FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2895055721> ?p ?o ?g. }

• W2895055721 endingPage "1095" @default.
• W2895055721 startingPage "1094" @default.
• W2895055721 abstract "Chronic obstructive pulmonary disease (COPD) is a major incurable global health burden and is currently the fourth largest cause of death in the world.1 The burden of COPD in Asia is currently greater than that in the developed Western countries and accounts for the majority of COPD deaths worldwide due to epidemic exposure to tobacco smoke and air pollution.2 Importantly, much of the disease burden and healthcare utilization in COPD are associated with the management of its co-morbidities (e.g. skeletal muscle wasting, vascular and heart diseases, cognitive dysfunction, anxiety and depression disorders, lung cancer, osteoporosis, metabolic syndrome and diabetes) and infective viral and bacterial acute exacerbations (AECOPD).1 Moreover, respiratory infections can aggravate these co-morbidities and further deteriorate the patient's condition.1 It is currently not clear whether these co-morbidities are independent coexisting conditions (as a result of shared risk factors such as advanced age or smoking history of the patient) or a direct consequence of the progressive lung pathology in COPD patients. Current pharmacological treatments for COPD and its co-morbidities are relatively ineffective and the development of effective therapies has been severely hampered by the lack of understanding of the mechanisms and mediators underlying COPD co-morbidities. Since co-morbidities have a tremendous impact on the prognosis and severity of COPD, the 2015 American Thoracic Society/European Respiratory Society (ATS/ERS) Research Statement on COPD urgently called for studies to elucidate the pathobiological mechanisms linking COPD to its co-morbidities.3 Consequently, significant research has been channelled towards developing preclinical mouse models of co-morbidities associated with COPD to (i) determine the mechanisms underlying these conditions and (ii) identify and test novel therapeutic options for these patients. As cigarette smoke is the major cause of COPD, ‘smoking animal’ models that accurately reflect lung pathophysiology have been established to help identify pathogenic mechanisms. In addition, preclinical models are an integral part of the drug discovery pipeline as they allow for testing of potential therapies. Among the many species (including monkeys, sheep, dogs, guinea pigs and rodents) used, mice have been the most popular choice by investigators given the ability to produce animals with genetic modifications that shed light on specific processes within COPD, the abundance of antibody probes, the availability of many mouse strains with different reactions to cigarette smoke and the low cost. Whilst pathological processes such as airway inflammation and airspace enlargement/emphysema have been successfully targeted in mice,4 the targeting of systemic co-morbidities in experimental models remain an emerging and topical area of research. We have developed sophisticated preclinical models of cigarette smoke-induced skeletal muscle wasting in mice. Using these models, we have recently shown that mice exposed chronically to cigarette smoke had reduced hind limb skeletal muscles mass (gastrocnemius, tibialis anterior and soleus), grip strength (index of muscle strength) and aerobic endurance.4 In addition, cigarette smoke altered the expression of a number of genes associated with the regulation of skeletal muscle mass including insulin-like growth factor-I, atrogin-1, MuRF-1 and IL-6. Importantly, we have shown that targeting oxidant-dependent processes that drive cigarette smoke-induced lung inflammation not only reduced lung inflammation but also significantly reduced skeletal muscle wasting (Ivan Bernardo, Steven Bozinovski and Ross Vlahos, unpublished observations). Others have shown that skeletal muscles from cigarette smoke-exposed mice had decreased skeletal muscle capillarization and reduced muscle fibre cross-sectional area and exercise tolerance when compared with air-exposed mice.5 Thus, these studies highlight that chronic exposure to cigarette smoke causes systemic features that closely resemble extrapulmonary manifestations observed in COPD patients, and that these murine models are a useful tool in exploring therapeutics aimed at treating skeletal muscle wasting and dysfunction observed in human COPD. While skeletal muscle wasting and dysfunction is the best developed COPD co-morbidity in mice, we and others are developing clinically relevant animal models to investigate the link between COPD and cardiovascular, cognitive and metabolic co-morbidities.6, 7 A current limitation is that the smoke exposure mouse models do not cause severe COPD, where a complementary genetic susceptibility strategy may be required to develop a more severe model of COPD co-morbidities. In conclusion, COPD is a complex disease and the mechanisms that drive its induction and progression are poorly understood. Moreover, the mechanisms underlying co-morbidities of COPD are also poorly understood but the identification of common disease pathways may redirect drug discovery research in COPD towards drugs targeting the lung and co-morbidities (e.g. skeletal muscle wasting) concurrently. Preclinical models of COPD and its co-morbidities are essential to provide insights into the cellular and molecular mechanisms driving the pathogenesis of COPD co-morbidities and are necessary for the development and testing of new therapies. However, it is critical that our understanding of the co-morbidities we are modelling is adequate, in order to develop preclinical models that predict drug efficacy. Finally, when directed by knowledge gained through clinical research, animal models utilizing cigarette smoke exposure are a powerful tool to validate new therapeutic targets for COPD and its co-morbidities." @default.
• W2895055721 created "2018-10-12" @default.
• W2895055721 creator A5060211723 @default.
• W2895055721 creator A5079475266 @default.
• W2895055721 date "2018-10-04" @default.
• W2895055721 modified "2023-10-16" @default.
• W2895055721 title "Modelling COPD co‐morbidities in preclinical models" @default.
• W2895055721 cites W2019851932 @default.
• W2895055721 cites W2127157938 @default.
• W2895055721 cites W2154013090 @default.
• W2895055721 cites W2407358117 @default.
• W2895055721 cites W2531799775 @default.
• W2895055721 cites W2583265473 @default.
• W2895055721 doi "https://doi.org/10.1111/resp.13416" @default.
• W2895055721 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30284760" @default.
• W2895055721 hasPublicationYear "2018" @default.
• W2895055721 type Work @default.
• W2895055721 sameAs 2895055721 @default.
• W2895055721 citedByCount "6" @default.
• W2895055721 countsByYear W28950557212019 @default.
• W2895055721 countsByYear W28950557212020 @default.
• W2895055721 countsByYear W28950557212022 @default.
• W2895055721 countsByYear W28950557212023 @default.
• W2895055721 crossrefType "journal-article" @default.
• W2895055721 hasAuthorship W2895055721A5060211723 @default.
• W2895055721 hasAuthorship W2895055721A5079475266 @default.
• W2895055721 hasBestOaLocation W28950557211 @default.
• W2895055721 hasConcept C126322002 @default.
• W2895055721 hasConcept C134018914 @default.
• W2895055721 hasConcept C139719470 @default.
• W2895055721 hasConcept C162324750 @default.
• W2895055721 hasConcept C177713679 @default.
• W2895055721 hasConcept C2776780178 @default.
• W2895055721 hasConcept C2776867660 @default.
• W2895055721 hasConcept C2779134260 @default.
• W2895055721 hasConcept C2779159551 @default.
• W2895055721 hasConcept C2779764123 @default.
• W2895055721 hasConcept C555293320 @default.
• W2895055721 hasConcept C71924100 @default.
• W2895055721 hasConceptScore W2895055721C126322002 @default.
• W2895055721 hasConceptScore W2895055721C134018914 @default.
• W2895055721 hasConceptScore W2895055721C139719470 @default.
• W2895055721 hasConceptScore W2895055721C162324750 @default.
• W2895055721 hasConceptScore W2895055721C177713679 @default.
• W2895055721 hasConceptScore W2895055721C2776780178 @default.
• W2895055721 hasConceptScore W2895055721C2776867660 @default.
• W2895055721 hasConceptScore W2895055721C2779134260 @default.
• W2895055721 hasConceptScore W2895055721C2779159551 @default.
• W2895055721 hasConceptScore W2895055721C2779764123 @default.
• W2895055721 hasConceptScore W2895055721C555293320 @default.
• W2895055721 hasConceptScore W2895055721C71924100 @default.
• W2895055721 hasIssue "12" @default.
• W2895055721 hasLocation W28950557211 @default.
• W2895055721 hasOpenAccess W2895055721 @default.
• W2895055721 hasPrimaryLocation W28950557211 @default.
• W2895055721 hasRelatedWork W1033578521 @default.
• W2895055721 hasRelatedWork W1912936344 @default.
• W2895055721 hasRelatedWork W1974526650 @default.
• W2895055721 hasRelatedWork W1981261777 @default.
• W2895055721 hasRelatedWork W2067958944 @default.
• W2895055721 hasRelatedWork W2114200376 @default.
• W2895055721 hasRelatedWork W3130963457 @default.
• W2895055721 hasRelatedWork W3161153624 @default.
• W2895055721 hasRelatedWork W3207487408 @default.
• W2895055721 hasRelatedWork W4307630664 @default.
• W2895055721 hasVolume "23" @default.
• W2895055721 isParatext "false" @default.
• W2895055721 isRetracted "false" @default.
• W2895055721 magId "2895055721" @default.
• W2895055721 workType "article" @default.