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IntroductionPeople with hazardous alcohol use are more susceptible to viral, bacterial, and fungal infections due to the effect of alcohol on immune system cell function. Metabolized ethanol reduces NAD+ to NADH, affecting critical metabolic pathways. Here, our aim was to investigate whether alcohol is metabolized by bone marrow cells and if it impacts the metabolic pathways of leukocyte progenitor cells. This is said to lead to a qualitative and quantitative alteration of key metabolites which may be related to the immune response.MethodsWe addressed this aim by using C57BL/6 mice under chronic ethanol administration and evaluating the metabolomic profile of bone marrow total cells by gas chromatography–coupled mass spectrometry (GC–MS).ResultsWe identified 19 metabolites. Our data demonstrated that chronic ethanol administration alters the metabolomic profile in the bone marrow, resulting in a statistically diminished abundance of five metabolites in ethanol-treated animals: uracil, succinate, proline, nicotinamide, and tyrosine.DiscussionOur results demonstrate for the first time in the literature the effects of alcohol consumption on the metabolome content of hematopoietic tissue and open a wide range of further studies to investigate mechanisms by which alcohol compromises the cellular function of the immune system.

Aging is not a matter of choice; it is our fate. The “time-dependent functional decline that affects most living organisms” is coupled with several alterations in cellular processes, such as cell senescence, epigenetic alterations, genomic instability, stem cell exhaustion, among others. Age-related morphological changes in dental follicles have been investigated for decades, mainly motivated by the fact that cysts and tumors may arise in association with unerupted and/or impacted teeth. The more we understand the physiology of dental follicles, the more we are able to contextualize biological events that can be associated with the occurrence of odontogenic lesions, whose incidence increases with age. Thus, our objective was to assess age-related changes in metabolic pathways of dental follicles associated with unerupted/impacted mandibular third molars from young and adult individuals. For this purpose, a convenience sample of formalin-fixed paraffin-embedded (FFPE) dental follicles from young (26 y.o., n = 7) individuals was selected. Samples were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS)-based untargeted metabolomics. Multivariate and univariate analyses were conducted, and the prediction of altered pathways was performed by mummichog and Gene Set Enrichment Analysis (GSEA) approaches. Dental follicles from young and older individuals showed differences in pathways related to C21-steroid hormone biosynthesis, bile acid biosynthesis, galactose metabolism, androgen and estrogen biosynthesis, starch and sucrose metabolism, and lipoate metabolism. We conclude that metabolic pathways differences related to aging were observed between dental follicles from young and adult individuals. Our findings support that similar to other human tissues, dental follicles associated with unerupted tooth show alterations at a metabolic level with aging, which can pave the way for further studies on oral pathology, oral biology, and physiology.

Leishmaniasis is a neglected tropical disease (NTD) caused by parasites belonging to the Leishmania genus for which there is no vaccine available for human use. Thus, the aims of this study are to evaluate the immunoprotective effect of a first-generation vaccine against L. amazonensis and to identify its immunodominant antigens. BALB/c mice were inoculated with phosphate buffer sodium (PBS), total L. amazonensis antigens (TLAs), or TLA with Poly (I:C) and Montanide ISA 763. The humoral and cellular immune response was evaluated before infection. IgG, IgG1, and IgG2a were measured on serum, and IFN-γ, IL-4, and IL-10 cytokines as well as cell proliferation were measured on a splenocyte culture from vaccinated mice. Immunized mice were challenged with 104 infective parasites of L. amazonensis on the footpad. After infection, the protection provided by the vaccine was analyzed by measuring lesion size, splenic index, and parasite load on the footpad and spleen. To identify immunodominant antigens, total proteins of L. amazonensis were separated on 2D electrophoresis gel and transferred to a membrane that was incubated with serum from immunoprotected mice. The antigens recognized by the serum were analyzed through a mass spectrometric assay (LC-MS/MS-IT-TOF) to identify their protein sequence, which was subjected to bioinformatic analysis. The first-generation vaccine induced higher levels of antibodies, cytokines, and cell proliferation than the controls after the second dose. Mice vaccinated with TLA + Poly (I:C) + Montanide ISA 763 showed less footpad swelling, a lower splenic index, and a lower parasite load than the control groups (PBS and TLA). Four immunodominant proteins were identified by mass spectrometry: cytosolic tryparedoxin peroxidase, an uncharacterized protein, a kinetoplast-associated protein-like protein, and a putative heat-shock protein DNAJ. The identified proteins showed high levels of conserved sequence among species belonging to the Leishmania genus and the Trypanosomatidae family. These proteins also proved to be phylogenetically divergent to human and canine proteins. TLA + Poly (I:C) + Montanide ISA 763 could be used as a first-generation vaccine against leishmaniasis. The four proteins identified from the whole-protein vaccine could be good antigen candidates to develop a new-generation vaccine against leishmaniasis.