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1.
Molecules ; 27(3)2022 Jan 27.
Article in English | MEDLINE | ID: covidwho-1674736

ABSTRACT

Butyrate is a major gut microbiome metabolite that regulates several defense mechanisms against infectious diseases. Alterations in the gut microbiome, leading to reduced butyrate production, have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A new butyrate releaser, useful for all the known applications of butyrate, presenting physiochemical characteristics suitable for easy oral administration, (N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), has been recently developed. We investigated the protective action of FBA against SARS-CoV-2 infection in the human small intestine and enterocytes. Relevant aspects of SARS-CoV-2 infection were assessed: infectivity, host functional receptor angiotensin-converting enzyme-2 (ACE2), transmembrane protease serine 2 (TMPRSS2), neuropilin-1 (NRP1), pro-inflammatory cytokines expression, genes involved in the antiviral response and the activation of Nf-kB nuclear factor (erythroid-derived 2-like) 2 (Nfr2) pathways. We found that FBA positively modulates the crucial aspects of the infection in small intestinal biopsies and human enterocytes, reducing the expression of ACE2, TMPRSS2 and NRP1, pro-inflammatory cytokines interleukin (IL)-15, monocyte chemoattractant protein-1 (MCP-1) and TNF-α, and regulating several genes involved in antiviral pathways. FBA was also able to reduce the number of SARS-CoV-2-infected cells, and ACE2, TMPRSS2 and NRP1 expression. Lastly, through the inhibition of Nf-kB and the up-regulation of Nfr2, it was also able to reduce the expression of pro-inflammatory cytokines IL-15, MCP-1 and TNF-α in human enterocytes. The new butyrate releaser, FBA, exerts a preventive action against SARS-CoV-2 infection. It could be considered as an innovative strategy to limit COVID-19.


Subject(s)
Butyrates/pharmacology , COVID-19/drug therapy , SARS-CoV-2/metabolism , Antiviral Agents/pharmacology , Butyrates/metabolism , COVID-19/metabolism , Caco-2 Cells , Enterocytes/drug effects , Enterocytes/metabolism , Gene Expression/genetics , Gene Expression Regulation/genetics , Humans , Intestines/drug effects , Intestines/metabolism , Male , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
2.
J Mater Chem B ; 9(44): 9221-9229, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1550364

ABSTRACT

Ethyl butyrate (EB) was identified in recent research as a prominent biomarker of COVID-19, as concentrations of EB were higher in exhaled breath of COVID-19 patients. Electronic sensitivities of pristine, Al- and Si-doped BC3 nanosheets to the EB molecule were investigated in this study using density functional theory. It is found that the pure BC3 was ineffective in sensing EB due to low adsorption energy and sensitivity. Aluminum- and silicon-doped BC3 nanosheets were effective in forming a strong interaction with EB and were also sensitive. Our calculations show that the band gaps of the Al-doped and Si-doped BC3 sheets were significantly decreased upon EB adsorption, which increased the electrical conductance of the sheets and the sensitivity. However, Si-doped BC3 had a recovery time of almost 22 hours, making it less potent than Al-doped BC3, which had a recovery time of just 7.7 minutes. The shorter recovery time of the Al-doped BC3 sheet is due to its moderate adsorption energy of 25.8 kcal mol-1. These results can help facilitate the development of an EB biosensor for COVID-19 testing and other similar applications.


Subject(s)
Biomarkers/metabolism , Butyrates/metabolism , COVID-19 Testing/methods , COVID-19/metabolism , Nanostructures , SARS-CoV-2/isolation & purification , Adsorption , COVID-19/virology , Humans
3.
Cells ; 10(12)2021 11 25.
Article in English | MEDLINE | ID: covidwho-1542428

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.


Subject(s)
Arachidonic Acids/therapeutic use , Endocannabinoids/therapeutic use , Gastrointestinal Microbiome , Gastrointestinal Tract/pathology , Lung/pathology , Polyunsaturated Alkamides/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/microbiology , Animals , Arachidonic Acids/pharmacology , Butyrates/metabolism , Cecum/pathology , Cell Separation , Colon/drug effects , Colon/pathology , Discriminant Analysis , Dysbiosis/complications , Dysbiosis/microbiology , Endocannabinoids/pharmacology , Enterotoxins , Female , Gastrointestinal Tract/drug effects , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymphocyte Activation/drug effects , Mice, Inbred C57BL , Pneumonia/drug therapy , Pneumonia/microbiology , Polyunsaturated Alkamides/pharmacology , Respiratory Distress Syndrome/complications , T-Lymphocytes/drug effects
4.
J Mater Chem B ; 9(44): 9221-9229, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1493243

ABSTRACT

Ethyl butyrate (EB) was identified in recent research as a prominent biomarker of COVID-19, as concentrations of EB were higher in exhaled breath of COVID-19 patients. Electronic sensitivities of pristine, Al- and Si-doped BC3 nanosheets to the EB molecule were investigated in this study using density functional theory. It is found that the pure BC3 was ineffective in sensing EB due to low adsorption energy and sensitivity. Aluminum- and silicon-doped BC3 nanosheets were effective in forming a strong interaction with EB and were also sensitive. Our calculations show that the band gaps of the Al-doped and Si-doped BC3 sheets were significantly decreased upon EB adsorption, which increased the electrical conductance of the sheets and the sensitivity. However, Si-doped BC3 had a recovery time of almost 22 hours, making it less potent than Al-doped BC3, which had a recovery time of just 7.7 minutes. The shorter recovery time of the Al-doped BC3 sheet is due to its moderate adsorption energy of 25.8 kcal mol-1. These results can help facilitate the development of an EB biosensor for COVID-19 testing and other similar applications.


Subject(s)
Biomarkers/metabolism , Butyrates/metabolism , COVID-19 Testing/methods , COVID-19/metabolism , Nanostructures , SARS-CoV-2/isolation & purification , Adsorption , COVID-19/virology , Humans
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