Metabolic Adaptations Correlated with Antibody Response after Immunization with Inactivated SARS-CoV-2 in Brazilian Subjects.

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.

The remodel of the "central dogma": a metabolomics interaction perspective.

BACKGROUND: In 1957, Francis Crick drew a linear diagram on a blackboard. This diagram is often called the "central dogma." Subsequently, the relationships between different steps of the "central dogma" have been shown to be considerably complex, mostly because of the emerging world of small molecules. It is noteworthy that metabolites can be generated from the diet through gut microbiome metabolism, serve as substrates for epigenetic modifications, destabilize DNA quadruplexes, and follow Lamarckian inheritance. Small molecules were once considered the missing link in the "central dogma"; however, recently they have acquired a central role, and their general perception as downstream products has become reductionist. Metabolomics is a large-scale analysis of metabolites, and this emerging field has been shown to be the closest omics associated with the phenotype and concomitantly, the basis for all omics. AIM OF REVIEW: Herein, we propose a broad updated perspective for the flux of information diagram centered in metabolomics, including the influence of other factors, such as epigenomics, diet, nutrition, and the gut- microbiome. KEY SCIENTIFIC CONCEPTS OF REVIEW: Metabolites are the beginning and the end of the flux of information.

Real-Time Pure Shift HSQC NMR for Untargeted Metabolomics.

Sensitivity and resolution are key considerations for NMR applications in general and for metabolomics in particular, where complex mixtures containing hundreds of metabolites over a large range of concentrations are commonly encountered. There is a strong demand for advanced methods that can provide maximal information in the shortest possible time frame. Here, we present the optimization and application of the recently introduced 2D real-time BIRD 1H-13C HSQC experiment for NMR-based metabolomics of aqueous samples at 13C natural abundance. For mouse urine samples, it is demonstrated how this real-time pure shift sensitivity-improved heteronuclear single quantum correlation method provides broadband homonuclear decoupling along the proton detection dimension and thereby significantly improves spectral resolution in regions that are affected by spectral overlap. Moreover, the collapse of the scalar multiplet structure of cross-peaks leads to a sensitivity gain of about 40-50% over a traditional 2D HSQC-SI experiment. The experiment works well over a range of magnetic field strengths and is particularly useful when resonance overlap in crowded regions of the HSQC spectra hampers accurate metabolite identification and quantitation.

Type 1 Diabetes Brazilian patients exhibit reduced frequency of recent thymic emigrants in regulatory CD4+CD25+Foxp3+T cells.

To control immune responses, regulatory CD4+CD25+Foxp3+ T cells (Treg) maintain their wide and diverse repertoire through continuous arrival of recent thymic emigrants (RTE). However, during puberty, the activity of RTE starts to decline as a natural process of thymic involution, introducing consequences, not completely described, to the repertoire. Type 1 diabetes (T1D) patients show quantitative and qualitative impairments on the Treg cells. Our aim was to evaluate peripheral Treg and RTE cell frequencies, in T1D patients from two distinct age groups (young and adults) and verify if HLA phenotypes are concomitant associated. To this, blood samples from Brazilian twenty established T1D patients (12 young and 8 adults) and twenty-one healthy controls (11 young and 10 adults) were analyzed, by flow cytometry, to verify the percentages of CD4, Treg (CD4+CD25+Foxp3+) and the subsets of CD45RA+ (naive) and CD31+(RTE) within then. Furthermore, the HLA typing was also set. We observed that the young established T1D patients feature decreased frequencies in total Treg cells and naive RTE within Treg cells. Significant prevalence of HLA alleles, associated with risk, in T1D patients, was also identified. Performing a multivariate analysis, we confirmed that the cellular changes described offers significant variables that distinct T1D patients from the controls. Our data collectively highlight relevant aspects about homeostasis imbalances in the Treg cells of T1D patients, especially in young, and disease prognosis; that might contribute for future therapeutic strategies involving Treg cells manipulation.