课程文献中心 更多>>

关键词： CHIKV   gut microbiota   interferon   gastrointestinal infection   integrative analysis  

摘要： Chikungunya virus (CHIKV) infection causes joint damage and gastrointestinal clinical symptoms, including vomiting and diarrhea, particularly in elderly populations, reflecting the potential role of gut immunity in infection. However, the mechanisms by which CHIKV induces gastrointestinal diseases remain largely unexplored. This study investigated the characteristics of fecal and gut microbiota, gut metabolites, and gut immunity post-infection using multi-omics analysis. The role of gut microbiota was further validated through Oral antibiotic depletion (Abx). Importantly, a systematic comparison of age-dependent differences in gut microbiota composition and immune responses following CHIKV infection was conducted to elucidate the involvement of gut microbiota in CHIKV pathogenesis. CHIKV joint inoculation induces gastrointestinal infection and histological damage, drives fluctuations in gut microbiota, markedly increasing the abundance of Bacteroides fragilis and Prevotella sp. and upregulates conjugates of taurine and bile acids. CHIKV infection further exacerbates systemic inflammatory burden and activates intestinal interferon (IFN) signaling cascades, which supports gut repair and mucosal regeneration, but low antiviral responses to CHIKV infection compared with that of adult animals. Our results suggest that the gastrointestinal tract, along with its microbes and metabolites, modulates CHIKV infection in an age-dependent manner, providing critical insights for diagnosis, treatment, and novel therapeutic development.

关键词： Chronic hepatitis B   peginterferon alpha-2a   hepatitis B surface antigen clearance   B-cell  

摘要： Background B-cell may participate in the cellular immune process of hepatitis B antigen clearance. However, the function and specific mechanism of B-cell during interferon-pegylated interferon alpha-2a (Peg-IFN-alpha) treatment in chronic hepatitis B (CHB) patients have not yet been described. Methods A total of 150 CHB patients enrolled in this study, who received 48 weeks of Peg-IFN alpha treatment. The differentiation clusters CD19, CD24, CD27, CD38, CD40, and CD80 of B cell surface markers in CHB patients were detected by flow cytometry. Spearman correlation and Logistic regression analysis were performed for the analysis. Results The clearance rate of HBsAg increased significantly with the duration of Peg-IFN-alpha treatment, reaching 32.2% by 48 weeks. During the Peg-IFN-alpha therapy, the frequency of B-cell and its subsets increased significantly. However, we did not observe any significant difference in the frequency of the B-cell and its subsets in patients with or without HBsAg clearance after 48 weeks Peg-IFN-alpha treatment. The change in HBsAg value was negatively related to the change in plasmablasts (CD19(+)CD38(+)) level before and after 48 weeks treatment (r = -0.326, p = 0.006). Moreover, the results showed that HBsAg <288.70 IU/mL at baseline and HBsAg <58.05 IU/mL at 12 weeks were strong predictors of HBsAg clearance in patients with 48 weeks Peg-IFN-alpha treatment. Conclusion The remodeling of B cell subsets, especially plasmablasts (CD19(+)CD38(+)), during Peg-IFN-alpha treatment was closed associated with the clearance of hepatitis B antigen.

关键词： Alistipes   inflammation   IBD   colitis   gut microbes   sulfonolipids   OMVs   Il10-deficient mice  

摘要： Correlative studies have linked human gut microbes to specific health conditions. Alistipes is one such microbial genus negatively linked to inflammatory bowel disease (IBD). However, the protective role of Alistipes in IBD is understudied, and the underlying molecular mechanisms remain unknown. In this study, colonization of Il10-deficient mice with Alistipes timonensis DSM 27924 delays colitis development. Colonization does not significantly alter the gut microbiome composition, but instead shifts the host plasma lipidome, increasing phosphatidic acids while decreasing triglycerides. Outer membrane vesicles (OMVs) derived from Alistipes are detected in the plasma of colonized mice, carrying potentially immunomodulatory metabolites into the host circulatory system. Fractions of A. timonensis OMVs suppress LPS-induced Il6, Il1b, and Tnfa expression in vitro in murine macrophages. We detect putative bioactive lipids in the OMVs, including immunomodulatory sulfonolipids (SoLs) in the active fraction, which are also increased in the blood of colonized mice. Treating Il10-deficient mice with purified SoL B, a representative SoL, suppresses colitis development, suggesting its contribution to the anti-inflammatory phenotype observed with A. timonensis colonization. Thus, A. timonensis OMVs represent a potential mechanism for Alistipes-mediated delay of colitis in Il10-deficient mice via delivery of immunomodulatory lipids and modulation of the host plasma lipidome.

关键词： Anti-IL-23   anti-IL-17   psoriasis   neoplasms  

摘要： Background: Interleukin (IL) inhibitors are increasingly used in the management of moderate-to-severe plaque psoriasis. However, their use in patients with a history of cancer is ***: We conducted a multicenter retrospective study across nine Italian Dermatology Units to assess the real-world effectiveness and safety of IL inhibitors (IL-23, IL-17, IL-12/23) in 136 oncological patients with moderate-to-severe plaque psoriasis. In particular, we evaluated 116 patients who developed the neoplasm before starting the biologic with a mean time from diagnosis of neoplasia to the first biologic dose of 8.31 years. We also assessed 20 patients who received a diagnosis of neoplasm during treatment with IL inhibitors after a mean time of 2.41 years from the start of the biologic with a cumulative incidence of 3.06 per 1000 ***: Three patients experienced neoplasm recurrence during treatment with IL inhibitors, which led to the discontinuation of these drugs. In our study, biologics have demonstrated safety and effectiveness as treatment options for patients with both a history of neoplasm and those with concurrent tumors. However, further investigation is needed, particularly through larger and longer multicenter studies.

关键词： Group A Streptococcus   immunization   protective immunity   adaptive immune memory   innate immune memory  

摘要： Group A Streptococcus (GAS;Streptococcus pyogenes) is an important bacterial pathogen causing over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into >250 distinct emm (M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyse the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and although significant levels of GAS-specific antibodies are produced, these are redundant for protection. Instead, our data show that the immunization-dependent protection in this model is induced in the absence of B and T cells and is accompanied by the induction of an altered acute cytokine profile upon subsequent infection, noticeable e.g. by the absence of classical pro-inflammatory cytokines and increased IFN-gamma production. Further, the ability of immunized mice to survive a lethal infection is dependent on macrophages and the macrophage-activating cytokine IFN-gamma. To our knowledge these findings are the first to suggest that GAS may have the ability to induce forms of trained innate immunity. Taken together, the current study proposes a novel role for the innate immune system in response to GAS infections that potentially could be leveraged for future development of effective vaccines.

关键词： Advanced cancer   HLA subtype   immune checkpoint   predictive biomarkers  

摘要： Specific shared HLA-I alleles were linked to the response to immune checkpoint blockade (ICB). We aimed to identify the HLA-A subtypes associated with maximum benefit from ICB. We compiled a clinical dataset of patients who underwent a CLIA-approved germline HLA status testing as part of various advanced immune and cell therapy trials undertaken at the Christie NHS Foundation Trust. A total of 285 patients were eligible for final analysis. We identified 15 HLA-A subtypes, the most common alleles being HLA-A02, HLA-A01, and HLA-A03. A02:01 showed a tumor lineage-specific distribution. One hundred and forty patients received ICB and had evaluable response status. Patients with A01 were associated with better clinical outcomes. No significant associations were observed between HLA-A subtypes and the incidence of immune-related adverse effects. HLA genotyping should be incorporated early in the diagnostic work-up of patients with solid cancers as a predictive and selective biomarker.

关键词： Anti-IL-17A monoclonal antibody   Efficacy   Immunogenicity   Pharmacokinetics   QX002N   Safety  

摘要： Background: To investigate the safety, pharmacokinetics, preliminary efficacy, pharmacodynamics, and immunogenicity of QX002N, an interleukin-17 A monoclonal antibody, in Chinese patients with active ankylosing spondylitis (AS). Methods: In this phase 1b, double-blind, placebo-controlled, multiple ascending dose study, eligible patients with active AS were randomized into three dose (40, 80, or 160 mg) cohorts, with a 4:1 ratio in each cohort to subcutaneously receive either QX002N or a placebo once every 2 weeks with six doses in total. All patients were followed for 14 weeks (98 days) after the last dose. The primary endpoints were the safety and pharmacokinetics of QX002N, and the secondary endpoints included its preliminary efficacy, pharmacodynamics, and immunogenicity. Results: Thirty patients (n = 10 in each cohort) were included, with 24 receiving QX002N and 6 receiving a placebo. A total of 85 adverse drug reactions, predominantly Grade 1–2, were identified in 20 out of 24 patients (83.3%) who took QX002N. The exposure to QX002N increased proportionally with the dose escalating from 40 mg to 160 mg. Patients taking 160 mg QX002N achieved higher response rates (ASAS20: 87.6% at Week 8 [Day 56]);ASAS40: 50.0% at Week 12 [Day 78]), than those taking 40-mg or 80-mg QX002N. An increase in interleukin-17 A and a decrease in interleukin-6 levels in the serum, with decreases in the erythrocyte sedimentation rate and high-sensitivity C-reactive protein levels, were observed. Anti-drug antibodies were detected in only one of 24 patients taking QX002N. Conclusions: Subcutaneous administration of QX002N demonstrates a favorable safety profile, with linear pharmacokinetic characteristics. Promising clinical responses in pharmacodynamics and preliminary efficacy have been observed. Immunogenicity does not appear to be a concern. Trial registration: This study was registered with *** (CTR20201277), the data of registration was in 20 Jul, 2020. © The Aut

关键词： Coronary heart disease   Diagnosis   IL-29   Logistic regression   ROC   SYNTAX score  

摘要： Background: Coronary heart disease (CHD) is a chronic inflammatory disease carrying high morbidity and mortality. Interleukin (IL)-29 may be used as a biomarker for autoimmune diseases. This paper investigates the diagnostic value of serum IL-29 in CHD patients. Methods: A total of 90 CHD patients (39 mild and 51 severe patients) and 90 controls were included. Serum IL-29 levels were detected by ELISA, and the diagnostic value of IL-29 in CHD was analyzed by ROC curve. According to the median value of serum IL-29 level, CHD patients were categorized into IL-29 low-level group and high-level group. The correlation between IL-29 and pathological indexes of CHD patients was analyzed by chi-square test. SYNTAX score was used to classify CHD patients into mild CHD and moderate/severe CHD. Pearson coefficient analyzed the correlation between IL-29 and CHD severity. Multivariate logistic regression analyzed the risk factors for CHD exacerbation. Results: IL-29 serum levels were elevated in CHD patients. The AUC for CHD diagnosis by serum IL-29 was 0.789 (65.6% sensitivity and 76.7% specificity). IL-29 was correlated with BMI, PHASE score, and CRP. IL-29 serum level was positively correlated with CHD severity. The AUC for differentiating mild and moderate/severe CHD patients by IL-29 level was 0.739 (70.6% sensitivity and 66.7% specificity). IL-29 was an independent risk factor for CHD exacerbation, and each one-unit increase in IL-29 increased the risk of exacerbation in CHD patients by 1.065-fold. Conclusion: IL-29 is highly expressed in CHD patients and has auxiliary diagnostic value for CHD. © The Author(s) 2025.

关键词： Flexography printing   Graphite   Carbon dots   Interleukin 8   Non-faradaic biosensor   Disability  

摘要： Interleukin-8 (IL-8) is a key biomarker linked to inflammation and disability in neonates. However, current IL-8 detection methods are often costly, labor-intensive, and require highly trained personnel. While electrochemical techniques have been employed for sensitive IL-8 quantification, they typically rely on redox probes and threeelectrode electrochemical cells, leading to issues such as toxicity, prolonged fabrication time, and increased waste generation. Additionally, conventional electrochemical biosensors fabrication techniques are expensive and time-consuming, limiting their scalability for mass disease screening. In this study, we introduce a low-cost, non-faradaic electrochemical nanobiosensor for the direct detection of IL-8. The sensor consists of interdigitated graphite/carbon dot conjugates flexographically printed onto a flexible polyimide substrate. The printed layer's physical properties were systematically characterized using SEM, AFM and surface profilometer, and biofunctionalization was achieved using aminopropyltriethoxysilane (APTES) and glutaraldehyde. Successful surface modification was confirmed through ATR-FTIR and EDS elemental mapping. Electrochemical impedance spectroscopy (EIS) analysis demonstrated the nanobiosensor's response to varying IL-8 concentrations, with capacitance, Zmod, Zreal, and Zimag measurements. Among these, Zimag exhibited the highest sensitivity, with a response of 2.7 k Omega/log(ng/mL) and a detection limit of 50 pg/mL-well below the clinically established threshold of 600 pg/mL. This study demonstrates that, in addition to capacitance, there are multiple parameters that warrant exploration in non-faradaic biosensors to improve their sensing performance. The nanobiosensor fabrication via flexographic printing enables scalable, cost-effective production while maintaining high sensitivity and selectivity through a non-faradaic detection mechanism. This work paves the way for the development of affordable, mass-produ

摘要： Glioblastoma remains a challenging indication for immunotherapy: the blood-brain barrier hampers accessibility for systemic treatments and the immunosuppressive microenvironment impedes immune attack. Intratumoral therapy with the proinflammatory cytokine interleukin-12 (IL-12) can revert immunosuppression but leakage into the circulation causes treatment-limiting toxicity. Here we engineer an IL-12Fc fusion cytokine with reduced binding to the neonatal Fc receptor FcRn. FcRn-silenced IL-12Fc avoids FcRn-mediated brain export, thus exhibits prolonged brain retention and reduced blood levels, which prevents toxicity. In murine glioblastoma, FcRn-silenced IL-12Fc induces more durable responses with negligible systemic cytokine exposure and boosts the efficacy of radio- and chemotherapy. It triggers anti-tumor responses independently of peripheral T cell influx or lymphopenia and leads to inflammatory polarization of the tumor microenvironment in patient-derived glioblastoma explants. FcRn-silencing of IL-12Fc may unlock the full potential of IL-12 for brain cancer therapy and could be further applied to containing the activity of other therapeutics targeting neurological diseases. © The Author(s) 2025.