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关键词： Chemokine   Chikungunya   Chronic chikungunya arthritis   Cytokine  

摘要： BACKGROUND:Cytokines and chemokines play a crucial role in orchestrating the immune response to chikungunya virus (CHIKV) infection, influencing disease course and outcome. Although significant efforts have been made to understand the cytokine signatures associated with CHIKV infection, the identification of specific cytokine biomarkers across different disease stages remains incomplete. MATERIAL AND METHOD:We have assessed CHIKV-specific cytokine, chemokine profiles of 17 analytes in 50 acute chikungunya patients, 31 chronic chikungunya arthritis patients, 30 recovered individuals, and 23 healthy controls. The cytokine and chemokines were measured in the supernatant of PBMCs stimulated in vitro with inactivated chikungunya virus. RESULTS:It was observed that chronic chikungunya arthritis patients exhibited significantly higher levels of IL-1β, IL-6, and GM-CSF compared to all other groups. MCP-1 levels were elevated in patient groups compared to recovered and control individuals. IL-1β emerged as a potential biomarker for chronic chikungunya arthritis based on ROC analysis. A negative correlation between IFN-γ levels and CHIKV load was observed in acute patients, suggesting its antiviral role. IL-12 levels were higher in recovered individuals compared to all other groups, while IFN-γ levels were elevated in recovered individuals compared to acute patients. CONCLUSION:Our findings highlight IL-1β as a potential biomarker for chronic chikungunya arthritis and suggest that GM-CSF inhibition could serve as a therapeutic intervention for disease-associated chronic inflammation. The observed co-regulation of IL-12 and IFN-γ in recovered individuals needs further investigation into their role in disease resolution. These insights provide a deeper understanding of the immunopathogenesis of CHIKV infection and may contribute in future diagnostic and therapeutic strategies.

关键词： IL‐33   Leydig cells   aging   mesenchymal cells   steroidogenesis  

摘要： BACKGROUND:Serum testosterone (T) concentration declines with aging in men, potentially affecting reproduction, mental and physical well-beings. A role of immune factors in Leydig cell (LC) function is well-known, but the specific factors involved, especially these playing roles in LC aging, are still unclear. This study investigated effects of interleukin 33 (IL-33) on LC function and its expression during testicular aging. METHODS:Immunohistochemistry and Western blotting were used to determine IL-33 and its receptor IL1RL1 expressions in testes of young (3-month-old) and old (19-24-month-old) Wistar rats. In vitro, the effects of IL-33 on sex steroid hormone productions were evaluated in primary and MLTC-1 LCs over 2-24 h. Different steroidogenic stimulators or signaling molecules (luteinizing hormone [LH], 8-Br-cAMP, Forskolin, pertussis toxin, and MAPK activators) were compared with elucidate mechanisms. Steroidogenic pathway proteins and potential signaling molecules were explored by Western blotting. RESULTS:IL-33 is expressed by mesenchymal cells, with the number increasing significantly with aging. IL1RL1, its receptor, is expressed by LCs and remains unchanged. In vitro, IL-33 acutely inhibited LC steroidogenesis in a dose-dependent manner (1-100 ng/mL) within 2-24 h. The effect was LH-dependent; replacing LH with either 8-Br-cAMP or Forskolin abolished the inhibition. IL-33 mainly affected STAR in the steroidogenic pathway. Signaling molecules involving STAR regulation (AKT and MAPK) were down-regulated while PKA phosphorylation was increased. P38 MAPK involvement was confirmed as increased Tyr182 phosphorylation of P38 by SB203580 partly reversed the IL-33-induced steroidogenesis inhibition. CONCLUSION:Testicular mesenchymal cells can synthesize IL-33, and LCs express the receptor IL1RL1. IL-33 inhibits LC steroidogenesis in vitro, partially via inhibiting P38 MAPK phosphorylation. As IL-33-expressing cell numbers rise significantly with aging, its role

关键词： Anti-IL23   Psoriasis   biologic treatment   efficacy   guselkumab   risankizumab   tildrakizumab  

摘要： INTRODUCTION:Psoriasis is a chronic, systemic inflammatory disease with significant physical and psychosocial burden. Advances in understanding the pathogenesis of psoriasis, particularly the role of interleukin (IL)23/Th17 axis, have led to the development of selective drugs targeting these cytokines. Among these, IL23 inhibitors (guselkumab, risankizumab, and tildrakizumab), represent the most recent class of biologic drugs approved for the management of moderate-to-severe plaque psoriasis. Since their approval, real-life data on the use of anti-IL23 have confirmed their high efficacy, durability, and favorable safety profile. AREAS COVERED:This narrative review summarizes real-world data on the effectiveness, also in difficult-to-treat areas, safety, and drug survival of IL23 inhibitors in psoriasis. EXPERT OPINION:Real-world evidence consistently confirms the strong efficacy, favorable safety profile, and long-term treatment durability of IL23 inhibitors across various patient subgroups, including those with comorbidities, prior biologic failures, and the involvement of difficult-to-treat areas. IL23 inhibitors have become key components of the therapeutic arsenal in psoriasis, and their performance in real-world settings continues to support their widespread adoption in clinical practice.

关键词： biofilm‐infected diabetic ulcers   core‐shell microneedle   macrophage polarization   spatiotemporal immunomodulatory  

摘要： Macrophage phenotypic dysregulation, spatially by biofilm and dynamically in time, impedes the healing of diabetic ulcers (DUs). Effective treatment requires enabling spatiotemporal regulation of macrophage polarization, balancing the M1 pro-inflammatory antimicrobial response with the M2 anti-inflammatory tissue-regeneration response. Here, a core-shell microneedle system (LM-MG@MN) is proposed with spatiotemporal immunomodulation features, designed to spatially disrupt biofilm barriers and sequentially induce macrophage polarization from M0 to M1 and subsequently to M2 by regulating the NLRP3/IL-1β pathway. Glucose oxidase (GOX)-loaded 2D MXene nanosheets (MG) are encapsulated in a hyaluronic acid-β-cyclodextrin (HA-β-CD) matrix as the MN shell layer. The rapid dissolution of this shell triggers MG to induce pro-inflammatory polarization of macrophages from M0 to M1, aiding in clearing biofilm infections. Liposomes (LM) carrying the NLRP3 inflammasome inhibitor MCC950 are embedded within a methacrylate hyaluronic acid (HAMA) matrix in the MN core. In the later stages of wound healing, LM is released gradually from the core, promoting the anti-inflammatory polarization of macrophages from M1 to M2 and accelerating tissue regeneration by enhancing crosstalk with fibroblasts and endothelial cells. Additionally, RNA sequencing indicates that LM-MG@MN regulates macrophage metabolic reprogramming to enhance DUs healing. This spatiotemporal immunomodulation strategy offers a promising approach for clinical DUs treatment.

关键词： HLA‐B27   uveitis   vitamin D  

摘要： Hybrid solid-state electrolytes, which combine ionic liquids with metal-organic frameworks, offer a promising approach to enhancing the safety and energy density of next-generation batteries. A thorough understanding of the interplay between the solid and liquid phases in hybrid solid-state electrolytes is crucial for optimizing their performance as battery electrolytes. This study investigates how interactions between different ionic liquid-based electrolytes and the metal-organic framework ZIF-8 influence the coordination and dynamics of Li in confinement. To this end, we examine five different ionic liquids, varying the chemical nature of the cation. Raman spectroscopy, supported by 2D solid-state NMR and simulations, are used to elucidate Li coordination and ion-wall interactions. The impact of these interactions on local Li dynamics and charge transport in the ionic liquid-ZIF-8 hybrid system is investigated using Li spin relaxation, impedance spectroscopy, and simulations. The results reveal a competitive interaction between Li and the ionic liquid cation with the ZIF-8 framework, which can be fine-tuned by modifying the molecular structure of the ionic liquid cation. As a consequence, local Li dynamics is enhanced, depending on the ionic liquid cation. The beneficial interactions in the confined system can even make Li the fastest diffusing species, in contrast to bulk electrolyte, where Li transport is limited by strong Li-anion clusters. Thus, blocking Li-framework interactions through other competitive interactions might be an effective strategy to enhance Li dynamics and increase Li conductivity in a hybrid solid-state electrolyte. Although confinement within the ZIF-8 model system leads to an overall decrease in conductivity, this study provides valuable insights into the design of hybrid electrolytes for next-generation battery applications.

关键词： 抗Claudin18.2单抗   抗体依赖性细胞吞噬作用   生物学活性   转基因细胞   报告基因   优化   验证  

摘要： 目的 建立抗Claudin18.2单抗（mAb）的抗体依赖性细胞吞噬作用（ADCP）生物学活性检测方法。方法 以Jurkat/NFAT/CD32a-FcεRIγ转基因细胞系作为效应细胞，HEK293T-Claudin18.2细胞系作为靶细胞，通过萤光素酶检测系统(OneGloTMLuciferase Assay System)检测抗Claudin18.2单抗的ADCP生物学活性，并进行实验参数优化与方法学验证。结果 抗Claudin18.2单抗在该报告基因法中存在量效关系，且符合四参数方程：y=（A-D）/[1+（x/C）B]+D。方法经多个实验参数筛选和优化，确定抗体工作浓度为0.02～200 000 ng/mL，靶细胞和效应细胞的接种量均为每孔5×10～4个，诱导时间为6 h。该方法具有良好的专属性；5个不同稀释组回收率样本经3次检测，相对效价分别为（48.90±2.36）%、（71.87±2.62）%、（99.64±2.12）%、（135.42±1.12）%和（151.16±6.91）%；回收率为96%～108%,RSD均小于6%，线性检测范围为50%～150%。结论 本研究成功建立基于报告基因的抗Claudin18.2单抗ADCP生物学活性测定方法，该方法具有良好的专属性、重复性和准确性，可作为抗Claudin18.2单抗ADCP生物学活性的评价方法。

关键词： HLA‐G 14‐bp   meta‐analysis   polymorphism   recurrent spontaneous abortion  

摘要： We performed a meta-analysis to study the relationship between HLA-G 14-bp insertion/deletion polymorphism and recurrent spontaneous abortion (RSA). All literature was searched from PubMed, Web of Science, Embase and Wanfang databases. Statistical analyses were performed by the STATA software (Version 16.0). A total of 35 studies were analysed which included 3652 women with RSA and 3331 normal control subjects. The current meta-analysis revealed that 14-bp insertion/deletion polymorphism has a significant association with RSA (I vs. D: OR: 1.17; 95% CI (1.05-1.30); II + ID vs. DD: OR: 1.33; 95% CI (1.11-1.59); II vs. DD: OR: 1.34; 95% CI (1.07-1.66); ID vs. DD: OR: 1.30; 95% CI (1.08-1.58)). Subgroup analysis by the number of abortions indicated that there was no significant association between HLA-G 14-bp insertion/deletion polymorphism and RSA risk in women with two or more abortions. However, HLA-G 14-bp insertion/deletion polymorphism was associated with the risk of RSA in women with three or more abortions as well as the overall population (I vs. D: OR: 1.26; 95% CI (1.04-1.52); II + ID vs. DD: OR: 1.47; 95% CI (1.09-1.98); II vs. DD: OR: 1.52; 95% CI (1.08-2.13); ID vs. DD: OR: 1.45; 95% CI (1.06-1.99)). Subgroup analysis by ethnicity indicated that HLA-G 14-bp insertion/deletion polymorphism increased RSA risk in both Asian ancestry group (II + ID vs. DD: OR: 1.35; 95% CI (1.06-1.73); ID vs. DD: OR: 1.37; 95% CI (1.06-1.78)) and European ancestry group (I vs. D: OR: 1.25; 95% CI (1.08-1.45); II vs. ID + DD: OR: 1.48; 95% CI (1.14-1.91); II vs. DD: OR: 1.61; 95% CI (1.19-2.18)). A p value of < 0.05 was considered statistically significant for these analyses. Our current meta-analysis demonstrated that the HLA-G 14-bp insertion/deletion polymorphism increased the risk of RSA in Asian ancestry group and European ancestry group.