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1.
Naunyn Schmiedebergs Arch Pharmacol ; 396(5): 983-1000, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36576506

RESUMO

Ulcerative colitis (UC) is a chronic nonspecific intestinal inflammatory disease, which belongs to a subtype of inflammatory bowel disease, but still lacks effective drug treatment. Bletilla striata (B. striata) is one of the most valuable traditional Chinese medicines (TCMs) in China, can stop bleeding, can promote wound healing, and can regulate immunity. Based on data mining, B. striata was found to be a common TCM for the treatment of UC, but the exact therapeutic mechanism is not yet known. This study aims to explore the potential mechanisms of B. striata in the treatment of UC using network pharmacology, molecular docking techniques, and in vivo experimental research. We extracted the active ingredients and targets of B. striata from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform. We retrieved and screened the corresponding UC-related target genes in multiple databases. Subsequently, we constructed an herb-ingredient-target-disease-network, generated a protein-protein interaction network, performed Gene Ontology enrichment analysis, and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify potential treatment mechanisms. After screening for key active ingredients and target genes, we performed molecular docking using AutoDock Vina software to select the best binding target for molecular docking and validate the binding activity. The UC model was established in mice, and the results of network pharmacology and molecular docking were verified by in vivo experiments. In all, 5 compounds were obtained from the TCMSP database, and 74 UC-related pathogenic genes were obtained from GeneCards, DisGeNET, OMIM, TTD, and DrugBank. After KEGG enrichment analysis, pathways in cancer, the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway, and metabolic pathways were identified as the top three signalling pathways associated with UC treatment. The results of molecular docking showed that the active components of B. striata have good binding activities to the pivotal targets epidermal growth factor receptor (EGFR) and PIK3CA. In a dextran sulphate sodium-induced colitis model, we found that B. striata can alleviate the symptoms of UC, decrease the secretion of the inflammatory cytokines interleukin-6 and tumour necrosis factor-α, and downregulate the expression levels of EGFR, PIK3CA, and p-AKT. In conclusion, the treatment of UC with B. striata may alleviate the inflammatory response of the colon, and B. striata mainly inhibits the EGFR/PI3K/AKT signalling pathways.


Assuntos
Colite Ulcerativa , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores ErbB , Classe I de Fosfatidilinositol 3-Quinases
2.
World J Gastroenterol ; 27(11): 1076-1089, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33776374

RESUMO

BACKGROUND: Fatigue is a very common but relatively neglected problem in patients with inflammatory bowel disease (IBD). The prevalence rate of IBD in China is the highest in Asia, but there is little research on fatigue in patients with IBD. Neither the relationship between fatigue and quality of life (QoL) nor the relationship between fatigue and work productivity (WP) in Chinese IBD patients has been reported. AIM: To investigate the prevalence of fatigue related to IBD in Eastern China, to identify the risk factors associated with fatigue, to assess the impact of fatigue on QoL, and to evaluate the relationship between fatigue and WP. METHODS: A cross-sectional study was conducted in a Regional Tertiary IBD Diagnostic and Treatment Center in Eastern China. Clinical data of patients were collected, and disease activity was evaluated. Blood samples were analyzed to assess anemia, albumin, and inflammation. Fatigue was assessed using the multidimensional fatigue inventory. QoL and WP were measured using the short inflammatory bowel disease questionnaire and the work productivity and activity impairment general health questionnaire, respectively. The patients also completed assessments of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder 7-item Scale). RESULTS: A total of 311 IBD patients, comprising 168 Crohn's disease patients and 143 ulcerative colitis patients, were enrolled. The prevalence of fatigue in patients with IBD was 60.77%. In a univariate logistic regression analysis, factors such as disease activity, depression, anxiety, anemia, and IBD-related surgery were individually related to a significantly increased risk of fatigue in IBD patients. Multivariate logistic regression analysis indicated that depression [odds ratio (OR) = 8.078, 95% confidence interval (CI): 4.113-15.865], anxiety (OR = 2.373, 95%CI: 1.100-5.119), anemia (OR = 2.498, 95%CI: 1.290-4.834), and IBD-related surgery (OR = 2.035, 95%CI: 1.084-3.819) were related to fatigue in IBD patients. There was a negative correlation between fatigue and QoL (r = -0.831; P < 0.0001) but a positive correlation between fatigue and WP loss. CONCLUSION: The prevalence of fatigue in IBD patients in Eastern China is remarkably high even in clinical remission. Factors such as depression, anxiety, anemia, and IBD-related surgery are major risk factors for fatigue in IBD patients. In addition, fatigue has a negative impact on QoL and is positively correlated with WP loss.


Assuntos
Doenças Inflamatórias Intestinais , Qualidade de Vida , Ásia , China/epidemiologia , Estudos Transversais , Fadiga/epidemiologia , Fadiga/etiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Inquéritos e Questionários
3.
World J Gastroenterol ; 17(28): 3347-52, 2011 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-21876624

RESUMO

AIM: To analyze the clinical risk factors for early variceal rebleeding after endoscopic variceal ligation (EVL). METHODS: 342 cirrhotic patients with esophageal varices who received elective EVL to prevent bleeding or rebleeding at our endoscopy center between January 2005 and July 2010. were included in this study. The early rebleeding cases after EVL were confirmed by clinical signs or endoscopy. A case-control study was performed comparing the patients presenting with early rebleeding with those without this complication. RESULTS: The incidence of early rebleeding after EVL was 7.60%, and the morbidity of rebleeding was 26.9%. Stepwise multivariate logistic regression analysis showed that four variables were independent risk factors for early rebleeding: moderate to excessive ascites [odds ratio (OR) 62.83, 95% CI: 9.39-420.56, P < 0.001], the number of bands placed (OR 17.36, 95% CI: 4.00-75.34, P < 0.001), the extent of varices (OR 15.41, 95% CI: 2.84-83.52, P = 0.002) and prothrombin time (PT) > 18 s (OR 11.35, 95% CI: 1.93-66.70, P = 0.007). CONCLUSION: The early rebleeding rate after EVL is mainly affected by the volume of ascites, number of rubber bands used to ligate, severity of varices and prolonged PT. Effective measures for prevention and treatment should be adopted before and after EVL.


Assuntos
Endoscopia/métodos , Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/etiologia , Ligadura/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fatores de Risco , Prevenção Secundária , Resultado do Tratamento , Adulto Jovem
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