Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and an aberrant microbiota of the lung. Microbial colonization contributes to chronic neutrophilic ...inflammation in COPD. Nontypeable Haemophilus influenzae (NTHi) is frequently found in lungs of stable COPD patients and is the major pathogen triggering exacerbations. The epithelial cytokine interleukin-17C (IL-17C) promotes the recruitment of neutrophils into inflamed tissues. The purpose of this study was to investigate the function of IL-17C in the pulmonary tumor microenvironment. We subjected mice deficient for IL-17C (IL-17C
) and mice double deficient for Toll-like receptor 2 and 4 (TLR-2/4
) to a metastatic lung cancer model. Tumor proliferation and growth as well as the number of tumor-associated neutrophils was significantly decreased in IL-17C
and TLR-2/4
mice exposed to NTHi. The NTHi-induced pulmonary expression of IL-17C was dependent on TLR-2/4. In vitro, IL-17C increased the NTHi- and tumor necrosis factor-α-induced expression of the neutrophil chemokines keratinocyte-derived chemokine and macrophage inflammatory protein 2 in lung cancer cells but did not affect proliferation. Human lung cancer samples stained positive for IL-17C, and in non-small cell lung cancer patients with lymph node metastasis, IL-17C was identified as a negative prognostic factor. Our data indicate that epithelial IL-17C promotes neutrophilic inflammation in the tumor microenvironment and suggest that IL-17C links a pathologic microbiota, as present in COPD patients, with enhanced tumor growth.
It has been shown that pollen information services are an important self-management tool for patients with pollen-related allergic rhinitis (AR) and allergic asthma (AA). This study aimed to design ...an online application for patients with AR and AA, which supports patients to better manage their disease as well as to evaluate the app and present the first results of the pilot study. The pollen data were obtained from the electronic pollen information network of Bavaria, Germany. Participants were asked to fill in their allergy-related complaints in the app over a 60-day period. Subsequently, the app was evaluated. Indices and diagrams visualized the participants' individual complaints as well as the daily pollen concentration in the air. In order to motivate participants to complete the app on a daily basis, we used elements of gamification. Two thirds of the participants (N = 46) reported feeling better informed about pollen counts and their allergy when using the app. The app's simple and comprehensible design was rated positively. More than 80% of the participants would recommend the app to their family and friends. The app can be a tool for patients with AR and AA to better understand their disease.
The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence ...in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities.
One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up.
One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year.
These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency.
Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3.
Antimicrobial peptides, such as the cathelicidin LL-37/hCAP-18 and its mouse homolog cathelicidin-related antimicrobial peptide (CRAMP), are important effectors of the innate immune system with ...direct anti-bacterial activity. Cathelicidin is possibly involved in the regulation of tumor cell growth. The aim of this study was to characterize the role of cathelicidin expressed in non-tumorous cells in a preclinical mouse model of tumor growth. Wild-type and CRAMP-deficient animals were exposed to cigarette smoke (CS) and Lewis lung carcinoma cells were injected to initiate the growth of tumors in the lung. CS exposure significantly increased the proliferation of lung tumors in wild-type mice, but not in CRAMP-deficient mice. CS exposure induced the recruitment of myeloid cell into tumor tissue in a CRAMP-dependent manner. Mice lacking RelA/p65 specifically in myeloid cells showed impaired recruitment of CRAMP-positive cells into the lung. In vitro studies with human cells showed that LL-37/hCAP-18 in macrophages is induced by soluble factors derived from cancer cells. Taken together, these data indicate that cathelicidin expressed from myeloid cells promotes CS-induced lung tumor growth by further recruitment of inflammatory cells. The regulation of cathelicidin expression involves myeloid p65/RelA and soluble factor from tumor cells.
MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are ...important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed mild to moderate COPD. Therefore, we analyzed these biomarkers as potential predictors of mortality in recently diagnosed mild to moderate COPD.
The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional proatrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable "recently diagnosed mild to moderate COPD" defined by GOLD grades 0-2 and diagnosis of COPD ≤ 5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP.
655 patients with recently diagnosed mild to moderate COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p < 0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0-4 (n = 1470 finally).
In patients with recently diagnosed mild to moderate COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD.
Spermatogenesis is the process by which spermatogonial stem cells divide and differentiate to produce sperm. In vitro sperm production has been difficult to achieve because of the lack of a culture ...system to maintain viable spermatogonia for long periods of time. Here we report the in vitro generation of spermatocytes and spermatids from telomerase-immortalized mouse type A spermatogonial cells in the presence of stem cell factor. This differentiation can occur in the absence of supportive cells. The immortalized spermatogonial cell line may serve as a powerful tool in elucidating the molecular mechanisms of spermatogenesis. Furthermore, through genomic modification and transplantation techniques, this male germ cell line may be used to generate transgenic mice and to develop germ cell gene therapy.
Proteins of unknown function comprise a significant fraction of sequenced genomes. Defining the roles of these proteins is vital to understanding cellular processes. Here, we describe a method to ...determine a protein function based on the identification of its natural ligand(s) by the crystallographic screening of the binding of a metabolite library, followed by a focused search in the metabolic space. The method was applied to two protein families with unknown function, PF01256 and YjeF_N. The PF01256 proteins, represented by YxkO from Bacillus subtilis and the C-terminal domain of Tm0922 from Thermotoga maritima, were shown to catalyze ADP/ATP-dependent NAD(P)H-hydrate dehydratation, a previously described orphan activity. The YjeF_N proteins, represented by mouse apolipoprotein A-I binding protein and the N-terminal domain of Tm0922, were found to interact with an adenosine diphosphoribose-related substrate and likely serve as ADP-ribosyltransferases. Crystallographic screening of metabolites serves as an efficient tool in functional analyses of uncharacterized proteins.
► Crystallographic screening of ligand binding can be used in protein function analysis ► Proteins from family PF01256 serve as ADP/ATP-dependent NAD(P)H-hydrate dehydratases ► Proteins of family YjeF_N interact with substrate structurally related to ADP-ribose
Proteins of unknown function comprise a significant fraction of sequenced genomes. Here, Shumilin et al. describe a method to determine protein function based on identification of its natural ligand(s) by crystallographic screening of a metabolite library, followed by a focused search in the metabolic space.
In order to investigate whether covalent histone modifications may be involved in early embryonic reprogramming events, changes in global levels of a series of histone tail modifications were studied ...during oocyte maturation and pre-implantation mouse development using indirect immunofluorescence and scanning confocal microscopy. Results showed that histone modifications could be classified into two strikingly distinct categories. The first contains stable 'epigenetic' marks such as histone H3 lysine 9 methylation Me(Lys9)H3, histone H3 lysine 4 methylation Me(Lys4)H3 and histone H4/H2A serine 1 phosphorylation Ph(Ser1)H4/H2A. The second group contains dynamic and reversible marks and includes hyperacetylated histone H4, histone H3 arginine 17 methylation Me(Arg17)H3 and histone H4 arginine 3 methylation Me(Arg3)H4). Our results also showed that removal of these marks in eggs and early embryos occurs during metaphase suggesting that the enzymes responsible for the loss of these modifications are probably cytoplasmic in nature. Finally, we provide data demonstrating that treatment of cellular histones with peptidylarginine deiminase (PAD) results in loss of staining for the histone H4 arginine 3 methyl mark, suggesting that PADs can reverse histone arginine methyl modifications.
Background: Bioaerosol pollution of workplace and home environments mainly affects airways and mucous membranes. The effect of environmental outdoor residential bioaerosol pollution, for example, ...livestock holdings, farming, and waste disposal plants, is unclear. Aims: To investigate the perceived health of residents living in areas with measurable outdoor bioaerosol pollution (for example, spores of Aspergillus fumigatus and actinomycetes), and effects of accompanying odours. Methods: In a cross sectional study, double blinded to ongoing microbial measurements, doctors collected 356 questionnaires from residents near a large scale composting site, and from unexposed controls in 1997. Self reported prevalence of health complaints during the past year, doctors’ diagnoses, as well as residential odour annoyance were assessed. Microbiological pollution was measured simultaneously in residential outdoor air. Results: Concentrations of >105 colony forming units of thermophilic actinomycetes, moulds, and total bacteria/m3 air were measured 200 m from the site, dropping to near background concentrations within 300 m. Positive adjusted associations were observed for residency within 150–200 m from the site versus unexposed controls for self reported health complaints: “waking up due to coughing”, odds ratio (OR) 6.59 (95% confidence interval (CI) 2.57 to 17.73); “coughing on rising or during the day”, OR 3.18 (95% CI 1.24 to 8.36); “bronchitis”, OR 3.59 (95% CI 1.40 to 9.4); and “excessive tiredness”, OR 4.27 (95% CI 1.56 to 12.15). Reports of irritative airway complaints were associated with residency in the highest bioaerosol exposure, 150–200 m (versus residency >400–500 m) from the site, and period of residency more than five years, but not residential odour annoyance. Lifetime prevalence of self reported diseases did not differ with exposure. Conclusions: Bioaerosol pollution of residential outdoor air can occur in concentrations found in occupational environments. For the first time residents exposed to bioaerosol pollution were shown to report irritative respiratory complaints similar to mucous membrane irritation independently of perceived odours.
Abstract
Background
Health promotion in the workplace is intended to enhance employee health and well-being. Yoga programmes are easy to implement and have been effective in the management of various ...health conditions.
Aims
To assess the evidence regarding the effectiveness of yoga programmes at work.
Methods
A search of electronic databases of published studies up until the 1st of April 2017. Inclusion criteria for the systematic review were randomized controlled trials of adult employees and yoga in the workplace. Quality appraisal was carried out using the Cochrane Collaboration’s tool for assessing risk of bias in randomized trials.
Results
Of 1343 papers identified, 13 studies met the inclusion criteria. Nine out of 13 trials were classified as having an unclear risk of bias. The overall effects of yoga on mental health outcomes were beneficial, mainly on stress. Most of the cardiovascular endpoints showed no differences between yoga and controls. Other outcomes reported positive effects of yoga or no change.
Conclusions
The findings of this study suggest that yoga has a positive effect on health in the workplace, particularly in reducing stress, and no negative effects were reported in any of the randomized controlled trials. Further larger studies are required to confirm this.
PDF
