Bosentan and ambrisentan in the treatment of idiopathic pulmonary fibrosis: a meta-analysis.

OBJECTIVE: The aim is to showcase the effectiveness and safety of bosentan or ambrisentan in individuals diagnosed with idiopathic pulmonary fibrosis (IPF) and offer fresh evidence for the management of this condition. MATERIALS AND METHODS: For this research, we conducted a meta-analysis of randomized controlled trials by searching various databases, including the Cochrane Library, Excerpta Medica Database, PubMed, and Web of Science. The retrieval was conducted until November 2021. We analyzed the variances in 6-minute walk distance (6MWD), death, diffusion capacity for carbon monoxide (DLCO), forced vital capacity (FVC), hospitalization, IPF worsening, mean pulmonary arterial pressure, serious adverse events (SAEs), Short Form-36 improved, and St. George's Respiratory Questionnaire between the treatment and control groups. RESULTS: A sum of six studies involving 1,928 participants were found to meet the inclusion criteria. The quality of evidence was high. The control group had significantly higher values for 6MWD, DLCO, and FVC compared to the ambrisentan treatment group. The rates of hospitalization and IPF worsening were considerably greater in comparison with the control group. The bosentan group exhibited significantly reduced rates of hospitalization and IPF worsening in comparison with the control group. Both drugs did not cause any raising in death or SAEs when in comparison with the control group. CONCLUSIONS: The findings of this research validate the effectiveness and safety of bosentan for treating IPF patients. This medication can enhance the quality of life for individuals with IPF without causing any significant increase in SAEs. However, it does not have a notable influence on the long-term prognosis. The findings of this research do not endorse the utilization of ambrisentan in individuals diagnosed with IPF.

Circular RNA hsa_circ_0006168 contributes to cell proliferation, migration and invasion in esophageal cancer by regulating miR-384/RBBP7 axis via activation of S6K/S6 pathway.

OBJECTIVE: Esophageal cancer (EC) ranks as the sixth leading cause of cancer-related mortality worldwide. Circular RNAs (circRNAs) are involved in the pathogenesis of different cancers. However, the regulatory mechanism of circ_0006168 in EC progression is still unclear. MATERIALS AND METHODS: The expression of circ_0006168, microRNA (miR)-384, and retinoblastoma binding protein 7 (RBBP7) in tumors and cells was measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The stability of circ_0006168 was analyzed after RNase R treatment. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was conducted to evaluate cell viability. Transwell assay was applied to determine cell migration and invasion. Glucose consumption and lactate production were detected using glucose detection and lactic acid detection kits. The interaction between miR-384 and circ_0006168 or RBBP7 was certified by Dual-Luciferase reporter system. Protein expression of pyruvate kinase (PK), RBBP7, S6 ribosomal protein kinase (S6K), phosphorylated S6K (p-S6K), S6, phosphorylated S6 (p-S6) was analyzed by Western blot. RESULTS: Circ_0006168 and RBBP7 were over-expressed while miR-384 was low-expressed in EC tumors and cells. The repression of circ_0006168 attenuated cell proliferation, migration, invasion, and glycolysis in EC. Of note, circ_0006168 functioned as a sponge while RBBP7 acted as a target of miR-384 in EC. Rescue experiment revealed that miR-384 inhibitor abrogated circ_0006168 silencing-induced repression on cell proliferation, migration, and invasion in EC. Meanwhile, upregulation of RBBP7 restored the inhibition of miR-384 on EC cell progression. Moreover, circ_0006168 was able to improve RBBP7 level by interacting with miR-384. Also, circ_0006168 could activate S6K/S6 pathway by regulating RBBP7 expression. CONCLUSIONS: Abundance of circ_0006168 contributes to cell proliferation, migration, invasion, and glycolysis in EC by competitively sponging miR-384 to facilitate RBBP7 expression, representing prospective targets for EC therapy.

[Role of reactive oxygen species in hypoxia-induced non-small cell lung cancer migration].

Objective: To explore reactive oxygen species (ROS) generation and its role on A549 cell migration under hypoxic condition. Methods: Human non-small cell lung cancer (NSCLC) cell line A549 was incubated in a hypoxic environment (1%O(2), hypoxia group) or in a normoxic environment (21%O(2), normoxia group). The generation of ROS was measured by flow cytometry. The cell motility of A549 cells was detected by Transwell assay. The protein levels of protein kinase B (AKT), p38 mitogen-activated protein kinase (p38) were determined by Western blot analysis. Results: After 16 h hypoxic treatment, the migration of A549 cells in hypoxia group was significantly more than that of normoxia group [(85±10) vs (56±7) per lower magnification, P<0.001]. Besides, the generation of ROS was in a time-depended manner in hypoxia group. The ROS level was increased with the prolonged hypoxia time. It was significantly higher at 24 h than that in normoxia group [(273±4)% vs (102±6)%, P<0.001]. The migrated cells in hypoxia group co-treated with 2 mmol/L NAC for 16 h were less than that with hypoxic treatment alone [(47±13) vs (105±14) per lower magnification, P=0.011]. Meanwhile, the phosphorylation of AKT and p38 increased after 12 h hypoxic treatment in hypoxia group, however, 2 mmol/L NAC co-treatment attenuated this effect. Furthermore, inhibition of phosphorylated AKT with 0.1 µmol/L allosteric AKT inhibitor (MK-2206) in hypoxia group for 16 h reversed the hypoxia-induced A549 cell migration. The migrated cells in hypoxia+ MK-2206 group were significantly less than that in hypoxia group [(155±21) vs (249±32) per lower magnification, P<0.001]. Conclusions: Hypoxia increases the generation of ROS in A549, resulting from oxidative stress under hypoxia. The increased ROS level promotes cell motility through the activation of AKT.

[Clinical application of AMPLATZER Vascular Plug â ¡ in transcatheter closure of congenital coronary artery fistula in children].

OBJECTIVE: To evaluate the feasibility of applying AMPLATZER Vascular Plug Ⅱ (AVP Ⅱ) in transcatheter closure of congenital coronary artery fistula in children. METHOD: Transcatheter closure procedure applying AVP Ⅱ was carried out in 7 patients (3 males and 4 females, age 1.2-12.0 years) with congenital coronary artery fistula between May 2014 and September 2015 in Pediatric Cardiology Department of Guangdong Cardiovascular Institute. Selective coronary artery angiography and aortic root angiography were performed after the release of the device to evaluate the immediate therapeutic effect. Echocardiography and electrocardiography were performed at 1 day, 1 month, 3 months, 6 months, 1 year post procedure and repeated once a year during the follow-up period. RESULT: Transcatheter deployment of the device was successfully accomplished in all patients. The narrowest diameter of the fistula was (8.6±2.8) mm (4.0-12.5 mm), and the size of the deployed device ranged from 10.0 to 16.0 mm. Immediate selective coronary artery angiography revealed no residual shunt in 5 patients and trivial residual shunt in 2 patients. During a mean follow-up period of 2.7 (1.0-16.0) months, echocardiography showed that 3 patients remained no residual shunt, while 2 patients had trivial residual shunt, 2 patients developed small residual shunt. Cardiac murmur disappeared post procedure in all patients. Electrocardiography showed no ST-T changes. No migration or detachment of the device was found. CONCLUSION: AVP Ⅱ is a safe and effective choice in transcatheter closure of congenital coronary artery fistula in children.

Soluble CD86 protein in serum samples of patients with asthma.

BACKGROUND: Previous studies have reported that soluble (s) CD86 is involved in the initiation of the immune response. A study was undertaken to investigate the concentrations of sCD86 in serum samples from patients with bronchial asthma and to determine the cell origin of sCD86. METHODS: Serum sCD86 concentrations were measured in 52 asthmatic subjects and 25 non-atopic normal volunteers using an enzyme linked immunosorbent assay, and the relationship of serum sCD86 concentrations to asthma severity and to total and differential white cell counts was analysed. Each type of white blood cell was purified and cultured in vitro to determine the cell origin of serum sCD86. RESULTS: Serum samples from patients with an acute asthma exacerbation had much higher levels of sCD86 (585.4 (20.5) IU/ml) than those from stable asthmatics (479.6 (15.7) IU/ml, p<0.001) and healthy individuals (435.1 (13.8) IU/ml, p<0.001), and there was no difference between the latter two groups (p = 0.079). In asthmatic subjects the serum sCD86 level was inversely correlated with airway responsiveness, forced expiratory volume in 1 second, and with arterial carbon dioxide tension. In addition, the serum sCD86 level was positively correlated with numbers of lymphocytes, eosinophils, monocytes, but not neutrophils. The in vitro experiments indicated that sCD86 was produced by monocytes. CONCLUSIONS: The serum sCD86 protein level was significantly increased in asthmatic subjects during an exacerbation and correlated with the severity of asthma. sCD86 is most probably derived from monocytes in the peripheral blood.

Effect of inhaled interleukin-5 on number and activity of eosinophils in circulation from asthmatics.

The aim of the present study was to examine the effects of interleukin-5 (IL-5) inhalation on changes in the activity and number of circulating eosinophils, as well as concentrations of serum total IgE, in allergic asthmatics. A randomized double-blind, placebo-controlled study design was employed in which each subject acted as his or her own control. Eight nonsmoking patients with allergic asthma were administered recombinant human IL-5 by nebulization. Total white blood cell counts and differentials, as well as concentrations of ECP and total IgE in serum, were determined before and at 2, 24, and 48 h after inhalation. Our results demonstrated that eosinophil numbers increased from baseline (3.6 +/- 1.1 x 10(5)/ml) to 6.3 +/- 1.2 x 10(5)/ml (P < 0.01) at 24 h and to 5.7 +/- 0.9 x 10(5)/ml (P < 0.01) at 48 h after IL-5 inhalation in asthmatics. Accompanying this significantly increased blood eosinophilia were significantly elevated serum ECP levels. Compared with baseline (6.3 +/- 1.1 ng/ml), ECP levels increased with time following IL-5 inhalation, reaching 17.6 +/- 2.8 ng/ml (P < 0.01) at 24 h and remaining elevated at 48 h (18.1 +/- 2.9 ng/ml, P < 0.01). IL-5 inhalation had no significant effect on levels of serum total IgE, however. These findings provide direct evidence that nebulized IL-5 not only induces a significant blood eosinophilia but also results in the activation of circulating eosinophils. Our data further support the importance of IL-5 in the pathogenesis of bronchial asthma in humans.

Effect of inhaled interleukin-5 on airway hyperreactivity and eosinophilia in asthmatics.

In order to investigate the role of interleukin-5 (IL-5) in airway hyperreactivity and eosinophilia, we observed the effect of inhaled recombinant human IL-5 on airway responsiveness to methacholine and cell populations in induced sputum in eight patients with allergic bronchial asthma using a placebo-controlled study design. Our results demonstrated that the inhalation of IL-5 did not alter lung function in allergic asthmatics. In the control experiments receiving either vehicle or 0.4 ng of endotoxin, methacholine PC20 values did not change nor did the numbers of eosinophils or eosinophil cationic protein (ECP) sputum values change from baseline. In contrast, after IL-5 inhalation, methacholine PC20 fell from baseline (0.90 +/- 166 mg/ml) to 0.32 +/- 1.63 mg/ml (p < 0.01) at 24 h, and to 0.55 +/- 1.49 mg/ml (p < 0.05) at 48 h. Accompanying this increased airway sensitivity was a significant eosinophilia and elevated concentrations of ECP in induced sputum. Our data provided direct evidence that IL-5 increases airway responsiveness and infiltration of activated eosinophils into the airway in patients with allergic bronchial asthma. It also could be concluded that the observed airway hyperreactivity and eosinophilia were not endotoxin related.

[A clinical study of the effect of wuzi yanzong solution in retarding aging process].

Eighty men ranging from 60 to 80 years old were selected, in whom no disease was found through a thorough check-up except for some senility manifestation diagnosed as deficiency of the kidney. They were randomly divided into two groups, wuzi yanzong solution (WYS) being administered in 50 cases and placebo in 30. After 5 weeks' treatment, symptoms such as hypomnsis, tinnitus, and aching of the back and legs, dribbling after urinary voiding, and nocturia were remarkably improved in the WYS group, but they remained as before in the placebo group. Before the treatment, plasma lipid peroxide (LPO), erythrocyte superoxide dismutase (SOD), blood glutathione peroxidase (GSH-Px), serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), plasma testosterone (T) and estradiol (E2) levels were determined. In comparison with the results obtained in 33 young men in their twenties, LPO, FSH, LH level and E2/T ratio in the aged were greatly elevated, and SOD, GSH-Px and T markedly lowered. After the treatment, there was remarkable reduction of LPO and E2/T, and increase of SOD and T in the WYS group, but no significant change in the placebo group. The above results not only indicate the beneficial effect of WYS in retarding the aging process, but also suggest the possible mechanism of reducing the peroxidation of fatty acids by enhancing the antioxidant enzymes to inhibit free radical activity.

[Plasma cortisol concentration and blood leukocyte content of glucocorticoid receptors in patients with deficiency-cold vs deficiency-heat syndromes].

Plasma cortisol concentration and blood leukocyte content of glucocorticoid receptors (GCR) were assayed in 20 patients with deficiency syndromes, 10 cold in property (deficiency-cold), the other 10 hot in property (deficiency-heat), and also in 10 healthy individuals as normal control for the purpose of investigating the nature of cold and heat syndromes. As a result, the cases of deficiency-cold syndrome (DCS) had a normal concentration of plasma cortisol but a lowered content of GCR in leukocytes when compared with the normal control (P less than 0.05); the cases of deficiency-heat syndrome (DHS) had a higher concentration of plasma cortisol than the normal control (P less than 0.05) and a slightly higher content of GCR in leukocytes. It was concluded that the DCS is characterized by diminished biological effects of adrenocortical activity, while the DHS, by augmented biological effects of adrenocortical activity.

[Urine excretion of PGE2, PGF2 alpha in patients with deficiency-cold syndrome and deficiency-heat syndrome].

The 3 hours' urine excretion of PGE2 and PGF2 alpha in 32 patients and 19 healthy persons were determined by RIA. According to TCM, the patients were divided into two groups: 17 cases of deficiency-cold syndrome and 15 cases of deficiency-heat syndrome. The result showed that in patients with deficiency-cold syndrome, the excretion of urine PGE2 was lower than that of the normal control (P less than 0.05), while the excretion of urine PGF2 alpha higher than that of the normal control (P less than 0.01) and hence the PGE2/PGF2 alpha ratio was much lower (P less than 0.01); in those with deficiency-heat syndrome, the excretion of urine PGE2 was higher (P less than 0.01), the excretion of urine PGF2 alpha had no significant change (P greater than 0.05) from the normal, and the PGE2/PGF2 alpha ratio was higher (P less than 0.01). The above result indicates a close relationship between prostaglandins and the cold and heat nature of syndromes in TCM. In connection with our previous studies that showed decreased functioning of the sympathetic-adrenomedullary system and/or increased functioning of the parasympathetic nervous system with diminished catecholamines and reduced cAMP/cGMP ratio in deficiency-cold syndrome while increased functioning of the sympathetic-adrenomedullary system with augmented catecholamines and cAMP in deficiency-heat syndrome, the change of prostaglandins level can be considered as an intermediate link in the pathogenesis of syndromes different in cold and heat nature.