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1.
Metabolites ; 13(7)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37512587

RESUMEN

Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients' sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.

2.
J Proteome Res ; 22(6): 1908-1922, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37167433

RESUMEN

The adsorbed vaccine SARS-CoV-2 (inactivated) produced by Sinovac (SV) was the first vaccine against COVID-19 to be used in Brazil. To understand the metabolic effects of SV in Brazilian subjects, NMR-based metabolomics was used, and the immune response was studied in Brazilian subjects. Forty adults without (group-, n = 23) and with previous COVID-19 infection (group+, n = 17) were followed-up for 90 days postcompletion of the vaccine regimen. After 90 days, our results showed that subjects had increased levels of lipoproteins, lipids, and N-acetylation of glycoproteins (NAG) as well as decreased levels of amino acids, lactate, citrate, and 3-hydroxypropionate. NAG and threonine were the highest correlated metabolites with N and S proteins, and neutralizing Ab levels. This study sheds light on the immunometabolism associated with the use of SV in Brazilian subjects from Rio de Janeiro and identifies potential metabolic markers associated with the immune status.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Brasil , Formación de Anticuerpos , Vacunas contra la COVID-19 , Inmunización , Anticuerpos Antivirales
3.
Front Immunol ; 9: 2139, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30298073

RESUMEN

Leptin is a cytokine, produced mainly by mature adipocytes, that regulates the central nervous system, mainly to suppress appetite and stimulate energy expenditure. Leptin also regulates the immune response by controlling activation of immunomodulatory cells, including eosinophils. While emerging as immune regulatory cells with roles in adipose tissue homeostasis, eosinophils have a well-established ability to synthesize pro-inflammatory molecules such as lipid mediators, a key event in several inflammatory pathologies. Here, we investigated the impact and mechanisms involved in leptin-driven activation of eicosanoid-synthesizing machinery within eosinophils. Direct in vitro activation of human or mouse eosinophils with leptin elicited synthesis of lipoxygenase as well as cyclooxygenase products. Displaying selectivity, leptin triggered synthesis of LTC4 and PGD2, but not PGE2, in parallel to dose-dependent induction of lipid body/lipid droplets biogenesis. While dependent on PI3K activation, leptin-driven eosinophil activation was also sensitive to pertussis toxin, indicating the involvement of G-protein coupled receptors on leptin effects. Leptin-induced lipid body-driven LTC4 synthesis appeared to be mediated through autocrine activation of G-coupled CCR3 receptors by eosinophil-derived CCL5, inasmuch as leptin was able to trigger rapid CCL5 secretion, and neutralizing anti-RANTES or anti-CCR3 antibodies blocked lipid body assembly and LTC4 synthesis induced by leptin. Remarkably, autocrine activation of PGD2 G-coupled receptors DP1 and DP2 also contributes to leptin-elicited lipid body-driven LTC4 synthesis by eosinophils in a PGD2-dependent fashion. Blockade of leptin-induced PGD2 autocrine/paracrine activity by a specific synthesis inhibitor or DP1 and DP2 receptor antagonists, inhibited both lipid body biogenesis and LTC4 synthesis induced by leptin stimulation within eosinophils. In addition, CCL5-driven CCR3 activation appears to precede PGD2 receptor activation within eosinophils, since neutralizing anti-CCL5 or anti-CCR3 antibodies inhibited leptin-induced PGD2 secretion, while it failed to alter PGD2-induced LTC4 synthesis. Altogether, sequential activation of CCR3 and then PGD2 receptors by autocrine ligands in response to leptin stimulation of eosinophils culminates with eosinophil activation, characterized here by assembly of lipidic cytoplasmic platforms synthesis and secretion of the pleiotropic lipid mediators, PGD2, and LTC4.


Asunto(s)
Eosinófilos/inmunología , Leptina/metabolismo , Leucotrieno C4/biosíntesis , Receptores CCR3/metabolismo , Receptores Inmunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Animales , Células Cultivadas , Quimiocina CCL5/antagonistas & inhibidores , Quimiocina CCL5/metabolismo , Eosinófilos/citología , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Femenino , Humanos , Hidantoínas/farmacología , Oxidorreductasas Intramoleculares/antagonistas & inhibidores , Oxidorreductasas Intramoleculares/metabolismo , Leptina/inmunología , Leucotrieno C4/inmunología , Gotas Lipídicas/inmunología , Gotas Lipídicas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Piperidinas/farmacología , Cultivo Primario de Células , Prostaglandina D2/metabolismo , Receptores CCR3/antagonistas & inhibidores , Receptores CCR3/inmunología , Receptores Inmunológicos/antagonistas & inhibidores , Receptores Inmunológicos/inmunología , Receptores de Prostaglandina/antagonistas & inhibidores , Receptores de Prostaglandina/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo
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