RESUMO
Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPDFE) phenotype, identify potential metabolic biomarkers associated with COPDFE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPDFE and patients with nonfrequent exacerbation of COPD (COPDNE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPDFE and COPDNE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for Dfructose 1,6bisphosphate (AUC=0.871), arginine (AUC=0.836), L2hydroxyglutarate (L2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitineC18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitineC18:2 and L2HG were significantly different between patients with COPDFE and those with COPDNE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPDFE phenotype.
Assuntos
Biomarcadores , Metabolômica , Fenótipo , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Masculino , Feminino , Metabolômica/métodos , Idoso , Biomarcadores/sangue , Pessoa de Meia-Idade , Curva ROC , Metaboloma , Progressão da Doença , Carnitina/sangue , Carnitina/análogos & derivadosRESUMO
Lung cancer is one of the most fatal cancers due to its high metastatic rate. Traditional Chinese medicine has been used in cancer patients for decades to improve quality of life and prolong survival time. The present study used a novel Qiyusanlong (QYSL) decoction composed of 10 kinds of Chinese medicine including astragalus membranaceus (Huangqi), polygonatumod oratum (yuzu), scolopendra (tianlong), pberetima (dilong), solanum nigrum (longkui), herbahedyotis (baihushecao), semen coicis (yiyiren), euphorbia helioscopia (zeqi), curcuma longa (eshu) and tendril-leaved fritillary bulb (chuanbei). The effects and function of the QYSL decoction remain to be elucidated. The present study established a mouse xenograft model using Lewis lung carcinoma cell injection and administered different doses of QYSL decoction to the mice. It was demonstrated that the chemotherapy drug Cisplatin (DDP) and QYSL decoction repressed lung tumor growth, and the inhibitory effect of DDP was more significant. Furthermore, QYSL decoction and DDP modulated the expression of regulatory proteins in the Wnt/ßcatenin pathway, including Wnt1, Wnt2, Wnt5a and glycogen synthase kinase 3ß, detected by western blotting, and affected the signals of cluster of differentiation 44 variation 6 and Survivin in tumor tissues, examined via immunohistochemistry. The combination of QYSL decoction and DDP enhanced the inhibitory effect. These data demonstrated that the QYSL decoction repressed lung tumor development via the Wnt/ßcatenin pathway. The therapeutic effect of QYSL decoction alone was milder compared with DDP, however the combination of QYSL decoction and chemotherapy exhibited an increased the rapeutic effect compared with the treatments administered alone. These findings revealed the function of QYSL decoction as a lung cancer treatment and provided insight for a novel lung cancer therapy.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To study T lymphocyte related genes with differential expression in patients with chronic obstructive pulmonary disease (COPD) of Fei-qi deficiency (FQD) syndrome type by gene chips. METHODS: Lymphocytes in peripheral blood were isolated by Ficoll technique from blood samples collected from COPD patients of FQD syndrome type, Fei-yin deficiency (FYD) syndrome type, and also from healthy subjects for control. They were sorted and purified by flow cytometry, and the different expressed genes were screened from them by gene chip technique. RESULTS: There were 15 genes with high differential expression between patients of FQD type and those of FYD syndrome type, and between patients of FQD type and healthy subjects. CONCLUSION: Gene chip technique could be used for studying the gene expression profiles of TCM syndrome, and the T-lymphocyte related genes with differential expression in COPD patients with FQD were screened preliminarily.