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1.
Int J Pharm ; 650: 123683, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38092264

RESUMO

Curcumin has gained great prominence for the prevention and treatment of inflammatory bowel disease. However, studies have reported the low bioavailability of orally administered curcumin. This work aimed to evaluate the characteristics, stability and effects of a curcumin-carrying nanoemulsion in preventing intestinal damage induced by indomethacin. Nanoemulsions containing curcumin were prepared by spontaneous emulsification method and it was characterized by dynamic light scattering (DLS), zeta potential and the morphology was evaluated by scanning electron microscopy (SEM). Its stability was tested under different conditions of pH, temperature at 0, 7, 14, 21 and 28 days. In animal experimentation, 36 male mice of the Mus musculus lineage (C57BL/6) were used. The intestinal inflammation was evaluated based on macroscopic, histopathological and metagenomic analysis. It was found a stable nanoemulsion with a size of 409.8 nm, polydispersion index (PDI) of 0.132 and zeta potential of -18.8 mV. However, these lost charge in pH2, showing instability in acidic media (p < 0.05). In animal experiments, the nanoemulsion did not significantly improve intestinal inflammation. However, the group treated with curcumin nanoemulsion showed a higher relative abundance of the genus Lactobacillus (p < 0.05). In conclusion, the curcumin nanoemulsion was relevant in the modulation of the intestinal microbiota.


Assuntos
Curcumina , Camundongos , Masculino , Animais , Emulsões/química , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Inflamação
2.
J Pediatr ; 265: 113800, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37866678

RESUMO

OBJECTIVES: To test the utility of various biomarkers as indicators of gut dysfunction in cystic fibrosis (CF) and determine whether intraindividual variations in these measures are repeatable over short intervals and whether interindividual variations correlate with clinical outcomes. STUDY DESIGN: We performed a cross-sectional, limited longitudinal study of children with CF aged 1-21 years who provided blood and stool samples at 2 or 3 visits, 2 weeks and 3 months apart, which were assayed for markers of intestinal inflammation (fecal calprotectin [fCal], lipocalin-2 [fLcn2], neopterin), and permeability (plasma lipopolysaccharide [LPS] antibodies, LPS-binding protein) by enzyme immunoassays. Control specimens were obtained from children without CF who had undergone esophagogastroduodenoscopy and had no evidence of gut inflammation. RESULTS: Twenty-six of 29 participants with CF completed the study. Sixty-nine stools (57 case/12 control) and 76 plasmas (60 case/16 control) were analyzed. LPS antibody had reliable intraindividual stability. fCal, fLcn2, and neopterin were significantly greater in CF than in control samples. fCal was negatively correlated with 3-month interval change (Δ) in weight-for-age z-score, body mass index/weight-for-length z-score, and forced expiratory volume in 1 second. fLcn2 was negatively correlated with FEV1 but not with anthropometrics. No marker correlated with Δbody mass index/weight-for-length z-score or ΔFEV1. CONCLUSIONS: fLcn2 is elevated in people with CF and might predict worse interval pulmonary function. Expanded studies are warranted to test if fLcn2 correlates with changes in additional outcomes.


Assuntos
Fibrose Cística , Criança , Humanos , Fibrose Cística/complicações , Fibrose Cística/metabolismo , Estudos Longitudinais , Neopterina , Estudos Transversais , Lipopolissacarídeos , Inflamação/metabolismo , Anticorpos
3.
Arq. gastroenterol ; Arq. gastroenterol;61: e24003, 2024. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1533814

RESUMO

ABSTRACT Background: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. Objective: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. Methods: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea­sured utilizing immunoassay techniques. Results: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. Conclusion: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis.


RESUMO Contexto: O tratamento da pancreatite crônica não resolve de forma consistente as anomalias intestinais e, apesar da implementação de várias medidas terapêuticas, os pacientes muitas vezes continuam a apresentar diarreia persistente. Portanto, é imperativo reconhecer que a diarreia pode resultar de fatores além da insuficiência pancreática, e a inflamação intestinal surge como um potencial fator contribuinte. Objetivo: O objetivo deste estudo foi avaliar os níveis fecais de lactoferrina e calprotectina como indicadores de inflamação intestinal em pacientes com pancreatite crônica com diarreia persistente. Métodos: Neste estudo, 23 pacientes do sexo masculino com pancreatite crônica atribuída principalmente ao consumo de álcool e apresentando diarreia (classificada na escala de fezes de Bristol tipo 6 ou 7), foram submetidos a uma avaliação abrangente de seu estado clínico e nutricional. Os níveis fecais de lactoferrina e calprotectina foram medidos utilizando técnicas de imunoensaio. Resultados: A idade média dos participantes foi de 54,8 anos, 43,5% tinham diabetes e 73,9% eram fumantes. Apesar de receber terapia de reposição enzimática e abster-se de álcool por mais de 4 anos, todos os participantes apresentaram diarreia persistente, acompanhada por níveis elevados de calprotectina e lactoferrina, indicativos de inflamação intestinal contínua. Conclusão: Os achados deste estudo ressaltam que a inflamação intestinal, evidenciada pelos biomarcadores fecais elevados calprotectina e lactoferrina, pode contribuir para explicar a persistência da diarreia em pacientes com pancreatite crônica.

4.
Food Res Int ; 173(Pt 1): 113334, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803644

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the gastrointestinal tract. The etiology is not fully understood, but environmental, microbial, and immunologic factors, as well as a genetic predisposition, play a role. UC is characterized by episodes of abdominal pain, diarrhea, bloody stools, weight loss, severe colonic inflammation, and ulceration. Despite the increase in the frequency of UC and the deterioration of the quality of life, there are still patients who do not respond well to available treatment options. Against this background, natural products such as polysaccharides are becoming increasingly important as they protect the intestinal mucosa, promote wound healing, relieve inflammation and pain, and restore intestinal motility. In this study, we investigated the effect of a polysaccharide isolated from the biomass of Campomanesia adamantium and Campomanesia pubescens (here referred to as CPW) in an experimental model of acute and chronic ulcerative colitis induced by dextran sulfate sodium (DSS). CPW reversed weight loss, increased disease activity index (DAI), bloody diarrhea, and colon shortening. In addition, CPW reduced visceral mechanical hypersensitivity, controlled oxidative stress and inflammation, and protected the mucosal barrier. CPW is not absorbed in the intestine, does not inhibit cytochrome P450 proteins, and does not exhibit AMES toxicity. These results suggest that CPW attenuates DSS-induced acute and chronic colitis in mice and may be a potential alternative treatment for UC.


Assuntos
Colite Ulcerativa , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Qualidade de Vida , Modelos Animais de Doenças , Inflamação , Redução de Peso , Diarreia
5.
Cancers (Basel) ; 15(8)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37190329

RESUMO

Dietary supplementation with pterostilbene (PS) and/or a probiotic (PRO) may ameliorate the intestinal microbiota in disease conditions. This study aims to evaluate PS and PRO for the chemoprevention of putative precursor lesions for colorectal cancer (CRC) in an experimental model of intestinal carcinogenesis with 1,2-dimethylhydrazine (1,2-DMH). Sixty male Wistar rats were equally divided into five groups: Sham, 1,2-DMH, 1,2-DMH + PS, 1,2-DMH + PRO, and 1,2-DMH + PS + PRO. PRO (5 × 107/mL) was offered in water, and PS (300 ppm) was provided in the diet ad libitum. 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. PRO alone and PRO combined with PS were the best intervention strategies to improve experimental 1,2-DMH-induced CRC regarding several parameters of carcinogenesis. Our findings may contribute to the development of novel preventive strategies for CRC and may help to identify novel modulators of colon carcinogenesis.

6.
Front Microbiol ; 14: 1157544, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138633

RESUMO

Mucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including in vitro and in vivo results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by Lactococcus lactis strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers Nfkb1, Nlrp3, Tnf, and upregulation of Il10 in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant L. lactis (pExu:gdf11) could offer a potential gene therapy for intestinal mucositis induced by 5-FU.

7.
Pharmaceuticals (Basel) ; 16(4)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37111267

RESUMO

Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor related to stress response and cellular homeostasis that plays a key role in maintaining the redox system. The imbalance of the redox system is a triggering factor for the initiation and progression of non-communicable diseases (NCDs), including Inflammatory Bowel Disease (IBD). Nrf2 and its inhibitor Kelch-like ECH-associated protein 1 (Keap1) are the main regulators of oxidative stress and their activation has been recognized as a promising strategy for the treatment or prevention of several acute and chronic diseases. Moreover, activation of Nrf2/keap signaling pathway promotes inhibition of NF-κB, a transcriptional factor related to pro-inflammatory cytokines expression, synchronically promoting an anti-inflammatory response. Several natural coumarins have been reported as potent antioxidant and intestinal anti-inflammatory compounds, acting by different mechanisms, mainly as a modulator of Nrf2/keap signaling pathway. Based on in vivo and in vitro studies, this review focuses on the natural coumarins obtained from both plant products and fermentative processes of food plants by gut microbiota, which activate Nrf2/keap signaling pathway and produce intestinal anti-inflammatory activity. Although gut metabolites urolithin A and urolithin B as well as other plant-derived coumarins display intestinal anti-inflammatory activity modulating Nrf2 signaling pathway, in vitro and in vivo studies are necessary for better pharmacological characterization and evaluation of their potential as lead compounds. Esculetin, 4-methylesculetin, daphnetin, osthole, and imperatorin are the most promising coumarin derivatives as lead compounds for the design and synthesis of Nrf2 activators with intestinal anti-inflammatory activity. However, further structure-activity relationships studies with coumarin derivatives in experimental models of intestinal inflammation and subsequent clinical trials in health and disease volunteers are essential to determine the efficacy and safety in IBD patients.

8.
Pharmaceutics ; 15(4)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37111572

RESUMO

Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein's LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric infections and malnutrition is closely related to environmental-driven enteric dysfunction early in life, and such chronic inflammatory conditions may blunt the developmental trajectories of children with worrisome and often irreversible physical and cognitive faltering. This window of time for microbiota maturation and brain plasticity is key to protecting cognitive domains, brain health, and achieving optimal/full developmental potential. This review summarizes the potential role of promising apoE mimetic peptides to improve the function of the gut-brain axis, including targeting the blood-brain barrier in children afflicted with malnutrition and enteric infections.

9.
Metabolites ; 13(1)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36677021

RESUMO

Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn's disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-kB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-kB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

11.
Front Physiol ; 13: 948378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267581

RESUMO

Trace mineral minerals Zn, Cu, and Mn play important roles in breeder production and progeny performance. The objective of this study was to determine maternal supplementation of trace mineral minerals on breeder production and progeny growth and development. A total of 540 broiler breeders, Cobb 500 (Slow feathering; 0-66 weeks old) were assigned to one of three treatment groups with the same basal diet and three different supplemental trace minerals: ITM-inorganic trace minerals in sulfates: 100, 16, and 100 ppm of Zn, Cu, and Mn respectively; MMHAC -mineral methionine hydroxy analog chelate: 50, 8, and 50 ppm of bis-chelated MINTREX®Zn, Cu and Mn (Novus International, Inc.), and TMAAC - trace minerals amino acid complex: 50, 8, and 50 ppm of Zn, Cu, and Mn. At 28 weeks of age, eggs from breeder treatments were hatched for progeny trial, 10 pens with 6 males and 6 female birds per pen were fed a common diet with ITM for 45 days. Breeder production, egg quality, progeny growth performance, mRNA expression of gut health associated genes in breeder and progeny chicks were measured. Data were analyzed by one-way ANOVA; means were separated by Fisher's protected LSD test. A p-Value ≤ 0.05 was considered statistically different and 0.1 was considered numerical trend. Breeders on ITM treatment had higher (p < 0.05) body weight (BW), weight gain and lower (p < 0.05) feed conversion ratio (FCR) from 0 to 10 weeks, when compared to birds fed MMHAC. MMHAC significantly improved egg mass by 3 g (p < 0.05) and FCR by 34 points (0.05 < p < 0.1) throughout the reproductive period (26-66 weeks) in comparison to ITM. MMHAC improved (p < 0.01) egg yolk color versus (vs.) ITM and TMAAC in all periods, except 28 weeks, increased (p < 0.01) eggshell thickness and resistance vs. TMAAC at 58 weeks, and reduced (p < 0.05) jejunal NF-κB gene expression vs. TMAAC at 24 weeks. There was a significant reduction in tibial dry matter weight, Seedor index and resistance for the breeders that received MMHAC and/or TMAAC when compared to ITM at 18 weeks. Lower seedor index but numerically wider tibial circumference was seen in hens fed MMHAC at 24 weeks, and wider tibial circumference but lower tibial resistance in hens fed TMAAC at 66 weeks. Maternal supplementation of MMHAC in breeder hens increased (p < 0.0001) BW vs. ITM and TMAAC at hatching, reduced (p < 0.05) feed intake vs. ITM at d14 and d28, and improved (p < 0.01) FCR and performance index vs. TMAAC at d28, reduced (p < 0.01) NF-κB gene expression and increased (p < 0.05) A20 gene expression vs. TMAAC on d0 and vs. ITM on d14, reduced (p < 0.05) TLR2 gene expression vs. ITM on d0 and vs. TMAAC on d14, increased (p < 0.05) MUC2 gene expression vs. both ITM and TMAAC on d45 in progeny jejunum. Overall, these results suggest that supplementation with lower levels of MHA-chelated trace minerals improved breeder production and egg quality and reduced breeder jejunal inflammation while maintaining tibial development in comparison to those receiving higher inorganic mineral supplementation, and it also carried over the benefits to progeny with better growth performance, less jejunal inflammation and better innate immune response and gut barrier function in comparison to ITM and/or TMAAC.

12.
Front Immunol ; 13: 909896, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35799778

RESUMO

Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and we hypothesized that intestinal epithelial cells are the cell source of eotaxin-3 or CCL26, a potent chemoattractant for eosinophils. We analyzed colorectal polyps (n=50) from pediatric patients with rectal bleeding by H&E staining and eosin staining, and different pro-inflammatory cytokines were assessed by RT-qPCR and ELISA. IgE and CCL26 were investigated by RT-qPCR, ELISA and confocal microscopy. Finally, the intracellular signaling pathway that mediates the CCL26 production was analyzed using a kinase array and immunoblotting in human intestinal Caco-2 cell line. We found a dense cell agglomeration within the polyps, with a significantly higher frequency of eosinophils than in control adjacent tissue. IL-4 and IL-13 were significantly up-regulated in polyps and CCL26 was elevated in the epithelial compartment. Experiments with Caco-2 cells showed that the type-2 cytokine IL-13 increased STAT3 and STAT6 phosphorylation and eotaxin-3 secretion. The addition of the blocking antibody Dupilumab or the inhibitor Ruxolitinib to the cytokine-stimulated Caco-2 cells diminished the CCL26 secretion to basal levels in a dose-dependent manner. In conclusion, our findings demonstrate a high frequency of eosinophils, and elevated levels of type-2 cytokines and eotaxin-3 in the inflammatory stroma of colorectal polyps from pediatric patients. Polyp epithelial cells showed to be the main cell source of CCL26, and IL-13 was the main trigger of this chemokine through the activation of the STAT3/STAT6/JAK1-2 pathway. We suggest that the epithelial compartment actively participates in the recruitment of eosinophils to the colonic polyp-confined inflammatory environment.


Assuntos
Pólipos do Colo , Interleucina-13 , Células CACO-2 , Quimiocina CCL26 , Quimiocinas CC/metabolismo , Criança , Citocinas/metabolismo , Eosinófilos/metabolismo , Células Epiteliais/metabolismo , Humanos , Interleucina-13/metabolismo
13.
Biomed Pharmacother ; 145: 112414, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34808552

RESUMO

Inflammatory bowel diseases, irritable bowel syndrome, and mucositis are characterized by intestinal inflammation, but vary according to their pathological mechanisms, severity, location, and etiology. Significant intestinal inflammation that occurs in these diseases induces weight loss, nutritional depletion, and gastrointestinal tract dysfunction. Nutritional support is important in alleviating symptoms and improving patients' quality of life. In this review, we summarize some nutritional components used to manage intestinal disorders. These include fatty acids, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and low FODMAP (LFD) diets. These components and LFD diets have been studied and clinical trials have been designed to develop new strategies to alleviate intestinal inflammation and improve the quality of life. Clinical trials on their use in intestinal inflammation do not allow firm conclusions to be drawn mainly because of the heterogeneity of the dose used and the study design or their inconclusive results. However, in the majority of cases, the use of omega-3, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and LFD improve the health.


Assuntos
Suplementos Nutricionais , Inflamação/terapia , Enteropatias/terapia , Animais , Humanos , Inflamação/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Enteropatias/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/terapia , Mucosite/fisiopatologia , Mucosite/terapia , Apoio Nutricional/métodos , Qualidade de Vida
14.
Immunology ; 165(3): 355-368, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34964126

RESUMO

Mucositis is a major clinical complication associated with cancer treatment and may limit the benefit of chemotherapy. Leukocytes and inflammatory mediators have been extensively associated with mucositis severity. However, the role of eosinophils in the pathophysiology of chemotherapy-induced mucositis remains to be elucidated. Here, using GATA-1-deficient mice, we investigated the role of eosinophils in intestinal mucositis. There was marked accumulation of eosinophils in mice given irinotecan and eosinophil ablation inhibited intestinal mucositis. Treatment with Evasin-4, a chemokine receptor antagonist, reduced the recruitment of eosinophils and decreased irinotecan-induced mucositis. Importantly, Evasin-4 did not interfere negatively with the antitumour effects of irinotecan. Evasin-4 was of benefit for mice given high doses of irinotecan once Evasin-4-treated mice presented delayed mortality. Altogether, our findings suggest that Evasin-4 may have significant mucosal-protective effects in the context of antineoplastic chemotherapy and may, therefore, be useful in combination with anticancer treatment in cancer patients.


Assuntos
Antineoplásicos , Mucosite , Animais , Antineoplásicos/uso terapêutico , Camptotecina/efeitos adversos , Eosinófilos/patologia , Humanos , Mucosa Intestinal/patologia , Irinotecano/efeitos adversos , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/patologia
15.
J Neuroimmunol ; 362: 577764, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823118

RESUMO

Muscarinic-acetylcholine-receptors (mAChRs) modulate intestinal homeostasis, but their role in inflammation is unclear; thus, this issue was the focus of this study. BALB/c mice were treated for 7 days with muscarine (mAChR/agonist), atropine (mAChR/antagonist) or saline. Small-intestine samples were collected for histology and cytofluorometric assays in Peyer's patches (PP) and lamina propria (LP) cell-suspensions. In LP, goblet-cells/leukocytes/neutrophils/MPO+ cells and MPO/activity were increased in the muscarine group. In PP, IFN-γ+/CD4+ T or IL-6+/CD4+ T cell numbers were higher in the muscarine or atropine groups, respectively. In LP, TNF-α+/CD4+ T cell number was higher in the muscarine group and lower in the atropine.


Assuntos
Inflamação/imunologia , Mucosa Intestinal/imunologia , Receptores Muscarínicos/imunologia , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Agonistas Muscarínicos/farmacologia , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/imunologia
16.
Front Physiol ; 12: 714846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366901

RESUMO

Intestinal mucositis is a clinically relevant side effect of anticancer therapies. It is experienced by 60-100% of patients undergoing treatment with high doses of chemotherapy, radiation therapy, and bone marrow transplantation. Intestinal mucositis can manifest as pain, weight loss, inflammation, diarrhea, rectal bleeding, and infection; affecting normal nutritional intake and intestinal function. It often impacts adherence to anticancer therapy as it frequently limits patient's ability to tolerate treatment, causing schedule delays, interruptions, or premature discontinuation. In some cases, local and systemic secondary infections are observed, increasing the costs toward medical care and hospitalization. Several strategies for managing mucositis are available which do not always halt this condition. In this context, new therapeutic strategies are under investigation to prevent or treat intestinal mucositis. Polysaccharides from natural resources have recently become promising molecules against intestinal damage due to their ability to promote mucosal healing and their anti-inflammatory actions. These effects are associated with the protection of intestinal mucosa and regulation of microbiota and immune system. This review aims to discuss the recent advances of polysaccharides from natural resources as potential therapies for intestinal mucositis. The source, species, doses, treatment schedules, and mechanisms of action of polysaccharides will be discussed in detail.

17.
Porcine Health Manag ; 7(1): 48, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429170

RESUMO

BACKGROUND: Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs. RESULTS: Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method. CONCLUSIONS: Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation.

18.
Molecules ; 26(2)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467396

RESUMO

Inflammatory bowel disease (IBD) is a non-communicable disease characterized by a chronic inflammatory process of the gut and categorized into Crohn's disease and ulcerative colitis, both currently without definitive pharmacological treatment and cure. The unclear etiology of IBD is a limiting factor for the development of new drugs and explains the high frequency of refractory patients to current drugs, which are also related to various adverse effects, mainly after long-term use. Dissatisfaction with current therapies has promoted an increased interest in new pharmacological approaches using natural products. Coumarins comprise a large class of natural phenolic compounds found in fungi, bacteria, and plants. Coumarin and its derivatives have been reported as antioxidant and anti-inflammatory compounds, potentially useful as complementary therapy of the IBD. These compounds produce protective effects in intestinal inflammation through different mechanisms and signaling pathways, mainly modulating immune and inflammatory responses, and protecting against oxidative stress, a central factor for IBD development. In this review, we described the main coumarin derivatives reported as intestinal anti-inflammatory products and its available pharmacodynamic data that support the protective effects of these products in the acute and subchronic phase of intestinal inflammation.


Assuntos
Cumarínicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Cumarínicos/farmacologia , Humanos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico
19.
J Appl Microbiol ; 130(5): 1412-1424, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32955761

RESUMO

Lactic acid bacteria (LAB), widely used as starter cultures for the fermentation of a large variety of food, can improve the safety, shelf life, nutritional value and overall quality of the fermented products. In this regard, the selection of strains delivering health-promoting compounds is now the main objective of many researchers. Although most LAB are auxotrophic for several vitamins, it is known that certain strains have the capability to synthesize B-group vitamins. This is an important property since humans cannot synthesize most vitamins, and these could be obtained by consuming LAB fermented foods. This review discusses the use of LAB as an alternative to fortification by the chemical synthesis to increase riboflavin and folate concentrations in food. Moreover, it provides an overview of the recent applications of vitamin-producing LAB with anti-inflammatory/antioxidant activities against gastrointestinal tract inflammation. This review shows the potential uses of riboflavin and folates producing LAB for the biofortification of food, as therapeutics against intestinal pathologies and to complement anti-inflammatory/anti-neoplastic treatments.


Assuntos
Ácido Fólico/biossíntese , Alimentos Fortificados , Doenças Inflamatórias Intestinais/terapia , Lactobacillales/metabolismo , Mucosite/terapia , Riboflavina/biossíntese , Animais , Antioxidantes/análise , Fermentação , Alimentos Fermentados , Ácido Fólico/análise , Humanos , Lactobacillales/isolamento & purificação , Riboflavina/análise , Vitaminas/análise , Vitaminas/biossíntese
20.
Curr Res Immunol ; 2: 142-154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35492385

RESUMO

The short-chain fatty acids (SCFAs) are metabolites originated from the fermentation of dietary fibers and amino acids produced by the bacteria of the intestinal microbiota. The most abundant SCFAs, acetate, propionate, and butyrate, have been proposed as a treatment for inflammatory bowel diseases (IBDs) due to their anti-inflammatory properties. This work aimed to analyze the effects of the treatment of three combined SCFAs in TNBS-induced intestinal inflammation in zebrafish larvae. Here, we demonstrated that SCFAs significantly increased the survival of TNBS-exposed larvae, preserved the intestinal endocytic function, reduced the expression of inflammatory cytokines and the intestinal recruitment of neutrophils caused by TNBS. However, SCFAs treatment did not appear to avoid TNBS-induced tissue damage in the intestinal wall and did not restore the number of mucus-producing goblet cells. Finally, exposure to TNBS induced dysbiosis of the microbiota with an increase in Betaproteobacteria and Actinobacteria, while the treatment with SCFAs maintained these population levels similar to control. Thus, we demonstrate that the treatment of three combined SCFAs presented anti-inflammatory properties previously seen in mammals, opening an opportunity to use zebrafish to explore the potential benefit of these and other metabolites to treat inflammation.

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