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1.
Nat Med ; 30(5): 1384-1394, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38740997

RESUMEN

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.


Asunto(s)
Cadenas HLA-DRB1 , Humanos , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Lactante , Población Negra/genética , Vacunas contra Hepatitis B/inmunología , Sitios de Carácter Cuantitativo , Masculino , Femenino , Uganda , Formación de Anticuerpos/genética , Formación de Anticuerpos/inmunología , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/genética , Vacunación , Tos Ferina/prevención & control , Tos Ferina/inmunología , Tos Ferina/genética
2.
Artículo en Inglés | MEDLINE | ID: mdl-38718950

RESUMEN

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. OBJECTIVES: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ. CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

3.
Cell Rep Med ; 5(6): 101583, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38781962

RESUMEN

Little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS2) vaccine breakthrough infections (BTIs) on the magnitude and breadth of the T cell repertoire after exposure to different variants. We studied samples from individuals who experienced symptomatic BTIs during Delta or Omicron waves. In the pre-BTI samples, 30% of the donors exhibited substantial immune memory against non-S (spike) SARS2 antigens, consistent with previous undiagnosed asymptomatic SARS2 infections. Following symptomatic BTI, we observed (1) enhanced S-specific CD4 and CD8 T cell responses in donors without previous asymptomatic infection, (2) expansion of CD4 and CD8 T cell responses to non-S targets (M, N, and nsps) independent of SARS2 variant, and (3) generation of novel epitopes recognizing variant-specific mutations. These variant-specific T cell responses accounted for 9%-15% of the total epitope repertoire. Overall, BTIs boost vaccine-induced immune responses by increasing the magnitude and by broadening the repertoire of T cell antigens and epitopes recognized.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Vacunas contra la COVID-19 , COVID-19 , Epítopos de Linfocito T , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/virología , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Vacunas contra la COVID-19/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Memoria Inmunológica/inmunología , Femenino , Adulto , Masculino , Mutación , Persona de Mediana Edad , Linfocitos T/inmunología , Infección Irruptiva
4.
Food Chem ; 449: 139254, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38583403

RESUMEN

The study investigated Chenopodium berlandieri to analyze its oleanolic acid (OA) content. Response surface methodology with central composite design was used to improve saponin extraction, varying temperature, ethanol, and sample-to-solvent ratio. Best conditions (65 °C, 50% ethanol, 1:10 ratio) yielded 53.45 ± 0.63 mg/g of extract from Huauzontle seeds. Temperature linearly impacted extract yield, while temperature and ethanol influenced total saponin content. Hydrolyzing saponin-rich extracts produced OA-rich extracts. Characterization via HPLC-ELSD and LC-MS identified OA4 as the most concentrated OA saponin (5.54 ± 0.16 mg/g). OA alone reached 2.02 ± 0.12 mg/g. Acid hydrolysis increased OA content by up to 3.27×, highlighting the potential of hydrolyzed Huauzontle extracts as a natural ingredient for various industries due to enhanced OA content.


Asunto(s)
Chenopodium , Ácido Oleanólico , Extractos Vegetales , Saponinas , Ácido Oleanólico/química , Ácido Oleanólico/análisis , Saponinas/química , Hidrólisis , Extractos Vegetales/química , Chenopodium/química , Cromatografía Líquida de Alta Presión , Semillas/química
5.
Cell Rep Methods ; 4(3): 100731, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38490204

RESUMEN

Systems vaccinology studies have identified factors affecting individual vaccine responses, but comparing these findings is challenging due to varying study designs. To address this lack of reproducibility, we established a community resource for comparing Bordetella pertussis booster responses and to host annual contests for predicting patients' vaccination outcomes. We report here on our experiences with the "dry-run" prediction contest. We found that, among 20+ models adopted from the literature, the most successful model predicting vaccination outcome was based on age alone. This confirms our concerns about the reproducibility of conclusions between different vaccinology studies. Further, we found that, for newly trained models, handling of baseline information on the target variables was crucial. Overall, multiple co-inertia analysis gave the best results of the tested modeling approaches. Our goal is to engage community in these prediction challenges by making data and models available and opening a public contest in August 2024.


Asunto(s)
Multiómica , Vacunas , Humanos , Vacunología/métodos , Reproducibilidad de los Resultados , Simulación por Computador
6.
Hum Immunol ; 85(3): 110770, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38433036

RESUMEN

Post-acute sequelae of COVID-19 (PASC), or Long COVID, is a chronic condition following acute SARS-CoV-2 infection. Symptoms include exertion fatigue, respiratory issues, myalgia, and neurological manifestations such as 'brain fog,' posing concern for their debilitating nature and potential role in other neurological disorders. However, the underlying potential pathogenic mechanisms of the neurological complications of PASC is largely unknown. Herein, we investigated differences in antigen-specific T cell responses from the peripheral blood towards SARS-CoV-2, latent viruses, or neuronal antigens in 14 PASC individuals with neurological manifestations (PASC-N) versus 22 individuals fully recovered from COVID-19. We employed Activation Induced Marker (AIM), ICS and FluoroSpot assays to determine the specificity and magnitude of CD4+ and CD8+ T cell responses towards SARS-CoV-2 (Spike and rest of proteome), latent viruses (CMV, EBV), and several neuronal antigens. Overall, we observed similar antigen-specific T cell frequencies and cytokine effector T cell responses between PASC donors compared to recovered controls for all antigens tested (viral or autoantigen) in both CD4+ and CD8+ T cell compartments. Our findings suggest that PASC-N does not appear to be associated with changes in antigen-specific T cell responses towards a subset of disease-relevant targets, but more studies in a larger cohort are needed to confirm these unaltered responses.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , COVID-19 , Síndrome Post Agudo de COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/complicaciones , SARS-CoV-2/inmunología , Masculino , Persona de Mediana Edad , Linfocitos T CD8-positivos/inmunología , Femenino , Linfocitos T CD4-Positivos/inmunología , Adulto , Anciano , Autoinmunidad/inmunología , Citocinas/metabolismo , Citocinas/inmunología , Autoantígenos/inmunología
7.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38396707

RESUMEN

We studied T-cell responses to SARS-CoV-2 in 19 pregnant subjects at different gestational weeks who received three doses of mRNA-based vaccination to prevent COVID-19. SARS-CoV-2 peptide pools were used for T-cell recognition studies: peptides were 15 amino acids long and had previously been defined in COVID-19-convalescent subjects. T-cell activation was evaluated with the AIM assay. Most subjects showed coordinated, spike-specific CD4+ and CD8+ T-cell responses and the development of T cell memory. Non-spike-specific T cells in subjects who were not aware of previous COVID-19 infection suggested a prior undetected, asymptomatic infection. CD4- CD8- double negative (DN) T cells were numerous, of which a percentage was specific for SARS-CoV-2 spike peptides. Regulatory T cells (Treg), both spike- and non-spike-specific, were also greatly expanded. Two Treg populations were defined: a population differentiated from naïve T cells, and pTreg, reverting from pro-inflammatory T cells. The Treg cells expressed CCR6, suggesting homing to the endometrium and vaginal epithelial cells. The pregnant women responded to SARS-CoV-2 vaccination. Asymptomatic COVID-19 was revealed by the T cell response to the non-spike peptides. The numerous DN T cells and Treg pointed our attention to new aspects of the adaptive immune response in vaccine recipients.


Asunto(s)
COVID-19 , Linfocitos T Reguladores , Embarazo , Femenino , Humanos , SARS-CoV-2 , Mujeres Embarazadas , COVID-19/prevención & control , Vacunas contra la COVID-19 , Vacunación , Linfocitos T CD8-positivos , Péptidos , Anticuerpos Antivirales
8.
Sci Rep ; 14(1): 1146, 2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-38212400

RESUMEN

A supercritical CO2 method was optimized to recover naringenin-rich extract from Mexican oregano (Lippia graveolens), a flavanone with high antioxidant and anti-inflammatory activity. The effect of the extraction parameters like pressure, temperature, and co-solvent on naringenin concentration was evaluated. We used response surface methodology to optimize the naringenin extraction from oregano; the chemical composition by UPLC-MS of the optimized extract and the effect of simulated gastrointestinal digestion on its antioxidant capacity and total phenolic content were also evaluated. The optimum conditions were 58.4 °C and 12.46% co-solvent (ethanol), with a pressure of 166 bar, obtaining a naringenin content of 46.59 mg/g extract. Also, supercritical optimized extracts yielded high quantities of cirsimaritin, quercetin, phloridzin, apigenin, and luteolin. The results indicated that the naringenin-rich extract obtained at optimized conditions had higher total phenolic content, antioxidant capacity by TEAC and ORAC, and flavonoid content, compared with the methanolic extract, and the simulated gastrointestinal digestion reduced all these values.


Asunto(s)
Flavanonas , Lippia , Origanum , Antioxidantes/química , Lippia/química , Origanum/química , Dióxido de Carbono , Cromatografía Liquida , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectrometría de Masas en Tándem , Fenoles , Solventes/química , Digestión
9.
Nanoscale Adv ; 6(1): 51-71, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38125589

RESUMEN

The world faces threats that the United Nations has classified into 17 categories with different objectives as solutions for each challenge that are enclosed in the Sustainable Development Goals (SDGs). These actions involved the widespread use of science and technology as pathways to ensure their implementation. In this regard, sustainability science seeks the research community's contribution to addressing sustainable development challenges. Specifically, nanotechnology has been recognized as a key tool to provide disruptive and effective strategies to reach the SDGs. This review proposes the application of bimetallic nanoparticle substances capable of providing possible solutions to achieve target SDG 3: good health and well-being, SDG 6: clean water and sanitation, and SDG 12: responsible consumption and production. Furthermore, the term green nanotechnology is introduced in each section to exemplify how green synthesized bimetallic nanoparticles have been used to resolve each target SDG. This review also outlines the current scenario regarding the utilization of metallic nanomaterials in the market, together with the upscaling challenges and the lack of understanding of the long-term effects and hazards to the environment regarding bimetallic nanoparticles.

10.
Curr Protoc ; 3(11): e934, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37966108

RESUMEN

Epitopes recognized by T cells are a collection of short peptide fragments derived from specific antigens or proteins. Immunological research to study T cell responses is hindered by the extreme degree of heterogeneity of epitope targets, which are usually derived from multiple antigens; within a given antigen, hundreds of different T cell epitopes can be recognized, differing from one individual to the next because T cell epitope recognition is restricted by the epitopes' ability to bind to MHC molecules, which are extremely polymorphic in different individuals. Testing large pools encompassing hundreds of peptides is technically challenging because of logistical considerations regarding solvent-induced toxicity. To address this issue, we developed the MegaPool (MP) approach based on sequential lyophilization of large numbers of peptides that can be used in a variety of assays to measure T cell responses, including ELISPOT, intracellular cytokine staining, and activation-induced marker assays, and that has been validated in the study of infectious diseases, allergies, and autoimmunity. Here, we describe the procedures for generating and testing MPs, starting with peptide synthesis and lyophilization, as well as a step-by-step guide and recommendations for their handling and experimental usage. Overall, the MP approach is a powerful strategy for studying T cell responses and understanding the immune system's role in health and disease. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Generation of peptide pools ("MegaPools") Basic Protocol 2: MegaPool testing and quantitation of antigen-specific T cell responses.


Asunto(s)
Linfocitos T CD8-positivos , Epítopos de Linfocito T , Humanos , Ensayo de Immunospot Ligado a Enzimas , Péptidos , Linfocitos T CD4-Positivos
11.
Foods ; 12(22)2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38002219

RESUMEN

It has been reported that pineapple (Ananas comosus) contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. However, a substantial amount of pineapple residue is produced due to a lack of valorization applications at the industrial scale, resulting in the loss of valuable nutrients. Solid-state fermentation (SSF) is proposed as an innovative strategy to enhance the release of bound phenolics from pineapple residues. In this work, the effects of SSF of pineapple peels with Lactobacillus plantarum, Lactobacillus rhamnosus, and Aspergillus oryzae on the release of phenolic compounds and their antioxidant and anti-inflammatory activities were evaluated, respectively. Pineapple peel extracts after SSF showed an increase in the release of phenolic compounds (248.11% with L. plantarum, 182% with A. oryzae, and 180.10% with L. rhamnosus), which led to an increase in the cellular antioxidant (81.94% with L. rhamnosus) and anti-inflammatory potential (nitric oxide inhibition of 62% with L. rhamnosus) compared to non-fermented extracts. Therefore, SSF of pineapple peels with L. plantarum, L. rhamnosus, and A. oryzae thrives as a new approach for the production of secondary metabolites with remarkable biological benefits, which can be the precursors for novel biofortified and nutraceutical-enriched foods that meet the needs of the most demanding and health-conscious consumers.

12.
Front Public Health ; 11: 1150261, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37900038

RESUMEN

Nursing students, as the future healthcare workforce, hold immense potential in providing quality care to older adults and becoming advocates for promoting aging and public health, thus contributing significantly to addressing the multifaceted challenges of our aging society. Nurses' knowledge and attitudes about aging affect health care quality. Negative and unattractive representations of the social problems associated with aging contaminate nursing students' attitudes. Nursing schools are challenged to develop new curricula to prepare future nurses for the inherent complexity of an aging society. This study aims to assess the knowledge and attitudes of nursing students toward older adults and identify the variables that can influence these attitudes. Quantitative research was carried out through the application of an online survey using a cross-sectional descriptive research design. A total of 182 nursing students completed the online survey. Progression in the nursing course was statistically significant; the more students advanced, the more positive attitudes and knowledge they revealed about aging; 39% of students have daily contact with their grandparents; however, only 14.8% would like to work with older adults. Multiple linear regression revealed that the most important factor for positive attitudes and knowledge about aging was regular contact with grandparents, followed by progression in the nursing course. The students' age was not a significant factor in improving attitudes or expanding knowledge regarding older adults. In a multidimensional logic, the deepening of knowledge about aging and the socialization of students with older adults are central factors that should reinforce curricula in nursing education.


Asunto(s)
Educación en Enfermería , Estudiantes de Enfermería , Humanos , Anciano , Competencia Clínica , Estudios Transversales , Actitud del Personal de Salud
13.
Nat Immunol ; 24(10): 1711-1724, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37735592

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific cluster of differentiation (CD)4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production and primary responses to nonspike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.

14.
bioRxiv ; 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37693565

RESUMEN

Computational models that predict an individual's response to a vaccine offer the potential for mechanistic insights and personalized vaccination strategies. These models are increasingly derived from systems vaccinology studies that generate immune profiles from human cohorts pre- and post-vaccination. Most of these studies involve relatively small cohorts and profile the response to a single vaccine. The ability to assess the performance of the resulting models would be improved by comparing their performance on independent datasets, as has been done with great success in other areas of biology such as protein structure predictions. To transfer this approach to system vaccinology studies, we established a prototype platform that focuses on the evaluation of Computational Models of Immunity to Pertussis Booster vaccinations (CMI-PB). A community resource, CMI-PB generates experimental data for the explicit purpose of model evaluation, which is performed through a series of annual data releases and associated contests. We here report on our experience with the first such 'dry run' for a contest where the goal was to predict individual immune responses based on pre-vaccination multi-omic profiles. Over 30 models adopted from the literature were tested, but only one was predictive, and was based on age alone. The performance of new models built using CMI-PB training data was much better, but varied significantly based on the choice of pre-vaccination features used and the model building strategy. This suggests that previously published models developed for other vaccines do not generalize well to Pertussis Booster vaccination. Overall, these results reinforced the need for comparative analysis across models and datasets that CMI-PB aims to achieve. We are seeking wider community engagement for our first public prediction contest, which will open in early 2024.

15.
Foods ; 12(16)2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37627988

RESUMEN

Ultrasound-assisted extraction (UAE) is an efficient and sustainable method for extracting bioactive compounds from agro-industrial by-products. Moreover, it has been reported that ultraviolet A (UVA) radiation can induce the biosynthesis and accumulation of bioactive phenolic compounds. This study optimized the efficiency of ultrasound-assisted extraction (UAE) for recovering ultraviolet A (UVA)-induced phenolic compounds in strawberry by-products (RF-N). The impact of three factors (solid-liquid ratio, ethanol concentration, and ultrasound power) on total phenolic compound (TPC) kinetics using Peleg's model was investigated. The developed model showed a suitable fit for both RF-N and strawberry by-products treated with UVA (RF-E). The optimal UAE conditions obtained were of a 1:30 ratio, 46% ethanol, and 100% ultrasound power, resulting in an average yield of 13 g total phenolics kg-1. The bioaccessibility of phenolic compounds during in-vitro digestion was 36.5%, with agrimoniin being the predominant compound. UAE combined with UVA treatment increased the bioactivity of RF extracts, displaying significant anti-proliferative effects on HT29 and Caco-2 cancer cell lines, as well as anti-inflammatory potential and cellular antioxidant activity. The ultrasound proved to be a sustainable and effective technique for extracting phenolic compounds from RF, contributing to the valorization of strawberry agro-industrial by-products, and maximizing their nutraceutical potential.

16.
Plants (Basel) ; 12(14)2023 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-37514343

RESUMEN

Plants of the Phoradendron genus have been traditionally used for their lipid- and glucose-lowering effects. However, the compounds responsible for these effects and the overall chemical profile of these plants have not been thoroughly investigated. We aimed to characterize the metabolome of leaves, stems, and aerial parts of the Phoradendron brachystachyum plant. We used mass spectrometry and colorimetric screening techniques (with various solvents) to identify and characterize the metabolites present. We also evaluated the antioxidant (FRAP, ORAC, TEAC, and DPPH assays) and inhibitory effects on pancreatic lipase and α-glucosidase enzymes of hydrophilic extracts. Furthermore, we compared the molecular fingerprints between the identified metabolites and FDA-approved drugs to gain insights into the metabolites that might be responsible for the observed effects on enzymes. Our findings revealed the presence of 59 putative metabolites, primarily flavonoids. However, we also hint at the presence of peptide and carbohydrate derivatives. The leaf extracts demonstrated the most promising metrics across all assays, exhibiting strong antioxidant and enzyme inhibitory effects as well as high levels of phenolic compounds, flavonoids, and tannins. Fingerprint analysis suggested potential peptide and carbohydrate metabolites as pancreatic lipase and α-glucosidase inhibitors. Overall, our study provides evidence on specific metabolites in Phoradendron brachystachyum that could be responsible for the therapeutic effects noted in obese and type 2 diabetes subjects.

17.
Cell Host Microbe ; 31(8): 1404-1416.e4, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37490913

RESUMEN

The incidence of whooping cough due to Bordetella pertussis (BP) infections has increased recently. It is believed that the shift from whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines may be contributing to this rise. While T cells are key in controlling and preventing disease, nearly all knowledge relates to antigens in aP vaccines. A whole-genome mapping of human BP-specific CD4+ T cell responses was performed in healthy vaccinated adults and revealed unexpected broad reactivity to hundreds of antigens. The overall pattern and magnitude of T cell responses to aP and non-aP vaccine antigens are similar regardless of childhood vaccination, suggesting that asymptomatic infections drive the pattern of T cell reactivity in adults. Lastly, lack of Th1/Th2 polarization to non-aP vaccine antigens suggests these antigens have the potential to counteract aP vaccination Th2 bias. These findings enhance our insights into human T cell responses to BP and identify potential targets for next-generation pertussis vaccines.


Asunto(s)
Bordetella pertussis , Tos Ferina , Adulto , Humanos , Tos Ferina/prevención & control , Inmunización Secundaria , Vacuna contra la Tos Ferina , Vacunación
18.
J Immunol Methods ; 519: 113520, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37390890

RESUMEN

Protocols for the isolation of peripheral blood mononuclear cells (PBMCs) from whole blood vary greatly between laboratories, especially in published studies of SARS-CoV-2-specific T cell responses following infection and vaccination. Research on the effects of different wash media types or centrifugation speeds and brake usage during the PBMC isolation process on downstream T cell activation and functionality is limited. Blood samples from 26 COVID-19-vaccinated participants were processed with different PBMC isolation methods using either PBS or RPMI as the wash media with high centrifugation speed and brakes or RPMI as the wash media with low speed and brakes (RPMI+ method). SARS-CoV-2 spike-specific T cells were quantified and characterized via a flow cytometry-based activation induced markers (AIM) assay and an interferon-γ (IFNγ) FluoroSpot assay and responses were compared between processing methods. Samples washed with RPMI showed higher AIM+ CD4 T cell responses than those washed with PBS and showed a shift away from naïve and towards an effector memory phenotype. The activation marker OX40 showed higher SARS-CoV-2 spike-induced upregulation on RPMI-washed CD4 T cells, while differences in CD137 upregulation were minimal between processing methods. The magnitude of the AIM+ CD8 T cell response was similar between processing methods but showed higher stimulation indices. Background frequencies of CD69+ CD8 T cells were increased in PBS-washed samples and were associated with higher baseline numbers of IFNγ-producing cells in the FluoroSpot assay. Slower braking in the RPMI+ method did not improve detection of SARS-CoV-2-specific T cells and caused longer processing times. Thus, the use of RPMI media with full centrifugation brakes during the wash steps of PBMC isolation was found to be most effective and efficient. Further studies are needed to elucidate the pathways involved in RPMI-mediated preservation of downstream T cell activity.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Leucocitos Mononucleares , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos
19.
Foods ; 12(11)2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37297394

RESUMEN

The health-related compounds present in kale are vulnerable to the digestive process or storage conditions. Encapsulation has become an alternative for their protection and takes advantage of their biological activity. In this study, 7-day-old Red Russian kale sprouts grown in the presence of selenium (Se) and sulfur (S) were spray-dried with maltodextrin to assess their capacity to protect kale sprout phytochemicals from degradation during the digestion process. Analyses were conducted on the encapsulation efficiency, particle morphology, and storage stability. Mouse macrophages (Raw 264.7) and human intestinal cells (Caco-2) were used to assess the effect of the intestinal-digested fraction of the encapsulated kale sprout extracts on the cellular antioxidant capacity, the production of nitric oxide (NOx), and the concentrations of different cytokines as indicators of the immunological response. The highest encapsulation efficiency was observed in capsules with a 50:50 proportion of the hydroalcoholic extract of kale and maltodextrin. Gastrointestinal digestion affected compounds' content in encapsulated and non-encapsulated kale sprouts. Spray-dried encapsulation reduced the phytochemicals' degradation during storage, and the kale sprouts germinated with S and Se showed less degradation of lutein (35.6%, 28.2%), glucosinolates (15.4%, 18.9%), and phenolic compounds (20.3%, 25.7%), compared to non-encapsulated ones, respectively. S-encapsulates exerted the highest cellular antioxidant activity (94.2%) and immunomodulatory activity by stimulating IL-10 production (88.9%) and COX-2 (84.1%) and NOx (92.2%) inhibition. Thus, encapsulation is an effective method to improve kale sprout phytochemicals' stability and bioactivity during storage and metabolism.

20.
Antioxidants (Basel) ; 12(6)2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37371904

RESUMEN

The genus Opuntia spp. includes plants capable of growing in arid, temperate and tropical climates. The vast majority of wild species grow in Mexico, but O. ficus-indica (prickly pear or nopal) is cultivated around the world and it is one of the most studied. This review shows the currently available knowledge concerning the action of O. ficus-indica and other Opuntia species (Opuntia vulgaris, Opuntia robusta, Opuntia streptacantha, Opuntia microdasys, Opuntia dillenii and Opuntia dejecta) on liver health. The available data demonstrate the positive effects of extracts, vinegar, juices or seed oil of the Opuntia genus on the alterations induced in the liver by inadequate feeding patterns or the administration of chemicals. In this regard, the potential beneficial effects of nopal are related to the attenuation of triglyceride accumulation, oxidative stress and/or inflammation. Nevertheless, there is no information concerning the bioactive compound's characterisation in most of these studies; consequently, it is not possible to link the therapeutic effects of these plants to the presence of specific compounds in the nopal extracts. Therefore, further research is needed to confirm if the positive effects observed in animal models are also found in humans, in order to determine whether Opuntia can represent an effective tool to prevent and/or manage hepatic alterations.

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