The Underappreciated Role of Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease and Its Strong Link to Lung Cancer.

The World Health Organisation reported COPD to be the third leading cause of death globally in 2019, and in 2020, the most common cause of cancer death was lung cancer; when these linked conditions are added together they come near the top of the leading causes of mortality. The cell-biological program termed epithelial-to-mesenchymal transition (EMT) plays an important role in organ development, fibrosis and cancer progression. Over the past decade there has emerged a substantial literature that also links EMT specifically to the pathophysiology of chronic obstructive pulmonary disease (COPD) as primarily an airway fibrosis disease; COPD is a recognised strong independent risk factor for the development of lung cancer, over and above the risks associated with smoking. In this review, our primary focus is to highlight these linkages and alert both the COPD and lung cancer fields to these complex interactions. We emphasise the need for inter-disciplinary attention and research focused on the likely crucial roles of EMT (and potential for its inhibition) with recognition of its strategic place mechanistically in both COPD and lung cancer. As part of this we discuss the future potential directions for novel therapeutic opportunities, including evidence-based strategic repurposing of currently used familiar/approved medications

Phylogeny of Artemisia L.: Recent developments

In this review, classification and phylogeny of genus Artemisia L. is discussed. Its centers of diversity lie in the temperate and cold temperate regions of the Eurasia, North America and Asia. Artemisia has two basic chromosome numbers, with ploidy levels x=9 and x=8. Chromosome number in diploid is most often 2n=18 or 16. The genus is divided into five large groups Absinthium DC., Artemisia L., Dracunculus Besser, Seriphidium Besser and Tridantatae (Rydb.) McArthur. Its phylogeny was based on the two hypothesized evolutionary trends, loss of fertility in the disc florets and loss of ray florets. Recently its molecular phylogeny based on internally transcribed spacer (ITS), externally transcribed spacer (ETS) regions of the DNA and chloroplast DNA suggested that the genus Artemisia is a monophyletic but it could not resolve the problem of infra-generic classification. This study revealed that there is need to search new genome regions to establish a natural classification based on modern molecular techniques

Foliar epidermal anatomy and its systematic implication within the genus Sida L. (malvaceae)

Micro morphological investigations of the foliar epidermal anatomy, particularly the diversity and distribution of glandular and eglandular trichomes on leaves of Sida alba L., S. alii S. Abedin var. alii, S.cordata (Burm. F.) Brss, S. mysorensis Wight and Arn, S. ovata Forssk. S. spinosa L and S.yunnanensis S.Y.Hu have been carried out to assess the systematic relevance of epidermal features and trichome diversity within the genus Sida L. Configuration of epidermal cells is polygonal to irregular with smooth or undulating outline. Leaves are amphistomatic and amphitrichomic. Six diverse morphological types of glandular and eglandular foliar trichomes are described. Stellate and peltate types of trichomes are characteristically found in all taxa studied. S. alii and S.spinosa are distinct in having long-stalked and short-stalked capitate trichomes. S. mysorensis is characterized by multicellular uniseriate trichomes, but these are not observed in other taxa of genus Sida. The results of foliar epidermal anatomy, especially type, distribution and structure of foliar trichomes are of high systematic value in this genus of family Malvaceae

β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction.

COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking. The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer. We have investigated expression of these transcription factors and their "cellular localization" in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls. An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP). β-catenin and Snail1 expression was generally high in all subjects throughout the airway wall with marked cytoplasmic to nuclear shift in COPD (P < 0.01). Twist expression was generalised in the epithelium in normal but become more basal and nuclear with smoking (P < 0.05). In addition, β-catenin and Snail1 expression, and to lesser extent of Twist, was related to airflow obstruction and to expression of a canonical EMT biomarker (S100A4). The β-catenin-Snail1-Twist transcription factor cluster is up-regulated and nuclear translocated in smokers and COPD, and their expression is closely related to both EMT activity and airway obstruction

The main rhinovirus respiratory tract adhesion site (ICAM-1) is upregulated in smokers and patients with chronic airflow limitation (CAL).

BACKGROUND: ICAM-1 is a major receptor for ~60% of human rhinoviruses, and non-typeable Haemophilus influenzae, two major pathogens in COPD. Increased cell-surface expression of ICAM-1 in response to tobacco smoke exposure has been suggested. We have investigated epithelial ICAM-1 expression in both the large and small airways, and lung parenchyma in smoking-related chronic airflow limitation (CAL) patients. METHODS: We evaluated epithelial ICAM-1 expression in resected lung tissue: 8 smokers with normal spirometry (NLFS); 29 CAL patients (10 small-airway disease; 9 COPD-smokers; 10 COPD ex-smokers); Controls (NC): 15 normal airway/lung tissues. Immunostaining with anti-ICAM-1 monoclonal antibody was quantified with computerized image analysis. The percent and type of cells expressing ICAM-1 in large and small airway epithelium and parenchyma were enumerated, plus percentage of epithelial goblet and submucosal glands positive for ICAM- 1. RESULTS: A major increase in ICAM-1 expression in epithelial cells was found in both large (p < 0.006) and small airways (p < 0.004) of CAL subjects compared to NC, with NLFS being intermediate. In the CAL group, both basal and luminal areas stained heavily for ICAM-1, so did goblet cells and sub-mucosal glands, however in either NC or NLFS subjects, only epithelial cell luminal surfaces stained. ICAM-1 expression on alveolar pneumocytes (mainly type II) was slightly increased in CAL and NLFS (p < 0.01). Pack-years of smoking correlated with ICAM-1 expression (r = 0.49; p < 0.03). CONCLUSION: Airway ICAM-1 expression is markedly upregulated in CAL group, which could be crucial in rhinoviral and NTHi infections. The parenchymal ICAM-1 is affected by smoking, with no further enhancement in CAL subjects

Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators.

Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted

Increased myofibroblasts in the small airways, and relationship to remodelling and functional changes in smokers and COPD patients: potential role of epithelial-mesenchymal transition

Introduction: Previous reports have shown epithelial–mesenchymal transition (EMT) as an active processthat contributes to small airway fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells thatsecrete excessive and altered extracellular matrix (ECM). Here we relate small airway myofibroblastpresence with airway remodelling, physiology and EMT activity in smokers and COPD patients.Methods: Lung resections from nonsmoker controls, normal lung function smokers and COPD currentand ex-smokers were stained with anti-human α-smooth muscle actin (SMA), collagen 1 and fibronectin.αSMA+ cells were computed in reticular basement membrane (Rbm), lamina propria and adventitia andpresented per mm of Rbm and mm2 of lamina propria. Collagen-1 and fibronectin are presented as apercentage change from normal. All analyses including airway thickness were measured using Image-proplus 7.0.Results: We found an increase in subepithelial lamina propria (especially) and adventitia thickness in allpathological groups compared to nonsmoker controls. Increases in αSMA+ myofibroblasts were observedin subepithelial Rbm, lamina propria and adventitia in both the smoker and COPD groups compared tononsmoker controls. Furthermore, the increase in the myofibroblast population in the lamina propria wasstrongly associated with decrease in lung function, lamina propria thickening, increase in ECM proteindeposition, and finally EMT activity in epithelial cells.Conclusions: This is the first systematic characterisation of small airway myofibroblasts in COPD based ontheir localisation, with statistically significant correlations between them and other pan-airway structural,lung function and ECM protein changes. Finally, we suggest that EMT may be involved in such changes

Male mating biology

Before sterile mass-reared mosquitoes are released in an attempt to control local populations, many facets of male mating biology need to be elucidated. Large knowledge gaps exist in how both sexes meet in space and time, the correlation of male size and mating success and in which arenas matings are successful. Previous failures in mosquito sterile insect technique (SIT) projects have been linked to poor knowledge of local mating behaviours or the selection of deleterious phenotypes during colonisation and long-term mass rearing. Careful selection of mating characteristics must be combined with intensive field trials to ensure phenotypic characters are not antagonistic to longevity, dispersal, or mating behaviours in released males. Success has been achieved, even when colonised vectors were less competitive, due in part to extensive field trials to ensure mating compatibility and effective dispersal. The study of male mating biology in other dipterans has improved the success of operational SIT programmes. Contributing factors include inter-sexual selection, pheromone based attraction, the ability to detect alterations in local mating behaviours, and the effects of long-term colonisation on mating competitiveness. Although great strides have been made in other SIT programmes, this knowledge may not be germane to anophelines, and this has led to a recent increase in research in this area

Genetic variation of male reproductive success in a laboratory population of Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>For Anopheline mosquitoes, the vectors of human malaria, genetic variation in male reproductive success can have important consequences for any control strategy based on the release of transgenic or sterile males.</p> <p>Methods</p> <p>A quantitative genetics approach was used to test whether there was a genetic component to variation in male reproductive success in a laboratory population of <it>Anopheles gambiae</it>. Swarms of full sibling brothers were mated with a fixed number of females and their reproductive success was measured as (1) proportion of ovipositing females, (2) proportion of ovipositing females that produced larvae, (3) proportion of females that produced larvae, (4) number of eggs laid per female, (5) number of larvae per ovipositing female and (6) number of larvae per female.</p> <p>Results</p> <p>The proportion of ovipositing females (trait 1) and the proportion of ovipositing females that produced larvae (trait 2) differed among full sib families, suggesting a genetic basis of mating success. In contrast, the other measures of male reproductive success showed little variation due to the full sib families, as their variation are probably mostly due to differences among females. While age at emergence and wing length of the males were also heritable, they were not associated with reproductive success. Larger females produced more eggs, but males did not prefer such partners.</p> <p>Conclusion</p> <p>The first study to quantify genetic variation for male reproductive success in <it>A. gambiae </it>found that while the initial stages of male reproduction (i.e. the proportion of ovipositing females and the proportion of ovipositing females that produced larvae) had a genetic basis, the overall reproductive success (i.e. the mean number of larvae per female) did not.</p