A promotor polymorphism in the Interleukin 11 gene is associated with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder characterized by irreversible airflow obstruction due to chronic inflammation. Hence, the gene encoding the anti-inflammatory cytokine IL 11 is a good candidate for being involved in the genetic predisposition to COPD. In order to evaluate the role of the Interleukin 11 (IL 11) gene in the genetic predisposition for COPD, a dinucleotide microsatellite polymorphism in the promoter region has been genotyped in 153 patients with COPD (including 25 non-smokers) and 463 healthy controls. Frequencies of the IL 11.A2 microsatellite allele and of IL 11.A2 homozygous individuals were significantly decreased among the patients with COPD (p < 0.012 and p < 0.022, respectively) as compared to controls. Both frequencies were even more drastically reduced among the nonsmoking patients. Tight linkage of this microsatellite allele with another polymorphism in the promotor region was established. Altered expression of IL 11 may be involved in the genetic predisposition to COPD.     

Searching for biomarkers of chronic obstructive pulmonary disease using proteomics: The current state

Detection of proteins which may be potential biomarkers of disorders represents a big step forward in understanding the molecular mechanisms that underlie pathological processes. In this context proteomics plays the important role of opening a path for the identification of molecular signatures that can potentially assist in early diagnosis of several clinical disturbances. Aim of this report is to provide an overview of the wide variety of proteomic strategies that have been applied to the investigation of chronic obstructive pulmonary disease (COPD), a severe disorder that causes an irreversible damage to the lungs and for which there is no cure yet. The results in this area published over the past decade show that proteomics indeed has the ability of monitoring alterations in expression profiles of proteins from fluids/tissues of patients affected by COPD and healthy controls. However, these data also suggest that proteomics, while being an attractive tool for the identification of novel pathological mediators of COPD, remains a technique mainly generated and developed in research laboratories. Great efforts dedicated to the validation of these biological signatures will result in the proof of their clinical utility.     

An integrated approach based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry,network pharmacology,and molecular docking to study the key effective compounds and mechanism of action of Platycodi Radix in the treatment of chronic obstructive pulmonary disease

Platycodi Radix (PR) is a valuable herb that is widely used in the treatment of chronic obstructive pulmonary disease in clinics. However, the mechanism of action for the treatment of chronic obstructive pulmonary disease remains unclear due to the lack of in vivo studies. Our study established a novel integrated strategy based on ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry, network pharmacology, and molecular docking to systematically analyze the tissue distribution and active compounds of PR in vivo and the therapeutic mechanism of chronic obstructive pulmonary disease. First, tissue distribution studies have shown that the lung is the organ with the highest distribution of PR compounds. Subsequently, network pharmacology results showed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and mitogen-activated protein kinase signaling pathway were the critical mechanisms of PR against chronic obstructive pulmonary disease. Ultimately, molecular docking results showed that the key targets were stably bound to the corresponding active compounds of PR. Our study is of great significance for the screening of the key effective compounds and the study of the mechanism of action in traditional Chinese medicine and provides data to support the further development and utilization of PR.     

Determination of creatinine-related molecules in saliva by reversed-phase liquid chromatography with tandem mass spectrometry and the evaluation of hemodialysis in chronic kidney disease patients

The serum concentrations of creatinine (Cre) and urea are used for the determination of the renal function. However, the use of blood is not always suitable due to the invasive, hygienic and infection problems during its sample collection and handling. In contrast, saliva is relatively clean and the samples can be quickly and noninvasively collected and easily stored. Therefore, the simultaneous determination of Arginine (Arg), creatine (Cr) and Cre in the saliva of chronic kidney disease (CKD) patients was performed by UPLC-ESI-MS/MS together with the saliva of healthy volunteers. The evaluation of hemodialysis of CKD patients was also carried out by the determinations before and after the dialysis. An HS-F5 column was used for the simultaneous determination of Arg, Cr and Cre in the saliva. These molecules were rapidly separated within 4 min and sensitively determined by the multiple reaction monitoring (MRM) of the precursor ion [M+H]⁺ → product ions (m/z 175.1 → 70.1 for Arg; m/z 132.0 → 44.1 for Cr; m/z 114.0 → 44.1 for Cre). The concentration of Cre in the CKD patients was higher than that in the healthy persons. The concentrations of Cre in the saliva of the patients before hemodialysis were moderately correlated with the serum Cre concentrations (R² = 0.661). Furthermore, the concentration in the saliva obviously decreased after hemodialysis (before 0.73 mg/dL, after 0.25 mg/dL; p < 0.02). Thus, the proposed detection method using saliva by UPLC-MS/MS is useful for the evaluation of the renal function in CKD patients. The present method offers a new option for monitoring the hemodialysis of CKD patients.     

Detection of volatile organic compounds (VOCs) in exhaled breath of patients with chronic obstructive pulmonary disease (COPD) by ion mobility spectrometry

COPD is a disease characterised by a chronic inflammation of the airways and a not fully reversible airway obstruction. The spirometry is considered as gold-standard to diagnose the disease and to grade its severity. In this study we used the methodology of Ion Mobility Spectometry in order to detect Volatile Organic Compounds (VOCs) in exhaled breath of patients with COPD. The purpose of this study was to investigate if the VOCs detected in patients with COPD were different from the VOCs detected in exhaled breath of healthy controls. 13 COPD patients and 33 healthy controls were included in the study. Breath samples were collected via a side-steam Teflon tube and directly measured by an ion mobility spectrometer coupled to a multi capillary column (MCC/IMS). One peak was identified only in the patients group compared to the healthy control group. Consequently, the analysis of exhaled breath could be a useful tool to diagnose COPD.     

Ultrafast gas chromatography coupled to electronic nose to identify volatile biomarkers in exhaled breath from chronic obstructive pulmonary disease patients: A pilot study

An analytical method to identify volatile organic compounds (VOCs) in the exhaled breath from patients with a diagnosis of chronic obstructive pulmonary disease (COPD) using a ultrafast gas chromatography system equipped with an electronic nose detector (FGC eNose) has been developed. A prospective study was performed in 23 COPD patients and 33 healthy volunteers; exhalation breathing tests were performed with Tedlar bags. Each sample was analyzed by FCG eNose and the identification of VOCs was based on the Kovats index. Raw data were reduced by principal component analysis (PCA) and canonical discriminant analysis [canonical analysis of principal coordinates (CAP)]. The FCG eNose technology was able to identify 17 VOCs that distinguish COPD patients from healthy volunteers. At all stages of PCA and CAP the discrimination between groups was obvious. Chemical prints were correctly classified up to 82.2%, and were matched with 78.9% of the VOCs detected in the exhaled breath samples. Receiver operating characteristic curve analysis indicated the sensitivity and specificity to be 96% and 91%, respectively. This pilot study demonstrates that FGC eNose is a useful tool to identify VOCs as biomarkers in exhaled breath from COPD patients. Further studies should be performed to enhance the clinical relevance of this quick and ease methodology for COPD diagnosis.     

Proteomic biomarkers in plasma that differentiate rapid and slow decline in lung function in adult cigarette smokers with chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of morbidity and mortality in the United States and cigarette smoking is a primary determinant of the disease. COPD is characterized by chronic airflow limitation as measured by the forced expiratory volume in one second (FEV₁). In this study, the plasma proteomes of 38 middle-aged or older adult smokers with mild to moderate COPD, with FEV₁ decline characterized as either rapid (RPD, n?=?20) or slow or absent (SLW, n?=?18), were interrogated using a comprehensive high-throughput proteomic approach, the accurate mass and time (AMT) tag technology. This technology is based upon a putative mass and time tag database (PMT), high-resolution LC separations and high mass accuracy measurements using FT-ICR MS with a 9.4-T magnetic field. The peptide and protein data were analyzed using three statistical approaches to address ambiguities related to the high proportion of missing data inherent to proteomic analysis. The RPD and SLW groups were differentiated by 55 peptides which mapped to 33 unique proteins. Twelve of the proteins have known roles in the complement or coagulation cascade and, despite an inability to adjust for some factors known to affect lung function decline, suggest potential mechanistic biomarkers associated with the rate of lung function decline in COPD. Whether these proteins are the cause or result of accelerated decline will require further research.     

降钙素原在指导慢性阻塞性肺疾病急性加重期抗感染治疗中的价值

目的观察并分析降钙素原在指导慢性阻塞性肺疾病急性加重期抗感染治疗中的价值。方法研究对象选取2015年5月期间来湖北省宜昌市第二人民医院就诊的100例慢性阻塞性肺疾病急性加重期病例,根据随机数字表法将其分为对照组与观察组各50例,对照组结合临床实际情况制订抗生素治疗方案,观察组则根据血清降钙素原(PCT)指导抗生素应用,对比两组抗生素应用时间、临床治疗效果、住院时间、病情加重与死亡率,并对研究结果相关数据作统计学处理。结果与对照组比,观察组抗生素使用时间、住院时间更短,组间差异显著而具有统计学意义(P0.05);两组临床治疗效果,病情加重率与死亡率差异并无统计学意义(P0.05)。结论在慢性阻塞性肺疾病急性加重期,监测血清降钙素原水平以指导抗感染治疗可有效降低抗生素使用量,促进患者康复,具有积极的临床意义。     

The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeutic effects of melatonin against COPD, focusing on determining whether it is a PDE4 inhibitor via in vivo and in vitro experiment using cigarette smoke (CS) and cigarette smoke condensate (CSC), respectively. In the in vivo experiments, melatonin treatment reduced inflammatory responses, including inflammatory cell counts. Melatonin treatment also suppressed the CS-exposure-induced upregulation of cytokine and matrix metalloproteinase (MMP)-9, reduced the PDE4B expression, and elevated cAMP levels. In addition, these effects were synergistic, as melatonin and roflumilast cotreatment eventually ameliorated the CS-exposure-induced worsening of lung function. In the CSC-stimulated NCI-H292 cells, melatonin inhibited elevation in the levels of inflammatory cytokines, MMP-9, and PDE4, and elevated cAMP levels. Furthermore, melatonin and roflumilast cotreatment was more effective on inflammatory responses than only melatonin or roflumilast treatment. Our results indicate that melatonin relieves inflammatory response and loss of lung function in COPD, which is associated with decreased PDE4 expression. Therefore, we suggest that melatonin is a putative candidate for the treatment of COPD.     

Development of an HPLC method with electrochemical detection of femtomoles of 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine in the presence of uric acid

A selective method based on high performance liquid chromatography with electrochemical detection (HPLC-ECD) was developed to enable simultaneous detection of 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), products of DNA oxidative damage, in the presence of uric acid (UA), a strong interferent in their electrochemical detection. The method developed consists of HPLC isocratic elution with amperometric detection on a glassy carbon electrode, enabling a detection limit for 8-oxoGua and 8-oxodGuo lower than 1 nM in standard mixtures. Detection of low concentrations up to 25 nM of 8-oxoGua and 8-oxodGuo in the presence of UA in a 10⁴-fold higher concentration was achieved after one-step solid phase extraction (SPE). The method was tested with urine samples and it was possible to detect and quantify the presence of 8-oxoGua, and to confirm that UA was eliminated after uricase degradation and SPE. The LOD found in urine samples was about 80 nM, a value higher than in standard mixtures, due to the increase of background current in the urine matrix. The results presented here contribute to the development of a methodological approach to simultaneous determination of 8-oxoGua and 8-oxodGuo in urine samples.     

A novel,rapid and sensitive UPLC–MS/MS method for the determination of macitentan in patients with pulmonary arterial hypertension

Macitentan is an endothelin receptor antagonist commonly used in the treatment of pulmonary arterial hypertension (PAH). A novel, rapid, simple and sensitive UPLC–MS/MS method was developed and validated for pharmacokinetic study and the determination of macitentan in PAH patients. Macitentan and bosentan, which are used as internal standards, were detected using atmospheric pressure chemical ionization in positive ion and multiple reaction monitoring mode by monitoring the mass transitions m/z 589.1 → 203.3 and 552.6 → 311.5, respectively. Chromatographic separation was performed on a reverse‐phase C18 column (5 μm, 4.6 × 150 mm) with an isocratic mobile phase, which consisted of water containing 0.2% acetic acid–acetonitrile (90:10, v/v) at a flow rate of 1 mL/min. Retention times were 1.97 and 1.72 min for macitentan and IS, respectively. The calibration curve with high correlation coefficient (0.9996) was linear in the range 1–500 ng/mL. The lower limit of quantitation and average recovery values were determined as 1 ng/mL and 89.8%, respectively. This method is the first UPLC–MS/MS method developed and validated for the determination of macitentan from human plasma. The developed analytical method was fully validated for linearity, selectivity, specificity, accuracy, precision, sensitivity, stability, matrix effect and recovery according to US Food and Drug Administration guidelines. The developed method was applied successfully for pharmacokinetic study and the determination of macitentan in PAH patients.     

Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

Genetic polymorphisms may be linked to inter-individual differences in erythropoietin (EPO) resistance. We investigated the -511C/T polymorphism of the IL-1B gene and the I/D polymorphism of the ACE gene for any association with EPO resistance index (ERI) in maintenance hemodialysis patients (n=167). Because EPO responsiveness is multi-factorial, we also included other possible influences (age, sex, time on dialysis, ACE inhibitor or angiotensin receptor blocker use, ferritin, transferrin saturation, intact PTH, high sensitivity C-reactive protein, albumin, Kt/V, and presence of diabetes mellitus) on ERI in our analyses. Multiple regression analysis showed significant association of the IL-1B-511CC and ACE DD polymorphisms with ERI (P=0.038 and P=0.004 in the recessive model, respectively). The combination (C) of alleles of two loci showed that C1 (I-T) was significantly associated with ERI in the co-dominant and recessive models (P=0.005 and P=0.0001, respectively). Subjects who did not carry C1 showed significantly decreased ERI (10.10+/-5.15 IU/kg weight/g hemoglobin) compared to other study subjects (C1/C1 and C1/-; 12.97+/-4.90 and 15.12+/-7.43 IU/kg weight/g hemoglobin, respectively). Our study indicates that the IL-1B-511C/T and ACE I/D polymorphisms may be useful genetic markers of EPO requirement in hemodialysis patients. These findings might also provide a new perspective on therapeutic approaches to the treatment of end stage renal disease patients with anemia.     

Selective liquid-phase oxidation of toluene over heterogeneous Mn@ZIF-8 derived catalyst with molecular oxygen in the solvent-free conditions

In this work, liquid-phase catalytic oxidation of toluene was carried out under solvent-free conditions, and highly selective synthesis of benzaldehyde (BAL) and benzyl alcohol (BOL) and benzoic acid (BAC) in the presence of Mn@ZIF-8 calcined material as catalyst with oxygen molecules. As a heterogeneous catalyst, the zeolitic imidazolate framework Mn@ZIF-8 derived material exhibited reasonable substrate-product selectivity (70.3% of selectivity to BAL and BOL, 95.1 % of selectivity to BAL, BOL and BAC) and conversion (6.5%) under optimum reaction conditions. The catalysts were characterized by BET-specific surface area determination, XRD, XPS, FT-IR, TG-DTG and SEM-EDS-Mapping. The results demonstrated that the catalytic capacity of the catalysts was enhanced by the good dispersion of amorphous Mn species in ZIF-8 derivatives and high specific surface area. The possible reaction pathway for the catalytic oxidation of toluene was also suggested. Maybe this method employing Mn@ZIF-8 as efficient catalyst affords a new and environmentally friendly route for the synthesis of BOL and BAL from the selective oxidation of toluene.     

Stereoselectivity, periselectivity, and regioselectivity in the cycloadditions of 8-(p-chlorophenyl)-8-azaheptafulvene with cyclopentadiene and fulvenes

The stereoselectivity, periselectivity, and regioselectivity in the cycloaddition reactions of 8-(p-chlorophenyl)-8-azaheptafulvene with cyclopentadiene and symmetrical/unsymmetrical fulvenes is described.     

A conductance study of the association of alkali cations with 1,13-dibenzo-24-crown-8 in acetonitrile

A conductance study concerning the association of Na⁺, K⁺, Rb⁺, and Cs⁺ with 1,13-dibenzo-24-crown-8 in acetonitrile has been carried out at 35, 30, 25, 20, and 15°C. The observed molar conductivities were found to decrease significantly for mole ratios less than unity. A model involving 11 stoichiometry has been used to analyze the conductivity data. The stability constant, K, and the molar conductivity _C for each 11 complex were determined from the conductivity data by using a nonlinear least squares curve fitting procedure. The binding sequence, based on the value of log K at 25°C, is found to be Rb⁺>Cs⁺>K⁺>Na⁺. Values of H^o and S^o are reported and their significance is discussed.     

Biocatalysts Synthesized with Lipase from Pseudomonas cepacia on Glycol-Modified ZIF-8: Characterization and Utilization in the Synthesis of Green Biodiesel

This research presents results on the production of biodiesel from the transesterification of acylglycerides present in palm oil, using the biocatalysts ZIF-8-PCL and Gly@ZIF-8-PCL synthesized by immobilization of Pseudomonas Cepacia Lipase as catalytic materials and using pure ZIF-8 and Gly@ZIF-8 (modified ZIF-8) as supports. The Gly@ZIF-8 carbonaceous material was prepared by wet impregnation of ZIF-8 with ethylene glycol as the carbon source, and then thermally modified. The calcination conditions were 900 °C for two hours with a heating rate of 7 °C/min in an inert atmosphere. A textural characterization was performed, and results showed superficial changes of materials at the microporous and mesoporous levels for the Gly@ZIF-8 material. Both the starting materials and biocatalysts were characterized by infrared spectroscopy (FTIR) and Raman spectroscopy. During the transesterification, using the two biocatalysts (ZIF-8-PCL and Gly@ZIF-8-PCL), two supernatant liquids were generated which were characterized by infrared spectroscopy (FTIR), gas chromatography coupled to mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR). The results show that the two routes of synthesis of supports from ZIF-8 will be configured as effective methods for the generation of effective biocatalysts for biodiesel production.     

Novel UHPLC‐MS/MS method for the determination of rotigotine in the plasma of patients with Parkinson's disease

A novel ultra‐high‐pressure liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of the dopamine receptor agonist rotigotine in human plasma. Following liquid–liquid extraction with tert‐ butyl methyl ether from 500 μL plasma, the chromatographic analysis was performed on a Gemini NX3 column using 5 mm pH 5.0 ammonium acetate–5 mm ammonium acetate in methanol as binary gradient mobile phase, at a flow rate of 0.3 mL/min. The MS/MS ion transitions were 316.00 → 147.00 for rotigotine and 256.10 → 211.00 for the internal standard (lamotrigine). The lower limit of quantitation was 50 pg/mL and the linearity was determined from 50 to 2500 pg/mL. The mean recovery was 96.9%. Both intra‐ and interassay imprecision and inaccuracy were ≤15% at all quality control concentrations. The method was successfully applied to measure morning trough plasma rotigotine concentrations in a series of patients with Parkinson's disease on chronic treatment. The present study describes the first fully validated method for rotigotine determination in human plasma.     

Indirect determination of superoxide anion radical in the plant of red sage based on vanillin-8-aminoquinoline with fluorescence

A novel spectrofluorimetric method using vanillin-8-aminoquinoline (VAQ) as fluorescent probe was developed for the determination of superoxide anion radical (O₂⁻). The new fluorescent probe was characterized by elemental analysis and IR spectra. Under the optimum conditions of the determination, the linear calibration range and the detection limit of the developed method for superoxide anion radical were in the range (0.0-1.0)×10⁻⁵ and 2.0×10⁻⁸ mol l⁻¹, respectively. The effect of interferences was studied. The proposed method was applied to determine the generation rate of superoxide anion radical in the course of aging in red sage successfully.     

Application of monodisperse TiO2 nanoparticles with the size of 8–10 nm in dye-sensitized solar cells

In this paper, the commercial monodisperse TiO₂ nanoparticles with the size of 8–10 nm were successfully applied to the photoelectrode for dye-sensitized solar cells (DSCs) and the influence of the thickness of the TiO₂ thin films on the photovoltaic performance of the DSCs was investigated. The result revealed that the DSCs with the TiO₂ thin film thickness of 3.6, 8.0, 11.6 and 20.0 μm gave the photoelectric conversion efficiency of 3.67%, 5.92%, 6.71% and 7.03%, respectively, under the illumination of simulated AM 1.5 sunlight (100 mW cm⁻²).