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  • 1
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    Image_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 11 ( 2021-2-3)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2021-2-3)
    Abstract: Dendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, B 2 T dendrimers displaying two copies of the major type O FMDV antigenic B-cell epitope located on the virus capsid [VP1 (140–158)], covalently linked to a heterotypic T-cell epitope from either non-structural protein 3A [3A (21–35)] or 3D [3D (56–70)], named B 2 T-3A and B 2 T-3D, respectively, elicit high levels of neutralizing antibodies (nAbs) and IFN-γ-producing cells in pigs. To assess whether the inclusion and orientation of T-3A and T-3D T-cell epitopes in a single molecule could modulate immunogenicity, dendrimers with T epitopes juxtaposed in both possible orientations, i.e., constructs B 2 TT-3A3D and B 2 TT-3D3A, were made and tested in pigs. Both dendrimers elicited high nAbs titers that broadly neutralized type O FMDVs, although B 2 TT-3D3A did not respond to boosting, and induced lower IgGs titers, in particular IgG2, than B 2 TT-3A3D. Pigs immunized with B 2, a control dendrimer displaying two B-cell epitope copies and no T-cell epitope, gave no nABs, confirming T-3A and T-3D as T helper epitopes. The T-3D peptide was found to be an immunodominant, as it produced more IFN-γ expressing cells than T-3A in the in vitro recall assay. Besides, in pigs immunized with the different dendrimeric peptides, CD4 + T-cells were the major subset contributing to IFN-γ expression upon in vitro recall, and depletion of CD4 + cells from PBMCs abolished the production of this cytokine. Most CD4 + IFN-γ + cells showed a memory (CD4 + 2E3 − ) and a multifunctional phenotype, as they expressed both IFN-γ and TNF-α, suggesting that the peptides induced a potent Th1 pro-inflammatory response. Furthermore, not only the presence, but also the orientation of T-cell epitopes influenced the T-cell response, as B 2 TT-3D3A and B 2 groups had fewer cells expressing both cytokines. These results help understand how B 2 T-type dendrimers triggers T-cell populations, highlighting their potential as next-generation FMD vaccines.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2020.621537
    DOI: 10.3389/fimmu.2020.621537.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 2
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Psychology Vol. 12 ( 2022-2-3)
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    In: Frontiers in Psychology, Frontiers Media SA, Vol. 12 ( 2022-2-3)
    Abstract: Antipsychotic-induced weight gain is a contributing factor in the reduced life expectancy reported amongst people with psychotic disorders. CYP2D6 is a liver enzyme involved in the metabolism of many commonly used antipsychotic medications. We investigated if CYP2D6 genetic variation influenced weight or BMI among people taking antipsychotic treatment. Methods We conducted a systematic review and a random effects meta-analysis of publications in Pubmed, Embase, PsychInfo, and CENTRAAL that had BMI and/or weight measurements of patients on long-term antipsychotics by their CYP2D6-defined metabolic groups (poor, intermediate, normal/extensive, and ultra-rapid metabolizers, UMs). Results Twelve studies were included in the systematic review. All cohort studies suggested that the presence of reduced-function or non-functional alleles for CYP2D6 was associated with greater antipsychotic-induced weight gain, whereas most cross-sectional studies did not find any significant associations. Seventeen studies were included in the meta-analysis with clinical data of 2,041 patients, including 93 poor metabolizers (PMs), 633 intermediate metabolizers (IMs), 1,272 normal metabolizers (NMs), and 30 UMs. Overall, we did not find associations in any of the comparisons made. The estimated pooled standardized differences for the following comparisons were (i) PM versus NM; weight = –0.07 (95%CI: –0.49 to 0.35, p = 0.74), BMI = 0.40 (95%CI: –0.19 to 0.99, p = 0.19). (ii) IM versus NM; weight = 0.09 (95% CI: –0.04 to 0.22, p = 0.16) and BMI = 0.09 (95% CI: –0.24 to 0.41, p = 0.60). (iii) UM versus EM; weight = 0.01 (95% CI: –0.37 to 0.40, p = 0.94) and BMI = –0.08 (95%CI: –0.57 to 0.42, p = 0.77). Conclusion Our systematic review of cohort studies suggested that CYP2D6 poor metabolizers have higher BMI than normal metabolizers, but the data of cross-sectional studies and the meta-analysis did not show this association. Although our review and meta-analysis constitutes one of the largest studies with comprehensively genotyped samples, the literature is still limited by small numbers of participants with genetic variants resulting in poor or UMs status. We need further studies with larger numbers of extreme metabolizers to establish its clinical utility in antipsychotic treatment. CYP2D6 is a key gene for personalized prescribing in mental health.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyg.2021.768748
    DOI: 10.3389/fpsyg.2021.768748.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2563826-9
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  • 3
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    Immunogenicity of a Dendrimer B2T Peptide Harboring a T-Cell Epitope From FMDV Non-structural Protein 3D
    Frontiers Media SA ; 2020
    In:  Frontiers in Veterinary Science Vol. 7 ( 2020-8-11)
    Details
    In: Frontiers in Veterinary Science, Frontiers Media SA, Vol. 7 ( 2020-8-11)
    Type of Medium: Online Resource
    ISSN: 2297-1769
    URL: Article
    DOI: 10.3389/fvets.2020.00498
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2834243-4
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  • 4
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-2-1)
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    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-2-1)
    Abstract: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. Methods Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. Results We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p & lt; 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p & lt; 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p & lt; 0.001) than native patients. Family history of IBD (9 vs. 14%, p & lt; 0.001) and smoking (30 vs. 40%, p & lt; 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p & lt; 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p & lt; 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92–2.58, p & lt; 0.001)] and using biologics [OR: 1.13 (1.0–1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. Conclusions Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.823900
    DOI: 10.3389/fmed.2022.823900.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 5
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    Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-6-9)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-6-9)
    Abstract: MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.918565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 6
    Online Resource
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    Table_2.XLSX
    Frontiers Media SA ; 2021
    In:  Frontiers in Genetics Vol. 12 ( 2021-6-14)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-6-14)
    Abstract: Several recent studies have demonstrated the role of long non-coding RNAs (lncRNAs) in regulating the defense mechanism against parasite infections, but no studies are available that investigated their relevance for immune response to nematode infection in sheep. Thus, the aim of the current study was to (i) detect putative lncRNAs that are expressed in the abomasal lymph node of adult sheep after an experimental infection with the gastrointestinal nematode (GIN) Teladorsagia circumcincta and (ii) to elucidate their potential functional role associated with the differential host immune response. We hypothesized that putative lncRNAs differentially expressed (DE) between samples from animals that differ in resistance to infection may play a significant regulatory role in response to nematode infection in adult sheep. To obtain further support for our hypothesis, we performed co-expression and functional gene enrichment analyses with the differentially expressed lncRNAs (DE lncRNAs). In a conservative approach, we included for this predictive analysis only those lncRNAs that are confirmed and supported by documentation of expression in gastrointestinal tissues in the current sheep gene atlas. We identified 9,105 putative lncRNA transcripts corresponding to 7,124 gene loci. Of these, 457 were differentially expressed lncRNA loci (DELs) with 683 lncRNA transcripts. Based on a gene co-expression analysis via weighted gene co-expression network analysis, 12 gene network modules (GNMs) were found significantly correlated with at least one of 10 selected target DE lncRNAs. Based on the principle of “guilt-by-association,” the DE genes from each of the three most significantly correlated GNMs were subjected to a gene enrichment analysis. The significant pathways associated with DE lncRNAs included ERK5 Signaling, SAPK/JNK Signaling, RhoGDI Signaling, EIF2 Signaling, Regulation of eIF4 and p70S6K Signaling and Oxidative Phosphorylation pathways. They belong to signaling pathway categories like Cellular Growth, Proliferation and Development, Cellular Stress and Injury, Intracellular and Second Messenger Signaling and Apoptosis. Overall, this lncRNA study conducted in adult sheep after GIN infection provided first insights into the potential functional role of lncRNAs in the differential host response to nematode infection.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    URL: Article
    URL: Article
    URL: Article
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    URL: Article
    URL: Article
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    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fgene.2021.685341
    DOI: 10.3389/fgene.2021.685341.s001
    DOI: 10.3389/fgene.2021.685341.s002
    DOI: 10.3389/fgene.2021.685341.s003
    DOI: 10.3389/fgene.2021.685341.s004
    DOI: 10.3389/fgene.2021.685341.s005
    DOI: 10.3389/fgene.2021.685341.s006
    DOI: 10.3389/fgene.2021.685341.s007
    DOI: 10.3389/fgene.2021.685341.s008
    DOI: 10.3389/fgene.2021.685341.s009
    DOI: 10.3389/fgene.2021.685341.s010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606823-0
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