RESUMO
Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.
Assuntos
Asma , Autofagia , Inflamação , Saponinas , Linfócitos T , Triterpenos , Animais , Saponinas/farmacologia , Asma/tratamento farmacológico , Triterpenos/farmacologia , Triterpenos/química , Camundongos , Autofagia/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Inflamação/tratamento farmacológico , Camundongos Nus , Estrutura Molecular , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
Background: Cancer and psychiatric symptoms are associated. Fear of cancer recurrence (FCR) is the most common psychological problem for cancer survivors. Pharmacological interventions can help, but also have major drawbacks. Music therapy and music interventions have been shown to be a safe and practical complementary treatment. Objective: This randomized, controlled trial aimed to investigate the effects of music therapy and music intervention in attenuating non-small cell lung cancer (NSCLC) patients' anxiety related to FCR. Methods: NSCLC patients with FCR were randomly allocated to a music therapy and intervention group (G1) and Control group (G2). Patients' anxiety was measured using the State-Trait Anxiety Inventory scores and heart rates. Primary outcome measure were PET scans. Secondary measures were salivary cortisol, salivary α-amylase levels and heart rate. Findings: Patients in G1 showed higher glucose metabolism of 18F-FDG in the superior frontal gyrus, anterior cingulate, superior temporal gyrus, and parahippocampal gyrus, compared to those in G2 (all P < .001). Heart rates and salivary α-amylase area under the curve (AUC) and relative variation (VAR) in G1 were significantly lower than those in G2 (all P < .05). State-Trait Anxiety Inventory scores and cortisol AUC in G1 were significantly lower than those in G2 (all P < .05). Conclusions: Music therapy and interventions can reduce anxiety and endocrinological responses and change glucose metabolism of 18F-FDG in fear-related brain regions.Trial registration: Registered retrospectively, ISRCTN Registry, www.isrctn.com, ISRCTN23276302Clinical Implications: Cancer treatment centers and physical examination centers should consider providing music therapy and intervention to the appropriate patients as a routine component of a comprehensive clinical care during medical examinations.
Assuntos
Ansiedade , Carcinoma Pulmonar de Células não Pequenas , Medo , Neoplasias Pulmonares , Musicoterapia , Tomografia por Emissão de Pósitrons , Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/psicologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Pessoa de Meia-Idade , Musicoterapia/métodos , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/terapia , Medo/psicologia , Medo/fisiologia , Tomografia por Emissão de Pósitrons/métodos , Ansiedade/terapia , Ansiedade/metabolismo , Recidiva Local de Neoplasia/psicologia , Recidiva Local de Neoplasia/metabolismo , Idoso , Hidrocortisona/metabolismo , Hidrocortisona/análise , Frequência Cardíaca/fisiologia , Fluordesoxiglucose F18RESUMO
Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.