RESUMO
OBJECTIVE: To investigate the alleviation of Nippostrongylus brasiliensis infection on dextran sulfate sodium salt (DSS)-induced ulcerative colitis in mice, and to explore the underlying mechanism. METHODS: Thirty male C57BL/6J mice of the SPF grade, each weighing approximately 25 g, were randomly divided into three groups, including the blank control group (NC group), DSS modeling group (DSS group), and N. brasiliensis treatment group (Nb + DSS group), of 10 mice in each group. Mice in the DSS group were orally administered with 3.5% DSS daily since day 1 (D0) for 6 successive days, and given normal drinking water since D6, and animals in the Nb + DSS group were subcutaneously injected with the third-stage larvae of N. brasiliensis at a dose of 500 larvae per mice 5 days prior to D0, followed by oral administration with 3.5% DSS daily since D0 for 6 successive days and normal drinking water since D6, while mice in the NC group were given normal drinking water. Mouse body weight and stool were observed and the disease activity index (DAI) was scored in each group during the study period. All mice were sacrificed on D9. The mouse colon length was measured, and mouse colon specimens were subjected to hematoxylin-eosin (HE) staining and histopathological scoring. In addition, the mRNA and protein expression of interleukin (IL)-1ß and IL-10 was quantified in mouse colon specimens using quantitative fluorescent real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expression of mucosal repair-associated molecules zonula occludens-1 (ZO-1), mucin 2 (MUC2) and claudin-1 was detected in mouse colon specimens using qPCR assay and immunofluorescence assay. RESULTS: The mice body weights, DAI scores and colon lengths were (26.26 ± 1.93), (22.39 ± 1.65), (25.00 ± 1.58) g (F = 8.06, P < 0.01); (1.89 ± 0.34), (0.47 ± 0.39), 0 points (F = 57.61, P < 0.000 1); and (42.50 ± 5.75), (56.20 ± 5.96) mm and (61.17 ± 7.88) mm (F = 13.72, P < 0.001) in the NC, DSS and Nb + DSS groups on D9, respectively, and elevated mouse body weight (P < 0.05), reduced DAI score (P < 0.000 1) and increased colon length (P < 0.01) were observed in the Nb + DSS group relative to the DSS group on D9. Pathological examinations showed that the colonic crypts were relatively intact and the inflammatory cell infiltration was lower in the mouse colon specimens in the Nb + DSS group than in DSS the group. There was a significant difference in the histopathological scores of mouse colon specimens among the NC group (0 point), the DSS group [(2.00 ± 1.22) points] and the Nb + DSS group [(0.20 ± 0.45) points] (F = 10.71, P < 0.01), respectively, and the histopathological score of mouse colon specimens was significantly higher in the DSS group than in the NC and Nb + DSS groups (both P values < 0.01). qPCR assay quantified that the relative IL-10 and IL-1ß mRNA expression was 1.25 ± 0.08, 0.44 ± 0.14 and 1.30 ± 0.45 (F = 10.66, P < 0.01), and 0.22 ± 0.13, 1.14 ± 0.31 and 0.41 ± 0.19 (F = 16.89, P < 0.001) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and higher IL-10 mRNA expression and lower IL-1ß mRNA expression were found in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.01). The relative MUC2, claudin-1 and ZO-1 mRNA expression was 0.87 ± 0.25, 0.34 ± 0.26 and 4.21 ± 0.55 (F = 121.60, P < 0.000 1), 1.05 ± 0.41, 0.16 ± 0.09 and 0.22 ± 0.11 (F = 14.00, P < 0.01), and 1.03 ± 0.10, 0.60 ± 0.11 and 1.64 ± 0.28 (F = 32.16, P < 0.000 1) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and significantly higher MUC2 and ZO-1 mRNA expression was quantified in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). The mean fluorescence intensities of ZO-1 and claudin-1 were 17.18 ± 2.08, 12.38 ± 1.21 and 18.06 ± 2.59 (F = 8.95, P < 0.01) and 13.50 ± 1.63, 9.66 ± 2.03 and 13.61 ± 0.97 (F = 6.96, P < 0.05) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and the mean fluorescence intensities of ZO-1 and claudin-1 were significantly greater in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). CONCLUSIONS: N. brasiliensis infection may remarkably alleviate DSS-induced ulcerative colitis in mice through promoting expression of anti-inflammatory cytokines, inhibiting expression of pro-inflammatory cytokines and facilitating mucosal repair in colon tissues.
Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Nippostrongylus , Infecções por Strongylida , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/terapia , Camundongos Endogâmicos C57BL , Masculino , Animais , Camundongos , Colo/patologia , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica , Perfilação da Expressão Gênica , Modelos Animais de DoençasRESUMO
BACKGROUND: Endometriosis is a complex gynecological disorder characterized by the ectopic growth of endometrial tissue. Symptoms of endometriosis are known to impair the quality of life of patients, and among these are found dysmenorrhea, chronic pelvic pain, and gastrointestinal (GI) issues. GI issues such as painful bowel movements, bloating and constipation or diarrhea, are one of the common reasons for misdiagnosis with irritable bowel syndrome (IBS). Enteric glial cells (EGC) are known to play a role in pain associated with IBS, and reactive gliosis has been reported in patients with IBS, but the role of EGC in endometriosis has yet to be elucidated. We hypothesized that endometriosis will induce reactive gliosis, with increased expression of the glial fibrillary acidic protein (GFAP) and S100B, in the myenteric plexus of colonic sections in an animal model of endometriosis. METHODS: In the present study animal experiments were employed to explore the impact of endometriosis on the gastrointestinal tract. Using a surgically induced endometriosis rat model, we collected ileal and colonic segments for analysis. We used H&E to assess microscopic damage in colon and ileum, immunofluorescence to measure GFAP and S100B expression in the colon, and toluidine blue staining to measure mast cell infiltration in colon and ileum. Immunofluorescence images were captured using confocal microscope and analyzed using ImageJ software. RESULTS: All endometriosis animals developed vesicles. These animals had a significant increase in the colonic macroscopic damage compared to Sham and Naïve controls. Colonic and ileal sections didn't show statistical differences in microscopic damage between groups, yet endometriosis ileum had significantly increased mast cell infiltration compared to Naïve. GFAP immunostaining showed significantly increased integrated density in endometriosis when compared to Sham or Naïve, while no statistical difference was found in S100B integrated density between groups. CONCLUSIONS: We conclude that endometriosis can alter GI homeostasis by inducing colon inflammation, reactive gliosis, and ileal mast cell infiltration. Taken together this suggests endometriosis can mimic IBS histopathology beyond the symptomatology, reinforcing this disease's complexity and the need to treat it beyond the gynecological setting.
Assuntos
Endometriose , Proteína Glial Fibrilar Ácida , Síndrome do Intestino Irritável , Neuroglia , Subunidade beta da Proteína Ligante de Cálcio S100 , Endometriose/complicações , Endometriose/patologia , Feminino , Animais , Síndrome do Intestino Irritável/patologia , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/metabolismo , Neuroglia/patologia , Neuroglia/metabolismo , Ratos , Proteína Glial Fibrilar Ácida/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Modelos Animais de Doenças , Colo/patologia , Ratos Sprague-Dawley , Gliose/patologia , Inflamação/patologia , Plexo Mientérico/patologia , Sistema Nervoso Entérico/patologiaRESUMO
During intestinal and liver invasion by the protozoan parasite Entamoeba histolytica, extensive tissue destruction linked to large neutrophil infiltrates is observed. It has been proposed that microbicidal components of neutrophils are responsible for the damage, however, the mechanism by which they are released and act in the extracellular space remains unknown. In previous studies, we have shown that E. histolytica trophozoites induce NET formation, leading to the release of neutrophil granule content into extruded DNA. In this work, we evaluate the possible participation of NETs in the development of amoeba-associated pathology and analyze the contribution of anti-microbial components of the associated granules. E. histolytica-induced NETs were isolated and their effect on the viability and integrity of HCT 116 colonic and Hep G2 liver cultures were evaluated. The results showed that simple incubation of cell monolayers with purified NETs for 24 h resulted in cell detachment and death in a dose-dependent manner. The effect was thermolabile and correlated with the amount of DNA and protein present in NETs. Pretreatment of NETs with specific inhibitors of some microbicidal components suggested that serine proteases, are mostly responsible for the damage caused by NETs on HCT 116 cells, while the MPO activity was the most related to Hep G2 cells damage. Our study also points to a very important role of DNA as a scaffold for the activity of these proteins. We show evidence of the development of NETs in amoebic liver abscesses in hamsters as a preamble to evaluate their participation in tissue damage. In conclusion, these studies demonstrate that amoebic-induced NETs have potent cytotoxic effects on target cells and, therefore, may be responsible for the intense damage associated with tissue invasion by this parasite.
Assuntos
Entamoeba histolytica , Armadilhas Extracelulares , Peroxidase , Serina Proteases , Entamoeba histolytica/enzimologia , Humanos , Animais , Serina Proteases/metabolismo , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Peroxidase/metabolismo , Células Hep G2 , Colo/parasitologia , Colo/patologia , Fígado/parasitologia , Fígado/patologia , Células HCT116 , Neutrófilos/imunologia , Entamebíase/parasitologia , Entamebíase/imunologia , Hepatócitos/parasitologia , Mesocricetus , CricetinaeRESUMO
Colonic polyp refers to lesions that exhibit a protrusion of the mucosa, regardless of histology. The most recent WHO classification is based on a better understanding of these lesions; however, its application in daily practice could be subject to interobserver variability biases that could have clinical implications. OBJECTIVES: To determine the interobserver variability in the histopathological reporting and grading of dysplasia of samples obtained from elevated colon lesions in a private laboratory in the city of Lima. MATERIALS AND METHODS: Observational, descriptive, and prospective study: Case series type. All biopsies of elevated colon lesions received over a period of 3 months were evaluated by two observers without clinical information of the cases, to diagnose the lesions according to the WHO classification. In cases of diagnostic differences, the cases were evaluated together to reach a consensus. RESULTS: A Kappa coefficient value of 0.458 was obtained in the diagnostic classification of elevated colon lesions, while a Kappa value of 0.416 in the evaluation of dysplasia; indicating moderate agreement. CONCLUSIONS: Despite achieving moderate agreement between evaluators, this work demonstrates the importance of not only relying on morphological criteria for diagnostic classification, but also including criteria of location and size of these lesions to increase diagnostic accuracy.
Assuntos
Pólipos do Colo , Variações Dependentes do Observador , Humanos , Estudos Prospectivos , Peru , Pólipos do Colo/patologia , Pólipos do Colo/classificação , Pólipos do Colo/diagnóstico , Feminino , Masculino , Biópsia , Pessoa de Meia-Idade , Neoplasias do Colo/patologia , Neoplasias do Colo/classificação , Neoplasias do Colo/diagnóstico , Colo/patologia , Idoso , AdultoRESUMO
Colorectal cancer (CRC) is influenced by perturbations in the colonic microbiota, characterized by an imbalance favoring pathogenic bacteria over beneficial ones. This dysbiosis contributes to CRC initiation and progression through mechanisms such as carcinogenic metabolite production, inflammation induction, DNA damage, and oncogenic signaling activation. Understanding the role of external factors in shaping the colonic microbiota is crucial for mitigating CRC progression. This study aims to elucidate the gut microbiome's role in CRC progression by analyzing paired tumor and mucosal tissue samples obtained from the colon walls of 17 patients. Through sequencing of the V3-V4 region of the 16S rRNA gene, we characterized the tumor microbiome and assessed its association with clinical variables. Our findings revealed a significant reduction in alpha diversity within tumor samples compared to paired colon biopsy samples, indicating a less diverse microbial environment within the tumor microenvironment. While both tissues exhibited dominance of similar bacterial phyla, their relative abundances varied, suggesting potential colon-specific effects. Fusobacteriota enrichment, notably in the right colon, may be linked to MLH1 deficiency. Taxonomy analysis identified diverse bacterial genera, with some primarily associated with the colon wall and others unique to this region. Conversely, several genera were exclusively expressed in tumor tissue. Functional biomarker analysis identified three key genes with differential abundance between tumor microenvironment and colon tissue, indicating distinct metabolic activities. Functional biomarker analysis revealed three key genes with differential abundance: K11076 (putrescine transport system) and K10535 (nitrification) were enriched in the tumor microenvironment, while K11329 (SasA-RpaAB circadian timing mediator) dominated colon tissue. Metabolic pathway analysis linked seven metabolic pathways to the microbiome. Collectively, these findings highlight significant gut microbiome alterations in CRC and strongly suggest that long-term dysbiosis profoundly impacts CRC progression.
Assuntos
Colo , Neoplasias Colorretais , Progressão da Doença , Microbioma Gastrointestinal , Humanos , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Masculino , Feminino , Colo/microbiologia , Colo/patologia , Colo/metabolismo , Pessoa de Meia-Idade , Idoso , Microambiente Tumoral , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificaçãoRESUMO
PURPOSE: To investigate the impact of the Chinese medicine compound Ento-PB on oxazolone (OXZ)-induced ulcerative colitis (UC) in rats. METHODS: UC rats induced by OXZ were treated with Ento-PB. The damage to the colon was assessed using several measures, including the disease activity index (DAI), colon length, colon weight/length ratio, colonic mucosal damage index, and histological score. The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), epidermal growth factor (EGF), inducible nitric oxide synthase, and total nitric oxide synthase (tNOS) in rat serum, as well as the levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rat colon tissue, were determined using enzyme-linked immunosorbent assay and conventional kits. RESULTS: After being treated with Ento-PB, the DAI score and macroscopic lesion score of OXZ-induced UC rats were significantly reduced. Ento-PB prevented the shortening of rat colons, reduced the ratio of colon weight to length, and improved colon tissue lesions. Meanwhile, Ento-PB could significantly inhibit the activities of proinflammatory cytokines TNF-α, IL-13, and MPO, as well as tNOS and iNOS, while upregulating the expression of anti-inflammatory cytokines IL-4 and IL-10. Moreover, a significant increase in the expression level of EGF was observed in UC rats treated with Ento-PB, indicating that Ento-PB could enhance the repair of damaged intestinal epithelial tissue. CONCLUSIONS: Ento-PB demonstrates significant anti-UC activities in OXZ-induced UC rats by regulating the expression levels of inflammatory factors and promoting the repair of colon tissue. This study provides scientific evidence to support the further development of Ento-PB.
Assuntos
Colite Ulcerativa , Colo , Oxazolona , Peroxidase , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Masculino , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Peroxidase/análise , Peroxidase/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Modelos Animais de Doenças , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Ratos , Ensaio de Imunoadsorção Enzimática , Fator de Crescimento Epidérmico/análise , Citocinas/metabolismo , Interleucina-13/análise , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Lactobacillus delbrueckii CIDCA 133 is a promising health-promoting bacterium shown to alleviate intestinal inflammation. However, the specific bacterial components responsible for these effects remain largely unknown. Here, we demonstrated that consuming extractable proteins from the CIDCA 133 strain effectively relieved acute ulcerative colitis in mice. This postbiotic protein fraction reduced the disease activity index and prevented colon shortening in mice. Furthermore, histological analysis revealed colitis prevention with reduced inflammatory cell infiltration into the colon mucosa. Postbiotic consumption also induced an immunomodulatory profile in colitic mice, as evidenced by both mRNA transcript levels (Tlr2, Nfkb1, Nlpr3, Tnf, and Il6) and cytokines concentration (IL1ß, TGFß, and IL10). Additionally, it enhanced the levels of secretory IgA, upregulated the transcript levels of tight junction proteins (Hp and F11r), and improved paracellular intestinal permeability. More interestingly, the consumption of postbiotic proteins modulated the gut microbiota (Bacteroides, Arkkemansia, Dorea, and Oscillospira). Pearson correlation analysis indicated that IL10 and IL1ß levels were positively associated with Bacteroides and Arkkemansia_Lactobacillus abundance. Our study reveals that CIDCA 133-derived proteins possess anti-inflammatory properties in colonic inflammation.
Assuntos
Anti-Inflamatórios , Modelos Animais de Doenças , Microbioma Gastrointestinal , Lactobacillus delbrueckii , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Microbioma Gastrointestinal/efeitos dos fármacos , Citocinas/metabolismo , Proteínas de Bactérias/farmacologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Probióticos/farmacologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/patologia , Colo/microbiologia , Colo/metabolismo , MasculinoRESUMO
Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.
Assuntos
Focos de Criptas Aberrantes , Arbutina , Azoximetano , Antígeno Nuclear de Célula em Proliferação , Proteína X Associada a bcl-2 , Animais , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Focos de Criptas Aberrantes/prevenção & controle , Focos de Criptas Aberrantes/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Masculino , Arbutina/farmacologia , Ratos , Proteína X Associada a bcl-2/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Ratos Wistar , Fluoruracila , CarcinógenosRESUMO
OBJECTIVE: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded. KEY FINDINGS: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo. CONCLUSION: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.
Assuntos
Colite Ulcerativa , Malondialdeído , Estresse Oxidativo , Extratos Vegetais , Própole , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Própole/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Extratos Vegetais/farmacologia , Malondialdeído/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Peroxidase/metabolismo , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Dexametasona/farmacologia , Traqueófitas/química , Catalase/metabolismo , Relação Dose-Resposta a Droga , Antioxidantes/farmacologia , Glutationa Transferase/metabolismoRESUMO
Yerba Mate (YM) (Ilex paraguariensis) is a natural herbal supplement with a well-described anti-inflammatory capacity and beneficial effects in different inflammatory contexts such as insulin resistance or obesity. However, whether YM could improve other inflammatory conditions such as colitis or the immune cell population that can be modulated by this plant remains elusive. Here, by using 61 male and female C57BL/6/J wild-type (WT) mice and the dextran sodium sulfate (DSS)-induced acute colitis model, we evaluated the effect of YM on colitis symptoms and macrophage polarization. Our results showed that the oral administration of YM reduces colitis symptoms and improves animal survival. Increasing infiltration of anti-inflammatory M2 macrophage was observed in the colon of the mice treated with YM. Accordingly, YM promoted M2 macrophage differentiation in vivo. However, the direct administration of YM to bone marrow-derived macrophages did not increase anti-inflammatory polarization, suggesting that YM, through an indirect mechanism, is able to skew the M1/M2 ratio. Moreover, YM consumption reduced the Eubacterium rectale/Clostridium coccoides and Enterobacteriaceae groups and increased the Lactobacillus/Lactococcus group in the gut microbiota. In summary, we show that YM promotes an immunosuppressive environment by enhancing anti-inflammatory M2 macrophage differentiation, reducing colitis symptoms, and suggesting that YM consumption may be a good cost-effective treatment for ulcerative colitis.
Assuntos
Anti-Inflamatórios , Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Ilex paraguariensis , Macrófagos , Camundongos Endogâmicos C57BL , Extratos Vegetais , Animais , Macrófagos/efeitos dos fármacos , Ilex paraguariensis/química , Colite/tratamento farmacológico , Colite/induzido quimicamente , Masculino , Feminino , Anti-Inflamatórios/farmacologia , Camundongos , Extratos Vegetais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Modelos Animais de Doenças , Colo/efeitos dos fármacos , Colo/patologia , Diferenciação Celular/efeitos dos fármacosRESUMO
This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. The ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using Western blotting, immunohistochemistry, and qPCR. The results indicated a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure and an increase in NFκB from 7 to 90 days in the substantia nigra, while in the jejunum, a significant increase was observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 showed an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of alpha-synuclein and induces the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.
Assuntos
Colo , Jejuno , Ozônio , Substância Negra , alfa-Sinucleína , Animais , Masculino , Ratos , alfa-Sinucleína/metabolismo , Colo/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Inflamação/metabolismo , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-17/metabolismo , Jejuno/metabolismo , Jejuno/efeitos dos fármacos , Jejuno/patologia , NF-kappa B/metabolismo , Ozônio/toxicidade , Ratos Wistar , Substância Negra/metabolismo , Substância Negra/efeitos dos fármacos , Substância Negra/patologiaRESUMO
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with growing incidence worldwide. Our group reported the compound 5-choro-1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (LINS01007) as H4R antagonist (pKi 6.2) and therefore the effects and pharmacological efficacy on a DSS-induced mice model of UC were assessed in this work. Experimental acute colitis was induced in male BALB/c mice (n = 5-10) by administering 3 % DSS in the drinking water for six days. The test compound LINS01007 was administered daily i.p. (5 mg/kg) and compared to control group without treatment. Body weight, water and food consumption, and the presence of fecal blood were monitored during 7-day treatment period. The levels of inflammatory markers (PGE2, COX-2, IL-6, NF-κB and STAT3) were also analyzed. Animals subjected to the acute colitis protocol showed a reduction in water and food intake from the fourth day (p < 0.05) and these events were prevented by LINS01007. Histological signs of edema, hyperplasia and disorganized intestinal crypts, as well as neutrophilic infiltrations, were found in control mice while these findings were significantly reduced in animals treated with LINS01007. Significant reductions in the levels of PGE2, COX-2, IL-6, NF-κB and STAT3 were observed in the serum and tissue of treated animals. The results demonstrated the significant effects of LINS01007 against DSS-induced colitis, highlighting the potential of H4R antagonism as promising treatment for this condition.
Assuntos
Benzofuranos , Sulfato de Dextrana , Piperazinas , Receptores Histamínicos H4 , Animais , Masculino , Camundongos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Benzofuranos/uso terapêutico , Benzofuranos/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Colo/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Interleucina-6/metabolismo , Interleucina-6/sangue , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Receptores Histamínicos H4/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidoresRESUMO
Phytotherapy is an attractive strategy to treat inflammatory bowel disease (IBD) that could be especially useful in developing countries. We previously demonstrated the intestinal anti-inflammatory effect of the total ethereal extract from the Physalis peruviana (Cape gooseberry) calyces in TNBS-induced colitis. This work investigates the therapeutic potential of Peruviose A and B, two sucrose esters that constitute the major metabolites of its calyces. The effect of the Peruvioses A and B mixture on TNBS-induced colitis was studied after 3 (preventive) and 15-days (therapy set-up) of colitis induction in rats. Colonic inflammation was assessed by measuring macroscopic/histologic damage, MPO activity, and biochemical changes. Additionally, LPS-stimulated RAW 264.7 macrophages were treated with test compounds to determine the effect on cytokine imbalance in these cells. Peruvioses mixture ameliorated TNBS-induced colitis in acute (preventive) or established (therapeutic) settings. Although 3-day treatment with compounds did not produce a potent effect, it was sufficient to significantly reduce the extent/severity of tissue damage and the microscopic disturbances. Beneficial effects in the therapy set-up were substantially higher and involved the inhibition of pro-inflammatory enzymes (iNOS, COX-2), cytokines (TNF-α, IL-1ß, and IL-6), as well as epithelial regeneration with restoration of goblet cells numbers and expression of MUC-2 and TFF-3. Consistently, LPS-induced RAW 264.7 cells produced less NO, PGE2, TNF-α, IL-6, and MCP-1. These effects might be related to the inhibition of the NF-κB signaling pathway. Our results suggest that sucrose esters from P. peruviana calyces, non-edible waste from fruit production, might be useful as an alternative IBD treatment.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Physalis , Ribes , Ratos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Ésteres/metabolismo , Sacarose/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Citocinas/metabolismo , Colo/patologia , Doenças Inflamatórias Intestinais/patologia , Ácido Trinitrobenzenossulfônico/toxicidadeRESUMO
The perineuronal net (PNN) is a well-described highly specialized extracellular matrix structure found in the central nervous system. Thus far, no reports of its presence or connection to pathological processes have been described in the peripheral nervous system. Our study demonstrates the presence of a PNN in the spinal afferent innervation of the distal colon of mice and characterizes structural and morphological alterations induced in an ulcerative colitis (UC) model. C57Bl/6 mice were given 3% dextran sulfate sodium (DSS) to induce acute or chronic UC. L6/S1 dorsal root ganglia (DRG) were collected. PNNs were labeled using fluorescein-conjugated Wisteria Floribunda (WFA) l lectin, and calcitonin gene-related peptide (CGRP) immunofluorescence was used to detect DRG neurons. Most DRG cell bodies and their extensions toward peripheral nerves were found surrounded by the PNN-like structure (WFA+), labeling neurons' cytoplasm and the pericellular surfaces. The amount of WFA+ neuronal cell bodies was increased in both acute and chronic UC, and the PNN-like structure around cell bodies was thicker in UC groups. In conclusion, a PNN-like structure around DRG neuronal cell bodies was described and found modulated by UC, as changes in quantity, morphology, and expression profile of the PNN were detected, suggesting a potential role in sensory neuron peripheral sensitization, possibly modulating the pain profile of ulcerative colitis.
Assuntos
Colite Ulcerativa , Colo , Gânglios Espinais , Camundongos Endogâmicos C57BL , Animais , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Camundongos , Gânglios Espinais/patologia , Gânglios Espinais/metabolismo , Colo/inervação , Colo/patologia , Colo/metabolismo , Masculino , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Matriz Extracelular/patologia , Matriz Extracelular/metabolismo , Sulfato de Dextrana/toxicidade , Rede Nervosa/patologia , Rede Nervosa/metabolismoRESUMO
INTRODUCTION: Defining histological variables that make it possible to establish the activity of Crohn's disease (CD) and predict the patients who may present a higher risk of clinical complications and surgical interventions could lead to timely adjustments in medical therapy and elective surgeries that represent a lower risk of complications. The purpose of the study is to determine the relation between the histopathological findings using the Naini and Cortina (N&C) score, the clinical severity, and the indication for surgery in a group of patients with CD. MATERIALS AND METHODS: Descriptive, retrospective, cross-sectional study of 44 patients diagnosed with CD, treated at the San Vicente Fundación University Hospital in Medellín, Colombia, between 2010 and 2022. RESULTS: Of the 44 patients, 36 ileum samples and 34 colon samples were obtained. Of the patients with inflammatory behavior, 87.5% did not have surgical intervention (P=.022), a value that remained significant in the ileum subgroup (P=.0058). 91.3% of the patients with ileal involvement did not develop perianal disease (P=.01). Granulomas only occurred in two patients with a colon sample (5.8%). In the histological score of N&C both in the ileum and in the colon, no statistically significant differences were obtained in relation to the surgical outcome (P=.34 and P=.054, respectively). CONCLUSION: The histological index of N&C was not a predictor in Crohn's disease (CD) related to the surgical outcome.
Assuntos
Doença de Crohn , Índice de Gravidade de Doença , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/patologia , Estudos Transversais , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Colo/patologia , Colo/cirurgia , Íleo/patologia , Íleo/cirurgia , AdolescenteRESUMO
Based on the effectiveness of resveratrol and curcumin in carcinogenesis, (E)-3-(4-hydroxy-3-methoxyphenyl)-N'-((E)-4-methoxybenzylidene) acrylohydrazide (PQM-162), curcumin-resveratrol hybrid derivative, was designed by molecular hybridization using a hydrazone functionality as a spacer moiety between pharmacophoric fragments inspired by the parent compounds. OBJECTIVES: The present study aimed to evaluate the chemopreventive effects of the hybrid against pre-neoplastic lesions induced in the colon of rodents. METHODS: The doses were determined based on the reduction in DNA damage induced by doxorubicin [15 mg/kg body weight (b.w.)] in peripheral blood of Swiss mice. Doses of 8, 16, 32, and 64 mg/kg b.w. were antimutagenic. For the evaluation of pre-neoplastic lesions in the colon, Wistar rats were treated with PQM-162 at doses of 0.5, 1, and 2 mg/kg b.w. for 6 weeks using three approaches: simultaneous treatment, pre-treatment, and post-treatment. Pre-neoplastic lesions were induced with 1,2 dimethylhydrazine (160 mg/kg b.w.). KEY FINDINGS: PQM-162 reduced the formation of aberrant crypt foci in the simultaneous treatment and post-treatment. TNF-α and COX-2 mRNA levels decreased, while Nrf2 mRNA levels increased. PQM-162 also reduced the expression of COX-2, PCNA, and ß-catenin protein markers and increased Nrf2 expression. CONCLUSION: Our findings suggest a chemopreventive potential of PQM-162 in colorectal carcinogenesis, which acts on anti-inflammatory, antioxidant, and cell proliferation pathways.
Assuntos
Anti-Inflamatórios , Antioxidantes , Curcumina , Ratos Wistar , Resveratrol , Via de Sinalização Wnt , Animais , Curcumina/farmacologia , Resveratrol/farmacologia , Camundongos , Via de Sinalização Wnt/efeitos dos fármacos , Masculino , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Ratos , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Lesões Pré-Cancerosas/prevenção & controle , Lesões Pré-Cancerosas/induzido quimicamente , Fator 2 Relacionado a NF-E2/metabolismo , beta Catenina/metabolismo , Anticarcinógenos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Estilbenos/farmacologia , Dano ao DNA/efeitos dos fármacos , 1,2-Dimetilidrazina/toxicidade , Doxorrubicina , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
Ulcerative colitis (UC) is an important chronic and multifactorial disease, which alters the colon mucosal with a significant impact on life quality affecting both men and women. The difference between genders causes changes in the inflammatory processes, modulating the development of several diseases. The available drugs to treat UC exhibit limited outcomes and side effects; thus, new therapies are needed. Photobiomodulation (PBM) emerges as potential treatment by modulating the inflammatory process without side effects and low costs. The aim of this study was to evaluate the effects of PBM in acetic acid-induced UC comparing the responses between male and females. For this purpose, male and female Wistar rats (36) were submitted to induction of UC by rectal administration of 10% acetic acid (colitis group) and treated or not with PBM (colitis-PBM group) (LED, 660 nm, 100 mW, 150 s) in three points: right side and left of the ventral surface and in the external anal region. Non-manipulated rats were used as control (basal group). We investigated the disease activity index (DAI score), myeloperoxidase enzyme activity (MPO) and release of cytokines in the intestine homogenates, and histological analysis. PBM reduces DAI score, MPO activity, and mast cell degranulation while increased mucous production in both females and males. Moreover, PBM reduced histopathological score as well as the levels of IL-6 and IL-4 in the bowel only in males. We also showed reduced levels of IL-1beta and TNF-alpha after PBM in both males and females, while the levels of IL-10 and IFN-gamma were increased. In conclusion, despite our study has shown some differences between males and females, PBM attenuated the biomarkers of UC in both genders constituting a potential combined treatment that is non-invasive and low cost.
Assuntos
Colite Ulcerativa , Colite , Humanos , Feminino , Ratos , Masculino , Animais , Ácido Acético , Ratos Wistar , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/radioterapia , Colite Ulcerativa/tratamento farmacológico , Citocinas , Colo/patologia , AntioxidantesRESUMO
OBJECTIVE: Fluorodeoxyglucose is not a tumor-specific agent and it can also be involved in benign conditions, which may cause diagnostic confusion. This research aims to elucidate the colonoscopic findings of patients who underwent colonoscopy due to colon involvement in positron emission tomography/computerized tomography. METHODS: A total of 71 patients who underwent colonoscopy due to colonic involvement in positron emission tomography/computerized tomography at SBU Keçiören Training and Research Hospital Gastroenterology Clinic Endoscopy Unit have been analyzed retrospectively. Demographic characteristics of the patients, areas of involvement in positron emission tomography/computerized tomography, and severity have been obtained from the hospital database. RESULTS: The gastrointestinal involvement area of 22.5% (n=16) of the patients was ascending colon, 15.5% (n=11) was sigmoid, 15.5% (n=11) was rectum, 12.7% (n=9) was stomach, 11.3% (n=8) was transverse colon, 8.5% (n=6) was anal canal, 5.6% (n=4) was esophagus, and 5.6% (n=4) was descending colon. The endoscopic findings of 19.7% (n=14) patients were normal, whereas 29.6% (n=21) had polyps, 9.9% (n=7) had cancer, 2.8% (n=2) had an ulcer, 15.5% (n=11) had gastritis, 14.1% (n=10) had hemorrhoids, and 7% (n=5) had colitis. CONCLUSION: Fluorodeoxyglucose-positron emission tomography can detect unexpected distant metastases with high sensitivity because it allows whole-body imaging. Curative resection significantly contributes to the choice of treatment modality in the pre-operative period of colorectal cancer patients with planned surgery.
Assuntos
Colo , Neoplasias Colorretais , Humanos , Estudos Retrospectivos , Colo/diagnóstico por imagem , Colo/patologia , Colonoscopia/métodos , Tomografia por Emissão de Pósitrons , Fluordesoxiglucose F18 , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodosRESUMO
Gastrointestinal submucosal lesions represent a diagnostic challenge, including benign or malignant lesions, so they are identified more accurately by histopathological study accompanied by immunohistochemistry. This is a case of a 21-year-old man with a bleeding submucosal lesion in the cecum. The patient underwent a right colectomy. Microscopic finding was compatible with Vanek's tumor.
Assuntos
Neoplasias Gástricas , Masculino , Humanos , Adulto Jovem , Adulto , Diagnóstico Diferencial , Neoplasias Gástricas/patologia , Colo/patologiaRESUMO
The management of inflammatory bowel diseases has been widely investigated, especially ulcerative colitis. Thus, studies with the application of new probiotic products are needed in the prevention/treatment of these clinical conditions. The objective of this work was to evaluate the effects of probiotic orange juice containing Pediococcus acidilactici CE51 in a murine model of colitis. 45 male Swiss lineage mice were used, divided into five groups (n = 9): control, colitis, colitis + probiotic (probiotic orange juice containing CE51), colitis + placebo (orange juice) and colitis + sulfasalazine (10 mg/kg/Weight). The induction of colitis was performed with dextran sodium sulfate (3%). The treatment time was 5 and 15 days after induction. Histopathological analysis, serum measurements of TNF-α and C-reactive protein and metagenomic analysis of feces were performed after euthanasia. Probiotic treatment reduced inflammation in the small intestine, large intestine and spleen. The probiotic did not alter the serum dosages of TNF-α and C-reactive protein. Their use maintained the quantitative ratio of the phylum Firmicutes/Bacteroidetes and increased Lactobacillus helveticus with 15 days of treatment (p < 0.05). The probiotic orange juice containing P. acidilactici CE51 positively modulated the gut microbiota composition and attenuated the inflammation induced in colitis.