RESUMEN
Evidence suggests that pro-inflammatory cytokines and cortisol play a crucial role in the etiology of chronic obstructive pulmonary disease (COPD) and depression. Depression occurs commonly among COPD patients and an earlier diagnosis would be beneficial. This study investigated the associations between depression, sputum cytokines and salivary cortisol in COPD patients. The diurnal rhythms of sputum IL-1, IL-6, TNF-α and salivary cortisol were measured in COPD patients with depression compared to those only with depression, or COPD and healthy controls. The area under the diurnal variation curves (AUC) over the 24h time course and relative diurnal variation (VAR) were calculated while correlation and regression analysis were performed. Patients with co-morbid depression and COPD showed an increasing sputum IL-1, sputum TNF-α AUC and a decreasing salivary cortisol VAR (P<0.001). The combination of sputum TNF-α AUC, sputum IL-1 AUC, sputum IL-6 AUC and salivary cortisol VAR performed best as a potential biomarker in the diagnosis of depression in COPD patients, with a sensitivity of 94.74% and a specificity of 96.67%. Positive correlations were found between sputum IL-1 AUC and sputum TNF-α AUC versus depressive symptoms, respectively a negative correlation was found between salivary cortisol VAR and depression. They were independently associated with depression in logistic regression models. Depression in COPD is associated with higher 24-h overall levels of sputum IL-1, TNF-α and flattened diurnal salivary cortisol. These non-invasive sputum and salivary biomarkers may serve as a simple clinical tool for the early diagnosis of depression in COPD patients.
Asunto(s)
Citocinas/metabolismo , Depresión/metabolismo , Depresión/psicología , Hidrocortisona/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/psicología , Adulto , Anciano , Depresión/etiología , Femenino , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Esputo/química , Esputo/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The objective of the present study was to investigate the therapeutic efficacy of flavonoid components in Scutellaria baicalensis on proliferation, metastasis and lung cancer-associated inflammation during nicotine induction in the A549 and H1299 lung cancer cell lines. After experimental period, augmentation of proliferation was observed, accompanied by marked decrease in apoptotic cells in nicotine-induced lung cancer cells; additionally, nicotine-exposed cells exhibited increased invasive and migratory abilities based on invasion and wound-healing assay. Flavones in Scutellaria, baicalin, baicalein and wogonin significantly counteracted the above deleterious changes. Moreover, assessment of tumor apoptotic and metastatic factors on mRNA levels by quantitative PCR and protein levels by western blotting revealed that these phytochemical treatments effectively negated nicotine-induced upregulated expression of bcl-2, bcl-2/bax ratio, caspase-3, matrix metalloproteinase (MMP)-2 and MMP-9 as well as downregulated expression of bax. Further analysis of inflammatory markers such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 in cell culture supernatant and mRNA and protein expression of nuclear transcription factor-kappaB (NF-κB) and I kappa B-alpha (IκB-α) was carried out to substantiate the anti-inflammatory effect of flavones in Scutellaria in nicotine-exposed lung cancer cells. The therapeutic effects observed in the present study are attributed to the potent potential against proliferation, metastasis and inflammatory microenvironment by flavonoid components in Scutellaria in nicotine-induced lung cancer cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Flavonoides/farmacología , Inflamación/patología , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia/patología , Nicotina/efectos adversos , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Flavanonas/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Técnicas In Vitro , Inflamación/inducido químicamente , Inflamación/complicaciones , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/complicaciones , Scutellaria baicalensisRESUMEN
Depression is common among lung cancer patients. Increasing evidence has suggested that hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines may play a key role in the pathophysiology of depression as well as cancer. This pilot study investigated the efficacy of sputum interleukin (IL)-6, tumor necrosis factor (TNF)-α and salivary cortisol as new markers to support the diagnosis of depression in lung cancer patients. The diurnal rhythms of sputum IL-6, sputum TNF-α and salivary cortisol were measured in lung cancer patients with and without depression as well as depressed controls and healthy controls. The area under the diurnal variation curves (AUC) over the 24h time course and relative diurnal variation (VAR) were calculated. Receiver operating characteristic (ROC) analysis was performed. Patients with co-morbid depression and lung cancer showed highest level of sputum IL-6 AUC, sputum TNF-α AUC and lowest level of cortisol VAR (P<0.001). As a biomarker for depression, salivary cortisol VAR demonstrated an optimal cutoff point at 77.8% (AUC=0.94; 95% CI, 0.85-0.98), which is associated with a sensitivity of 82.1% and a specificity of 96.0%. Sputum IL-6 AUC demonstrated a sensitivity of 74.4% and a specificity of 92.0% (AUC=0.81; 95% CI, 0.69-0.90). These findings suggested that higher 24h overall levels of sputum IL-6, TNF-α and flattened diurnal salivary cortisol slopes were associated with depression in lung cancer patients. Sputum IL-6 AUC and salivary cortisol VAR performed best as biomarkers in the diagnosis of depression in lung cancer patients.
Asunto(s)
Depresión , Hidrocortisona/metabolismo , Interleucina-6/metabolismo , Neoplasias Pulmonares/complicaciones , Saliva/metabolismo , Esputo/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Análisis de Varianza , Depresión/etiología , Depresión/metabolismo , Depresión/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Curva ROCRESUMEN
THE STUDY WAS THE FIRST TIME TO ESTABLISH AND COMPARE TWO RAT MODELS OF TWO COMMON SYNDROMES: Kidney Yang Deficiency syndrome (KYDS) in traditional Chinese medicine (TCM) and abnormal savda syndrome (ASS) in traditional Uighur medicine (TUM). Then, we also established and evaluated rat models of combining disease and syndrome models of asthma with KYDS or ASS. Results showed that usage of the high dose of corticosterone (CORT) injection or external factors could successfully establish the KYDS or ASS rat models, and the two models had similar changes in biological characterization, abnormal behaviors, dysfunction of hypothalamic-pituitary-target organ axes (HPTOA), and sympathetic/parasympathetic (S/P) nerve system but varied in different degrees. The rat models of combining disease and syndrome of asthma with KYDS or ASS had either pathological characteristics of asthma such as airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, which were more serious than allergy exposure alone, or the syndrome performance of Kidney Yang Deficiency in TCM and abnormal savda in TUM. These findings provide a biological rationale for further investigation of combining disease and syndrome model of asthma as an effective animal model for exploring asthma based on the theory of traditional medicine.