Rationale: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter airway epithelial cells (AECs). Objective: To determine what factors are associated with ACE2 expression particularly in patients with asthma and chronic obstructive pulmonary disease (COPD). Methods: We obtained upper and lower AECs from 145 people from two independent cohorts, aged 2-89, Newcastle (n=115), and from Perth (n= 30) Australia. The Newcastle cohort was enriched with people with asthma (n=37) and COPD (n=38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry were assessed by quantitative PCR, protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AECs. Results: Increased gene expression of ACE2 was associated with older age (p=0.02) and male sex (p=0.03), but not pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma (p=0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in asthma (p=0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface was increased (p=0.02). ACE2 protein levels were lower in endobronchial biopsies from asthma patients. Conclusions: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.
Cytokines influence the biological behaviour of prostate cancer (PC) and may influence patient outcome and serve as useful prognostic biomarkers. The aim of the present study was to evaluate cytokine expression levels in prostatic needle biopsy specimens and the association with clinicopathological characteristics of patients with PC. A total of 18 patients with PC who underwent transrectal ultrasound (TRUS) guided prostate biopsy were included in the clinical study. These patients were naïve to radiotherapy (RT) or androgen deprivation therapy prior to TRUS biopsy and clinical follow up data was collected. Cytokine expression levels were analysed by using immunohistochemistry and Spearman's correlation test was used to determine the correlation between cytokine expression and clinicopathological characteristics. Expression levels of pro-inflammatory TNF-α and IL-6 decreased as Gleason score (GS) increased; however, a statistically significant difference was not detected. A statically significant correlation was observed between needle biopsy specimen and pre-RT plasma sample expression levels of pro-inflammatory TNF-α and IL-6 (P=0.01 and P=0.05, respectively) and anti-inflammatory TGF-β1 (P= 0.05). However, further studies are needed to confirm these results using a larger sample size to confirm the prognostic value of pro-inflammatory TNF-α and IL-6 and anti-inflammatory TGF-β1 in patients with PC.
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