Senescent cells accumulate in tissues during aging and are considered to underlie several aging‐associated phenotypes and diseases. We recently reported that the elimination of p19ARF‐expressing senescent cells from lung tissue restored tissue function and gene expression in middle‐aged (12‐month‐old) mice. The aging of lung tissue increases the risk of pulmonary diseases such as emphysema, and cellular senescence is accelerated in emphysema patients. However, there is currently no direct evidence to show that cellular senescence promotes the pathology of emphysema, and the involvement of senescence in the development of this disease has yet to be clarified. We herein demonstrated that p19ARF facilitated the development of pulmonary emphysema in mice. The elimination of p19ARF‐expressing cells prevented lung tissue from elastase‐induced lung dysfunction. These effects appeared to depend on reduced pulmonary inflammation, which is enhanced after elastase stimulation. Furthermore, the administration of a senolytic drug that selectively kills senescent cells attenuated emphysema‐associated pathologies. These results strongly suggest the potential of senescent cells as therapeutic/preventive targets for pulmonary emphysema.
BackgroundCigarette smoke (CS) exposure causes an abnormal inflammatory response, which can result in chronic obstructive pulmonary disease (COPD). Previous studies show that this disorder predominantly occurs in peripheral or small-airway areas, whereas the same condition has not been identified in the larger airways during the course of COPD. However, the different biochemical and genetic alterations occurring in response to CS exposure among airway epithelial cells from different sites in the lungs have not been fully investigated.MethodsHuman small airway epithelial cells (SAECs) and normal human bronchial epithelial cells (NHBEs) were exposed to CS extract (CSE), and microarray analysis was used to determine gene- and protein-expression profiles and identify alterations following CSE exposure in both cell types. An in vivo smoking experiment was also performed to confirm differential responses to CS between sites in the lung.ResultsMicroarray analysis of SAECs and NHBEs following 24 h of CSE exposure showed that inflammatory related pathways and terms, including the tumor necrosis factor-signaling pathway, were overrepresented, especially in SAECs. Clustering analysis highlighted prostaglandin-endoperoxide synthase-2 [also known as cyclooxygenase (COX)-2] as a gene specifically upregulated in SAECs, with COX-2 mRNA and protein expression significantly elevated by CSE exposure in SAECs (3.1- and 3.1-fold, respectively), but not in NHBEs. Furthermore, time-course analysis of COX-2 expression revealed earlier increases in SAECs compared with NHBEs following CS exposure. Short-term exposure of mouse lungs to CS was found to predominantly induce COX-2 expression in the small airway.ConclusionsThe small airway is more susceptible to CSE than the large airway and could be the initial site of development of CS-related respiratory diseases, such as COPD.Electronic supplementary materialThe online version of this article (10.1186/s12890-018-0715-4) contains supplementary material, which is available to authorized users.
The emergency hospital is intended to prevent transmission of COVID-19 in the community by isolating patients without symptoms, with mild or moderate symptoms. This study evaluated the clinical characteristics and outcomes of COVID-19 patients who were admitted to this facility. This retrospective study reviewed data of patients treated at the National Emergency Hospital Wisma Atlet Kemayoran in Jakarta, Indonesia, from March 23 to April 30, 2020. Patient characteristics (clinical symptoms, laboratory test results, Chest X-Ray, SARS-CoV-2 immunoserology, and RT-PCR results from nasopharyngeal/ oropharyngeal preparations) were compared between severity groups. There were 413 COVID-19 cases analyzed, of which 190 (46%) were asymptomatic, 93 (22.5%) were mild, and 130 (31.5%) were moderate cases. Most asymptomatic cases were male, with young age, and without comorbidity. Mild cases were dominated by female and young patients, while most moderate cases were male and older patients. The number of patients with comorbidities was higher in mild and moderate cases. The patient’s overall outcome was good and did not differ based on the severity of symptoms. Despite the many challenges, patients with moderate symptoms can be safely treated in the emergency hospital.
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