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"Sánchez, Azucena"
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Evaluation of Different Machine Learning Approaches to Predict Antigenic Distance Among Newcastle Disease Virus (NDV) Strains
by
Zambon, Ilaria
,
Salomoni, Angela
,
Schivo, Alessia
in
Animal diseases
,
Animals
,
antigenic cartography
2025
Newcastle disease virus (NDV) continues to present a significant challenge for vaccination due to its rapid evolution and the emergence of new variants. Although molecular and sequence data are now quickly and inexpensively produced, genetic distance rarely serves as a good proxy for cross-protection, while experimental studies to assess antigenic differences are time consuming and resource intensive. In response to these challenges, this study explores and compares several machine learning (ML) methods to predict the antigenic distance between NDV strains as determined by hemagglutination-inhibition (HI) assays. By analyzing F and HN gene sequences alongside corresponding amino acid features, we developed predictive models aimed at estimating antigenic distances. Among the models evaluated, the random forest (RF) approach outperformed traditional linear models, achieving a predictive accuracy with an R2 value of 0.723 compared to only 0.051 for linear models based on genetic distance alone. This significant improvement demonstrates the usefulness of applying flexible ML approaches as a rapid and reliable tool for vaccine selection, minimizing the need for labor-intensive experimental trials. Moreover, the flexibility of this ML framework holds promise for application to other infectious diseases in both animals and humans, particularly in scenarios where rapid response and ethical constraints limit conventional experimental approaches.
Journal Article
Inter-laboratory comparison of eleven quantitative or digital PCR assays for detection of proviral bovine leukemia virus in blood samples
by
Barua, Subarna
,
Camargos, Marcelo Fernandes
,
De Brun, MLaureana
in
Animals
,
Antibodies
,
Asymptomatic
2024
Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis and causes a persistent infection that can leave cattle with no symptoms. Many countries have been able to successfully eradicate BLV through improved detection and management methods. However, with the increasing novel molecular detection methods there have been few efforts to standardize these results at global scale. This study aimed to determine the interlaboratory accuracy and agreement of 11 molecular tests in detecting BLV. Each qPCR/ddPCR method varied by target gene, primer design, DNA input and chemistries. DNA samples were extracted from blood of BLV-seropositive cattle and lyophilized to grant a better preservation during shipping to all participants around the globe. Twenty nine out of 44 samples were correctly identified by the 11 labs and all methods exhibited a diagnostic sensitivity between 74 and 100%. Agreement amongst different assays was linked to BLV copy numbers present in samples and the characteristics of each assay (i.e., BLV target sequence). Finally, the mean correlation value for all assays was within the range of strong correlation. This study highlights the importance of continuous need for standardization and harmonization amongst assays and the different participants. The results underscore the need of an international calibrator to estimate the efficiency (standard curve) of the different assays and improve quantitation accuracy. Additionally, this will inform future participants about the variability associated with emerging chemistries, methods, and technologies used to study BLV. Altogether, by improving tests performance worldwide it will positively aid in the eradication efforts.
Journal Article
BAFF system expression in double negative 2, activated naïve and activated memory B cells in systemic lupus erythematosus
by
Álvarez Gómez, Jhonatan Antonio
,
Muñoz-Valle, José Francisco
,
Palafox-Sánchez, Claudia Azucena
in
aNAV
,
Antiparasitic agents
,
atypical B cells
2023
IntroductionB cell activating factor (BAFF) has an important role in normal B cell development. The aberrant expression of BAFF is related with the autoimmune diseases development like Systemic Lupus Erythematosus (SLE) for promoting self-reactive B cells survival. BAFF functions are exerted through its receptors BAFF-R (BR3), transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) that are reported to have differential expression on B cells in SLE. Recently, atypical B cells that express CD11c have been associated with SLE because they are prone to develop into antibody-secreting cells, however the relationship with BAFF remains unclear. This study aims to analyze the BAFF system expression on CXCR5- CD11c+ atypical B cell subsets double negative 2 (DN2), activated naïve (aNAV), switched memory (SWM) and unswitched memory (USM) B cells.MethodsForty-five SLE patients and 15 healthy subjects (HS) were included. Flow cytometry was used to evaluate the expression of the receptors in the B cell subpopulations. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify the soluble levels of BAFF (sBAFF) and IL-21.ResultsWe found increased frequency of CXCR5- CD11c+ atypical B cell subpopulations DN2, aNAV, SWM and USM B cells in SLE patients compared to HS. SLE patients had increased expression of membrane BAFF (mBAFF) and BCMA receptor in classic B cell subsets (DN, NAV, SWM and USM). Also, the CXCR5+ CD11c- DN1, resting naïve (rNAV), SWM and USM B cell subsets showed higher mBAFF expression in SLE. CXCR5- CD11c+ atypical B cell subpopulations DN2, SWM and USM B cells showed strong correlations with the expression of BAFF receptors. The atypical B cells DN2 in SLE showed significant decreased expression of TACI, which correlated with higher IL-21 levels. Also, lower expression of TACI in atypical B cell DN2 was associated with high disease activity.DiscussionThese results suggest a participation of the BAFF system in CXCR5- CD11c+ atypical B cell subsets in SLE patients. Decreased TACI expression on atypical B cells DN2 correlated with high disease activity in SLE patients supporting the immunoregulatory role of TACI in autoimmunity.
Journal Article
Aberrant STAT3 activation and overproduction of IL-21 in systemic lupus erythematosus: role of miR-155 and miR-21 in target genes SOCS1, PTEN and PIAS3
by
De Arellano, Adrián Ramírez
,
Vega-Cornejo, Gabriel
,
Palafox-Sánchez, Claudia Azucena
in
Adult
,
Autoantibodies
,
Autoimmune diseases
2026
SLE is a chronic autoimmune disease characterized by immune system dysregulation, including aberrant activation of B and T lymphocytes and overproduction of proinflammatory cytokines such as IL-21. Through the STAT3 signaling pathway, this cytokine plays a key role in SLE-promoting autoantibody production and immune imbalance. It has been reported that miRNAs, such as miR-155 and miR-21, could be overexpressed in SLE and contribute to the STAT3 pathway dysregulation. We aimed to analyze the association between miR-155 and miR-21 and the expression of
,
,
, and
in PBMC from SLE patients.
PBMC isolation was performed by density gradient centrifugation using Histopaque-1077, culture overnight, and seeded at a concentration of 1x10
cells/mL in 24-well flat-bottom cell culture plates for subsequent stimulation with 0.5 μg/mL ionomycin and 2.5 μg/mL PMA. The expression levels of miR-155, miR-21,
, and
were measured using the RT-qPCR technique. Western blotting determined the expression of SOCS1, PTEN, PIAS3, IL-21, and p-STAT3 proteins. IL-17A levels in cell culture supernatant were determined using ELISA to assess cell stimulation.
Our results showed an increased expression of miR-155 and miR-21 in SLE patients compared to HC in both, stimulated and non-stimulated PBMC. The increased miR-155 and miR-21 expression were associated with a decreased gene expression of
and
. The
expression was observed in stimulated PBMC with higher levels in SLE patients. These also showed lower expression of SOCS1, PTEN, and PIAS3, while levels of IL-21 were increased in total protein from PBMC, culture cell supernatants and plasma levels. Overall, p-STAT3 was increased in the PBMC of SLE patients. Finally, miR-21 inversely correlated with
and
and miR-155 with SOCS1.
These findings highlight the association between miR-155 and miR-21 with target genes SOCS1, PTEN, and PIAS3, that may contribute to the aberrant activation of the STAT3 pathway and the overproduction of IL-21 in SLE patients.
Journal Article
Altered PTPN22 and IL10 mRNA Expression Is Associated with Disease Activity and Renal Involvement in Systemic Lupus Erythematosus
by
Cruz, Alvaro
,
Salazar-Camarena, Diana Celeste
,
Muñoz-Valle, José Francisco
in
Arthritis
,
Autoimmune diseases
,
Cytokines
2022
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with very heterogeneous clinical behavior between affected individuals. Therefore, the search for biomarkers clinically useful for the diagnosis, prognosis, and monitoring of the disease is necessary. Here, we determined the association between PTPN22, IL10, OAS2, and CD70 mRNA expression with the clinical characteristics and with the serum levels of IL-10, IFN-γ, and IL-17 in SLE patients. Forty patients with SLE and 34 control subjects (CS) were included, mRNA expression was determined by real-time qPCR and cytokine levels were quantified by a multiplex bead-based immunoassay. Compared to CS, SLE patients showed increased IL10 mRNA and high IL-10 and IL-17 serum levels; in contrast, PTPN22 mRNA and IFN-γ were decreased. PTPN22 and IL10 gene expression was negatively correlated with Mex-SLEDAI score and were notably downregulated in SLE patients with lupus nephritis. Interestingly, SLE patients with renal damage were the ones with the lowest levels of PTPN22 and IL10 mRNA and the highest SLEDAI scores. No associations were observed for OAS2 and CD70 mRNA and IL-10, IL-17, and IFN-γ. In conclusion, we suggest that the assessment of IL10 and PTPN22 mRNA could be useful for monitoring disease activity in SLE patients showing renal involvement.
Journal Article
Analysis of TNFSF13B polymorphisms and BAFF expression in rheumatoid arthritis and primary Sjögren's syndrome patients
by
Marín‐Rosales, Miguel
,
Cerpa‐Cruz, Sergio
,
Palafox‐Sánchez, Claudia Azucena
in
Antibodies
,
Arthritis
,
Autoantibodies
2022
Background The increased expression of B cell‐activating factor (BAFF) has been linked to autoantibody production in autoimmune diseases (ADs). The aim of this study was to investigate the association among TNFSF13B gene (OMIM: 603969) single nucleotide polymorphisms (SNPs), TNFSF13B mRNA, and soluble BAFF (sBAFF) expression in patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). The diagnostic value of sBAFF also was evaluated by the area under the curve (AUC) of receiver operating characteristic or receptor (ROC) curves. Methods Genotypes of the TNFSF13B rs9514827 (−2841 T > C), rs1041569 (−2701 A > T) and rs9514828 (−871 C > T) SNPs were determined by PCR‐RFLP assay. TNFSF13B mRNA and sBAFF expression were performed by RT‐qPCR and ELISA, respectively. The study included 320 RA patients, 101 pSS patients, and 309 healthy subjects (HS). Results The rs9514828 T allele and the TAT haplotype were associated with an increased risk to develop RA. In both ADs, the TNFSF13B mRNA levels were increased in comparison with HS. The rs9514828 (−871 C > T) polymorphism was associated with increased gene expression in RA patients. Also, sBAFF levels were higher in both ADs, however pSS patients showed the highest sBAFF levels. sBAFF showed higher diagnostic performance for pSS with an AUC of 0.968, with a similar accuracy of anti‐SSA/Ro antibody diagnosis (AUC = 0.974). Conclusions Our findings demonstrate that the TNFSF13B rs9514828 (−871 C > T) polymorphism is a risk factor for RA in the western Mexican population. sBAFF levels may be a potential diagnosis biomarker in pSS. TNFSF13B rs9514828 polymorphism is a risk factor for RA in western Mexican population. sBAFF levels are increased in RA and pSS patients. sBAFF showed higher diagnostic performance for pSS with AUC of 0.968, with similar accuracy of anti‐SSA/Ro antibody diagnosis.
Journal Article
Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes (Phoenicopterus spp.)
by
Vergara-Alert, Júlia
,
Busquets, Núria
,
Ramis, Antonio
in
Allergy and Immunology
,
Animals
,
Animals, Zoo - immunology
2016
•Vaccination against H5 IAV induces long-lasting immune responses in flamingoes.•Protective antibody titres were highly prevalent seven years after vaccination.•Evidence for a circulation of H1 IAV 12 years earlier was observed.•These results are relevant for IAV preventative programmes in wild birds.
Avian influenza (AI) can represent a threat to endangered wild birds, as demonstrated with the H5N1 highly pathogenic AI (HPAI) outbreaks. Vaccination against AI using inactivated H5-vaccines has been shown to induce humoral immune response in zoo bird species. In this study, the long-term efficacy of H5-vaccination was evaluated in flamingoes from Barcelona Zoo. Specific H5-antibody titres were maintained at high levels (geometric mean titres ≥32) for over 7 years after vaccination, both against the H5N9 and H5N3 vaccine strains, as well as H5N3 and H5N1 reference strains. In addition the breadth of the immune response was also studied by testing antibody production against H1-, H3-, H4-, H7-, and H10-subtypes. It was observed that most flamingoes presented specific antibodies against H1 virus subtypes, but titres to the other HA-subtypes were rarely detected. We show that AI-vaccines can induce immunity lasting seven years in flamingoes, which suggests that vaccination can provide long term protection from HPAI outbreaks in zoo birds.
Journal Article
Peripheral biomarkers of neuronal damage in neuropsychiatric systemic lupus erythematosus (NPSLE)
by
González-Palacios, Aarón
,
Palafox-Sánchez, Claudia Azucena
,
Marín-Rosales, Miguel
in
autoimmune disease
,
brain-specific biomarkers
,
CSF biomarkers
2026
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with heterogeneous clinical presentations, including Neuropsychiatric SLE (NPSLE), which comprises a spectrum of central and peripheral nervous system manifestations attributable to immune-mediated neuronal and glial injury. Currently, diagnosing NPSLE is challenging due to the heterogeneous clinical manifestations and the lack of specific biomarkers. Breakthrough biomarkers are essential for improving diagnostic accuracy, prognostic assessment, and therapeutic monitoring in NPSLE. Serum biomarkers have been thoroughly examined, including inflammatory molecules such as cytokines, chemokines, and autoantibodies; however, these biomarkers are not brain-specific and have also been associated with other clinical domains of SLE. The present review focuses on neuronal and glial damage biomarkers in the context of NPSLE, highlighting their potential utility as diagnostic or prognostic biomarkers, while underscoring the need for further research in this area. Here, we discuss correlations between serum and cerebrospinal fluid (CSF) levels, supporting the use of serum as a minimally invasive surrogate for CNS assessment. Furthermore, findings on serum biomarkers of neurological damage were reviewed to explore their associations with clinical, demographic, and routine laboratory variables, which could provide insights into disease mechanisms. We identified potential biomarkers and highlighted important research gaps that may guide future investigations.
Journal Article
Association of PTPN22 Haplotypes (−1123G>C/+1858C>T) with Rheumatoid Arthritis in Western Mexican Population
by
Muñoz-Valle, Jose F.
,
Palafox-Sánchez, Claudia Azucena
,
Hernández-Bello, Jorge
in
Disease
,
Enzymes
,
Genes
2017
Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (−1123G>C and +1858C>T) at PTPN22 gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population. We evaluated whether PTPN22 haplotypes (−1123G>C/+1858C>T) are associated with anti-CCP antibodies, as well as susceptibility to RA in a Western Mexican population. A total of 315 RA patients and 315 control subjects (CS) were included. The polymorphisms were genotyped by PCR-RFLP and the anti-CCP antibodies were determined by ELISA. The PTPN22 polymorphisms were in strong linkage disequilibrium (D′ = 1.00 in CS). The susceptibility haplotype CT was significantly more frequent in RA patients than in CS (OR 2.18, 95% CI 1.15–4.16, p=0.01). No association between haplotypes and anti-CCP antibodies levels was observed. In conclusion, this study confirmed that −1123G>C and +1858C>T PTPN22 polymorphisms are in strong linkage disequilibrium and the CT haplotype is a susceptibility marker to RA in Western Mexico. However, the PTPN22 haplotypes are not associated with anti-CCP antibodies.
Journal Article
Historical Museums of Guanajuato and their Recovery After COVID: A Panel Data Model
by
Rocha Ibarra, Jesús Ernesto
,
Pérez Vásquez, Jazmín
,
Rodríguez Sánchez, Clara Azucena
in
Cities
,
COVID-19
,
Culture
2025
According to Lobatón et al. (2020) the tourism contribution to the economy of the state of Guanajuato is substantial, in terms of Gross Domestic Product (GDP), with data from the Secretary of Economy (SE, 2023) the tourism GDP before the COVID-19 pandemic amounted to 92,674,800,202 constant pesos at 2018 prices. The participation of historical museums as destinations of interest to locals and tourists should be recognized. According to the Cultural Information System (SIC, 2022) of the Mexican Secretary of Culture, the state of Guanajuato has a total of 1,107 museums distributed in its different municipalities, however, the historical museums that concentrate the greatest dynamism in influx of people are: the Regional Museum of Guanajuato Alhóndiga de Granaditas located in Guanajuato city, followed by the Historical Museum of San Miguel de Allende, and the Casa de Hidalgo Museum. The objective of this research is to analyse the economic impact of tourism activity related to museum visits in the state of Guanajuato before the COVID-19 pandemic and after its emergence, that is, from 2016 to 2022. The analysis is based on a panel data econometric model, where the GDP of the State, and the following explanatory variables: the participation of tourism activity in municipalities with historical museums in the State, the number of residents per municipality, the flow of domestic and international visitors to historical museums in the State, investments in tourism and cultural activity. The results show that if the variable of investment in tourism activities is increased by 1%, an increase of 28.7% in the state’s tourism GDP would be expected. Its participation in the state’s total GDP would be close to 13.1%. In contrast, the main historical museums in Guanajuato are expected to receive 97,363 national and international visitors in 2021 and 266,656 in 2022. In terms of tourism GDP, this recovery has an impact on the economic environment of the state, emphasizing that the performance of historical museums is 16.39% of the total for the state. In summary, we can say that the economic effects of tourism activities are multifactorial, but the study of the environment and the participation of historical museums are essential to stimulate conditions that favour economic growth in the state of Guanajuato.
Journal Article