课程文献中心 更多>>

关键词： Melastoma dodecandrum   Polysaccharide   Allergic rhinitis   NLRP3   IL-17  

摘要： Allergic rhinitis (AR) is a prevalent nasal disorder characterized by chronic inflammation and hypersensitivity, with limited effective treatments. Melastoma dodecandrum polysaccharide (MDP), derived from a medicinal herb, exhibits anti-inflammatory and immunomodulatory properties, making it a potential therapeutic candidate for AR. This study evaluated the therapeutic efficacy of MDP in AR mice and explored its underlying mechanisms. An ovalbumin (OVA)-induced AR mouse model was established, with MDP administered via gavage or inhalation. MDP reduced sneezing and nasal scratching in AR mice. Treatment alleviated nasal mucosa thickness, goblet cell hyperplasia, and cellular disarray, as assessed by H&E and Alcian blue staining. MDP decreased serum IgE, IL-17, and IL-1(3 levels, as measured by ELISA, and reduced the proportion of Th17 cells, analyzed by flow cytometry. In nasal mucosa, MDP downregulated the expression of NLRP3, GSDMD, and IL-17A proteins, and reduced the mRNA levels of NLRP3, IL-17, IL-1(3, and IL-18, as determined by immunohistochemistry and qRT-PCR. MDP also mitigated tissue cell death, as shown by TUNEL staining. In vitro, MDP suppressed NLRP3 inflammasome activation and pyroptosis in bone marrow-derived macrophages (BMDMs) treated with LPS and nigericin. These effects were confirmed by western blot, qRT-PCR, and immunofluorescence, along with pyroptosis assessment and scanning electron microscopy, which revealed reduced pyroptosis and membrane damage. In conclusion, MDP effectively alleviates AR symptoms in mice, with its therapeutic effects involving the modulation of the NLRP3 inflammasome and the IL-17 signaling pathway, highlighting its clinical potential for AR management.

关键词： 防己黄芪汤   他克莫司   肾病综合征   免疫球蛋白   中西医结合治疗  

摘要： 剖析防己黄芪汤联合他克莫司对肾病综合征患者免疫球蛋白水平以及肾脏指标的影响,为临床治疗实践提供借鉴。方法 纳入 2024 年 1 - 12 月我院 100 例原发性肾病综合征患者,随机均分为对照组与观察组。对照组采用常规治疗联合他克莫司,观察组在此基础上加用防己黄芪汤,疗程 12 周。对比两组治疗前后免疫球蛋白(IgA、IgG、IgM)水平、24 小时尿蛋白定量及血清白蛋白水平变化。结果 治疗后,观察组 IgA、IgG、IgM 水平分别达(2.79±0.48)g/L、(9.82±1.15)g/L、(1.14±0.27)g/L,显著高于对照组(P<0.05);24 小时尿蛋白定量降至(1.62±0.42)g,血清白蛋白升至(38.65±3.24)g/L,改善程度均优于对照组(P<0.05)。结论 采用防己黄芪汤与他克莫司联合能有效调节患者免疫功能,促进肾脏指标好转,为肾病综合征的治疗呈上了更优的中西医结合办法。

关键词： spesolimab   non-coding RNAs   integrated pathway analysis   biomarker   EFFISAYIL   CXCL   C-X-C motif chemokine ligand   C/EBPα   CCAAT-enhancer-binding proteins alpha   DEFB4A   Defensin Beta 4A   FC   fold change   GPP   generalized pustular psoriasis   GPPASI   GPP Psoriasis Area and Severity Index   GPPGA   GPP Physician Global Assessment   IL   interleukin   miRNA   micro-ribonucleic acid   mRNA   messenger ribonucleic acid   PCA   principal component analysis   RT-qPCR   reverse transcription quantitative polymerase chain reaction   small RNA-seq   small RNA-sequencing  

关键词： IL‐1β   NLRP3   TLR2   immunohistochemistry   in vivo model   periapical lesion  

摘要： This study aimed to investigate the role of Toll-like receptor 2 (TLR2) in the progression of periapical lesions by evaluating NLRP3 inflammasome and interleukin-1 beta (IL-1β) expression in wild-type (WT) and TLR2 knockout (KO) mice. A total of 55 mice (28 WT, 27 TLR2-KO) underwent pulpal exposure of mandibular first molars and were euthanised at 7, 21, or 42 days post-exposure. Histological and immunohistochemical analyses were performed. TLR2-KO mice showed significantly larger periapical lesions and higher IL-1β expression than WT mice after 21 and 42 days, respectively. In contrast, NLRP3 expression was significantly greater in WT mice at both time points. A weak but significant positive correlation between NLRP3 and IL-1β expression was observed only in WT mice. These findings suggest that TLR2 plays a protective role in limiting periapical bone resorption and modulating inflammatory cytokine expression, independent of NLRP3 inflammasome activity.

关键词： Adaptive immunity   Cytokines   Immunology   Inflammation   Ophthalmology   T cells  

摘要： Recurrent acute anterior uveitis is a frequent extra-articular manifestation of the axial spondyloarthropathies (AxSpA); chronic inflammatory diseases affecting the spine, enthesis, peripheral joints, skin, and gastrointestinal tract. Pathology in AxSpA has been associated with local tissue-resident populations of interleukin (IL)-23 responsive lymphoid cells. Here we characterize a population of ocular T cell defined by CD3+CD4-CD8-CD69+gdTCR+IL-23R+ that reside within the anterior uvea as an ocular entheseal analogue of the mouse eye. Localised cytokine expression demonstrates that uveal IL-23R+ IL-17A-producing cells are both necessary and sufficient to drive uveitis in response to IL-23. This T cell population is also present in humans, occupying extravascular tissues of the anterior uveal compartment. Consistent with the concept of IL-23 as a unifying mediator in AxSpA, we present evidence that IL-23 can also act locally on tissue resident T cells in the anterior compartment of the eye at sites analogous to the enthesis to drive ocular inflammation.

关键词： Malat1   IL-10   Th2 cells   immune sexual dimorphism   lincRNAs  

摘要： Identifying cell intrinsic regulators of immune sexual dimorphism is critical for treatment of several immunopathologies. We show that Malat1 is required for appropriate cytokine expression in female but not male T helper 2 (Th2) cells. Malat1 deficiency impairs in vitro Th2 differentiation of naïve CD4+ T cells from female mice, characterized by transcriptome-wide effects and suppression of cytokine expression, particularly interleukin (IL)-10. Upon IL-10 receptor (IL10R) blockade a pronounced effect is also seen on IL-4 and IL-13. Mechanistically, naïve CD4+ T cells from Malat1-/- female mice demonstrate altered early activation kinetics and impaired early differentiation gene expression, including upregulation of an interferon-stimulated gene (ISG) module. This is followed by suppression of IL2Rα and IL2Rγ expression and IL-2-mediated differentiation. Mimicking the effect of Malat1 loss by maintaining early ISG expression in WT cells with interferon β treatment partially phenocopies the effects of Malat1 deficiency. A subset of the effects of Malat1 loss in female cells is also observed in male cells. However, this does not affect endpoint Th2 differentiation. Male CD4+ T cells demonstrate stronger early activation, higher ISG expression during early differentiation, maintenance of IL2Rα expression independently of Malat1, and lower sensitivity to exogenous IL-2 during late differentiation compared with female cells. In vivo, female, but not male, Malat1-/- mice demonstrate altered Th2 cytokine expression characterized by a reduction in IL-10+ Th2 cells in both lung and spleen following priming and challenge with Schistosoma mansoni eggs, a model of lung type 2 inflammation. Overall, these findings reveal Malat1 as a novel determinant of immune sexual dimorphism.

关键词： 小儿肺炎支原体感染   咳嗽   特布他林   孟鲁司特钠片  

摘要： 针对小儿肺炎支原体感染后咳嗽群体,观察应用孟鲁司特钠片+布地奈德联合用药的临床价值。方法 筛选2023年5月~2024年5月期间全州县咸水镇卫生院收治的84例肺炎支原体感染后咳嗽患儿,随机分为一般组(n=42例,采用常规对症治疗)和联合用药组(n=42例,在一般组上辅用孟鲁司特钠片+布地奈德),对比两组的疗效、炎症因子水平和不良反应。结果 联合用药组肺啰音、咳嗽、喘息等症状消失时间均更短(均P<0.05);治疗7d后联合用药组Th1水平高于一般组(P<0.05),Th2水平低于一般组(P<0.05);联合用药组不良反应发生率更低,但差异不具备显著性(P>0.05)。结论 对于肺炎支原体感染后咳嗽的患儿群体,孟鲁司特钠片+布地奈德的治疗方案能够显著提升临床治疗效果,并有效调节Th1、Th2细胞因子水平,同时在用药安全性方面表现良好。

关键词： Angiogenesis   Interleukin-8   Janus kinase 3   Dihydroartemisinin  

摘要： The tumor microenvironment plays a crucial role in tumor angiogenesis, yet the mechanism by which the microenvironment promotes tumor angiogenesis in esophageal squamous cell carcinoma (ESCC) is unclear. Here, transcriptomics revealed that IL-8 was the most significantly upregulated in HUVECs induced by ESCC cell supernatants, and the JAK3/STAT5A pathway was activated to regulate IL-8 during this process. Moreover, targeting JAK3 suppressed ESCC angiogenesis. Notably, dihydroartemisinin (DHA) directly targeted JAK3 and inhibited ESCC CM-induced HUVECs angiogenesis and the ESCC angiogenesis in vivo, similar to the clinical drugs Avastin or Apatinib. Mechanistically, STAT5A transcriptionally regulated IL-8, which could be inhibited by DHA. Besides, DHA inhibited ESCC angiogenesis through JAK3/STAT5A/IL-8 signaling in vivo and in vitro, and JAK3 blockade alleviated its effect. In conclusion, these findings demonstrate a critical role of the JAK3/STAT5A/IL-8 pathway in regulating ESCC angiogenesis, and DHA is an effective drug for targeting JAK3 against ESCC angiogenesis, providing a research basis and a new strategy for anti-ESCC angiogenesis therapy.

关键词： ATG-G (Grafalon)   Allogeneic hematopoietic stem cell transplantation (HSCT)   Anti-T-lymphocyte globulin (ATG)   GVHD prophylaxis   Graft-versus-host disease (GVHD)   Hematologic malignancies  

关键词： Ara h 3   柱层析   多抗血清   纯化  

摘要： 花生过敏蛋白Ara h 3广泛存在于各类花生制品中，少量摄入即可引发过敏反应，严重威胁花生过敏患者的健康。精准地识别Ara h 3便于开展后续免疫学检测，因此，制备高纯度、高特异性的抗体显得尤为重要。以花生脱脂粉为原料，通过HiTrap Q HP阴离子交换层析柱和HiLoad Superdex 200 pg 制备级分子筛层析柱，制备高纯度的花生致敏蛋白Ara h 3，将其与CNBr-activated SepharoseTM4B进行偶联，利用不同洗脱液对血清样品中的非特异性及特异性物质进行分离，制备高纯度、高特异性的抗Ara h 3多克隆抗体。经浓度测定，Gly-HCl洗脱的蛋白质量浓度为0.6 mg/mL；SDS-PAGE分析显示，多抗中的非特异性物质已被有效去除；免疫印迹和ELISA试验结果表明，纯化后的抗体仍具有较高的特异性，其效价达到1∶51 200。上述结果表明抗体成功纯化，为花生过敏原Ara h 3的检测研究奠定了基础。