Suchergebnisse

Abstract
Currently, any association between smoking and COVID-19 susceptibility is conflicted as there is limited research especially on the impact of vaping. This systematic literature review will identify genes and signalling pathways that are affected by smoking or vaping that may play a role in altering the susceptibility of an individual to COVID-19. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, OVID and Web of Science databases, were searched (1946 to Nov 2021). Abstracts and subsequent full texts were screened for eligibility by RB, with EM and AB screening 5% each. Discrepancies were discussed and agreed between all. Papers were excluded for reasons such as focussing on comorbidities, immune cells or those with no exposure. Data from included papers detailing the exposure (type, duration and dose if applicable), pathway or gene of interest, sample type (species and cell type) and the overall findings, were extracted. Pathway analysis was undertaken to identify those pathways in common between smoking, vaping, nicotine and COVID-19 (g:Profiler and Cytoscape). We identified genes within the respiratory tract involved in both the initial viral response and those affected by smoking, vaping or nicotine exposure. This enabled us to determine signalling pathways of interest and therefore areas for further study. This systematic review will inform further research to identify any altered susceptibility and the risk of severe COVID-19 posed to smokers and vapers. This will inform Public Health Policies, highlighting vulnerable groups and provide guidance of relevance to both COVID-19 and other respiratory viruses.

Abstract
Air-liquid interface (ALI) cultures are commonly used for 3D modelling of the human airways and to examine the effects of direct exposure to airborne toxicants. We explored the suitability of human epithelial cell lines (RPMI 2560, HBEC-3KT, CALU-3 and A549) and primary cells (nasal, bronchiolar and small airways) grown at ALI as a physiologically relevant model to examine whether environmental exposures can increase the susceptibility of the human airways to SARS-COV-2 infection. Cultures were kept at ALI for up to 28 days to allow differentiation. Trans-epithelial electrical resistance (TEER) was measured weekly. Cells were harvested at 0, 7, 14, 21 and 28 days, and transcriptional markers of basal, ciliated and mucus-producing cells together with SARS-COV-2 viral entry genes (ACE2, TMPRSS2 and Furin) and other genes of interest, were assessed by reverse-transcription quantitative PCR. Each cell line yielded differentiated models, with upregulation of markers of ciliated and mucus producing cells from day 7. In contrast to primary cells, immortalised cell lines did not produce cilia but, mucus was produced. TEER values increased with time, as expected, but values and therefore formation of tight junctions differed between models. Similarly, expression of viral entry genes increased as cells differentiated with marked differences across the different models. This study will be used to select the most appropriate ALI model for investigating the effect of environmental exposures such as smoking and vaping on susceptibility to SARS-COV-2 infection.

BACKGROUND: The delta opioid receptor (DOR) is broadly expressed throughout the nervous system; it regulates chronic pain, emotional responses, motivation, and memory. Neural circuits underlying DOR activities have been poorly explored by genetic approaches. We used conditional mouse mutagenesis to elucidate receptor function in GABAergic neurons of the forebrain. METHODS: We characterized DOR distribution in the brain of Dlx5/6-CreXOprd1(fl/fl) (Dlx-DOR) mice and tested main central DOR functions through behavioral testing. RESULTS: The DOR proteins were strongly deleted in olfactory bulb and striatum and remained intact in cortex and basolateral amygdala. Olfactory perception, circadian activity, and despair-like behaviors were unchanged. In contrast, locomotor stimulant effects of SNC80 (DOR agonist) and SKF81297 (D1 agonist) were abolished and increased, respectively. The Dlx-DOR mice showed lower levels of anxiety in the elevated plus maze, opposing the known high anxiety in constitutive DOR knockout animals. Also, Dlx-DOR mice reached the food more rapidly in a novelty suppressed feeding task, despite their lower motivation for food reward observed in an operant paradigm. Finally, c-fos protein staining after novelty suppressed feeding was strongly reduced in amygdala, concordant with the low anxiety phenotype of Dlx-DOR mice. CONCLUSIONS: We demonstrate that DORs expressed in the forebrain mediate the described locomotor effect of SNC80 and inhibit D1-stimulated hyperactivity. Our data also reveal an unanticipated anxiogenic role for this particular DOR subpopulation, with a potential novel adaptive role. In emotional responses, DORs exert dual anxiolytic and anxiogenic roles, both of which may have implications in the area of anxiety disorders. ; This work was supported by the Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, and Université de Strasbourg; the Fondation pour la Recherche Médicale (Grant No. FRM FDT20120925269), the U.S. National Institutes of Health (National Institute of Drug Addiction, Grant No. 05010, and National Institute on Alcohol Abuse and Alcoholism, Grant No. 16658); the Spanish Instituto de Salud Carlos III (Red de Trastornos Adictivos, Grant No. RD06/001/001), the Spanish Ministerio de Ciencia e Innovación (No. Ministerio de Ciencia e Innovación [Grant No. SAF2011-29864]), the Catalan Government (Grant No. SGR2009-00131), and Institucio Catalana de Recerca i Estudis Avançats Academia-2008; and NeuroPain (Framework programme 7, European Union)