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1.
Hepatology ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773257

RESUMO

Currently there is no FDA-approved drug to treat nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH. C57BL/6J mice were fed a choline-deficient high fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc subcutaneously every two days for four weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were utilized to evaluate direct peptide effect. Immunohistochemistry, qPCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, goblet cells of intestine compared to a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) in order to gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation and hepatic fibrosis. CONCLUSION: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

3.
Korean J Intern Med ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34695881

RESUMO

Background/Aims: The optimal tools for monitoring Crohn's disease (CD) are controversial. We compared radiology plus ileocolonoscopy and radiology alone in terms of prognosis prediction and evaluated the agreement between radiologic and ileocolonoscopic findings in patients with CD. Methods: Patients with CD who were followed up with computed tomography enterography (CTE) or magnetic resonance enterography (MRE) alone or CTE or MRE plus ileocolonoscopy were retrospectively recruited. Time to relapse was investigated to evaluate the difference in prognosis using the log-rank and Cox regression tests, and the agreement between radiologic and ileocolonoscopic findings was determined using a kappa value. Results: A total of 501 patients with CD in clinical remission who underwent CTE or MRE and/or ileocolonoscopy were analyzed. Of these, 372 (74.3%) patients underwent CTE or MRE alone and 129 (25.7%) patients underwent CTE or MRE plus ileocolonoscopy. The cumulative maintenance rate of clinical remission between the two groups was not significantly different (p = 0.526, log-rank test). In multivariate analysis, age <40 years (hazard ratio [HR], 2.756; 95% confidence interval [CI], 1.263 to 6.013) and a history of steroid use (HR, 2.212; 95% CI, 1.258 to 3.577) were found to independently predict an increased risk for clinical relapse in patients with CD in clinical remission. Radiologic and ileocolonoscopic findings had a moderate degree of agreement (κ = 0.401, -0.094 to 0.142). The comparison of agreement between radiologic and ileocolonoscopic findings was the highest in the anastomotic site (κ = 0.749, -0.168 to 0.377). Conclusions: Radiology plus ileocolonoscopy was not superior to radiology alone in predicting the prognosis of CD.

4.
BMC Gastroenterol ; 21(1): 362, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620099

RESUMO

BACKGROUND: Patients with intestinal Behçet's disease (BD) frequently undergo intestinal resections, which significantly affects postoperative morbidity and mortality. The aim of this study was to identify the association between C-reactive protein (CRP) levels and postoperative outcomes in patients with intestinal BD who underwent surgical bowel resection. METHODS: Patients who were diagnosed with intestinal BD and underwent intestinal surgery due to BD at Severance Hospital between November 2005 and April 2018 were retrospectively investigated. Clinical relapse was defined as a disease activity index of BD (DAIBD) > 40, existence of newly added medications, re-hospitalization, or re-operation related to intestinal BD. The relationship between CRP level and postoperative outcomes was analyzed, and a receiver operating characteristic (ROC) curve was drawn to specify a cut-off value. RESULTS: Ninety patients with intestinal BD were included. Among them, 44 were male (48.9%), and the median age at diagnosis was 38 years (range, 11-69 years). The median total disease follow-up duration was 130 months (range, 3-460 months). Forty patients (44.4%) underwent laparoscopic surgery. A higher CRP level immediately after surgery was significantly associated with postoperative complications (OR 1.01, 95% CI 1.004-1.018, p < 0.01), re-operation (hazard ratio [HR] 1.01, 95% CI 1.005-1.020, p < 0.01), and re-admission (HR 1.01, 95% CI 1.006-1.017 p < 0.01). The ROC curve showed that CRP predicts the risk of postoperative complications (p < 0.01) at a cut-off value of 41.9% with a sensitivity of 60.0% and specificity of 67.7%. CONCLUSIONS: Postoperative CRP levels in patients with intestinal BD undergoing surgical resection were associated with postoperative outcomes.


Assuntos
Síndrome de Behçet , Proteína C-Reativa , Enteropatias , Adolescente , Adulto , Idoso , Síndrome de Behçet/cirurgia , Proteína C-Reativa/análise , Criança , Feminino , Humanos , Enteropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Adulto Jovem
6.
Nat Rev Dis Primers ; 7(1): 67, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531393

RESUMO

Behçet syndrome is a systemic vasculitis with an unknown aetiology affecting the small and large vessels of the venous and arterial systems. The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest that multiple pathological pathways are involved in Behçet syndrome. These disease features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 as a genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bona fide disease, especially in non-endemic regions, suggests that other factors must also be operative in Behçet syndrome. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease, eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve. New treatment options and a better understanding of the underlying pathogenesis for various manifestations of this condition are required to further improve the management of the disease, which will improve patient quality of life.


Assuntos
Síndrome de Behçet , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiologia , Humanos , Prognóstico , Qualidade de Vida , Fatores de Risco
7.
Gut Liver ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34420935

RESUMO

Background/Aims: Many patients with Crohn's disease (CD) undergo intestinal resection during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of tumor necrosis factor α (TNF-α) inhibitors is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same TNF-α inhibitors postoperatively in patients who received TNF-ɑ inhibitors before surgery. Methods: This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who had undergone the first intestinal resection due to CD and divided them into two groups: TNF-α inhibitor users in both the preoperative and postoperative periods, and TNF-α inhibitor users in only the preoperative period. We compared the clinical outcomes between these two groups. Results: In total, 45 patients who used TNF-α inhibitors preoperatively were recruited. Among them, TNF-α inhibitors were used postoperatively in 20 patients (44.4%). The baseline characteristics except age at diagnosis were similar in both groups. The rates of surgical and endoscopic recurrence were not different between the two groups, but the cumulative clinical recurrence rate was significantly lower in the postoperative TNF-α inhibitors group (log-rank p=0.003). In multivariate Cox regression analysis, postoperative TNF-α inhibitors use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio, 0.204; 95% confidence interval, 0.060 to 0.691; p=0.011). Conclusions: Continuing TNF-α inhibitors postoperatively in patients who were receiving TNF-α inhibitors before surgery significantly reduced the rate of clinical recurrence. For patients with CD who received TNF-α inhibitors preoperatively, continuing their use after surgery could be recommended.

8.
Cell Rep ; 36(6): 109521, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380041

RESUMO

The gut metabolite composition determined by the microbiota has paramount impact on gastrointestinal physiology. However, the role that bacterial metabolites play in communicating with host cells during inflammatory diseases is poorly understood. Here, we aim to identify the microbiota-determined output of the pro-inflammatory metabolite, succinate, and to elucidate the pathways that control transepithelial succinate absorption and subsequent succinate delivery to macrophages. We show a significant increase of succinate uptake into pro-inflammatory macrophages, which is controlled by Na+-dependent succinate transporters in macrophages and epithelial cells. Furthermore, we find that fecal and serum succinate concentrations were markedly augmented in inflammatory bowel diseases (IBDs) and corresponded to changes in succinate-metabolizing gut bacteria. Together, our results describe a succinate production and transport pathway that controls the absorption of succinate generated by distinct gut bacteria and its delivery into macrophages. In IBD, this mechanism fails to protect against the succinate surge, which may result in chronic inflammation.

9.
Free Radic Biol Med ; 174: 110-120, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34358646

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract whose occurrence is attributed to various factors, including genetic factors, immune response, microbial changes, and oxidative stress. Microbial-targeted therapy has emerged as an alternative to immunosuppressive therapy for IBD. METHODS: The effects of an atypical commensal Escherichia coli strain harboring an additional catalase gene (compared to typical E. coli strain) on dextran sulfate sodium (DSS)-induced colitis were explored in mice. RESULTS: The atypical E. coli (atEc) significantly restored body weight, reduced disease activity score, and improved histological scores in mice with colitis. Hydrogen peroxide levels in colitis mice were noticeably decreased when the mice were administered atEc. The proinflammatory cytokine levels were decreased and regulatory T cell numbers were increased after the administration of atEc. The abundance of Firmicutes was significantly recovered, while that of Proteobacteria decreased in atEc -treated mice compared with that in vehicle-treated wild-type mice. To investigate the role of interleukin (IL)-17A in mediating the anti-inflammatory effects of the atEc, IL-17A‒knockout mice were orally administered atEc. Clinical and immune responses and microbial composition were significantly reduced in IL-17A‒knockout mice compared with those in wild-type mice. CONCLUSIONS: atEc ameliorates colonic inflammation by controlling hydrogen peroxide levels, immune responses (including regulatory T cells and IL-17A), and microbial composition. atEc could be a novel candidate of probiotic for IBD treatment.


Assuntos
Colite , Linfócitos T Reguladores , Animais , Catalase , Colite/induzido quimicamente , Colite/tratamento farmacológico , Citocinas , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Escherichia coli/genética , Peróxido de Hidrogênio , Interleucina-17 , Camundongos , Camundongos Knockout
10.
Korean J Intern Med ; 36(5): 1040-1048, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34344146

RESUMO

The incidence and prevalence rates of inf lammatory bowel disease (IBD) have been increasing in East Asian countries over the past few decades. Accordingly, the general understanding and awareness of IBD among healthcare professionals has increased considerably in this region. This increase is ultimately associated with the evolving focus of IBD clinicians devoted to comprehensive patient care, especially in establishing IBD clinics/centers capable of providing multidisciplinary counseling. Comprehensive IBD care at IBD clinics/centers usually includes surgical and medication decision-making, transition from pediatric to adult clinics, care of extraintestinal manifestations, care of infectious diseases in patients undergoing immunomodulatory or biologic therapies, and nutritional, psychosocial, socioeconomic, and pharmacological care. Team members comprise specialists from various departments related to IBD and can be divided into core and ad hoc members. Usually, the scope of work in IBD clinics/centers involves patient care, patient outreach, and system management. Considering the environmental changes in IBD treatment, it is necessary to perform comprehensive IBD patient care in the form of a program based on competencies, rather than simply following the organization of previous IBD centers. The present review summarizes recent trends in IBD patient care and offers perspectives regarding IBD center management.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Adulto , Criança , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia
11.
Therap Adv Gastroenterol ; 14: 17562848211024769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285716

RESUMO

Aim: This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea. Methods: A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method. Results: A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% (n = 43/77) achieved a clinical response and 18.2% (n = 14/77) achieved clinical remission. At week 14, 73.2% (n = 52/71) achieved a clinical response and 39.4% (n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% (n = 43/105) and 49.5% (n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785). Conclusions: In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.

12.
Gut Liver ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34312323

RESUMO

Background/Aims: Previous studies have investigated the relationship between visceral obesity and the risk of colorectal tumors. Visceral obesity may affect the outcome of colorectal cancer (CRC), including survival and metastasis. We investigated the associations between visceral adipose tissue and oncologic outcomes in stage III CRC. Methods: Four hundred seventy-two patients with stage III CRC were identified. Subcutaneous and visceral adipose tissue areas were measured volumetrically via computed tomography for each patient at different levels of the lumbar spine. After adjusting for age, sex, and other clinical factors, the effects of visceral adipose tissue area on mortality and recurrence were assessed using Cox proportional hazard regression. Results: In univariate and multivariate analyses, a higher visceral adipose tissue to total adipose tissue (VT) ratio (hazard ratio [HR], 1.041; 95% CI, 1.008 to 1.075; p=0.015) and higher visceral adipose tissue to subcutaneous adipose tissue (VS) ratio (HR, 1.016; 95% CI, 1.005 to 1.028; p=0.006) were both associated with poor CRC-specific survival. Interestingly, in the evaluation of each site of recurrence, a higher VT ratio (HR, 1.069; 95% CI, 1.010 to 1.131; p=0.020) and higher VS ratio (HR, 1.024; 95% CI, 1.003 to 1.045; p=0.023) were both related to a higher risk of peritoneal seeding and tumor recurrence. The VT ratio at the L3-L4 level was significantly associated with a higher risk of peritoneal seeding and tumor recurrence (HR, 4.969; 95% CI, 1.303 to 18.949; p=0.019), while other levels showed no such relationship. Conclusions: Visceral obesity is closely related to increased risks of CRC-specific mortality and peritoneal seeding metastasis in stage III CRC patients.

13.
Adv Ther ; 38(8): 4366-4387, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34250583

RESUMO

INTRODUCTION: Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS). METHODS: Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated. RESULTS: Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03-63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603-5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had ≥ 1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications. CONCLUSION: The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5 years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015).


Assuntos
Artrite Reumatoide , Medicamentos Biossimilares , Doenças Inflamatórias Intestinais , Espondilite Anquilosante , Anticorpos Monoclonais , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento
14.
Medicine (Baltimore) ; 100(27): e26290, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232167

RESUMO

ABSTRACT: This study examined the association between physical activity (PA) and quality of life (QOL) in Korean patients with inflammatory bowel disease (IBD).We enrolled 158 patients with IBD (81 men and 47 women). PA levels were assessed using the International PA questionnaire. Using self-reported frequency (day) and duration (h) of physical activities, the patients were categorized into 3 groups based on their total metabolic equivalent (MET-h/wk) values: least, moderate, and most active. The QOL of patients with IBD was assessed using the inflammatory bowel disease questionnaire (IBDQ), the Medical Outcomes Study 36-Item Short Form Version 2 (SF36v2), the EuroQOL five dimensions questionnaire (EQ5D), and the EuroQOL visual analog scale (EQ-VAS).Of 158 patients, 62, 73, and 23 patients with Crohn disease, ulcerative colitis, and intestinal Behçet disease, respectively, were included. The mean age was 45.96 ±â€Š17.58 years, and 97 (61.4%) patients were men. Higher PA levels correlated with higher EQ5D and EQ-VAS scores (P < .001 and P = .004 respectively). In addition, depending on the type of PA, the amount of leisure activity was associated with higher IBDQ (κ = 0.212, P = .018), physical function of SF36v2 (κ = 0.197, P = .026), EQ5D (κ = 0.255, P = .002), and EQ-VAS (κ = 0.276, P = .001) scores. The frequency of sweat-inducing exercise showed an inverse correlation with IBDQ (κ = -0.228, P = .011), physical function of SF36v2 (κ = -0.245, P = .006), EQ5D (κ = -0.225, P = .007), and EQ-VAS (κ = -0.246, P = .004) scores.Increased PA levels were associated with improved QOL in patients with IBD. More leisure activity and non-sweat-inducing exercise were associated with improved QOL in patients with IBD.


Assuntos
Exercício Físico/fisiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Adulto , Feminino , Humanos , Doenças Inflamatórias Intestinais/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários
15.
Sci Rep ; 11(1): 11019, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34040049

RESUMO

Intestinal Behçet's disease (BD) and Crohn's disease (CD) present similar manifestations, but there are no specific diagnostic tests to differentiate them. We used a proteomic approach to discover novel diagnostic biomarkers specific to intestinal BD. Colon mucosa tissue samples were obtained from patients with intestinal BD or CD using colonoscopy-guided biopsy of the affected bowel. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Using TMT/LC-MS/MS-based proteomic quantification, we identified 39 proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed higher intensity in the IHC staining of intestinal BD tissues than in CD tissues. The serum MGAM level was higher in intestinal BD patients. Proteomic analysis revealed that some proteins were differentially expressed in patients with intestinal BD compared with those with CD. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker.


Assuntos
Síndrome de Behçet , Doença de Crohn , Proteômica , Biomarcadores/sangue , Colonoscopia , Diagnóstico Diferencial , Humanos
16.
PLoS One ; 16(4): e0250083, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33852640

RESUMO

Prior studies have demonstrated the utility of microRNA assays for predicting some cancer tissue origins, but these assays need to be further optimized for predicting the tissue origins of adenocarcinomas of the liver. We performed microRNA profiling on 195 frozen primary tumor samples using 14 types of tumors that were either adenocarcinomas or differentiated from adenocarcinomas. The 1-nearest neighbor method predicted tissue-of-origin in 33 samples of a test set, with an accuracy of 93.9% at feature selection p values ranging from 10-4 to 10-10. According to binary decision tree analyses, the overexpression of miR-30a and the underexpression of miR-200 family members (miR-200c and miR-141) differentiated intrahepatic cholangiocarcinomas from extrahepatic adenocarcinomas. When binary decision tree analyses were performed using the test set, the prediction accuracy was 84.8%. The overexpression of miR-30a and the reduced expressions of miR-200c, miR-141, and miR-425 could distinguish intrahepatic cholangiocarcinomas from liver metastases from the gastrointestinal tract.


Assuntos
Colangiocarcinoma/genética , MicroRNAs/genética , Adenocarcinoma/genética , Adulto , Idoso , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Biomarcadores Tumorais/genética , Diferenciação Celular/genética , Colangiocarcinoma/metabolismo , Feminino , Neoplasias Gastrointestinais/genética , Trato Gastrointestinal/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Fígado/citologia , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica/genética
18.
Front Immunol ; 12: 650864, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767714

RESUMO

Triggering receptor expressed on myeloid cell-1 (TREM-1) signaling is expressed on neutrophils and monocytes that is necessary for the successful antimicrobial response and resolution of inflammation in the gut. In this study, we determined the effect of an anti-TREM-1 agonistic antibody (α-TREM-1) on colitis and identify its underlying mechanism of action. Administration of α-TREM-1 alleviated colitis in mice and resolved dysbiosis, which required TLR4/Myd88 signaling. α-TREM-1 increased the production of neutrophil extracellular traps and interleukin-22 by CD177+ neutrophils, which led to pathogen clearance and protection of the intestinal barrier. TREM-1 activation using an α-TREM-1 antibody protects against colitis by rebalancing the microbiota and protecting the epithelium against the immune response as well as modulates the function of neutrophils and macrophages. These results highlight the importance of the TREM-1 pathway in intestinal homeostasis and suggest that α-TREM-1 treatment may be an effective therapeutic strategy for inflammatory bowel disease.


Assuntos
Anticorpos/farmacologia , Proteínas Ligadas por GPI/imunologia , Inflamação/prevenção & controle , Intestinos/efeitos dos fármacos , Isoantígenos/imunologia , Neutrófilos/efeitos dos fármacos , Receptores de Superfície Celular/imunologia , Receptor Gatilho 1 Expresso em Células Mieloides/agonistas , Animais , Anticorpos/imunologia , Colite/imunologia , Colite/metabolismo , Colite/prevenção & controle , Disbiose/microbiologia , Disbiose/prevenção & controle , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/imunologia , Proteínas Ligadas por GPI/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/prevenção & controle , Interleucinas/imunologia , Interleucinas/metabolismo , Intestinos/imunologia , Intestinos/patologia , Isoantígenos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/imunologia , Neutrófilos/metabolismo , Receptores de Superfície Celular/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/imunologia
19.
Gut Liver ; 15(6): 858-866, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33767032

RESUMO

Background/Aims: Few studies have investigated terminal ileal lesions and their prognostic value in patients with ulcerative colitis (UC). We evaluated the clinical significance of these lesions as a prognostic factor in patients with UC who were in clinical remission. Methods: We retrospectively selected 567 of 4,066 colonoscopy reports that included positive findings from orificial observations of the terminal ileum (TI) and appendix in patients with UC. We finally recruited patients who were in clinical remission (n=204). We compared the clinical courses, including relapse and other prognostic parameters associated with UC, between the groups. Results: The baseline patient characteristics were not significantly different between patients with (n=69, TI+ group) and without TI lesions (n=135, TI- group), although there were more never-smokers in the TI+ group (n=57 [82.6%] in the TI+ group; n=86 [63.7%] in the TI- group; p=0.005). Of note, appendiceal orifice inflammation (AOI) was less frequently found in the TI+ group (14.5%) than in the TI- group (71.9%, p<0.001). The cumulative relapse rate was numerically higher in the TI- group, but it was not significantly different according to the Kaplan-Meier analysis (p=0.116). Multivariate Cox regression analysis also revealed advanced age at diagnosis as the most significant factor (adjusted hazard ratio, 0.964; 95% confidence interval, 0.932 to 0.998; p=0.037), but neither TI inflammation nor AOI were significantly associated with the cumulative relapse rate in patients with UC in clinical remission. Conclusions: For patients with UC in clinical remission, neither terminal ileal lesions nor AOI had significant clinical or predictive value for future relapse.


Assuntos
Colite Ulcerativa , Colite Ulcerativa/complicações , Colonoscopia , Humanos , Íleo , Inflamação , Prognóstico , Recidiva , Estudos Retrospectivos
20.
J Gastroenterol Hepatol ; 36(8): 2141-2148, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33554375

RESUMO

BACKGROUND AND AIM: Pattern analysis of big data can provide a superior direction for the clinical differentiation of diseases with similar endoscopic findings. This study aimed to develop a deep-learning algorithm that performs differential diagnosis between intestinal Behçet's disease (BD), Crohn's disease (CD), and intestinal tuberculosis (ITB) using colonoscopy images. METHODS: The typical pattern for each disease was defined as a typical image. We implemented a convolutional neural network (CNN) using Pytorch and visualized a deep-learning model through Gradient-weighted Class Activation Mapping. The performance of the algorithm was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 6617 colonoscopy images of 211 CD, 299 intestinal BD, and 217 ITB patients were used. The accuracy of the algorithm for discriminating the three diseases (all-images: 65.15% vs typical images: 72.01%, P = 0.024) and discriminating between intestinal BD and CD (all-images: 78.15% vs typical images: 85.62%, P = 0.010) was significantly different between all-images and typical images. The CNN clearly differentiated colonoscopy images of the diseases (AUROC from 0.7846 to 0.8586). Algorithmic prediction AUROC for typical images ranged from 0.8211 to 0.9360. CONCLUSION: This study found that a deep-learning model can discriminate between colonoscopy images of intestinal BD, CD, and ITB. In particular, the algorithm demonstrated superior discrimination ability for typical images. This approach presents a beneficial method for the differential diagnosis of the diseases.

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