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关键词： 超敏反应   尘螨科   Th2细胞   免疫球蛋白E   白细胞介素-13   白细胞介素-33   皮炎,特应性   婴儿  

摘要： 目的 探究孕晚期室内尘螨水平对母婴血液中Th2相关因子水平的影响。方法 选择于我院孕检并于2023年7月—2024年6月足月顺产单胎的78例健康产妇及其婴儿作为研究对象,根据产妇是否为特异性体质将产妇及婴儿分为特异性组和非特异性组,采用酶联免疫吸附试验（ELISA）测定孕晚期产妇家中尘螨暴露水平,并据此将产妇及婴儿进一步分为低、中、高暴露亚组。收集各组产妇的性别、年龄、体质量指数及婴儿性别、出生体质量、喂养方式等一般资料,采集产妇产前即刻的外周静脉血和婴儿出生时的脐带血,检测血清中Th2相关因子（IL-33、IL-13、IgE）的水平并进行比较,随访产后早期（3个月内）婴儿特应性皮炎（AD）发生情况。结果 特异性组中,中、高暴露亚组产妇血清IL-33、IL-13、IgE及婴儿血清IL-33、IL-13水平均显著高于低暴露亚组（F=3.764～9.454,P<0.05）;非特异性组中,高暴露亚组婴儿血清IgE水平显著高于低暴露亚组（F=3.327,P<0.05）。此外,特异性组中、高暴露亚组产妇血清IL-13、IgE水平及婴儿血清IL-33、IgE水平显著高于非特异性组中、高暴露亚组（t=2.552～8.604,P<0.05）。婴儿早期AD发病与其出生时血清IL-33、IgE水平,以及产妇的特异性体质和产前血清IL-33、IL-13、IgE水平有关（χ2=11.522,t=2.805～4.490,P<0.05）。结论 母婴围生期血清Th2相关因子水平升高与孕晚期室内尘螨水平升高有关,该关联在具有特异性体质的产妇中尤其明显,且遗传与环境的交互作用会增加婴儿早期患AD的风险。

关键词： 3D hESC-derived exosomes   hsa_circ_0076798/miR-1184/DICER1 axis   liver fibrosis   macrophages   TNF/NF-kappa B signaling pathway  

摘要： Here, we employed human embryonic stem cell spheroid (3D hESCs)-derived exosomes to assess inflammatory responses of macrophages in liver fibrosis, and found that 3D hESC-exosomes promoted the transformation of macrophages from M1 to M2 phenotype in vitro. The transplantation of 3D hESC-exosomes exhibited a notable decrease of pro-inflammatory factors, and significant increase of anti-inflammatory factors, and led to a reduction of CD86+M1 macrophages and an increase of Arg-1+M2 macrophages in the livers of treated fibrotic mice, restricting the advancement of liver fibrosis. hsa_circ_0076798, derived from 3D hESC-exosomes, acts as a molecular sponge that sequesters miR-1184, thereby mitigating miR-1184-mediated repression of DICER1 expression within macrophages. Further investigation revealed that DICER1 ultimately mitigated macrophage inflammation by deactivating TNF/NF-kappa B signaling pathway. Therefore, our findings demonstrated that 3D hESC-exosomes alleviated inflammatory responses by suppressing TNF/NF-kappa B pathway through hsa_circ_0076798/miR-1184/DICER1 axis, and offers insights into the targeted treatment of liver fibrosis via exosome-based cell-free therapy.

关键词： aging   canine inflammation   canine personality   cytokines  

摘要： As dogs live longer, they face an increased risk of functional age-related changes, including physiological and behavioral alterations. However, data on these age-related processes in domestic dogs remain limited. In this study, we assessed serum concentrations of cytokines (TNF-α, IL-6, IL-10), personality and cognition using validated scales (Dog Reinforcement Sensitivity Theory Personality Questionnaire (RSTQ-D), Dog Impulsivity Assessment Scale (DIAS), and Canine Cognitive Assessment Scale (CCAS)) in 44 healthy pet dogs from two non-overlapping age groups (1-4 years old and ≥11 years old). Generalized linear models revealed small but significant ( = 0.001) negative effects of age-by-cytokine interactions in predicting sensitivity to RST personality traits related to fear and anxiety in older dogs. Specifically, higher TNF-α and IL-10 levels predicted lower scores on the Fight/Flight/Freeze System (FFFS) and the Behavioral Inhibition System (BIS). These findings provide novel insights into previously unrecognized associations between the immune system and personality in healthy older dogs, possibly contributing to broader profiles of vulnerability or, conversely, resilience. Further research is needed to confirm these associations and clarify their functional meaning. Such knowledge could facilitate the early identification of complex aging-related phenotypes and inform individualized preventive strategies to support the health and well-being of aging companion dogs.

关键词： Ascites   Barcoding   CRISPR screening   Interferon   Lineage tracing   Metastasis   Omentum   Ovarian Cancer   Single cell analysis  

摘要： Metastasis is an emergent continuum, driven by evolving reciprocal adaptations between continuously disseminating tumor cells (DTCs) and the specialized metastatic niches of distant organs. The interplay between intrinsic and niche-driven mechanisms that enables DTCs to survive and home to distant organs remains incompletely understood. Here, using MetTag, a single-cell barcoding and transcriptome profiling approach with time-stamped batch identifiers (***), we mapped temporal, clonal dynamics of DTCs and the immune cell landscape across ovarian cancer metastatic niches. Deep sequencing of barcodes revealed preferred enrichment of early-disseminated clones across metastatic niches. Mechanistically, single-cell RNA sequencing (scRNA-seq) coupled with velocity analyses in ascites and metastasis-bearing omenta uncovered an emergent, distinct interferon-gamma (IFNγ) centric transcriptional trajectory, enriched among early seeding clones. Moreover, CRISPR/Cas9 screening of metastatic niche-specific signatures demonstrated that genes belonging to the ascites IFNγ signature, including , , are functionally important for peritoneal metastasis. Knockout of IFNγ receptor 1 () in tumor cells significantly reduced metastatic burden and extended survival, underscoring the importance of tumor cell intrinsic IFNγ signaling in ovarian cancer metastasis. Furthermore, we identified that the tumor intrinsic IFNγ response and ascites-derived tumor-associated macrophages (TAMs) protect cancer cells from anoikis-mediated death within the IFNγ-rich ascites environment. Our study resolves temporal dynamics of disseminating tumor cells and highlights an ascites-driven, IFNγ program as a necessary pro-metastatic adaptation in the ovarian metastasis cascade.

摘要： During (Mtb) infection, infected alveolar macrophages (AMs) initially up-regulate a NRF2 regulated cell-protective program, which is detrimental to host control and impedes AM activation, including MHC II expression. MHC II is critical for CD4+ T cell activation and host immunity during Mtb infection. We hypothesized that NRF2 regulates the MHC II pathway and AM antigen presentation to T cells. We found that NRF2 inhibits MHC II, but not MHC I, specifically in AMs, following Mtb infection and . NRF2 dampens and gene expression in uninfected AMs, and MHC II inhibition by NRF2 is retained following innate stimuli and IFNγ exposure. NRF2 expression in Mtb-infected AMs impedes their ability to activate ESAT6-specific CD4+ T cells. Thus, although NRF2 expression enhances cell-protective functions, it has the unexpected consequence of limiting innate-adaptive crosstalk, which can impair CD4+ T cell activation and host immunity during Mtb infection.

摘要： CD4Foxp3 regulatory T cells are essential for maintaining immune tolerance and preventing excessive inflammation, making them promising candidates for treating autoimmunity and GvHD. However, the translation of regulatory T cell therapy into clinical practice poses substantial challenges. Here, we show that adoptive regulatory T cell therapy increases IL-6 and TGF-β-dependent pathogenic Th17 cell differentiation in murine models of inflammatory bowel disease and experimental autoimmune encephalomyelitis. Regulatory T cells increase the p-stat3/p-stat5 ratio in effector T cells by suppressing IL-2 secretion and competitively consuming IL-2, thereby promoting Th17 cell differentiation. Notably, IL-2 signaling deficiency not only promotes a Th17 cell-associated transcriptional program, but also enhances the pro-inflammatory properties of Th17 cells. Strikingly, therapeutic blockade of IL-6/STAT3 signaling pathway can reverse pathogenic Th17 cell differentiation and enhance the therapeutic effect of regulatory T cell therapy. Thus, our findings could potentially advance the clinical research progress of adoptive regulatory T cell therapy.

关键词： host-guest interaction   lysosomal escape   nanoparticle aggregation   rheumatoid arthritis   siRNA delivery  

摘要： The inefficient lysosomal escape of small interfering RNA (siRNA) from immune cells remains a major barrier to therapeutic efficacy. To address this challenge, an innovative pH-triggered aggregation nanoplatform for enhanced siRNA delivery is developed. By using adamantane (Ad)-modified hyperbranched poly-L-lysine (HBPL-Ad) as a backbone, this nanoplatform incorporated acetalated beta-cyclodextrin (beta-ACD) as a pH-sensitive "gatekeeper", together with siRNA to prepare physiologically stable aggregated nanoparticles (ANPs). Triggered by the acidic lysosomal microenvironment, the beta-ACD hydrolysis exposed beta-CD cavities to enable strong host-guest (beta-CD/Ad) binding. This binding caused nanoparticle aggregation and subsequent mild lysosomal membrane permeabilization (LMP), facilitating efficient siRNA escape independent of the proton sponge effect. The ANPs demonstrated superior cellular uptake and significantly enhanced TNF-alpha silencing across macrophages, dendritic cells, and Jurkat immune cells in vitro. Intraperitoneal administration of ANPs loaded with TNF-alpha siRNA in a collagen-induced arthritis (CIA) model achieved 93% mRNA reduction and 95% protein reduction in joint TNF-alpha levels, significantly outperforming Lipo2000 (56% mRNA and 60% protein reduction), effectively attenuating synovitis and cartilage erosion without detectable systemic toxicity. This work establishes pH-triggered programmable aggregation as a potent and transformative strategy for overcoming immune cell delivery barriers, offering a promising clinically viable platform for RNAi-based immunotherapy.

摘要： INTRODUCTION:Behavioral and psychological symptoms of dementia (BPSD) significantly affect the quality of life for patients with Alzheimer's disease (AD) and contribute to caregiver burden. Although systemic inflammation is implicated in AD pathophysiology, the specific role of peripheral immune activity-particularly interleukin-6 (IL-6)-in relation to BPSD remains unclear, especially regarding its independent effects from central neuroinflammation. METHODS:We conducted a cross-sectional study of 23 biomarker-confirmed patients diagnosed with AD or prodromal AD. Plasma and cerebrospinal fluid (CSF) levels of IL-6, IL-1β, TNF-α, and C-reactive protein (CRP) were measured. BPSD was assessed using the Dementia Behavior Disturbance (DBD) scale. Central neuroinflammation was quantified via 11C-DPA-713 translocator protein positron emission tomography (TSPO-PET). Stepwise multiple linear regression and Bayesian analyses were used to identify predictors of BPSD severity. RESULTS:Plasma IL-6 emerged as the only significant predictor of DBD scores in frequentist and Bayesian regression models. Other demographic, cognitive, and inflammatory variables, including CSF IL-6 and TSPO-PET binding, showed no significant association with behavioral symptoms. No correlation was observed between plasma and CSF IL-6 levels, nor between plasma IL-6 and TSPO-PET measures. CONCLUSION:Peripheral IL-6 is significantly associated with BPSD severity in AD, independently of central inflammatory markers. This finding suggests a distinct peripheral immune mechanism underlying neuropsychiatric symptoms, potentially mediated through systemic pathways such as vagus nerve signaling or gut-brain-immune interactions. Peripheral IL-6 may serve as a clinically relevant biomarker and therapeutic target for behavioral disturbances in AD.

关键词： Atopic dermatitis   Super responder   Biologics therapy   Dupilumab   Predictive factors   Treatment optimization  

摘要： Introduction: Biologics have revolutionized the treatment of moderate-to-severe atopic dermatitis (AD), with dupilumab, an anti-interleukin-4R alpha monoclonal antibody, showing notable clinical efficacy. However, some patients achieve rapid and profound improvement-termed super responders (SRs), while others respond poorly. This study aimed to identify SRs to dupilumab in patients with AD and analyze their clinical characteristics to inform personalized treatment strategies. Methods: A retrospective analysis was conducted on patients with moderate-to-severe AD treated with dupilumab, sourced from the National Clinical Research Center for Skin and Immune Diseases in China. Clinical and follow-up data were reviewed. Categorical variables were compared using Chi-square or Fisher's exact tests, while continuous variables were compared via t-tests or Mann-Whitney U tests. Furthermore, a logistic regression model was employed to evaluate the predictive ability of clinical and demographic variables collected at baseline on the probability of becoming SRs. Results: Among 1,034 patients with AD, 125 (12.09%) were identified as SRs, achieving significant clinical improvement within 16 weeks. Further univariate analysis indicated that factors closely associated with SRs included: older age, higher body mass index, later disease onset, higher baseline scores of pruritus intensity (Peak pruritus Numerical Rating Scale, PP-NRS)/disease severity (Eczema Area and Severity Index, EASI)/quality of life (Dermatology Life Quality Index, DLQI), prior systemic therapy use, no prior biologics, elevated eosinophil count, high-dose dupilumab, shorter dosing intervals of dupilumab, and absence of concomitant therapies. Logistic regression identified moderate baseline pruritus (PP-NRS) and higher baseline DLQI scores (moderate-to-severe impact) as strong predictors of SRs (moderate pruritus Adj odds ratio (OR): 8.38, 95% confidence interval (CI) 2.56-27.42;moderate DLQI Adj OR: 11.01, 95% CI

关键词： HLA-B*27-positive vs. -negative   HLA-B27 status   clinical differences   immunological markers   inflammatory biomarkers   rheumatic diseases  

摘要： : Human leukocyte antigen B27 (HLA-B27) is a genetic marker strongly associated with various inflammatory rheumatic diseases, particularly those within the spondyloarthritis spectrum. Its presence influences disease onset, clinical severity, and therapeutic strategies. However, comparative data between HLA-B*27-positive and -negative patients, especially in Eastern European populations, remain limited. The study aimed to investigate the clinical, paraclinical, and psychosocial differences between HLA-B*27-positive and -negative individuals diagnosed with rheumatic diseases, in order to better understand the implications of HLA-B27 status on disease expression and patient quality of life. : A cross-sectional, observational study was conducted between June 2023 and December 2024 at the Emergency Clinical Hospital for Children "Sf Ioan" in Galati, Romania, in collaboration with "Dunarea de Jos" University. Fifty adult patients with various rheumatic conditions were enrolled and stratified into HLA-B*27-positive (n = 22) and -negative (n = 28) groups. Data collection included clinical evaluations, laboratory biomarkers (CRP = C-reactive protein; ESR = erythrocyte sedimentation rate), and a structured quality-of-life questionnaire. Statistical analysis was performed using SPSS v27. : HLA-B*27-positive patients were significantly younger (mean age 46.00 vs. 55.07 years, = 0.018) and had higher CRP levels (>1 mg/dL in 53.33% vs. 0%, = 0.001). Ankylosing spondylitis was more prevalent in this group (22.73% vs. 3.57%, = 0.039). Magnetic resonance imaging (MRI) was more frequently used (68.18% vs. 39.29%, = 0.042), indicating greater suspicion of axial involvement. HLA-B27-positive patients also reported higher perceived stress (mean score 2.41 vs. 1.21, < 0.001). : HLA-B*27 positivity is associated with earlier disease onset, increased systemic inflammation, greater axial involvement, and higher psychological stress. These findings emphasise the need for personalised, m