6/metabolismo , Ativação de Macrófagos , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/patologia , Inflamação , Modelos Animais de Doenças , Colo/patologia
18.
Biomed Pharmacother ; 170: 116098, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38154276

RESUMO

BACKGROUND: Inflammatory bowel diseases (IBD), such as severe colitis, are associated with the development of lung inflammation and tissue damage. Pueraria lobata (P. lobata) plays an essential role in controlling cytokines. However, the exact mechanism of the inflammation response is still unknown. PURPOSE: To investigate the effects of the P. lobata-derived exosomes-like nanovesicles (PLDENs) on colitis and their role in the lung inflammatory response. METHODS: In this study, we investigated the effects of PLDENs on the dextran sulfate sodium (DSS)-induced colitis and explored the mechanisms by forming the gut-lung axis. PLDENs were characterized by mass spectrometry-based proteomic analysis. RESULTS: The results showed that PLDENs had significant preventive effects in DSS-induced colitis and pathological changes in colons in a dose-dependent manner. Simultaneously, the treatment of PLDENs could effectively reduce inflammatory changes in the lung. PLDENs could selectively regulate the composition of gut microbiota. CONCLUSION: These data suggested that the treatment of PLDENs could 'attenuate DSS-induced colitis and lung inflammation, providing an efficacious supplement for reducing co-morbidities in IBD patients.


Assuntos
Colite , Exossomos , Doenças Inflamatórias Intestinais , Pneumonia , Pueraria , Humanos , Animais , Camundongos , Sulfato de Dextrana/toxicidade , Exossomos/patologia , Proteômica , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Citocinas , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Macrófagos/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Colo/patologia
19.
Int Immunopharmacol ; 127: 111385, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38113690

RESUMO

PR39 is an antimicrobial peptide (AMP) with a variety of biological functions, including antimicrobial, wound healing, leukocyte chemotaxis, angiogenesis, and immunomodulation; however, its therapeutic efficacy in colitis (IBD) has rarely been reported. For this reason, the present study aimed to investigate the therapeutic effect of PR39 on IBD and its underlying mechanisms. In this experiment, a mouse model of ulcerative colitis (UC) was induced with 3 % dextran sulfate (DSS) and administered by rectal injection of PR39. The results of the study showed that 5 mg/kg of PR39 was able to ameliorate the clinical manifestations of DSS-induced UC mice by improving the clinical symptoms, colonic tissue damage, up-regulating the expression of tight junction proteins, and alleviating the systemic inflammation in mice in various ways. The mechanism of action may involve inhibition of the phosphorylation level of proteins related to the NF-κB/MAPK signaling pathway and modulation of the relative abundance of potentially pathogenic (Bacteroides, Pseudoflavonifractor, Barnesiella, and Oscillibacter) and potentially beneficial bacteria (Candidatus_Saccharibacteria, Desulfovibrio, Saccharibacteria) in the intestinal flora. The results enriched the biological functions of PR-39 and also suggested that PR-39 may be able to be used as a novel drug for the treatment of IBD.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Animais , Suínos , NF-kappa B/metabolismo , Peptídeos Antimicrobianos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Transdução de Sinais , Colo/patologia , Inflamação/metabolismo , Modelos Animais de Doenças , Sulfato de Dextrana/farmacologia , Camundongos Endogâmicos C57BL
20.
J Clin Pathol ; 77(3): 145-150, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38123989

RESUMO

AIMS: Secondary mucosal colonisation by a carcinoma originating from a distant site is a pattern of metastasis to the intestines and hepatobiliary tract and a mimic of primary neoplasia. Although endometriosis is considered benign, its ability to spread widely underscores its quasi-neoplastic nature. After noting that endometriotic glands can colonise the colonic mucosa along the basement membrane, mimicking metastatic disease, we conducted an intradepartmental review of intestinal specimens showing endometriosis obtained from 2016 to 2023 to characterise and quantify the incidence of this phenomenon. METHODS: Material from 38 lower gastrointestinal specimens with a primary or ancillary diagnosis of endometriosis was identified from our surgical pathology database. Slides were reviewed, documenting the extent and micro-anatomic location affected by endometriosis, with a focus on identifying examples showing mucosal colonisation. RESULTS: The most common site of involvement was the distal colon (23 cases; 11 of rectum, 9 of sigmoid colon and 3 of rectosigmoid) followed by the appendix (N=10), cecum (N=2), small intestine (N=2) and 'colon not otherwise specified' (N=1). Mucosal involvement was identified in eight cases (21%), half of which demonstrated seamless colonisation of the epithelium by endometriotic glands. In two of these, the procedure was prompted by the presence of a rectal mass or stricture with concern for malignancy. CONCLUSION: Endometriosis occasionally (4/38; 10.5%) colonises colonic epithelium, potentially mimicking a metastasis or intraepithelial neoplasia/dysplasia. Although unusual, this phenomenon was observed in half of specimens from patients with mucosal involvement in whom a mass or stricture suggested malignancy, a potentially misleading pattern of endometriosis.


Assuntos
Carcinoma , Endometriose , Feminino , Humanos , Endometriose/diagnóstico , Endometriose/patologia , Constrição Patológica/complicações , Constrição Patológica/patologia , Colo/patologia , Reto/patologia , Carcinoma/patologia
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