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1.
Life Sci ; 239: 117021, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678552

RESUMO

OBJECTIVES: Clematichinenoside AR (AR) is a saponin extracted for traditional Chinese medicine with the effects of improving the expression of tight junction (TJ) proteins and mediating anti-inflammatory activities. However, its effect on Crohn's disease (CD) is still unknown. We aimed to investigate the impact of AR on CD-like colitis and determine the mechanism underlying its effects. METHODS: Interleukin-10 gene knockout (Il-10-/-) mice (male, fifteen weeks old) with spontaneous colitis were allocated to the positive control and AR-treated (32 mg/kg AR administered every other day by gavage for 4 weeks) groups. Wild-type (WT) mice (male, fifteen weeks old) composed the negative control group. The effects of AR on intestinal barrier function and structure and T cell responses as well as the potential mechanisms underlying these effects were investigated. RESULTS: AR treatment significantly improved spontaneous colitis in Il-10-/- mice as demonstrated by reductions in the inflammatory score, disease activity index (DAI) and levels of inflammatory factors. The effects of AR on colitis in Il-10-/- mice were related to protecting intestinal barrier function and maintaining immune system homeostasis (regulatory T cell (Treg)/T helper 17 (Th17) cell balance). The anticolitis effect of AR may partly act by downregulating PI3K/Akt signaling. CONCLUSIONS: AR may have therapeutic potential for treating CD in humans.

2.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1052-1058, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640951

RESUMO

OBJECTIVE: To explore association of the expression levels of adenylate cyclase-associated protein 2 (CAP2) in gastric cancer tissues with the histopathology and long-term prognosis of the malignancy. METHODS: This study was conducted among a total of 105 patients with gastric cancer undergoing radical gastrectomy in our hospital between January, 2010 and October, 2013. Immunohistochemistry was used to quantitatively assess the expression of CAP2 in gastric cancer tissues and the adjacent tissues. Based on the median relative expression level of CAP2 of 3.5, the patients were divided into low CAP2 expression group (n=52) and high CAP2 expression group (n=53). The Cox regression model was used to analyze the effect of CAP2 expression on the 5-year survival rate of the patients, and ROC curve analysis was used to assess the predictive value of CAP2 expression for the patients' long-term survival. RESULTS: Immunohistochemical analysis showed that the expression levels of CAP2 (P < 0.01) and Ki67 (P < 0.01) were significantly higher in gastric cancer tissues than in the adjacent tissues, and the expression level of CAP2 was positively correlated with Ki67 (P < 0.01), peripheral blood CEA (P < 0.01) and CA19-9 (P < 0.01). The percentages of patients with CEA≥5 µg/L, CA19-9≥37 kU/L, pathological grade of G3-G4, T stage of 3-4, and N stage of 2-3 were significantly higher in patients with high CAP2 expression than in those with low CAP2 expression (P < 0.05). Kaplan- Meier survival analysis showed that the 5-year survival rate was significantly lower in patients with a high CAP2 expression (P < 0.01). A high expression level of CAP2, CEA≥5µg/L, CA19-9≥37 and pathological grades G3-G4 were all independent risk factors for shortened 5-year survival after radical gastrectomy (P < 0.01). With the relative expression level of 3.45 as the cut-off value, the sensitivity of CAP2 was 70.15% for predicting death 5 years after the surgery, with a specificity of 71.05% and an area under the curve of 0.779 (P < 0.01). CONCLUSIONS: CAP2 is highly expressed in gastric cancer tissues in close relation with the tumor progression. CAP2 is an independent risk factor for 5-year survival rate after radical gastrectomy for gastric cancer and can be of clinical value in prognostic evaluation of the patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Gástricas/patologia , Gastrectomia , Humanos , Imuno-Histoquímica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(7): 778-783, 2019 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-31340909

RESUMO

OBJECTIVE: To investigate the protective effect of procyanidin B2 (PCB2) on the intestinal barrier and against enteritis in mice with trinitrobenzene sulphonic acid (TNBS)-induced colitis and explore the possible mechanism. METHODS: A mouse model of TNBS-induced colitis was established in male Balb/c mice aged 6-8 weeks. The successfully established mouse models were randomly divided into PCB2 treatment group (n=10) and model group (n=10) and were treated with daily intragastric administration of PCB2 (100 mg/kg, 0.2 mL) and 0.2 mL normal saline, respectively. After 4 weeks, the disease symptoms, intestinal inflammation, intestinal mucosal cell barrier function and the changes in PI3K/AKT signaling were evaluated using HE staining, immunofluorescence assay and Western blotting. RESULTS: The disease activity index of the mice was significantly lower and the mean body weight was significantly greater in PCB2 group than in the model group in the 3rd and 4th weeks of intervention (P < 0.05). The levels of colonic inflammation and intestinal mucosal inflammatory mediators IL-1ß and TNF-α were significantly lower while IL-10 was significantly higher in PCB2 group than in the model group (P < 0.05). Compared with those in the model group, the mice in PCB2 treatment group showed a significantly lower positive rate of bacterial translocation in the mesenteric lymph nodes and a lower thiocyanate-dextran permeability of the intestinal mucosa (P < 0.05). Western blotting showed that PCB2 treatment significantly increased the expressions of claudin-1 and ZO-1 (P < 0.05) and significantly lowered the expression levels of p-PI3K and p-AKT in the intestinal mucosa as compared with those in the model group (P < 0.05). CONCLUSIONS: PCB2 suppresses intestinal inflammation and protects intestinal mucosal functions and structural integrity by inhibiting intestinal PI3K/AKT signaling pathway, suggesting the potential of PCB2 as a new drug for Crohn's disease.


Assuntos
Colite , Enterite , Animais , Biflavonoides , Catequina , Colite/induzido quimicamente , Colo , Mucosa Intestinal , Masculino , Camundongos , Fosfatidilinositol 3-Quinases , Proantocianidinas , Ácido Trinitrobenzenossulfônico
4.
J Cell Mol Med ; 23(8): 5632-5641, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31211512

RESUMO

Immunity imbalance and barrier damage in the intestinal mucosa are the main pathogenic factors of Crohn's disease (CD). Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES) is a glutaminase 1 (Gls1) inhibitor with the dual functions of increasing glutamine levels and immune regulation. In this study, we focused on the role of BPTES in CD-like enteritis and the possible mechanisms. We found that Gls1 expression was significantly increased in CD intestinal tissue compared with control tissue. Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide treatment significantly ameliorated chronic colitis in the IL-10-/- , as manifested by decreased disease activity index, body weight change, histological inflammatory degree and inflammatory cytokine expression. Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide treatment exerted protective effects on CD that were associated with the maintenance of intestinal barrier integrity and the Th/Treg balance. Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide treatment may act in part through TCR-mediated mammalian target of rapamycin complex 1 (mTORC1) signalling activation. In conclusion, inhibition of Gls1 expression attenuated chronic colitis by maintaining intestinal barrier integrity and the Th/Treg balance, thereby ameliorating CD-like colitis.

5.
J Cell Mol Med ; 23(8): 5588-5599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31251471

RESUMO

Bryostatin-1 (Bry-1) has been proven to be effective and safe in clinical trials of a variety of immune-related diseases. However, little is known about its effect on Crohn's disease (CD). We aimed to investigate the impact of Bry-1 on CD-like colitis and determine the mechanism underlying this effect. In the present study, 15-week-old male Il-10-/- mice with spontaneous colitis were divided into positive control and Bry-1-treated (Bry-1, 30 µg/kg every other day, injected intraperitoneally for 4 weeks) groups. Age-matched, male wild-type (WT) mice were used as a negative control. The effects of Bry-1 on colitis, intestinal barrier function and T cell responses as well as the potential regulatory mechanisms were evaluated. We found that the systemic delivery of Bry-1 significantly ameliorated colitis in Il-10-/- mice, as demonstrated by decreases in the disease activity index (DAI), inflammatory score and proinflammatory mediator levels. The protective effects of Bry-1 on CD-like colitis included the maintenance of intestinal barrier integrity and the helper T cell (Th)/regulatory T cell (Treg) balance. These effects of Bry-1 may act in part through nuclear factor erythroid 2-related factor 2 (Nrf2) signalling activation and STAT3/4 signalling inhibition. The protective effect of Bry-1 on CD-like colitis suggests Bry-1 has therapeutic potential in human CD, particularly given the established clinical safety of Bry-1.

6.
J Crohns Colitis ; 13(7): 931-941, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30615095

RESUMO

BACKGROUND: Crosstalk between mesenteric adipose tissue [MAT] and the intestines affects the progression of Crohn's disease [CD]. The adipokine metrnl regulates adipocyte function and has anti-inflammatory activity. We aimed to explore metrnl expression in CD MAT, investigate the influence of metrnl on the experimental colitis disease course and determine the mechanism underlying this effect. METHODS: Metrnl expression in MAT specimens obtained from patients with and without CD was tested by immunohistochemistry. Male Il-10-/- mice with spontaneous enteritis were divided into positive control and metrnl-treated [Metrnl-Fc, 10 mg/kg/d, intraperitoneally, 8 weeks] groups. Age-matched male wild-type [WT] mice were used as negative controls. The effects of metrnl on enteritis and mesenteric lesions and the potential controlling mechanisms were evaluated. RESULTS: Metrnl expression was higher in human CD MAT than in control MAT. Systemic delivery of metrnl significantly ameliorated chronic colitis in Il-10-/- mice, as demonstrated by decreases in the disease activity index, inflammatory score and proinflammatory mediators. The protective effects of metrnl on MAT included reduced mesenteric hypertrophy, increased adipocyte size, improved adipocyte intrinsic function and ameliorated inflammation. Metrnl treatment activated STAT5/PPAR-γ signaling and promoted adipocyte differentiation in the MAT. CONCLUSIONS: Metrnl expression was increased in the MAT of CD patients. Metrnl administration attenuated mesenteric lesions by promoting adipocyte function and differentiation partly through STAT5/PPAR-γ signaling pathway activation, thereby ameliorating CD-like colitis in mice.

7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(8): 678-683, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30384864

RESUMO

Objective To evaluate the therapeutic effect and possible mechanism of IL-12 monoclonal antibody (IL-12 mAb) on IL-10 knockout(IL-10-/-) mice and its possible mechanism. Methods Sixteen male IL-10-/- mice of 15 weeks old were randomly divided into control group and IL-12 mAb treatment group. The IL-12 mAb treatment group were given intraperitoneal injection of IL-12 mAb (25 mg/kg, once per week), and the control group was given intraperitoneal injection of 0.2 mL of normal saline. After 4 weeks of intervention, the inflammatory bowel disease activity index (DAI) and HE staining were used to evaluate the intestinal inflammation symptoms and histological changes. The intestinal mucosal permeability test was used to evaluate the intestinal mucosal barrier function of the two groups. The expression of claudin-1 in intestinal mucosa was detected by Western blot analysis. The Th1/Th2 cell balance of intestinal mucosa was evaluated by flow cytometry. The ELISA was used to evaluate IL-13 and tumor necrosis factor alpha(TNF-α) of intestinal mucosal of the two groups. The expression of phosphorylated signal transducer and activator of transcription (p-STAT6) in intestinal mucosa was detected by Western blot nanlysis. Results Three and 4 weeks after IL-12 mAb treatment, the DAI and intestinal inflammation scores of IL-12 mAb treatment group were significantly lower than the control group. At the same time, the intestinal mucosal permeability of IL-12 mAb treatment group was significantly lower than that of the control group, and the expression of claudin-1 in intestinal mucosa was significantly higher than that of the control group. At the same time, IL-12 mAb treatment inhibited the proportion of Th1 cells in the intestinal mucosa and up-regulated the proportion of Th2 cells. In the signal pathway analysis, IL-12 mAb treatment increased the levels of p-STAT6 and IL-13 in the intestinal mucosa and inhibited the level of TNF-α. Conclusion IL-12 mAb effectively alleviates intestinal inflammation in the Crohn's disease animal model and protect the intestinal mucosal barrier, which may be through inhibition of Th1 cell immune response in the intestinal mucosa and up-regulation of STAT6 signaling.

8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(9): 787-793, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30463649

RESUMO

Objective To evaluate the therapeutic effect and possible mechanism of PPARγ agonist rosiglitazone on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Methods Twenty male BALB/c mice were selected to establish TNBS-induced colitis model and were randomly divided into rosiglitazone treated group and model group with 10 rats in each group. Rosiglitazone group was treated with rosiglitazone(0.2 mL, [20 mg/(kg.d)])and model group with normal saline(0.2 mL/d). After 6 weeks of administration, the mice were sacrificed. Inflammatory bowel disease disease activity index (DAI) and HE staining combined with Spencer colitis histological score were used to evaluate the degree of intestinal inflammation and histological changes in the two groups. ELISA was used to detect the levels of interleukin-1ß (IL-1ß), tumor necrosis factor alpha(TNF-α) and IL-10 in the intestinal mucosa, the levels of IL-6 and monocyte chemoattractant protein 1 (MCP-1) in the mesenteric adipose tissues. The mean diameter of adipocytes in the mesenteric adipose tissues was calculated under light microscope after HE staining.The number of F4/80+ macrophages and the expressions of peripherin, adiponectin and leptin in mesenteric adipose tissues were detected by immunohistochemical staining. The phosphorylation of NF-κBp65, IKK, IκB proteins in the mesenteric adipose tissues was detected by Western blot analysis. Results The DAI score of rosiglitazone group was significantly lower than that of model group at 5 and 6 weeks after rosiglitazone treatment. At the same time, the levels of IL-1ß and TNF-α in the intestinal mucosa of the treated group were significantly lower than those in the model group, while the IL-10 levels were significantly higher in the treated group than in the model group. Compared with the model group, the mesenteric adipocyte diameter and the perilipin level of adipocyte maturation markers in rosiglitazone treated mice were significantly higher than those in model group. Meanwhile, the number of infiltration of macrophages in mesenteric adipose tissues of mice treated with rosiglitazone and the levels of inflammatory mediators IL-6 and MCP-1 were significantly lower than that of the model group. Rosiglitazone significantly promoted the expression of adiponectin and inhibited the expression of leptin in mesenteric adipocytes. The phosphorylation of NF-κBp65, IKK and IκB proteins in mesenteric adipose tissues of rosiglitazone treated mice was significantly lower than those of model group. Conclusion Rosiglitazone significantly inhibites intestinal inflammation in TNBS-induced colitis in mice, which may be related to the inhibition of NF-κBp65 pathway in mesenteric adipose tissues.

9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(3): 237-241, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29773105

RESUMO

Objective To analyze the therapeutic effect of green tea polyphenols (GTP) in mice with colitis induced by TNBS and its possible mechanism. Methods Colitis was induced by TNBS in BALB/C mice. The mice were randomly divided into GTP group (n=10) and TNBS model group (n=10). Mice in the GTP group were given GTP [0.2 mL at a dose level of 100 mg/(kg.d)] by oral gavage, and mice in the model group were given normal saline [0.2 ml/d] by gavage. Four weeks later, the mice were sacrificed. Disease activity index (DAI) and inflammatory score were evaluated by HE staining. The levels of interleukin 10 (IL-10), IL-6 and tumor necrosis factor α (TNF-α) were detected by ELISA. The expressions and localization of ZO-1 and claudin-1 were identified with immunofluorescence technique. Western blot analysis was performed to detect the expressions of ZO-1, claudin-1, p-JAK2 and p-STAT3 proteins. Results GTP decreased the DAI and inflammatory score, and reduced the levels of TNF-α and IL-6 in TNBS-induced colitis mice at three and four weeks after the administration. Meanwhile, the levels of ZO-1 and claudin-1 increased in the mice of GTP group when compared with those in model group. Western blot analysis showed that GTP down-regulated the JAK2/STAT3 signaling pathway in the intestinal mucosa. Conclusion GTP has a significant therapeutic effect on TNBS-induced colitis through down-regulating the JAK2/STAT3 signaling pathway.


Assuntos
Camellia sinensis/química , Colite/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Janus Quinase 2/metabolismo , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Fator de Transcrição STAT3/metabolismo , Animais , Claudina-1/genética , Claudina-1/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Janus Quinase 2/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Chá/química , Ácido Trinitrobenzenossulfônico/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Biochem Pharmacol ; 148: 202-212, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29309764

RESUMO

Both mesenteric adipose tissue (MAT) and lymphatic vessels (LVs) play important roles in the pathogenesis of Crohn's disease (CD), and adipokines have been implicated in the crosstalk between MAT and LVs. Apelin, a newly identified adipokine, has been demonstrated to be crucial in the development and stabilization of LVs. We aimed to identify the expression of apelin in MAT of CD patients and explore whether apelin influences the disease course in murine colitis and determine its contributions to LVs. Expression of apelin in MAT specimens from patients with CD (n = 24) and without CD (control, n = 12) was detected. Il-10 deficient (Il-10-/-) mice with established colitis were administered apelin, and untreated and wild-type mice served as controls (n = 8 for each group). Disease activity and colonic inflammation was evaluated. The LV density, lymphatic drainage function and related signaling pathways were also analyzed. We found that MAT from CD patients expressed a higher level of apelin compared with that from controls. Systemic delivery of apelin significantly ameliorated chronic colitis in Il-10-/- mice, demonstrated by decreased disease activity index and inflammatory scores, and lower levels of Tnf-α, Il-1ß and Il-6. Increased LV density and podoplanin levels indicated that apelin promoted lymphangiogenesis. Evans blue dye and fluorescent lymphangiography revealed an enhanced lymphatic drainage function in apelin-treated mice. The role of apelin was found to be related to the activation of the Akt and Erk signaling pathways. These results indicate that the adipokine apelin was highly expressed in MAT of CD patients and has a promising role in ameliorating experimental colitis by promoting intestinal lymphatic functions, suggesting the potential crosstalk between adipokines and LVs in MAT in CD status. Therapies with adipokines, such as apelin, may be a novel approach for the treatment of CD.

11.
JPEN J Parenter Enteral Nutr ; 41(5): 824-829, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-26407598

RESUMO

BACKGROUND: In the battle against Crohn's disease, autophagy stimulation is a promising therapeutic option-one both new and newly rediscovered. In experimental models, docosahexaenoic acid (DHA)-a long-chain polyunsaturated fatty acid-has been demonstrated to be useful in the treatment of inflammatory bowel disease through inhibition of the nuclear factor-κB pathway. However, the impact of DHA on autophagy in the colon remains unclear. METHODS: Mice were divided into 3 groups: wild type (placebo), the interleukin 10 knockout group (IL-10-/-, placebo), and the DHA group (IL-10-/-, DHA). DHA was administered to IL-10-/- mice by gavage at a dosage of 35.5 mg/kg/d for 2 weeks. The severity of colitis, expression of proinflammatory cytokines, expression/distribution of LC3B, and mTOR signaling pathway were evaluated in the proximal colon tissues collected from all mice at the end of the experiment. RESULTS: DHA administration ameliorated experimental colitis in the IL-10-/- mice, as demonstrated by decreased proinflammatory cytokines (TNF-α and IFN-γ), reduced infiltration of inflammatory cells, and lowered histologic scores of the proximal colon mucosa. Moreover, in the DHA-treated mice, enhanced autophagy was observed to be associated with (1) increased expression and restoration of the distribution integrity of LC3B in the colon and (2) inhibition of the mTOR signaling pathway. CONCLUSION: This study showed that DHA therapy could attenuate experimental chronic colitis in IL-10-/- mice by triggering autophagy via inhibition of the mTOR pathway.


Assuntos
Autofagia/efeitos dos fármacos , Colite/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Interleucina-10/deficiência , Serina-Treonina Quinases TOR/genética , Animais , Doença Crônica , Colo/efeitos dos fármacos , Colo/metabolismo , Modelos Animais de Doenças , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
13.
Inflamm Bowel Dis ; 22(6): 1483-95, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27167572

RESUMO

Crohn's disease (CD) is a complex gastrointestinal disorder involving multiple levels of cross talk between the immunological, neural, vascular, and endocrine systems. The current dominant theory in CD is based on the unidirectional axis of dysbiosis-innate immunity-adaptive immunity-mesentery-body system. Emerging clinical evidence strongly suggests that the axis be bidirectional. The morphologic and/or functional abnormalities in the mesenteric structures likely contribute to the disease progression of CD, to a less extent the disease initiation. In addition to adipocytes, mesentery contains nerves, blood vessels, lymphatics, stromal cells, and fibroblasts. By the secretion of adipokines that have endocrine functions, the mesenteric fat tissue exerts its activity in immunomodulation mainly through response to afferent signals, neuropeptides, and functional cytokines. Mesenteric nerves are involved in the pathogenesis and prognosis of CD mainly through neuropeptides. In addition to angiogenesis observed in CD, lymphatic obstruction, remodeling, and impaired contraction maybe a cause and consequence of CD. Lymphangiogenesis and angiogenesis play a concomitant role in the progress of chronic intestinal inflammation. Finally, the interaction between neuropeptides, adipokines, and vascular and lymphatic endothelia leads to adipose tissue remodeling, which makes the mesentery an active participator, not a bystander, in the disease initiation and precipitation CD. The identification of the role of mesentery, including the structure and function of mesenteric nerves, vessels, lymphatics, and fat, in the intestinal inflammation in CD has important implications in understanding its pathogenesis and clinical management.


Assuntos
Doença de Crohn/fisiopatologia , Gordura Intra-Abdominal/fisiopatologia , Sistema Linfático/fisiopatologia , Mesentério/irrigação sanguínea , Mesentério/inervação , Humanos
14.
World J Surg ; 40(8): 1993-2000, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26940580

RESUMO

BACKGROUND: The impact of preoperative enteral nutrition (EN) on postoperative complications and recurrence in Crohn's disease (CD) has not been investigated to date. The purpose of the present study was to determine the effect of preoperative exclusive EN on postoperative complications and recurrence after bowel resection in patients with active CD. METHODS: Patient data were obtained from a prospectively maintained database. 81 patients who received bowel resection for ileal or ileocolonic CD were studied. Before operation, 42 CD patients received exclusive EN for 4 weeks, and the other patients had no nutritional therapy. All patients were followed up regularly for 2 years after surgery, and ileocolonoscopy was performed every 6 months after bowel resection. RESULTS: Patients receiving exclusive EN had a dramatic improvement of nutritional (BMI, albumin, pre-albumin, and Hb) and inflammatory (CRP and CDAI) status compared with baseline after the EN therapy for 4 weeks (P < 0.05). Furthermore, significantly lower incidence of both infectious and non-infectious complications was observed in patients receiving exclusive EN compared with those received no nutritional therapy (P < 0.05). Exclusive EN therapy for 4 weeks significantly reduced endoscopic recurrence rates after resection for CD 6 months after operation. However, during the 2-year follow-up, incidence of clinical recurrence was similar in both groups (P > 0.05). CONCLUSIONS: Preoperative exclusive EN therapy for 4 weeks reduced postoperative complications, which may be associated with improvement of nutritional and inflammatory status in patients with active CD.


Assuntos
Doença de Crohn/cirurgia , Nutrição Enteral , Cuidados Pré-Operatórios , Adulto , Proteína C-Reativa/análise , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias , Recidiva , Albumina Sérica , Índice de Gravidade de Doença
15.
J Crohns Colitis ; 10(9): 1076-86, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26944415

RESUMO

BACKGROUND: Enteral nutrition [EN] was reported to be as effective as steroids in achieving short-term remission in patients with Crohn's disease [CD], and exclusive EN [EEN] is widely used as primary therapy in children with CD. The aim of this study was to investigate the effect of a specific multi-fibre mix [MF], designed to match the fibre content of a healthy diet, on intestinal epithelial barrier function in IL-10 knockout [IL-10(-/-)] mice with spontaneous chronic colitis. METHODS: IL-10(-/-) mice aged 16 weeks, with established colitis, were used for the experiments with multi-fibre mix diet [MF] for 4 weeks. Severity of colitis, levels of short cahin fatty acids [SCFA] in caecum contents, expression of STAT 3 and STAT 4 proteins, CD4(+) CD45(+) lymphocytes, CD4(+)Foxp3(+) regulatory T cells [Tregs] and cytokines in the lamina propria [LP], epithelial expression of tight junction proteins, TNF-α/TNFR2 mRNA expression, and epithelial apoptosis in the proximal colon were measured at the end of the experiment. RESULTS: MF feeding effectively attenuated disease activity index and colitis associated with decreased lamina propria CD4(+) CD45(+) lymphocytes, IFN-γ/IL-17A mRNA expression, and p-STAT 3 and p-STAT 4 expression in colonic mucosa of IL-10(-/-) mice [p < 0.05]. Furthermore, CD4(+)Foxp3(+) Tregs in the LP and concentrations of total SCFA, acetate, propionate, and butyrate in the caecum were markedly increased after MF feeding in IL-10(-/-) mice. After MF feeding, increased epithelial expression and correct localisation of tight junction proteins [occludin and zona occludens protein 1], as well as reduced TNF-α/TNFR2 mRNA expression and epithelial apoptosis, were also observed in IL-10(-/-) mice. CONCLUSIONS: These results indicated that EEN supplemented with the tested fibre mix, known to modulate the intestinal microbiota composition and SCFA production, could possibly improve efficacy in inducing remission in patients with active CD.


Assuntos
Colite/dietoterapia , Colo/fisiopatologia , Fibras na Dieta/uso terapêutico , Nutrição Enteral/métodos , Interleucina-10/deficiência , Mucosa Intestinal/fisiopatologia , Polissacarídeos/uso terapêutico , Animais , Apoptose , Biomarcadores/metabolismo , Colite/imunologia , Colite/metabolismo , Colite/fisiopatologia , Colo/imunologia , Colo/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Permeabilidade , Prebióticos , Índice de Gravidade de Doença , Junções Íntimas/metabolismo , Resultado do Tratamento
16.
Gastroenterol Res Pract ; 2016: 5017856, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26858749

RESUMO

Background. The rate of anastomotic leakage is high in surgeries for Crohn's disease, and therefore a temporary diverting stoma is often needed. We conducted this study to investigate whether preoperative nutritional therapy could reduce the risk of anastomotic leakage while decreasing the frequency of temporary stoma formation. Methods. This was a retrospective study. Patients requiring bowel resections due to Crohn's disease were reviewed. The rate of anastomotic leakage and temporary diverting stoma was compared between patients who received preoperative nutritional therapy and those on a normal diet before surgery. Possible predictive factors for anastomotic leakage were also analyzed. Results. One hundred and fourteen patients undergoing 123 surgeries were included. Patients in nutritional therapy (NT) group had a significantly lower level of C-reactive protein on the day before surgery. Patients in NT group suffered less anastomotic leakage (2.3% versus 17.9%, P = 0.023) and less temporary diverting stoma (22.8% versus 40.9%, P = 0.036). Serum albumin of the day before surgery ≤35 g/L and preoperative nutritional therapy were identified as factors which independently affected the rate of anastomotic leakage. Conclusion. Preoperative nutritional therapy reduced the risk of anastomotic leakage and the frequency of temporary diverting stoma formation in patients with Crohn's disease requiring resections.

17.
Nutrients ; 8(1)2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26784223

RESUMO

Recently, numerous studies have shown that disruption of the mucus barrier plays an important role in the exacerbation of inflammatory bowel disease, particularly in ulcerative colitis. Alterations in the mucus barrier are well supported by published data and are widely accepted. The use of fluorescence in situ hybridization and Carnoy's fixation has revealed the importance of the mucus barrier in maintaining a mutualistic relationship between host and bacteria. Studies have raised the possibility that modulation of the mucus barrier may provide therapies for the disease, using agents such as short-chain fatty acids, prebiotics and probiotics. This review describes changes in the mucus barrier of patients with inflammatory bowel disease and in animal models of the disease. We also review the involvement of the mucus barrier in the exacerbation of the disease and explore the therapeutic potential of modifying the mucus barrier with short-chain fatty acids, prebiotics, probiotics, fatty acid synthase, H2S, neutrophil elastase inhibitor and phophatidyl choline.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/microbiologia , Doença de Crohn/patologia , Progressão da Doença , Ácido Graxo Sintases/uso terapêutico , Ácidos Graxos Voláteis/uso terapêutico , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Fosfatidilcolinas/uso terapêutico , Prebióticos , Probióticos/uso terapêutico , Proteínas Secretadas Inibidoras de Proteinases/uso terapêutico
18.
Inflamm Bowel Dis ; 22(1): 114-26, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26332309

RESUMO

BACKGROUND: Abnormalities in mesenteric adipose tissue (MAT) have long been recognized; however, the functional changes in the mesenteric adipocytes as well as the underlying mechanisms are not entirely clear. The aim of this study was to analyze the function and morphology of the MAT in patients with Crohn's disease (CD) and the underlying mechanism. METHODS: The MAT specimens were obtained from areas adjacent to the intestinal wall in patients with CD (n = 33) and without CD (control, n = 23) who underwent intestinal resection. For patients with CD, paired samples were obtained from the macroscopically hypertrophic mesenteric adipose tissue (htMAT), adjacent to the involved ileum, and the macroscopically normal mesenteric adipose tissue (nMAT), contiguous with the healthy segment of the ileum. Morphological and molecular techniques were used to detect the characteristics of the MAT of CD and compare them with the characteristics of the control tissues. Hypoxia was confirmed by a high expression of hypoxia-inducible factor 1α. RESULTS: The function and morphology of the nMAT in patients with CD were similar to those of the control tissues. htMAT of CD was dysfunctional based on the evidence that htMAT exhibited decreased lipid store, fatty acid synthase, and adipose triglyceride lipase, but increased levels of glucose transporter 1, aldolase C, and lactate when compared with those from nMAT and control tissues (P < 0.01). In addition, the structure of htMAT was found to be disorganized and characterized by higher levels of collagen content, interleukin 1ß, interleukin 6, tumor necrosis factor α, and MCP-1 when compared with nMAT and control tissues (P < 0.01). htMAT was in a hypoxic condition, based on the findings that htMAT had a higher level of hypoxia-inducible factor 1α and a decreased number of vessels per adipocyte compared with those of nMAT and the control tissues (P < 0.01). The transforming growth factor ß/Smad and nuclear factor-kappa B signaling pathways were found to be activated in htMAT, which may be associated with hypoxia. CONCLUSIONS: The disorganized structure and dysfunction of mesenteric adipocyte tissue in CD was confirmed, and these alterations may be associated with hypoxia. It is possible that amelioration of mesenteric adipocyte hypoxia may help attenuate CD with underlying MAT inflammation.


Assuntos
Adipócitos/patologia , Doença de Crohn/complicações , Citocinas/metabolismo , Hipóxia/etiologia , Mesentério/patologia , Adipócitos/metabolismo , Adulto , Western Blotting , Estudos de Casos e Controles , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Citocinas/genética , Feminino , Imunofluorescência , Seguimentos , Humanos , Hipóxia/patologia , Técnicas Imunoenzimáticas , Masculino , Mesentério/metabolismo , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Int Immunopharmacol ; 29(2): 423-432, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26603637

RESUMO

BACKGROUND AND AIMS: Crohn's disease is an autoimmune disease associated with imbalanced mucosal immunity, mediated with increased Th1 and Th17 cells. Laquinimod, an immunomodulatory drug, has shown efficacy in regulating the differentiation of T cells. The aim of the study was to investigate the therapeutic effect of laquinimod on spontaneous colitis in interleukin-10-gene-deficient mice, an animal model of Crohn's disease. METHODS: Male Il10(-/-) mice aged 16weeks in the laquinimod group were treated with laquinimod with distilled water at a dose of 25mg/kg by oral gavage, 3 times a week. Il10(-/-) mice in the IL-10-KO group and wild type mice received equal volume of phosphate buffered saline by oral gavage, 3 times a week. After 4weeks, mice were sacrificed for analysis. Severity of colitis, epithelial expression of T-cell-associated cytokines, expression and distribution of tight junction proteins in the lamina propria and NF-κB signaling pathway associated mRNA expression were measured at the end of the experiment. RESULTS: Laquinimod treatment ameliorated spontaneous colitis in Il10(-/-) mice, which was associated with decreased T-cell-associated pro-inflammatory cytokines. Increased expression and correct distribution of tight junction proteins (occludin and ZO-1) were found in Il10(-/-) mice treated with laquinimod. In addition, in mice treated with laquinimod, NF-κB signaling pathway associated mRNA in the colon was also downregulated. CONCLUSIONS: Our results indicated that laquinimod treatment ameliorates colitis in Il10(-/-) mice and improves intestinal barrier function, which may support a new therapeutic approach to Crohn's disease.


Assuntos
Colite/tratamento farmacológico , Colite/genética , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Interleucina-10/deficiência , Quinolonas/uso terapêutico , Animais , Citocinas/biossíntese , Interleucina-10/genética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Antígenos Comuns de Leucócito , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/genética , Permeabilidade
20.
Am J Med Sci ; 350(5): 345-51, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26473333

RESUMO

BACKGROUND: The traditional Chinese medicine, Tripterygium wilfordii Hook F (TwHF) is widely used to treat Crohn's disease (CD) in China. METHODS: The authors compared different doses of TwHF with mesalazine in 198 patients with CD over a 52-week period. Subjects were randomized to receive mesalazine (3 g/d), low-dose TwHF (1.5 mg·kg·d), or high-dose TwHF (2.0 mg·kg·d). RESULTS: A total of 137 patients completed the study. At week 52, a significant lower proportion of patients in the high-dose TwHF group (7/71) had clinical recurrence compared with patients in the low-dose TwHF (15/68, P = 0.047) or mesalazine group (17/59, P = 0.006), whereas the difference between the low-dose TwHF group and the mesalazine group was not significant (P = 0.503). Patients receiving mesalazine experienced less adverse events than those receiving high-dose TwHF (P = 0.029) and those receiving low-dose TwHF (P = 0.048), but no significant difference was found about drug adverse events resulted withdrawal in the 3 groups (P > 0.05). In addition, compared with low-dose TwHF and mesalazine, the authors also detected significant superiority of high-dose TwHF arm in the decrease of CDAI and SESCD (P < 0.05). CONCLUSION: A 2.0 mg/kg daily TwHF was well tolerated and prolonged remission in patients with CD.


Assuntos
Doença de Crohn/tratamento farmacológico , Medicina Tradicional Chinesa , Mesalamina , Fitoterapia/métodos , Tripterygium , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Mesalamina/administração & dosagem , Mesalamina/efeitos adversos , Gravidade do Paciente , Preparações de Plantas/administração & dosagem , Preparações de Plantas/efeitos adversos , Recidiva , Indução de Remissão/métodos , Resultado do Tratamento
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