PRMT5 activates KLF5 by methylation to facilitate lung cancer.

The highly expressed oncogenic factor Krüppel-like factor 5 (KLF5) promotes various cancerous processes, such as cell growth, survival, anti-apoptosis, migration and metastasis, particularly in lung cancer. Nevertheless, the modifications to KLF5 after translation are poorly understood. Protein arginine methyltransferase 5 (PRMT5) is considered as an oncogene known to be involved in different types of carcinomas, including lung cancer. Here, we show that the expression levels of PRMT5 and KLF5 are highly expressed lung cancer. Moreover, PRMT5 interacts with KLF5 and facilitates the dimethylation of KLF5 at Arginine 41 in a manner that depends on methyltransferase activity. Downregulation or pharmaceutical suppression of PRMT5 reduces the expression of KLF5 and its downstream targets both in vitro and in vivo. Mechanistically, the dimethylation of KLF5 by PRMT5 promotes the maintenance and proliferation of lung cancer cells at least partially by stabilising KLF5 via regulation of the Akt/GSK3ß signalling axis. In summary, PRMT5 methylates KLF5 to prevent its degradation, thereby promoting the maintenance and proliferation of lung cancer cells. These results suggest that targeting PRMT5/KLF5 axis may offer a potential therapeutic strategy for lung cancer.

The ability of volumetric capnography to distinguish between chronic obstructive pulmonary disease patients and normal subjects.

PURPOSE: The aim of our study was to evaluate volumetric capnography (VCap) in the differentiation between chronic obstructive pulmonary disease (COPD) patients and normal subjects. PATIENTS AND METHODS: Thirty-nine healthy male volunteers and 60 male COPD patients were enrolled. Regression equations between VCap indices and age, weight, height, and tidal volume in healthy volunteers were established by stepwise regression analysis. Predicted normal values of VCap indices in COPD patients were calculated. A paired t test was used to compare the difference between observed and predicted values for VCap indices in COPD patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the power of each VCap index alone in differentiating COPD patients and normal subjects. The power of the combination of VCap indices was assessed by discriminant analysis. RESULTS: All regression equations were significant (P < 0.01) as were the differences between the observed and predicted normal VCap indices in COPD patients (P < 0.001). ROC curve analysis showed that the volume between 25 and 50% of F CO2et (Vm25-50), slope of Phase II (dC2/dV), and slope of Phase III (dC3/dV) were valuable predictors. Nearly all (90.9%) subjects were correctly classified by discriminant analysis. CONCLUSION: Vm25-50, dC2/dV, or dC3/dV alone are valuable for differentiating COPD patients and normal subjects, but more powerful are the combinations of Vm25-50, dC2/dV, and dC3/dV, the ratio of dC2/dV to dC3/dV (SR23), dead space according to the Bohr method (VDB), and dead space according to the Wolff and Brunner methods (PIE).

Detection of the airway obstruction stage in asthma using impulse oscillometry system.

OBJECTIVE: Although spirometry is the most common method for evaluating the airway obstruction stage in asthma patients, it is difficult to perform in some patients. The aim of this study was to evaluate whether impulse oscillometry, an easy-to-perform technique, can detect asthmatic airway obstruction stage. METHODS: A total of 80 subjects, including healthy volunteers and patients with asthma, were enrolled in this study. The asthma patients were classified into three groups according to American Thoracic Society (ATS)/European Respiratory Society (ERS)-2005: the mild group (forced expiratory volume in 1 second (FEV(1)) ≥ 70% predicted (Pred), n = 20), the moderate group (50% Pred ≤ FEV(1) <70% Pred, n = 20), and the severe group (FEV(1) < 50% Pred, n = 20). Spirometry and impulse oscillometry (IOS) parameters were obtained from every subject. Correlation analysis was used to compare spirometry measurements and IOS parameters. One-way analysis of variance (ANOVA) was performed to compare IOS parameters among different groups. The potential of using all individual IOS parameters to detect the different stages of asthmatic airway obstruction was evaluated by the receiver operating characteristic (ROC) curve analysis. RESULTS: The correlation analysis showed that IOS parameters, such as respiratory resistance at 5 Hz (R(5)), respiratory resistance at 10 Hz (R(10)), respiratory resistance at 20 Hz (R(20)), difference in resistance between 5 Hz and 20 Hz (R(5-20)), impedance at 5 Hz (Z(5)), resonant frequency (Fres), and area of reactance (AX) were negatively correlated with FEV(1) and peak expiratory flow (PEF), while reactance at 5 Hz (X(5)) was positively correlated with FEV(1) and PEF. The increase in R(5), R(10), R(20), Z(5), R(5-20), Fres, (-X(5)), and AX parameters corresponded significantly with an increase in the airway obstruction stage, as determined by one-way ANOVA . ROC curve analysis revealed that all the IOS parameters studied, except for Fres, were capable of classifying asthmatic airway obstruction. R(5), R(5-20), and Z(5) were the most accurate parameters. CONCLUSION: IOS provides an accurate, reliable, and patient-friendly technique for classifying asthmatic airway obstruction.

A bibliometric analysis of the 100 most influential papers on COPD.

OBJECTIVE: We aimed to identify the 100 top-cited articles published on chronic obstructive pulmonary disease (COPD) and to analyze their characteristics so as to provide information on the achievement and development in COPD research over the past decades. METHODS AND MATERIALS: A comprehensive list of citation classics in COPD was generated by searching the Science Citation Index expanded database, using the keywords "COPD" or "chronic obstructive pulmonary disease" or "chronic obstructive pulmonary diseases". The 100 top-cited research papers were retrieved by reading the abstract or full text if needed. All eligible articles were read for basic information, including country of origin, organizations, article type, journals, research field, and authors. RESULTS: The 100 top-cited articles on COPD were published between 1966 and 2010. The number of citations ranged from 254 to 2,164, with a mean of 450 citations for each article. These citation classics were from 32 countries, with 38 from the United States. The Imperial College London led the list of classics, with 16 papers. The 100 top-cited articles were distributed in 18 journals, with the American Journal of Respiratory, Critical Care Medicine, and Journal of the American Medical Association topping the list. Among the various fields, both respiratory system (63%) and general internal medicine (63%) were the most common fields of study for the 100 articles. CONCLUSION: Our bibliometric analysis provides a historical perspective on the progress of scientific research on COPD. Articles originating from the United States and published in high-impact specialized respiratory journals are most likely to be cited in the field of COPD research.

[Clinical effects of sub-maximum ergometry exercise rehabilitation in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the rehabilitation effects ergometry on COPD patients. METHODS: Thirty COPD out-patients in our Hospital were randomly divided into 2 groups. Rehabilitation group, 15 patients, performed leg ergometry exercise of 80% peak Watt x 30min/d x 3d/w x 12w. Another 15 patients were control group without exercise. All patients received conventional therapy. Pulmonary function testing (PFT), cardiopulmonary exercise testing (CPET), arterial blood gas analysis (ABG), Borg and CAT sores were done at both baseline and 12 w. RESULTS: There was no statistically difference in lung function testing, blood gas analysis and cardiopulmonary exercise test when pre- exercises between 2 sub-groups. The IC, peak VO2 and peak, W of rehabilitation group significantly increased (P < 0.05); and Borg and CAT.scores significantly decreased (P < 0.05) from baseline; and other PFT and ABG did not change (P > 0.05). While there was no difference in control group (P > 0.05). CONCLUSION: Leg submaximal ergometry rehabilitation improves health condition and ameliorate dyspnea symptoms in COPD patients.