Caffeic acid phenethyl ester alleviates asthma by regulating the airway microenvironment via the ROS-responsive MAPK/Akt pathway.

In the pathophysiology of asthma, structural cell dysfunction and concomitant microenvironment changes in airways are crucial to pathological progression, which involves oxidative stress. Caffeic acid phenethyl ester (CAPE) is an active anti-oxidative component obtained from propolis, and has been shown to have beneficial effects on several respiratory disorders, such as chronic obstructive pulmonary disease and lung cancer. However, the impact of CAPE on asthma is not well understood. Therefore, this study investigated the advantages of using CAPE to treat asthma and demonstrated the roles of CAPE in the regulation of airway microenvironments. In ovalbumin (OVA)-sensitized mice, CAPE treatments notably reduced airway hyperresponsiveness, attenuated extensive inflammatory cell infiltration and inhibited goblet cell hyperplasia and collagen deposition and fibrosis. In addition, CAPE improved the airway microenvironment in a dose-dependent manner by inhibiting OVA-induced increases in immunoglobulin E, tumor necrosis factor alpha (TNF-α), transforming growth factor-ß1 (TGF-ß1), interleukin (IL)-4 and IL-13 and suppressing matrix metalloproteinase-9 and alpha-smooth muscle actin expression as well as malondialdehyde production. To determine the underlying mechanisms responsible for these effects, we used TNF-α-stimulated BECs and TGF-ß1-challenged human ASMCs to explore the impacts of CAPE on pro-inflammatory proteins and ASMC proliferation. The results indicated that CAPE significantly limited the secretion of eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1 and dramatically inhibited the proliferation of ASMCs. These effects were shown to be associated with decreased reactive oxidant species (ROS) levels. The phosphorylation of Akt and Mitogen-Activated Protein Kinase (MAPK) caused by increased ROS was significantly decreased by CAPE, which implied a contribution of ROS-MAPK/Akt signaling to the attenuation of asthma. Our findings indicated for the first time that CAPE alleviates airway inflammation and remodeling in chronic asthma by balancing the airway microenvironment, which highlights a novel profile of CAPE as a potent agent for asthma management.

Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling.

Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA-) sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs) were challenged by tumor necrosis factor alpha (TNF-α). The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL-) 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2',7'-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were abolished by morin, implying that ROS/MAPK signaling contributes to the relief of airway inflammation. Our findings indicate for the first time that morin alleviates airway inflammation in chronic asthma, which probably occurs via the oxidative stress-responsive MAPK pathway, highlighting a novel profile of morin as a potent agent for asthma management.

Galangin attenuates airway remodelling by inhibiting TGF-ß1-mediated ROS generation and MAPK/Akt phosphorylation in asthma.

Galangin, a natural flavonol, has attracted much attention for its potential anti-inflammatory properties. However, its role in the regulation of airway remodelling in asthma has not been explored. The present study aimed to elucidate the effects of galangin on chronic inflammation and airway remodelling and to investigate the underlying mechanisms both in vivo and in vitro. Ovalbumin (OVA)-sensitised mice were administered with galangin 30 min before challenge. Our results showed that severe inflammatory responses and airway remodelling occurred in OVA-induced mice. Treatment with galangin markedly attenuated the leakage of inflammatory cells into bronchoalveolar lavage fluid (BALF) and decreased the level of OVA-specific IgE in serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression. Lowered level of TGF-ß1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo. Consistently, the TGF-ß1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway. Taken together, the present findings highlight a novel role for galangin as a promising anti-remodelling agent in asthma, which likely involves the TGF-ß1-ROS-MAPK pathway.

Elimination of central sleep apnea by cardiac valve replacement: a continuous follow-up study in patients with rheumatic valvular heart disease.

BACKGROUND: Recent studies have suggested that cardiac surgery may affect sleep-disordered breathing (SDB) in chronic heart failure patients. However, the dynamic changes in sleep apnea and heart function after cardiac surgery and the mechanisms responsible for these changes remain unknown. METHODS: Patients with rheumatic valvular heart disease (RVHD) and SDB were enrolled and followed up at three, six and 12 months after cardiac valve replacement (CVR). Baseline and follow-up clinical data consisting of NYHA classification, 6min walk distance (6-MWD), medications, echocardiography, electrocardiography, chest X-ray, arterial blood gas, lung-to-finger circulation time (LFCT), and sleep data were collected and evaluated. RESULTS: Twenty-four central sleep apnea (CSA) patients and 15 obstructive sleep apnea (OSA) patients completed three follow-up assessments. Comparison of the baseline parameters between OSA patients and CSA patients showed that CSA patients had a worse baseline cardiac function assessed by higher NYHA class, shorter 6-MWD, larger left atrial diameter, longer LFCT, and enhanced chemosensitivity (higher pH and lower arterial carbon dioxide tension (PaCO2)). A continuous significant elevation in 6-MWD and left ventricular ejection fraction and decrease in NYHA class, plasma BNP, and left atrial diameter were found in both CSA and OSA patients. When comparing CSA and OSA patients, the CSA indices were remarkably reduced at month 3 post CVR and sustained throughout the trial, whereas there were no significant decreases in OSA index and hypopnea index. pH values and LFCT were markedly decreased and PaCO2 markedly increased in patients with CSA at the end of the third months following CVR. These changes were sustained until the end of the trial. CONCLUSIONS: CSA patients with RVHD had a worse baseline cardiac function, enhanced chemosensitivity and disordered hemodynamic as compared with OSA patients with RVHD. CSA were eliminated after CVR; however, there were no changes in OSA. The elimination of CSA, post CVR, is associated with the combined efficacies of improvement of cardiac function, normalized chemosensitivity, and stabilized hemodynamic.

Galangin Abrogates Ovalbumin-Induced Airway Inflammation via Negative Regulation of NF-κB.

Persistent activation of nuclear factor κB (NF-κB) has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA-) induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR) and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL-) 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1) levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.

Invasive examinations in patients with suspected lung cancer: more may be too many.

The recent article entitled "Principles of biopsy in suspected lung cancer: priority still based on invasion in the era of targeted therapy?" published in Journal of Thoracic Disease by Chen et al., concluded the principles of biopsy in suspected lung cancer should be prioritized in sequence based on weight in clinical management, acquisition of tissue, invasion, efficiency and cost. We reported a patient with a 30-year history of pulmonary silicosis, had been found no evidence of tumor after receiving a series of invasive examinations. We conclude that invasive examinations should be limited in patients with suspected lung cancer who had a defined history of underlying disease. Minimal invasion with careful acquisition of the appropriate quantity and quality of tissue should be adequate.

[Flexible bronchoscopic intervention for endobronchial hamartoma].

OBJECTIVE: To evaluate the effectiveness and safety of interventional treatment in the removal of endobronchial hamartoma by flexible bronchoscopy. METHODS: A retrospective analysis was conducted in 8 inpatients with histologically confirmed endobronchial hamartoma , diagnosed between May 2009 to January 2012 in the First Affiliated Hospital of Nanjing Medical University. The clinical, radiological and bronchoscopic features of hamartoma, and the clinical outcomes after bronchoscopic intervention were described. The endoscopic interventional treatments included resection by electrosurgical snare, electrocautery, argon plasma coagulation (APC) and cryotherapy. Thoracic computed tomography(CT)and bronchoscopy were used to evaluate the airway stenosis during follow-up. RESULTS: The 8 patients, 7 males and 1 female, aged (62 ± 8) years, underwent 13 times of interventional treatment for endobronchial hamartoma. Four patients were cured after receiving a single endoscopic treatment, while 3 patients had recurrence after initial interventional treatment but were cured after the second treatment. Three times of interventional treatment was carried out in 1 patient who had two relapses but later became stable with a 40% stenosis of the airway lumen. The rates of cure and effectiveness were 87.5% and 100%, respectively. Following interventional treatment, pneumothorax occurred in 1 patient who was cured after oxygen therapy. There were no serious complications such as massive haemorrhage, airway perforation, airway ignition and suffocation. CONCLUSION: Interventional treatments through flexible bronchoscopy appear to be safe and effective for removing endobronchial hamartoma.