50 research outputs found

    A Dominant EV71-Specific CD4+ T Cell Epitope is Highly Conserved Among Human Enteroviruses

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    CD4+ T cell-mediated immunity plays a central role in determining the immunopathogenesis of viral infections. However, the role of CD4+ T cells in EV71 infection, which causes hand, foot and mouth disease (HFMD), has yet to be elucidated. We applied a sophisticated method to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. Fifteen epitopes were identified, and three of them are dominant ones. The most dominant epitope is highly conserved among enterovirus species, including HFMD-related coxsackieviruses, HFMD-unrelated echoviruses and polioviruses. Furthermore, the CD4+ T cells specific to the epitope indeed cross-reacted with the homolog of poliovirus 3 Sabin. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection or vaccine

    Staphylococcus aureus Bacteriophage Suppresses LPS-Induced Inflammation in MAC-T Bovine Mammary Epithelial Cells

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    Several previous studies have shown that bacteriophages can significantly affect the production of various cytokines. The aim of this present study was to investigate the inflammatory effects and mechanisms of bacteriophage vB_SauM_JS25 in stimulated MAC-T bovine mammary epithelial cells by real-time polymerase chain reaction (PCR) and Western blotting. Experiments show that vB_SauM_JS25 reduces Staphylococcus aureus- or lipopolysaccharide (LPS)-induced levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, and regulated on activation, normal T cell expressed and secreted (RANTES) mRNA in MAC-T cells, in a manner expected to be unrelated to its antibacterial action. Moreover, S. aureus bacteriophage vB_SauM_JS25 suppressed the LPS-induced phosphorylation of nuclear factor (NF)-κB p65, which may represent an important mechanism mediating these effects. A carefully regulated balance between activation and inhibition by bacteriophages must be kept avoiding inappropriate inflammatory responses. The ability of vB_SauM_JS25 to influence the immune response highlights the potential development and application of bacteriophage-based therapies and may represent a novel anti-inflammatory therapeutic strategy

    A method to produce periodic varied structural composite yarn by forced migrations of convergence point between polymer filaments and the staple strand

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    A novel composite yarn with a novel structure is prepared by the three-strand conversion method of double polymer filaments to staple fiber, that is, double polymer filaments to staple fiber repeated migration movement. The geometric principle of different relative positions of filament to helix structure change is analyzed theoretically, and the effect of filament position on the spinning-triangle of composite yarn is demonstrated. Furthermore, the structure of six different composite yarns is modeled and compared with each other, which shows the influence of different filament helical structures on the performance of spinning composite yarns. The repeated migration of filaments is observed using the online observation technique in the dynamic rotating triangle region. In addition, changes in yarn structure are caused by different geometric configurations. The results show that the stem, strength, and hair of six new composite yarns with different helical structures are slightly weakened. In summary, the three-strand conversion method is an effective new method to control the structure of filament and staple fibers

    Interactions between oxidative stress and senescence in cancer: Mechanisms, therapeutic implications, and future perspectives

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    BACKGROUND: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. AIM: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. METHODS: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. CONCLUSION: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area

    Analysis of Characteristic Quality Indexes of Gaoyou Duck Eggs

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    To explore the quality characteristics of Gaoyou duck eggs, metabolomics was used to analyze the quality indexes, basic nutritional indexes and small molecule metabolites. The results showed that the mass, egg shape index, egg yolk color, Haugh unit, egg white height, egg yolk index and crude protein content of Gaoyou duck eggs were higher than those of the other studied breeds. The contents of total amino acids, umami amino acids, branched-chain amino acids, total fatty acids and unsaturated fatty acids were higher, and the content of saturated fatty acids was lower, indicating that sensory quality parameters, amino acids and fatty acids can characterize the quality of Gaoyou duck eggs. The characteristic components of Gaoyou duck eggs were uncovered by metabolomic fingerprinting, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and hierarchical cluster analysis (HCA). Totally 252 compounds and 22 differential compounds were identified in egg yolk, and 184 compounds and 40 differential compounds in egg white. Among them, uridine 5’-monophosphate, guanosine 5’-monophosphate, and N-acetyl-D-glucosamine were the main differential nutrients, and arachidonic acid in egg yolk was the unique nutrient of Gaoyou duck eggs, while indole was not detected in the egg white of Gaoyou duck eggs

    Insights Into the Bovine Milk Microbiota in Dairy Farms With Different Incidence Rates of Subclinical Mastitis

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    Bovine mastitis continues to be a complex disease associated with significant economic loss in dairy industries worldwide. The incidence rate of subclinical mastitis (IRSCM) can show substantial variation among different farms; however, the milk microbiota, which have a direct influence on bovine mammary gland health, have never been associated with the IRSCM. Here, we aimed to use high-throughput DNA sequencing to describe the milk microbiota from two dairy farms with different IRSCMs and to identify the predominant mastitis pathogens along with commensal or potential beneficial bacteria. Our study showed that Klebsiella, Escherichia–Shigella, and Streptococcus were the mastitis-causing pathogens in farm A (with a lower IRSCM), while Streptococcus and Corynebacterium were the mastitis-causing pathogens in farm B (with a higher IRSCM). The relative abundance of all pathogens in farm B (22.12%) was higher than that in farm A (9.82%). However, the genus Bacillus was more prevalent in farm A. These results may be helpful for explaining the lower IRSCM in farm A. Additionally, the gut-associated genera Prevotella, Ruminococcus, Bacteroides, Rikenella, and Alistipes were prevalent in all milk samples, suggesting gut bacteria can be one of the predominant microbial contamination in milk. Moreover, Listeria monocytogenes (a foodborne pathogen) was found to be prevalent in farm A, even though it had a lower IRSCM. Overall, our study showed complex diversity between the milk microbiota in dairy farms with different IRSCMs. This suggests that variation in IRSCMs may not only be determined by the heterogeneity and prevalence of mastitis-causing pathogens but also be associated with potential beneficial bacteria. In the future, milk microbiota should be considered in bovine mammary gland health management. This would be helpful for both the establishment of a targeted mastitis control system and the control of the safety and quality of dairy products

    Etudes des mécanismes cellulaires et moléculaires de la réponse immunitaire de type 2 dans la dermatite atopique

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    My thesis aimed at studying the Tfh cell differentiation, function and regulation in AD pathogenesis. To this aim, I employed our previously established AD mouse model in which MC903 (a vitamin D analog) topical treatment on the skin induces TSLP production bykeratinocytes, promotes Th2 cell response and drives the pathogenesis of AD. my thesis work investigated Tfh cell differentiation, its cytokine expression and germinal center formation using MC903-induced AD mouse model. By exploring the role of TSLP,Langerin+ DCs and OX40L signaling in Tfh cell differentiation and regulation, my study provides novel insights into the mechanisms underlying the type 2 immune response in AD pathogenesis. In the second part of my study, we examined the role of MC903 in regulating the psoriatic inflammation using Aldara-induced psoriasis model. We showed that MC903 inhibited IL-23/IL-17/IL-22 axis in mouse psoriasis. Moreover, this inhibition exhibited a dose-dependent manner. We further explored the role of TSLP and VDR in mediating such effect of MC903.Mon travail, lors de ma thèse, avait pour but d’étudier la différentiation des lymphocytes Tfh, ainsi que leur fonction et leur régulation dans la pathogenèse de la DA. Pour cela, j’ai utilisé un modèle murin précédemment établi au sein de notre laboratoire consistant en l’application topique de MC903 (un analogue de la vitamine D3) induisant la production de TSLP par les kératinocytes et, par conséquence, la réponse immunitaire Th2 et la pathogenèse de la DA. mon travail doctoral s’est porté sur la différentiation des lymphocytes Tfh, leur production cytokinique ainsi que la formation des centres germinatifs dans le contexte d’un modèle murin de DA induite par le MC903. Mes études ont démontré un rôle critique joué par TSLP dans la réponse Tfh et ont exploré le rôle potentiellement joué par les cellules dendritiques langerine+ et la signalisation OX40L dans le développement des réponses Tfh et de type 2. Ceci nous a permis d’approfondir nos connaissances concernant les mécanismes sous-tendant la réponse immunitaire de type 2 dans la pathogenèse de la DA. Dans la deuxième partie de ma thèse, nous avons examiné le rôle de MC903 dans la régulation de l’inflammation due au psoriasis, en utilisant un modèle de psoriasis induit par l’Aldara. Nous avons montré que MC903 inhibe l’axe 23/IL-17/IL-22 chez les souris souffrant de psoriasis. De plus, cette inhibition semblait être dose-dépendante. Nous avons en outre exploré le rôle de TSLP et VDR dans la médiation de cet effet dû au MC903

    Etudes des mécanismes cellulaires et moléculaires de la réponse immunitaire de type 2 dans la dermatite atopique

    No full text
    My thesis aimed at studying the Tfh cell differentiation, function and regulation in AD pathogenesis. To this aim, I employed our previously established AD mouse model in which MC903 (a vitamin D analog) topical treatment on the skin induces TSLP production bykeratinocytes, promotes Th2 cell response and drives the pathogenesis of AD. my thesis work investigated Tfh cell differentiation, its cytokine expression and germinal center formation using MC903-induced AD mouse model. By exploring the role of TSLP,Langerin+ DCs and OX40L signaling in Tfh cell differentiation and regulation, my study provides novel insights into the mechanisms underlying the type 2 immune response in AD pathogenesis. In the second part of my study, we examined the role of MC903 in regulating the psoriatic inflammation using Aldara-induced psoriasis model. We showed that MC903 inhibited IL-23/IL-17/IL-22 axis in mouse psoriasis. Moreover, this inhibition exhibited a dose-dependent manner. We further explored the role of TSLP and VDR in mediating such effect of MC903.Mon travail, lors de ma thèse, avait pour but d’étudier la différentiation des lymphocytes Tfh, ainsi que leur fonction et leur régulation dans la pathogenèse de la DA. Pour cela, j’ai utilisé un modèle murin précédemment établi au sein de notre laboratoire consistant en l’application topique de MC903 (un analogue de la vitamine D3) induisant la production de TSLP par les kératinocytes et, par conséquence, la réponse immunitaire Th2 et la pathogenèse de la DA. mon travail doctoral s’est porté sur la différentiation des lymphocytes Tfh, leur production cytokinique ainsi que la formation des centres germinatifs dans le contexte d’un modèle murin de DA induite par le MC903. Mes études ont démontré un rôle critique joué par TSLP dans la réponse Tfh et ont exploré le rôle potentiellement joué par les cellules dendritiques langerine+ et la signalisation OX40L dans le développement des réponses Tfh et de type 2. Ceci nous a permis d’approfondir nos connaissances concernant les mécanismes sous-tendant la réponse immunitaire de type 2 dans la pathogenèse de la DA. Dans la deuxième partie de ma thèse, nous avons examiné le rôle de MC903 dans la régulation de l’inflammation due au psoriasis, en utilisant un modèle de psoriasis induit par l’Aldara. Nous avons montré que MC903 inhibe l’axe 23/IL-17/IL-22 chez les souris souffrant de psoriasis. De plus, cette inhibition semblait être dose-dépendante. Nous avons en outre exploré le rôle de TSLP et VDR dans la médiation de cet effet dû au MC903

    Study of the mechanisms underlying the type 2 immune response in atopic dermatitis pathogenesis

    No full text
    Mon travail, lors de ma thèse, avait pour but d’étudier la différentiation des lymphocytes Tfh, ainsi que leur fonction et leur régulation dans la pathogenèse de la DA. Pour cela, j’ai utilisé un modèle murin précédemment établi au sein de notre laboratoire consistant en l’application topique de MC903 (un analogue de la vitamine D3) induisant la production de TSLP par les kératinocytes et, par conséquence, la réponse immunitaire Th2 et la pathogenèse de la DA. mon travail doctoral s’est porté sur la différentiation des lymphocytes Tfh, leur production cytokinique ainsi que la formation des centres germinatifs dans le contexte d’un modèle murin de DA induite par le MC903. Mes études ont démontré un rôle critique joué par TSLP dans la réponse Tfh et ont exploré le rôle potentiellement joué par les cellules dendritiques langerine+ et la signalisation OX40L dans le développement des réponses Tfh et de type 2. Ceci nous a permis d’approfondir nos connaissances concernant les mécanismes sous-tendant la réponse immunitaire de type 2 dans la pathogenèse de la DA. Dans la deuxième partie de ma thèse, nous avons examiné le rôle de MC903 dans la régulation de l’inflammation due au psoriasis, en utilisant un modèle de psoriasis induit par l’Aldara. Nous avons montré que MC903 inhibe l’axe 23/IL-17/IL-22 chez les souris souffrant de psoriasis. De plus, cette inhibition semblait être dose-dépendante. Nous avons en outre exploré le rôle de TSLP et VDR dans la médiation de cet effet dû au MC903.My thesis aimed at studying the Tfh cell differentiation, function and regulation in AD pathogenesis. To this aim, I employed our previously established AD mouse model in which MC903 (a vitamin D analog) topical treatment on the skin induces TSLP production bykeratinocytes, promotes Th2 cell response and drives the pathogenesis of AD. my thesis work investigated Tfh cell differentiation, its cytokine expression and germinal center formation using MC903-induced AD mouse model. By exploring the role of TSLP,Langerin+ DCs and OX40L signaling in Tfh cell differentiation and regulation, my study provides novel insights into the mechanisms underlying the type 2 immune response in AD pathogenesis. In the second part of my study, we examined the role of MC903 in regulating the psoriatic inflammation using Aldara-induced psoriasis model. We showed that MC903 inhibited IL-23/IL-17/IL-22 axis in mouse psoriasis. Moreover, this inhibition exhibited a dose-dependent manner. We further explored the role of TSLP and VDR in mediating such effect of MC903
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