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关键词： 山药多糖   硒化山药多糖   生长性能   免疫   抗氧化   肉兔  

摘要： 试验旨在探究饲粮中添加山药多糖及其硒化物对新西兰断奶肉兔生长性能、免疫、抗氧化指标及细胞免疫因子表达的影响。选取35日龄新西兰断奶肉兔112只，随机分为7组，每组4个重复，每个重复4只。对照组（A组）饲喂基础饲粮，B组、C组和D组分别在基础饲粮中添加150、300、450 mg/kg山药多糖，E组、F组和G组在基础饲粮分别添加150、300、450 mg/kg硒化山药多糖。预试期7 d，正式试验期28 d。结果显示，与A组相比，B组～G组平均日增重（ADG）均显著提高（P<0.05），料重比（F/G）显著降低（P<0.05），且G组F/G显著低于其他组（P<0.05）；各添加组血清免疫球蛋白A (IgA)、免疫球蛋白G (IgG)、免疫球蛋白M(IgM)、补体C3和补体C4含量均显著提高（P<0.05）,G组IgA和IgG含量均显著高于其他组（P<0.05）；各添加组肝脏中谷胱甘肽过氧化物酶（GSH-Px）活性显著升高（P<0.05）,E组～G组丙二醛（MDA）含量显著降低（P<0.05）;G组肝脏白细胞介素-10(IL-10)相对表达量显著上调（P<0.05），白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α (TNF-α)相对表达量显著下调（P<0.05）。研究表明，山药多糖和硒化山药多糖均可改善断奶肉兔的生长性能，增强免疫与抗氧化功能，且硒化山药多糖的效果优于普通山药多糖。

关键词： BETi   BRD4   IL‐17A   STAT3   Th17 cell differentiation   recurrent spontaneous abortion  

摘要： Purpose:Recurrent spontaneous abortion (RSA) is an abnormal phenomenon that severely affects women's quality of life. Inhibiting Th17 cell differentiation can alleviate RSA. This research explored the mechanism by which BRD4 Inhibitor (BETi) suppressed the differentiation of Th17 cells to mitigate RSA. Methods:PBMCs and Naive CD4 T cells were induced to differentiate into Th17 and Treg cells. An abortion-prone pregnancy mouse model was constructed by intraperitoneal injection of lipopolysaccharide. The Th17/Treg ratio was determined by flow cytometry. The association between STAT3 and IL-17A promoter was investigated by ChIP and dual luciferase assays. Co-IP and yeast two-hybrid assays were used to determine BRD4 binding to STAT3. The markers of Th17/Treg cell differentiation and lipid synthesis were checked by ELISA, IHC, RT-qPCR, and Western blot. Results:The Th17/Treg ratio and the expression levels of BRD4, STAT3, and IL-17A were elevated, while STAT5b expression was down-regulated in RSA patients. BETi or STAT3 knockdown decreased the differentiation of Th17 cells and lipid synthesis. BRD4 inhibition impaired STAT3-mediated IL-17A transcription. BETi inhibited embryo absorption in mice. Conclusions:BETi inhibits the differentiation of Th17 cells in RSA by reducing the STAT3-mediated IL-17A expression.

关键词： Cadmium   Spontaneous abortion   Decidualization   FBXO2   IL6ST/STAT3 signaling   K63-linked ubiquitination  

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关键词： AUTOIMMUNE ENCEPHALITIS   CLINICAL NEUROLOGY   GENETICS   HLA   NEUROIMMUNOLOGY  

摘要： BACKGROUND:Patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) encephalitis are typically elderly men that often carry human leucocyte antigen (HLA)- (≈90%). Herein, we aimed to investigate whether patients with atypical demographic profiles or not carrying have distinct clinical manifestations and outcome. METHODS:Retrospective chart review of LGI1-Ab patients diagnosed at the French Reference Centre and three other European centres. RESULTS:Among 238 patients included, median age at onset was 66 years (IQR: 60-73), 65% were male, 89% carried and 10% , another known secondary HLA association. We identified three age groups (young, typical, old) based on percentiles of age distribution. Young (≤51 years) patients were less commonly male (35%, p=0.004), while faciobrachial dystonic seizures (FBDS; 65%, p=0.047) and hyponatraemia (64%, p=0.046) were more frequent in old (≥79 years) patients. Old patients experienced poor outcome (modified Rankin Scale [mRS] >2 at last follow-up) more frequently (64%, p<0.001). There were no significant differences between males and females. non-carriers were younger (p=0.005) and less frequently male (47%, p=0.044), while non-carriers of both and experienced poor outcome more commonly (64%, p=0.005). Older age (adjusted OR: 1.08, 95% CI [1.02 to 1.14], p=0.008), higher mRS at nadir (4.22 [2.46-7.24], p<0.001) and non-carrier status (8.39 [1.88-37.44], p=0.005) were independently associated with poor outcome. Moreover, older age (1.08 [1.04-1.11], p<0.001), FBDS (2.20 [1.17-4.13], p=0.014) and hyponatraemia (2.30 [1.22-4.34], p=0.010) were associated with severe encephalitis (mRS >3 at nadir). CONCLUSIONS:Age appears to be the main driver of clinical presentation, severity and outcome in LGI1-Ab encephalitis. Remarkably, non-carriers are younger, more commonly female and experience poorer prognosis, reflecting a distinct pathophysiology.

关键词： Fungal infections   Immunology   Infectious disease   Neutrophils  

摘要： Aspergillus fumigatus is the most common cause of invasive aspergillosis (IA), a devastating infection in immunocompromised patients. Plasmacytoid DCs (pDCs) regulate host defense against IA by enhancing neutrophil antifungal properties in the lung. Here, we define the pDC activation trajectory during A. fumigatus infection and the molecular events that underlie the protective pDC-neutrophil crosstalk. Fungus-induced pDC activation began after bone marrow egress and resulted in pDC-dependent regulation of lung type I and type III IFN levels. These pDC-derived products acted on type I and type III IFN receptor-expressing neutrophils and controlled neutrophil fungicidal activity and ROS production via STAT1 signaling in a cell-intrinsic manner. Mechanistically, neutrophil STAT1 signaling regulated transcription and expression of Cybb, which encodes one of 5 NADPH oxidase subunits. Thus, the results indicate that pDCs regulate neutrophil-dependent immunity against inhaled molds by controlling local expression of a subunit required for NADPH oxidase assembly and activity in the lung.

关键词： Epithelial Barrier Function   Basal IFN lambda Signaling   Tight Junctions   Hippo Signaling Pathway   cGAS-STING Pathway  

摘要： Type-III interferons (or IFN lambda s) play important roles in antiviral defense and intestinal epithelial barrier integrity. While interferon expression has been primarily studied in response to pathogens, basal interferon expression also occurs in pathogen-free environments. However, the mechanisms regulating basal IFN-lambda expression and their functions have not yet been elucidated. Here, we show that basal IFN-lambda 2/3 expression is linked to the development of an intact cellular epithelium characterized by formation of tight junctions and establishment of barrier function. Our findings indicate that basal IFN-lambda 2/3 expression depends on cGAS-STING-mediated mitochondrial DNA detection, while it is inhibited by the Hippo mechanotransduction pathway at low cellular densities. Cells lacking basal IFN-lambda 2/3 expression fail to develop proper tight junctions and establish normal barrier function. Mechanistically, IFN-lambda 2/3 suppresses Claudin-2 expression, thereby promoting barrier formation as cells become confluent. These results demonstrate a previously unknown function of basal IFN lambda expression in regulating epithelial cell junction formation and highlight their importance not only during pathogen challenges but also in maintaining epithelial cell function under steady-state conditions.

关键词： atopic dermatitis   dibutyl phthalate   IL-5   semaphorin-plexin signaling  

摘要： Background: Several studies have reported an association between phthalate exposure and an increased risk of atopic dermatitis (AD). However, the molecular mechanism underlying this phenomenon in children remains *** In this study, we investigated the effect of dibutyl phthalate (DBP) on AD development from a birth cohort and explored the potential mechanisms using multi-omics. Methods: Urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) metabolites were measured in 222 children aged 7 years from the Exposome and Child Health with Omics-Cohort for Childhood of Asthma and Allergic Diseases (ECHO-COCOA) study. Physician diagnosed AD in these participants. Luminex multiplex assay, proteome, and transcriptome were performed on blood samples. The production of interleukin (IL)-5 and IL-10 was analyzed after MnBP exposure in human keratinocytes and macrophage. Results: Higher MnBP and MiBP levels increased the risk of AD development. These phthalates were positively correlated with eosinophils and IL-5. In total, 24 differentially expressed proteins (DEPs) and IL-5 were associated with MnBP and the development of AD. DEPs were predominantly enriched in the semaphorin-plexin signaling pathway. Plexin B1 was negatively correlated with IL-10 and interferon gamma and positively correlated with egg white specific immunoglobulin E. Moreover, mediation analysis indicated that IL-5 had a significantly positive mediation effect on the association between MnBP and eosinophils. The IL-5-mediated signaling pathway was enriched in the blood transcriptome. IL-10 was decreased and IL-5 was increased in a dose-dependent manner after MnBP exposure from THP-1 and HaCaT cells. Conclusion: Exposure to DBP affects childhood AD via semaphorin-plexin signaling and IL-5.

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关键词： Early fetal demise   CD14(+) monocytes   IFN-alpha 1  

摘要： Background Early fetal demise (EFD), defined as the absence of cardiac activity in a visible fetus, represents a severe form of pregnancy loss with incompletely understood mechanisms. While genetic factors constitute the primary etiology, emerging evidence implicates maternal immune dysregulation in EFD pathogenesis, though the specific cellular and molecular pathways remain undefined. Materials and methods We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from a 20-subject cohort comprising EFD patients, healthy pregnant women, and non-pregnant controls. Parallel murine studies involved GFP-labeled monocyte transfer into E8.5 pregnant mice, with subsequent embryonic viability assessment. Human villous tissues from EFD and control pregnancies were analyzed alongside functional characterization using primary neonatal rat cardiomyocytes exposed to IFN-alpha 1. Results ScRNA-seq revealed significant CD14(+) monocyte accumulation in EFD patients versus controls. In murine models, adoptively transferred maternal monocytes breached the placental barrier, inducing 25.7% embryonic lethality. EFD villous tissues exhibited CD14(+) monocyte infiltration with selective IFN-alpha 1 elevation (absent in IFN-alpha 2). Cardiomyocyte functional assays demonstrated IFN-alpha 1-mediated contractile impairment through significant reduction in beating frequency. Conclusion These findings establish maternal CD14(+) monocytes as key mediators of EFD via IFN-alpha 1-dependent cardiac dysfunction, revealing a targetable immune axis for pregnancy preservation. The study provides the first direct evidence linking monocyte trafficking with embryonic viability, offering new therapeutic paradigms for miscarriage prevention.

关键词： MHC   Genetic diversity   Mungos mungo   Balancing selection   Trans-species polymorphism   Carnivore   Phylogenetic mixed model  

摘要： Background The major histocompatibility complex's (MHC) role in the vertebrate adaptive immune response and its exceptional polymorphism make it a key target for studying adaptive gene evolution. However, studies on carnivore MHC often focus on populations with severe bottlenecks or conservation concerns, leading to small sample sizes and unreliable generalizations about MHC diversity. Furthermore, many studies focus on one MHC class and do not cover the whole peptide binding groove of the MHC molecule. Here, we characterize MHC class I (MHC-I) exon 2 and 3, encoding the alpha 1- and alpha 2-domains, as well as MHC-II DRB exon 2 for a large sample (N = 285-384) of a wild carnivore of least conservation concern but with high levels of inbreeding, the banded mongoose. Results MHC-I showed higher allelic and supertype diversity and polymorphism compared to MHC-II, consistent with findings in humans where MHC-I experiences stronger diversifying selection. MHC-I exon 3 exhibited the lowest diversity, likely due to its specific role in forming the peptide binding groove. Diversifying selection was stronger on MHC-I exon 2 (alpha 1 domain) than exon 3 (alpha 2 domain). Despite frequent inbreeding, banded mongooses showed MHC diversity comparable to other carnivores of least concern using phylogenetic mixed models. Phylogenetic analysis indicated a longer evolutionary trajectory for MHC-II compared to MHC-I and species-specific gene duplication of nonclassical MHC-I sequences clustering with classical sequences. Trans-species polymorphism in nonclassical MHC-I sequences suggested homology or convergent evolution. Conclusions This study is the first to characterize both MHC classes of a social, wild carnivore using high-throughput sequencing and a large sample size. Despite frequent inbreeding, banded mongooses exhibit MHC diversity comparable to other carnivores of least conservation concern, challenging assumptions that inbreeding universally reduces genetic diversity. Hig