Prostaglandin D2 (PGD2) signals via the DP1 and DP2 receptors. In Phase II trials, DP2 antagonism decreased airway inflammation and airway smooth muscle (ASM) area in moderate-to-severe asthma patients. However, in Phase III, DP2 antagonism failed to lower the rate of exacerbations, and DP2 as a target was shelved.
View Article and Find Full Text PDFBackground: Schistosomiasis is a disease that significantly impacts human health in the developing world. Effective diagnostics are urgently needed for improved control of this disease. CRISPR-based technology has rapidly accelerated the development of a revolutionary and powerful diagnostics platform, resulting in the advancement of a class of ultrasensitive, specific, cost-effective and portable diagnostics, typified by applications in COVID-19/cancer diagnosis.
View Article and Find Full Text PDFThe alarmins IL-33 and HMGB1 (high mobility group box 1) contribute to type 2 inflammation and asthma pathogenesis. To determine whether P2Y-R (P2Y receptor), a purinergic GPCR (G protein-coupled receptor) and risk allele for asthma, regulates the release of IL-33 and HMGB1. Bronchial biopsy specimens were obtained from healthy subjects and subjects with asthma.
View Article and Find Full Text PDFIFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV.
View Article and Find Full Text PDFTreatment options for COVID-19 remain limited, especially during the early or asymptomatic phase. Here, we report a novel SARS-CoV-2 viral replication mechanism mediated by interactions between ACE2 and the epigenetic eraser enzyme LSD1, and its interplay with the nuclear shuttling importin pathway. Recent studies have shown a critical role for the importin pathway in SARS-CoV-2 infection, and many RNA viruses hijack this axis to re-direct host cell transcription.
View Article and Find Full Text PDF: Respiratory syncytial virus (RSV) bronchiolitis causes significant infant mortality. Bronchiolitis is characterized by airway epithelial cell (AEC) death; however, the mode of death remains unknown.: To determine whether necroptosis contributes to RSV bronchiolitis pathogenesis via HMGB1 (high mobility group box 1) release.
View Article and Find Full Text PDFBackground: Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) is a transmembrane adaptor protein that affects immune receptor signaling in T and B cells. Evidence from genome-wide association studies of asthma suggests that genetic variants that regulate the expression of PAG1 are associated with asthma risk. However, it is not known whether PAG1 expression is causally related to asthma pathophysiology.
View Article and Find Full Text PDFAsthmatics are highly susceptible to respiratory viral infections, possibly due to impaired innate immunity. However, the exact mechanisms of susceptibility are likely to differ amongst viruses. Therefore, we infected primary nasal epithelial cells (NECs) from adults with mild-to-moderate asthma, with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in vitro and investigated the antiviral response.
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