Verónica García

University of Buenos Aires

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Joaquín Miguel Pellegrini

Aix-Marseille Université

Nancy Liliana Tateosian

Consejo Nacional de Investigaciones Científicas y Técnicas

Domingo Palmero

Hospital Muñiz

Virginia Pasquinelli

Consejo Nacional de Investigaciones Científicas y Técnicas

Nicolás Oscar Amiano

Fundación Ciencias Exactas y Naturales

Rosa Musella

Hospital Muñiz

María Paula Morelli

University of Buenos Aires

Rodrigo Emanuel Hernández Del Pino

National University of Northwestern Buenos Aires

Agustín Rolandelli

University of Maryland, Baltimore

Javier O. Jurado

University of Buenos Aires

Cooperative Institutions

Inserm

162

Centre National de la Recherche Scientifique

144

University of Michigan–Ann Arbor

129

University of Buenos Aires

129

Harvard University

128

Consejo Nacional de Investigaciones Científicas y Técnicas

123

Chinese Academy of Sciences

Consejo Superior de Investigaciones Científicas

National Institutes of Health

Istituti di Ricovero e Cura a Carattere Scientifico

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Perception of stereotypes about old age in university students in the city of Bucaramanga

Leidy Nayibe Hernández Almeida Verónica García Gloria Juliana Villamizar Pereira

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IL-12 DNA Displays Efficient Adjuvant Effects Improving Immunogenicity of Ag85A in DNA Prime/MVA Boost Immunizations

Frontiers in Cellular and Infection Microbiology (2020)

María Paula Morelli María Paula Del Médico Zajac Joaquín Miguel Pellegrini Nicolás Oscar Amiano Nancy Liliana Tateosian

Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice, and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA 85A induced a strong IFN-γ production to Ag85A in vitro, with a significant expansion of IFN-γ+CD4+ and IFN-γ+CD8+ anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8+CD107+ T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA 85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection.

Modified vaccinia Ankara

Tuberculosis vaccines

10.3389/fcimb.2020.581812

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Citations (6)

The Thoracic Inlet Length as a Reference Point to Radiographically Assess Cardiac Enlargement in Dogs with Myxomatous Mitral Valve Disease

Animals (2023)

David Marbella Fernández Verónica García Alexis José Santana José Alberto Montoya-Alonso

The diagnostic value of the vertebral heart size (VHS) in dogs with mitral valve degeneration (MVD) is compromised when middle thoracic vertebral anomalies are present. The objective of this study was to assess the use of the thoracic inlet heart score (TIHS) to identify left heart enlargement (LHE) secondary to MVD. The cardiac silhouette of 50 clinically healthy dogs and 106 MVD dogs in different stages was assessed on a right lateral chest radiograph. The TIHS and VHS value were calculated for each patient and compared. The TIHS was significantly different between the control dogs and the dogs with MMVD, increasing with disease stage, control 2.91 ± 0.23, Stage B1 2.98 ± 0.36, B2 3.25 ± 0.34, and C 3.53 ± 0.36, p < 0.05. A THIS ≥3.3 showed 69% sensitivity and 81% specificity to identify LHE. The TIHS showed moderate correlation with the VHS, LA/Ao, and LVIDDN 0.59, 0.42, and 0.62, respectively. The intraobserver and interobserver agreement were almost perfect, 0.96, and substantial, 0.73. The TIHS method can be used to identify LHE secondary to MMVD on dogs’ thoracic radiographs.

Chest radiograph

10.3390/ani13162666

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Citations (2)

Nrf2 is essential for timely M phase entry of replicating hepatocytes during liver regeneration

Yuhong Zou Min Hu Joonyong Lee Shashank Manohar Nambiar Verónica García

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates various cellular activities, including redox balance, detoxification, metabolism, autophagy, proliferation, and apoptosis. Several studies have demonstrated that Nrf2 regulates hepatocyte proliferation during liver regeneration. The aim of this study was to investigate how Nrf2 modulates the cell cycle of replicating hepatocytes in regenerating livers. Wild-type and Nrf2 null mice were subjected to 2/3 partial hepatectomy (PH) and killed at multiple time points for various analyses. Nrf2 null mice exhibited delayed liver regrowth, although the lost liver mass was eventually restored 7 days after PH. Nrf2 deficiency did not affect the number of hepatocytes entering the cell cycle but did delay hepatocyte mitosis. Mechanistically, the lack of Nrf2 resulted in increased mRNA and protein levels of hepatic cyclin A2 when the remaining hepatocytes were replicating in response to PH. Moreover, Nrf2 deficiency in regenerating livers caused dysregulation of Wee1, Cdc2, and cyclin B1 mRNA and protein expression, leading to decreased Cdc2 activity. Thus, Nrf2 is required for timely M phase entry of replicating hepatocytes by ensuring proper regulation of cyclin A2 and the Wee1/Cdc2/cyclin B1 pathway during liver regeneration.

Cyclin B1

Liver Regeneration

Cyclin A

Wee1

Cyclin E1

Cyclin A2

Cyclin B

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Pulmonary delivery of rifampicin-loaded soluplus micelles against Mycobacterium tuberculosis

Journal of Drug Delivery Science and Technology (2019)

Estefanía Grotz Nancy Liliana Tateosian Jimena Salgueiro Ezequiel Bernabeu Lorena González

Nanocarriers

10.1016/j.jddst.2019.101170

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Citations (63)

[Effective renal plasma flow with I-131-hipuran: evaluation of a method with four extractions].

PubMed (1998)

M. Roca R. Puchal Verónica García F Iglesias Véronique Gomès

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IFNG-mediated immune responses enhance autophagy againstMycobacterium tuberculosisantigens in patients with active tuberculosis

Autophagy (2014)

Ana I Rovetta Delfina Peña Rodrigo Emanuel Hernández Del Pino Gabriela M Recalde Joaquín Miguel Pellegrini

Protective immunity against Mycobacterium tuberculosis (Mtb) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent Mtb in macrophage cell lines. We investigated the contribution of autophagy to the defense against Mtb antigen (Mtb-Ag) in cells from tuberculosis patients and healthy donors (HD). Patients were classified as high responders (HR) if their T cells produced significant IFNG against Mtb-Ag; and low responders (LR) when patients showed weak or no T cell responses to Mtb-Ag. The highest autophagy levels were detected in HD cells whereas the lowest quantities were observed in LR patients. Interestingly, upon Mtb-Ag stimulation, we detected a positive correlation between IFNG and MAP1LC3B-II/LC3-II levels. Actually, blockage of Mtb-Ag-induced IFNG markedly reduced autophagy in HR patients whereas addition of limited amounts of IFNG significantly increased autophagy in LR patients. Therefore, autophagy collaborates with human immune responses against Mtb in close association with specific IFNG secreted against the pathogen.

10.4161/15548627.2014.981791

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Citations (64)

Bayesian Approach to Model CD137 Signaling in Human M. tuberculosis In Vitro Responses

PLoS ONE (2013)

Darío Fernández Do Porto Jerónimo Auzmendi Delfina Peña Verónica García Luciano Moffatt

Immune responses are qualitatively and quantitatively influenced by a complex network of receptor-ligand interactions. Among them, the CD137:CD137L pathway is known to modulate innate and adaptive human responses against Mycobacterium tuberculosis. However, the underlying mechanisms of this regulation remain unclear. In this work, we developed a Bayesian Computational Model (BCM) of in vitro CD137 signaling, devised to fit previously gathered experimental data. The BCM is fed with the data and the prior distribution of the model parameters and it returns their posterior distribution and the model evidence, which allows comparing alternative signaling mechanisms. The BCM uses a coupled system of non-linear differential equations to describe the dynamics of Antigen Presenting Cells, Natural Killer and T Cells together with the interpheron (IFN)-γ and tumor necrosis factor (TNF)-α levels in the media culture. Fast and complete mixing of the media is assumed. The prior distribution of the parameters that describe the dynamics of the immunological response was obtained from the literature and theoretical considerations Our BCM applies successively the Levenberg-Marquardt algorithm to find the maximum a posteriori likelihood (MAP); the Metropolis Markov Chain Monte Carlo method to approximate the posterior distribution of the parameters and Thermodynamic Integration to calculate the evidence of alternative hypothesis. Bayes factors provided decisive evidence favoring direct CD137 signaling on T cells. Moreover, the posterior distribution of the parameters that describe the CD137 signaling showed that the regulation of IFN-γ levels is based more on T cells survival than on direct induction. Furthermore, the mechanisms that account for the effect of CD137 signaling on TNF-α production were based on a decrease of TNF-α production by APC and, perhaps, on the increase in APC apoptosis. BCM proved to be a useful tool to gain insight on the mechanisms of CD137 signaling during human response against Mycobacterium tuberculosis.

CD137

10.1371/journal.pone.0055987

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Citations (5)

Free triiodothyronine levels and age influences the metabolic profile and COVID-19 severity parameters in euthyroid and levothyroxine-treated patients

Frontiers in Endocrinology (2022)

Inés Amich Eduardo Anguita Silvia Escribano-Serrat Cristina Alvarez Diego Rodríguez-Muñoz

Metabolic reprogramming is required to fight infections and thyroid hormones are key regulators of metabolism. We have analyzed in hospitalized COVID-19 patients: 40 euthyroid and 39 levothyroxine (LT4)-treated patients in the ward and 29 euthyroid and 9 LT4-treated patients in the intensive care unit (ICU), the baseline characteristics, laboratory data, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), the FT3/FT4 ratio, 11 antiviral cytokines and 74 metabolomic parameters. No evidence for significant differences between euthyroid and LT4-treated patients were found in the biochemical, metabolomic and cytokines parameters analyzed. Only TSH (p=0.009) and ferritin (p=0.031) showed significant differences between euthyroid and LT4-treated patients in the ward, and TSH (p=0.044) and FT4 (p=0.012) in the ICU. Accordingly, severity and mortality were similar in euthyroid and LT4-treated patients. On the other hand, FT3 was negatively related to age (p=0.012), independently of sex and body mass index in hospitalized COVID-19 patients. Patients with low FT3 and older age showed a worse prognosis and higher levels of the COVID-19 severity markers IL-6 and IL-10 than patients with high FT3. IL-6 negatively correlated with FT3 (p=0.023) independently of age, body mass index and sex, whereas IL-10 positively associated with age (p=0.035) independently of FT3, body mass index and sex. A metabolomic cluster of 6 parameters defined low FT3 ward patients. Two parameters, esterified cholesterol (p=4.1x10 -4 ) and small HDL particles (p=6.0x10 -5 ) correlated with FT3 independently of age, body mass index and sex, whereas 3-hydroxybutyrate (p=0.010), acetone (p=0.076), creatinine (p=0.017) and high-density-lipoprotein (HDL) diameter (p=8.3x10 -3 ) were associated to FT3 and also to age, with p-values of 0.030, 0.026, 0.017 and 8.3x10 -3 , respectively. In conclusion, no significant differences in FT3, cytokines, and metabolomic profile, or in severity and outcome of COVID-19, were found during hospitalization between euthyroid patients and hypothyroid patients treated with LT4. In addition, FT3 and age negatively correlate in COVID-19 patients and parameters that predict poor prognosis were associated with low FT3, and/or with age. A metabolomic cluster indicative of a high ketogenic profile defines non-critical hospitalized patients with low FT3 levels.

Levothyroxine

10.3389/fendo.2022.1025032

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Citations (3)

Age-dependent pulmonary clearance of Pseudomonas aeruginosa in a mouse model: diminished migration of polymorphonuclear leukocytes to N-formyl-methionyl-leucyl-phenylalanine

Infection and Immunity (1992)

Daniel O. Sordelli M Djafari Verónica García Patricia A. Fontán Gerd Döring

Ten-, 20-, and 35-day-old mice were subjected to an aerosol containing Pseudomonas aeruginosa. The lung clearance of the organism was decreased in mice under 20 days of age. This deficiency was accompanied by decreased migration of polymorphonuclear leukocytes (PMN) to the airways in response to the P. aeruginosa challenge. Similar results were obtained in both outbred, C5-sufficient Swiss mice and inbred, C5-deficient DBA/2 mice. The diminished clearance of P. aeruginosa was related to a transient, age-related decrease in PMN chemotaxis to formyl-methionyl oligopeptides. PMN chemotaxis levels similar to those seen in adults were regained by day 35 after birth.

Ratón

10.1128/iai.60.4.1724-1727.1992

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Citations (19)