[Show abstract][Hide abstract] ABSTRACT: Purpose:
Pigment epithelium-derived factor (PEDF) is a recently discovered antiangiogenesis protein. PEDF possesses powerful anti-inflammatory, antioxidative, antiangiogenic, and antifibrosis properties. It has been reported that PEDF can regulate vascular endothelial growth factor (VEGF) expression. This study aimed to evaluate whether recombinant PEDF protein could attenuate allergic airway inflammation and airway remodeling via the negative regulation of VEGF using a murine model of chronic ovalbumin (OVA)-induced asthma and BEAS-2B human bronchial epithelial cells.
In an in vivo experiment, mice sensitized with OVA were chronically airway challenged with aerosolized 1% OVA solution for 8 weeks. Treated mice were given injections of recombinant PEDF protein (50 or 100 μg/kg body weight) via the tail vein. In an in vitro experiment, we investigated the effects of recombinant PEDF protein on VEGF release levels in BEAS-2B cells stimulated with IL-1β.
Recombinant PEDF protein significantly inhibited eosinophilic airway inflammation, airway hyperresponsiveness, and airway remodeling, including goblet cell hyperplasia, subepithelial collagen deposition, and airway smooth muscle hypertrophy. In addition, recombinant PEDF protein suppressed the enhanced expression of VEGF protein in lung tissue and bronchoalveolar lavage fluid (BALF) in OVA-challenged chronically allergic mice. In the in vitro experiment, VEGF expression was increased after IL-1β stimulation. Pretreatment with 50 and 100 ng/mL of recombinant PEDF protein significantly attenuated the increase in VEGF release levels in a concentration-dependent manner in BEAS-2B cells stimulated by IL-1β.
These results suggest that recombinant PEDF protein may abolish the development of characteristic features of chronic allergic asthma via VEGF suppression, providing a potential treatment option for chronic airway inflammation diseases such as asthma.
Preview · Article · Jan 2016 · Allergy, asthma & immunology research
[Show abstract][Hide abstract] ABSTRACT: To explore the effects of chronic intermittent hypoxia (CIH) on oxidative stress and inflammatory response and the interventional roles of adiponectin (Ad).
A total of 45 male Wistar rats were randomly divided into three groups of control group, CIH and CIH+Ad (n = 15 each). The control group breathed room air while the CIH and CIH+Ad groups received CIH 8 h/d for 5 successive weeks. The CIH+Ad group Ad had an injection of 10 µg once a week through tail vein. At the end of experiment (Day 35), comparison was performed among three groups about Ad, tumor necrosis factor α (TNF-α), C-reactive protein (CRP) and interleukin (IL) 6 from serum as well as malondialdehyde, superoxide dismutase (SOD), myeloperoxidase (MPO), reactive oxygen spieces (ROS) and nuclear factor (NF) κB from genioglossus.
Serum Ad level in CIH group was lower than those in control and CIH+Ad groups ((4 208 ± 2 239) vs (7 051 ± 2 432) and (6 405 ± 2 384) ng/ml, all P < 0.05) with no statistic difference between control and CIH+Ad groups. Both serum levels of TNF-α and CRP were higher in CIH group than those in control and CIH+Ad groups ((70.87 ± 35.16) vs (26.54 ± 20.32) and (29.50 ± 22.54) pg/ml, as well as (31.84 ± 11.48) vs (22.68 ± 9.63), (25.32 ± 8.34) mg/L, all P < 0.05)with no significant difference between control and CIH+Ad groups. Serum IL-6 levels were all higher in CIH group and CIH+Ad group than that in control group ((30.54 ± 12.25) and (23.04 ± 13.) vs (14.10 ± 8.83) pg/ml, all P < 0.05) with no significant difference between CIH and CIH+Ad groups. Genioglossal malondialdehyde level was significantly elevated in CIH group than those in control and CIH+Ad groups ((8.05 ± 4.53) vs (5.18 ± 3.03) and ((5.74 ± 3.06) nmol/mg, all P < 0.01) with no significant difference between control and CIH+Ad groups. Genioglossal SOD activity was lower in CIH+Ad group than that in CIH group but higher than that in control group ((42.42 ± 23.17) vs (61.77 ± 36.38) and (18.62 ± 11.67) U/mg, all P < 0.05). Genioglossal MPO levels were significantly higher in both CIH and CIH+Ad groups than that in control group ((0.40 ± 0.29) and (0.31 ± 0.17) vs (0.17 ± 0.08) µU/mg, all P < 0.01), with no significance between CIH and CIH+Ad groups. The relative level of total reactive oxygen species (ROS) in genioglossus of CIH+Ad group was significantly lower than that in CIH group but higher than that in control group (1.94 ± 1.01 vs 3.31 ± 1.56 and 1.08 ± 0.38 all P < 0.05). The transcription of NF-κB was significantly higher in CIH group than that in control and CIH+Ad groups (2.24 ± 0.34 vs 0.78 ± 0.21, P < 0.05), but there was no statistical difference with CIH+Ad group (1.04 ± 0.27).
CIH may induce oxidative stress and inflammation possibly through NF κB pathway while a supplement of Ad attenuates the above CIH-induced responses.
No preview · Article · Apr 2015 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: To observe the effect of chronic intermittent hypoxia (CIH) on rat cardiac function and blood pressure, and the protective role of adiponectin (Ad).
A total of 24 male Wistar rats were randomly and equally divided into 3 groups: normal control group (NC group), chronic intermittent hypoxygen group (CIH group) and CIH+Ad group. Normal air breathing for NC group and CHI for CIH and CIH+Ad groups were conducted for 28 days. In addition, rats in CIH+Ad group were given intravenous adiponectin at a dosage of 20 µg each time, once a week for successive 4 weeks. The results of echocardiography, blood pressure, plasma adiponectin, endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) were compared among the three groups after 28 days.
HE stain showed that the myocardial cells of CIH rats were damaged by CIH. Compared with NC group, rats in CIH group presented with a greater heart/body weight ratio (0.070 ± 0.008 vs. 0.057 ± 0.009, P < 0.05) and systolic blood pressure [(132 ± 4) vs. (123 ± 6) mmHg(1 mmHg = 0.133 kPa), P < 0.05] and a lower LVEF [(70.3 ± 4.1)% vs. (84.1 ± 2.5)%, P < 0.05]. Plasma ET-1 was increased while NO(-)2/NO(-)3 and eNOS decreased in CIH group, compared with NC group [(26.2 ± 6.9) ng/L vs. (7.7 ± 2.7) ng/L, (37 ± 9) µmol/L vs. (65 ± 10) µmol/L, (18 ± 5)µg/L vs. (27 ± 6) µg/L, respectively; P < 0.05]. The heart/body weight ratio, blood pressure and LVEF were improved in CIH+Ad group compared with those in CIH group [0.064 ± 0.009 vs. 0.070 ± 0.008, (127 ± 6) mmHg vs. (132 ± 4) mmHg, P > 0.05; (79 ± 7)% vs. (70 ± 4)%, P < 0.05; respectively]. Plasma ET-1 levels in CIH+Ad and CIH groups showed no significant difference, but were significantly lower in NC group. However, rats in CIH+Ad group had a higher NO(-)2/NO(-)3 level than that in CIH group. Bivariate Correlations showed that NO(-)2/NO(-)3 and eNOS were negatively correlated with systolic blood pressure while heart/body weight ratio, LVEDs, ET-1 and NO(-)2/NO(-)3 were negatively correlated with left ventricular ejection fraction.
Through xidative stress, ET-1 and NO imbalance and impaired vascular endothelial function, cardiac function could be damaged by CIH in rats, while supplement of extrinsic adiponectin could improve these damages.
No preview · Article · Dec 2014 · Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases
[Show abstract][Hide abstract] ABSTRACT: Objective:
To evaluate the efficacies of transcutaneous stimulation of genioglossus on remaining mild-to-moderate obstructive sleep apnea syndrome (OSAS) after uvulopalatopharyngoplasty (UPPP).
A total of 22 patients diagnosed with mild-to-moderate OSAS by polysomnography (PSG) after UPPP were recruited from Sleep Center of First Affiliated Hospital, Nanjing Medical University from February 2013 to October 2013 and underwent transcutaneous stimulation of genioglossus therapy at night. Prior to and during treatment overnight polysomnography examination was performed. Moreover, the sleepiness of patients was assessed according to the Epworth sleepiness scale (ESS) before and after treatment. Comparison was made to observe the effects of treatment on PSG parameters and daytime ESS.
Compared with pre-treatment, nocturnal apnea hypopnea index (AHI) (9.3 ± 4.2 vs 18.3 ± 6.8), microarousal index (MAI) (6.5 ± 3.8 vs 11.2 ± 4.8), radio of duration pulse oxygen saturation (SpO2) < 90% to total sleep time (T90) ((5.1 ± 4.0)% vs (9.5 ± 4.0)%) and score of daytime ESS (8.8 ± 3.3 vs 9.4 ± 3.1) all significantly decreased (all P < 0.01) while mean SpO2 ((95.5 ± 1.0)% vs (94.4 ± 1.1)%) and minimal SpO2 ((88.6 ± 2.9)% vs (84.9 ± 4.6)%) were both significantly elevated (both P < 0.001). None of them experienced obvious discomforts during treatment.
Submental transcutaneous electrical stimulation of genioglossus is an effective treatment for remaining mild-to-moderate OSAS after UPPP surgery.
No preview · Article · Jun 2014 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: To explore the effects of continuous positive airway pressure (CPAP) treatment on the serum levels of associated inflammatory factors in patients with overlap syndrome (OS).
Seventy-four patients with obstructive sleep apnea syndrome (OSAS) or chronic obstructive pulmonary disease (COPD) or overlap syndrome (OS) were recruited from Department of Respirology and Affiliated Sleep Center of our hospital from March 2012 to September 2013. They were divided into OSAS (n = 25), COPD (n = 26) and OS (n = 23) groups according to the results of polysomnography (PSG) and spirometry. By enzyme linked immunosorbent assay (ELISA), the serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and asymmetric dimethylarginine (ADMA) were measured and compared before and at Day 30 post-CPAP in OSAS and OS groups.
At pre-CPAP, there was no statistical difference in serum levels of CRP ((7.2 ± 6.6),(8.4 ± 6.8),(8.5 ± 7.9) mg/L) and TNF-α ((33 ± 13),(52 ± 34),(41 ± 33) ng/L) among OSAS, COPD and OS groups (all P > 0.05).However, serum ADMA level in OSAS group were significantly lower than those in COPD group ((0.50 ± 0.08) vs (0.71 ± 0.31) µmol/L, P = 0.002). Compared with before and at Day 30 post-CPAP, although no significant difference existed in serum levels of ADMA (all P > 0.05), at Day 30 post-CPAP there were significantly lower serum levels of CRP ((4.5 ± 4.2) and (5.5 ± 4.1) mg/L) and TNF-α levels ((31 ± 9) and (35 ± 24) ng/L) than those pre-CPAP in OSAS and OS groups respectively (all P < 0.05).No significant difference existed between OSAS and OS groups (all P > 0.05).
CPAP treatment significantly reduces the serum levels of CRP and TNF-α so as to improve inflammation responses in OS and OSAS patients.
No preview · Article · Feb 2014 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: Sleep disordered breathing (SDB) is common in patients with chronic heart failure secondary to non-valvular heart disease; however, the prevalence and characteristics of SDB in patients with rheumatic valvular heart disease (RVHD) are unclear. This study was designed to determine the prevalence, characteristics, and risk factors for SDB in RVHD patients.
A cross-sectional study was conducted in 260 RVHD patients. The following data were recorded: types of heart valve lesions, electrocardiographic, echocardiographic, arterial blood gas analysis findings, baseline medication, 6-minute walk test (6MWT) distance, and sleep parameters.
Compared to patients with single leftsided valve lesions, patients with left- and rightsided valve lesions had a higher prevalence of SDB (46.2% vs. 31.2%, p = 0.013); the increased prevalence of SDB only involved central sleep apnea (CSA) (31.1% vs. 14.1%, p = 0.001). Patients with obstructive sleep apnea (OSA) or CSA were older and had a shorter 6MWT distance, lower left ventricle ejection fraction and PaO2, a longer lung-to-finger circulation time, and a higher prevalence of atrial fibrillation (AF) and hypertension (all p < 0.05) as compared with patients without SDB. Multinomial logistic regression analysis showed that PaO2 ≤ 85 mm Hg was the only risk factor for OSA. Male gender, AF, 6MWT distance ≤ 300 m, PaO2 ≤ 85 mmHg, and PaCO2 ≤ 40 mm Hg were risk factors for CSA.
Patients with RVHD had a high prevalence of SDB (predominantly CSA). RVHD patients with SDB, particularly those who had CSA, manifested more severe symptoms and greater impairment of cardiac function. Assessments of clinical manifestations of cardiac dysfunction may be important for predicting the risk factors for SDB.
Ding N; Ni BQ; Zhang XL; Huang HP; Su M; Zhang SL; Wang H. Prevalence and risk factors of sleep disordered breathing in patients with rheumatic valvular heart disease. J Clin Sleep Med 2013;9(8):781-787.
Full-text · Article · Aug 2013 · Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine
[Show abstract][Hide abstract] ABSTRACT: Chrysin, a flavonoid obtained from various natural sources, has been reported to possess anti-inflammatory, antitumor, antioxidant and anti-allergic activities. However, its anti-inflammatory and immunoregulatory activities in asthma animal models are poorly understood. In the present study, we examined the effects of chrysin on airway inflammation and the possible mechanisms through which it acts in a murine model of allergic asthma. BALB/c mice sensitized and challenged to ovalbumin (OVA) were administered intragastrically with chrysin at a dose of 50 mg/kg daily. Chrysin significantly suppressed OVA-induced airway hyperresponsiveness (AHR) to acetylcholine chloride (Ach). Chrysin administration significantly inhibited the total inflammatory cell and eosinophil counts in bronchoalveolar lavage fluid (BALF) and total immunoglobulin E (IgE) levels in serum. Histological examination of lung tissue demonstrated that chrysin significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. In addition, chrysin triggered a switch of the immune response to allergens towards a T-helper type 1 (Th1) profile by modulating the transcription factors T-bet and GATA-3 in allergic mice. These data suggest that chrysin exhibits anti-inflammatory and immunoregulatory properties and provides new insights into the immunopharmacological role of chrysin in terms of its effects in a murine model of asthma.
Preview · Article · Apr 2012 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: Nasal continuous positive airway pressure (nCPAP) usually reduces sleepiness in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, even with regular use of nCPAP, some OSAHS patients experience residual sleepiness (RS). The aim of this study was to evaluate the efficacy of adaptive servoventilation (ASV) on RS in OSAHS patients.
The Epworth Sleepiness Scale (ESS) score was used for assessment of RS. Following correct application of 1-month auto-CPAP (APAP) treatment and exclusion for other sleepiness-associated disorders, 42 RS patients with severe OSAS were recruited. All of them received 1-week ASV treatment with auto-CS2 ventilator. Comparisons between APAP and ASV treatments were made for the following data: polysomnographic parameters including apnea hypopnea index (AHI), central sleep apnea index (CSAI), micro-arousal index (MAI), minimal pulse oxygen saturation, etc.; daytime ESS score.
Compared with the parameters on day 30 of APAP treatment, there was a further significant decrease in AHI, CSAI, MAI, and daytime ESS score (P < 0.01) on day 7 of ASV treatment. ESS score before ASV treatment (10.89 ± 0.40) reduced to normal range (3.98 ± 1.26) on day 7 of ASV treatment (P < 0.01).
ASV treatment could significantly improved RS in OSAS patients; the mechanism of such an efficacy might be associated with further declined levels of AHI, CSAI, and arousal index.
Full-text · Article · Dec 2011 · Sleep And Breathing
[Show abstract][Hide abstract] ABSTRACT: ObjectiveTo investigate the relationship between adiponectin genotype polymorphisms and obstructive sleep apnea hypopnea syndrome (OSAHS).MethodsUsing the TaqMan polymerase chain reaction(PCR) method, the single nucleotide polymorphisms(SNP) at positions 45 and 276 in the adiponectin gene were determined in Chinese of the Han nationality in the Nanjing district. The OSAHS group consisted of 78 patients, and the control group contained 40 subjects. The association of adiponectin genotype polymorphisms at positions 45 and 276 with obstructive sleep apnea hypopnea syndrome was analyzed.ResultsNo evidence of a direct association was found between OSAHS and adiponectin genotype SNP at positions 45 and 276(P > 0.05). However, compared with those OSAHS patients having G/T+T/T genotype at position 276, the OSAHS patients with the G/G genotype showed a greater neck circumference(NC), a prolonged duration of the longest apnea event, and elevated levels of blood cholesterol and low-density lipoprotein cholesterol(P < 0.05).ConclusionNo direct association was detected between OSAHS and adiponectin genotype distribution at positions 45 and 276 in Chinese of Han nationality in the Nanjing district. However, OSAHS patients with the adiponectin G/G genotype at position 276 had a larger NC and the longest apnea event compared to those having the adiponectin SNP276 G/T +T/T genotype. This may have an indirect influence on the development of OSAHS,
No preview · Article · Jul 2009 · Journal of Nanjing Medical University
[Show abstract][Hide abstract] ABSTRACT: To investigate the efficacy of adaptive pressure support servo-ventilation (APSSV) on Cheyne-Stokes respiration (CSR) in congestive heart failure (CHF).
14 patients with CHF and CSR were recruited. During sleep, oxygen therapy and APSSV were separately performed. Comparison before and after each treatment was made for the following items: a) parameters of sleep respiration, sleep structure and quality; b) cardiac function index such as left ventricle ejection fraction (LVEF) and 6 minutes' walking distance; c) plasma endothelin-1 (ET-1) levels.
Compared with the baseline level before treatment, the apnea hypopnea index significantly decreased during oxygen therapy (P < 0.05) and further declined during APSSV (P < 0.01); on the contrary, the lowest pulse oxygen saturation increased during oxygen therapy (P < 0.05) and further elevated during APSSV (P < 0.01). Compared with arousal index before treatment, it was significantly lower during oxygen therapy (P < 0.05) and the lowest during APSSV (P < 0.01). Compared with both during oxygen therapy and before treatment, during APSSV the percentage ofI + II stage sleep time/total sleep time was significantly lower while the percentage of III + IV stage sleep time/total sleep time was significantly higher. The above percentages during oxygen therapy and before treatment showed no significant difference (P < 0.05). LVEF was significantly higher during APSSV than during oxygen therapy and before treatment (P < 0.05). Six minutes' walking distance was the shortest before treatment and the longest during APSSV. There was a significant difference among that before treatment, during oxygen therapy and APSSV (all P < 0.01). The plasma ET-1 level showed significantly lower during APSSV than that before and during oxygen treatment (P < 0.05), but no significant difference between the levels before and during oxygen treatment (P > 0.05).
APSSV, more effective than oxygen therapy, is of great clinical significance in improvement of CHF and its prognosis by a better sleep and breathing.
No preview · Article · Jun 2006 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: Congestive heart failure (CHF) is associated with Cheyne-Stokes respiration (CSR), which may hasten CHF. Adaptive servoventilation (ASV) is a novel method of ventilatory support designed for removal of CSF in CHF patients. This study compares the efficacy of ASV in patients with CHF and CSR with the efficacy of oxygen therapy.
Fourteen patients with CHF and CSR were recruited. During sleep, nasal oxygen therapy and ASV treatment were each performed for two weeks. Comparison before and after each treatment was made for the following items: a) parameters of sleep respiration, sleep structure and quality; b) left ventricle ejection fraction (LVEF) and 6-minute walk distance.
Compared with the baseline levels of apnoea hypopnoea index of 34.5 +/- 6.1 before treatment, the apnoea hypopnoea index significantly decreased following oxygen therapy to 27.8 +/- 8.2, P < 0.05 and further reduced following ASV treatment to 6.5 +/- 0.8, P < 0.01. The minimal pulse oxygen saturation markedly increased following oxygen therapy from a baseline of (84.3 +/- 2.6)% to (88.6 +/- 3.7)%, P < 0.05 and further increased following ASV treatment (92.1 +/- 4.9)%, P < 0.01. Stages I + II sleep as percentage of total sleep time decreased from (81.9 +/- 7.1)% to (78.4 +/- 6.7)% following oxygen therapy and further to (72.4 +/- 5.0)% following ASV treatment. Stages III + IV sleep as percentage of total sleep time decreased from (8.4 +/- 5.5)% to (6.0 +/- 3.0)% following oxygen therapy and but increased to (11.9 +/- 5.4)% following ASV treatment. The arousal index of 30.4 +/- 8.1 before treatment significantly decreased following oxygen therapy to 25.6 +/- 5.7, P < 0.05 and further declined following ASV treatment to 18.2 +/- 6.1, P < 0.01. No significant difference was shown in above percentages between day 14 of oxygen therapy and before treatment (P > 0.05). LVEF was significantly higher on day 14 of ASV treatment (37.2 +/- 4.1)% than on day 14 of oxygen therapy (33.2 +/- 5.1)% and before treatment (30.2 +/- 4.6)% (all P < 0.05). Six-minute walk distance was the shortest before treatment (226 +/- 28) m, longer on day 14 of oxygen therapy (289 +/- 26) m, and the longest on day 14 of ASV treatment (341 +/- 27) m (all P < 0.01).
ASV treatment is of better efficacy and greater clinical significance in improvement of CHF by eliminating CSR than oxygen therapy.
Full-text · Article · Apr 2006 · Chinese medical journal