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Sulphated glycosaminoglycans (GAGs) such as heparin are a major component of mast cell granules and form the matrix within which biogenic mediators are stored. Since GAGs released from mast cells also play an important role in helminth expulsion, understanding GAG storage can offer new insights into mast cell function. Sodium butyrate (NaBu), a short-chain fatty acid, causes ultrastructural changes within the granules of human mast cells (HMC-1) and increases their histamine content. Therefore, we hypothesized that NaBu treatment would also modify the storage of polysaccharides such as GAGs. NaBu (1 mM) significantly increased GAG content and granularity in a time- and concentration-dependent manner without affecting cell viability and metabolic activity. NaBu increased the expression of enzymes associated with heparin biosynthesis (GLCE, NDST1, NDST2, HS6ST1, and GALT1) in a time-dependent manner. A cholesteryl butyrate emulsion (CholButE) increased heparin content after 24 and 48 h and modestly altered the expression of genes involved in heparin biosynthesis. Similar to NaBu, CholButE reduced cell proliferation without significantly altering viability or metabolic activity. These data show that butyrate increases the synthesis and storage of heparin in human mast cells, perhaps by altering their metabolic pathways. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19), a serious respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS--CoV-2), has emerged as a global pandemic. Canada reported its first case of COVID-19 on the 25th January 2020. By March 2020, the virus had spread within Canadian communities reaching the most frail and vulnerable elderly population in long-term care facilities. The majority of cases were reported in the provinces of Quebec, Ontario, Alberta, and British Columbia, and the highest mortality was seen among individuals aged 65 years or older. Canada has the highest prevalence and incidence rates of several chronic inflammatory diseases, such as multiple sclerosis, inflammatory bowel disease, and Parkinson's disease. Many elderly Canadians also live with comorbid medical illnesses, such as hypertension, diabetes, cardiovascular disease, and chronic lung disease, and are more likely to suffer from severe COVID-19 with a poor prognosis. It is becoming increasingly evident that underlying inflammatory disease contributes to the pathogenesis of SARS--CoV-2. Here, we review the mechanisms behind SARS--CoV-2 infection, and the host inflammatory responses that lead to resolution or progression to severe COVID-19 disease. Furthermore, we discuss the landscape of COVID-19 therapeutics that are currently in development in Canada. Key words: Canada, COVID-19, coronavirus, inflammation, therapeutics, chronic disease. La maladie a coronavirus 2019 (COVID-19), une maladie respiratoire grave causee par le coronavirus 2 du syndrome respiratoire aigu severe (SRAS--CoV-2), a emerge comme pandemie mondiale. Le Canada a signale son premier cas de la COVID-19 le 25 janvier 2020. En mars 2020, le virus s'etait propage au sein des communautes canadiennes, atteignant les personnes agees les plus fragiles et les plus vulnerables dans les etablissements de soins de longue duree. La majorite des cas ont ete signales dans les provinces de Quebec, de l'Ontario, de l'Alberta et de la Colombie-Britannique, et la mortalite la plus elevee a ete observee chez les personnes agees de 65 ans ou plus. Le Canada presente les taux de prevalence et d'incidence les plus eleves de plusieurs maladies inflammatoires chroniques, telles que la sclerose en plaques, les maladies inflammatoires de l'intestin et la maladie de Parkinson. De nombreux Canadiens ages vivent egalement avec des maladies concomitantes, telles que l'hypertension, le diabete, les maladies cardiovasculaires et les maladies pulmonaires chroniques, et sont plus susceptibles de souffrir de formes graves de la COVID-19 associees a un mauvais pronostic. Il est de plus en plus evident que la maladie inflammatoire sous-jacente contribue a la pathogenese du SRAS--CoV-2. Les auteurs examinent ici les mecanismes de l'infection par le SRAS--CoV-2 et les reponses inflammatoires de l'hote qui conduisent a la resolution ou a la progression vers une forme grave de la COVID-19. En outre, ils examinent le spectre des therapies contre la COVID-19 en cours de developpement au Canada. [Traduit par la Redaction] Mots-cles : Canada, COVID-19, coronavirus, inflammation, therapeutique, maladie chronique., Introduction In the past two decades, three novel human coronaviruses (HCoVs) have caused millions of infections worldwide and resulted in hundreds of thousands of deaths: severe acute respiratory syndrome coronavirus [...]

Unlabelled: RNA viruses often depend on host factors for multiplication inside cells due to the constraints of their small genome size and limited coding capacity. One such factor that has been exploited by several plant and animal viruses is heat shock protein 70 (HSP70) family homologs which have been shown to play roles for different viruses in viral RNA replication, viral assembly, disassembly, and cell-to-cell movement. Using next generation sequence analysis, we reveal that several isoforms of Hsp70 and Hsc70 transcripts are induced to very high levels during cucumber necrosis virus (CNV) infection of Nicotiana benthamiana and that HSP70 proteins are also induced by at least 10-fold. We show that HSP70 family protein homologs are co-opted by CNV at several stages of infection. We have found that overexpression of Hsp70 or Hsc70 leads to enhanced CNV genomic RNA, coat protein (CP), and virion accumulation, whereas downregulation leads to a corresponding decrease. Hsc70-2 was found to increase solubility of CNV CP in vitro and to increase accumulation of CNV CP independently of viral RNA replication during coagroinfiltration in N. benthamiana. In addition, virus particle assembly into virus-like particles in CP agroinfiltrated plants was increased in the presence of Hsc70-2. HSP70 was found to increase the targeting of CNV CP to chloroplasts during infection, reinforcing the role of HSP70 in chloroplast targeting of host proteins. Hence, our findings have led to the discovery of a highly induced host factor that has been co-opted to play multiple roles during several stages of the CNV infection cycle., Importance: Because of the small size of its RNA genome, CNV is dependent on interaction with host cellular components to successfully complete its multiplication cycle. We have found that CNV induces HSP70 family homologs to a high level during infection, possibly as a result of the host response to the high levels of CNV proteins that accumulate during infection. Moreover, we have found that CNV co-opts HSP70 family homologs to facilitate several aspects of the infection process such as viral RNA, coat protein and virus accumulation. Chloroplast targeting of the CNV CP is also facilitated, which may aid in CNV suppression of host defense responses. Several viruses have been shown to induce HSP70 during infection and others to utilize HSP70 for specific aspects of infection such as replication, assembly, and disassembly. We speculate that HSP70 may play multiple roles in the infection processes of many viruses., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)