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关键词： HLA-matched   PTCY   allo-HCT   outcomes   peripheral blood   reduced dose  

摘要：

关键词： IFN   TNF   apoptosis   autophagy   cell death   inflammatory diseases   interferon   interferonopathy   necroptosis   skin inflammation   systemic lupus erythematosus   tumor necrosis factor  

摘要：

关键词： 布鲁氏菌   亚单位疫苗   抗原   表达系统   佐剂  

摘要： 布鲁氏菌病（brucellosis）是一种由布鲁氏菌（Brucella）引起的重要人兽共患病，在全球畜牧业密集地区广泛流行，每年报告病例数以百万计，不仅导致巨大的畜牧业经济损失，也严重威胁人类健康。目前该病防控主要依靠抗生素治疗和动物疫苗接种。然而，现有弱毒活疫苗存在宿主范围窄、毒力返强风险及干扰感染与免疫鉴别诊断等问题。相比之下，亚单位疫苗基于关键抗原成分激发免疫保护，安全性高、不易干扰诊断，但存在免疫原性弱、半衰期短等瓶颈。笔者系统总结了布鲁氏菌亚单位疫苗的最新研究进展，重点探讨了候选抗原筛选、表达系统优化及佐剂应用等关键策略，旨在为开发安全高效、适用于高危人群和流行地区的新型疫苗提供理论支撑与研发方向。

关键词： IL32   Periodontitis   bioinformatics   gingivitis   inflammation   polymorphism  

摘要： INTRODUCTION:Gingivitis is the initial manifestation of periodontal disease, characterized by bacteria and inflammatory mediators, such as IL-32. This study aimed to determine whether the rs45499297 genetic variant of the IL32 gene and its serum and salivary levels are associated with gingivitis. In addition, we investigated whether transcription factors bind differentially in the presence of this genetic variant. METHODS:The study was conducted with 147 subjects. The rs45499297 variant was analyzed using the PCR-RFLP technique, while cytokine levels were measured using the ELISA assay. The affinity of the transcription factors in the presence of the gene variant was analyzed using bioinformatics methods. The results suggest that schooling, salivary flow, lipids, and salivary IL-32 levels were associated with gingivitis. Furthermore, the TC genotype, in the presence of obesity, conferred an increased risk of gingivitis, which was associated with lower serum IL-32 levels. Bioinformatics analysis revealed that the transcriptional factor LRH1 binds with a higher affinity to the C allele than to the T allele of the studied genetic variant. RESULTS:The findings of this study demonstrate the multifactorial nature of gingivitis, wherein the interplay between genetics and obesity serves as a regulatory factor in inflammation and periodontal risk. The preferential binding of LRH1 to the C allele suggests a molecular link between the genetic variant, inflammatory dysregulation, and the altered metabolic environment in obesity. CONCLUSION:Our data show that the rs45499297 gene variant is only associated with gingivitis in the presence of obesity and affects serum cytokine levels. Additionally, we identified the potential involvement of LRH1 in regulating the IL-32 gene expression.

关键词： 前列腺癌   包膜外侵犯   前列腺特异性抗原密度   穿刺阳性针数百分比  

摘要： 目的 探讨前列腺特异性抗原密度(PSAD)和穿刺阳性针数百分比在前列腺癌包膜外侵犯(EPE)中的预测价值,以期指导临床治疗决策。方法 回顾性分析2019年10月—2022年4月于中国科学技术大学附属第一医院(安徽省立医院)接受根治性前列腺切除术的180例前列腺癌患者的临床资料。收集患者的年龄、穿刺阳性针数、穿刺病理Gleason评分、术后有无EPE、穿刺阳性针数百分比、总前列腺特异性抗原(tPSA)、PSAD、前列腺体积(PV)、身体质量指数(BMI)及前列腺穿刺方式(直肠/会阴)等资料。构建二元logistic回归模型筛选影响前列腺癌EPE的独立危险因素,采用受试者工作特征(ROC)曲线分析指标的诊断效能,并计算曲线下面积(AUC)。结果 术后病理证实有53例(29.4%,53/180)存在EPE。单因素logistic回归分析显示,穿刺阳性针数、穿刺病理Gleason评分、穿刺阳性针数百分比、tPSA、PSAD是影响前列腺癌EPE的相关因素(P<0.05)。多因素logistic回归分析显示PSAD(OR=6.008,P=0.007)和穿刺阳性针数百分比(OR=1.031,P=0.031)是影响前列腺癌EPE的独立预测因素。ROC曲线分析中,PSAD和穿刺阳性针数百分比的AUC分别为0.712和0.714,二者联合的AUC为0.745。结论PSAD和穿刺阳性针数百分比均可作为前列腺癌EPE的独立预测因子,二者联合具有较好的预测效能。

关键词： 白细胞介素17A(IL-17A)   成骨细胞   Wnt5a/β-catenin通路   增殖  

摘要： 目的　观察白细胞介素17A（IL-17A）对成骨细胞分化的影响，并深入分析其是否通过Wnt5a/β-catenin信号通路发挥作用。方法　使用IL-17A（0.01、0.1、1、10）ng/mL作用于小鼠胚胎成骨细胞前体细胞（MC3T3-E1）和小鼠骨髓间充质干细胞（BMSC）。CCK-8法检测细胞增殖；流式细胞术检测MC3T3-E1细胞凋亡；碱性磷酸酶（ALP）和茜素红S（ARS）染色评估成骨细胞分化能力；Western blot法检测磷酸化的核因子κB p65（p-NF-κB p65）、核因子κB亚基（NF-κB p65）、核因子κB抑制蛋白α（IκBα）、无翅基因5a（Wnt5a）、β连环蛋白（β-catenin）和Runt相关转录因子2（Runx2）蛋白的表达。结果　IL-17A呈时间与浓度依赖性促进MC3T3-E1细胞的增殖。与阳性对照组相比，IL-17A组显著抑制细胞的凋亡。IL-17A呈浓度依赖性增强两种细胞碱性磷酸酶的活性和矿化结节的能力。IL-17A显著上调p-NF-κB p65、Wnt5a、β-catenin和Runx2蛋白表达水平，同时显著降低IκBα蛋白的表达。结论　IL-17A可能通过Wnt5a/β-catenin通路影响成骨前体细胞的存活、增殖及成骨分化。

摘要： Eosinophils are traditionally associated with parasitic infections and allergic pathologies. However, emerging evidence highlights their underappreciated roles during mucosal bacterial infections. Using in vivo and in vitro approaches, we demonstrate that classical Bordetella spp. increase IL-1Ra production from both epithelial cells and eosinophils to facilitate immune evasion and persistence. Depletion of IL-1Ra via genetic knockout or antibody neutralization in vivo accelerated bacterial clearance. We show that the Bordetella type III secretion system (T3SS) effector, BteA, promotes AkT/mTOR pathway activation leading to IL-1Ra expression, which is independent of IL-1α or IL-1β production. Together, our findings uncover the molecular mechanism by which classical Bordetellae exploit host epithelial-eosinophil signaling to exclusively upregulate IL-1Ra and dampen host inflammation for persistence. These results provide therapeutic targets for controlling disease caused by long-term Bordetella infection and may have broader applications for other respiratory pathogens. Moreover, these insights expand our understanding of eosinophil function beyond traditional paradigms.

关键词： Acute liver injury   NF-kappa B/iNOS/COX-II   Nrf2/HO-1   SIRT-1   neferine   paracetamol  

摘要： Drug-induced hepatotoxicity is a significant public health issue that influences the development of novel pharmaceutical therapies and the retraction of numerous promising medications from the ***, the current study investigated the potential hepato-protective benefits of NEF against hepatotoxicity caused by paracetamol (APAP) in mice and assessed its underlying mechanisms. Mice were divided randomly into six groups; control (received normal saline), NEF control, APAP, N-acetylcysteine (NAC; served as a standard treatment) + APAP, NEF (10 mg/kg) + APAP, and NEF (20 mg/kg) + APAP. The serum and hepatic tissues were collected for different biochemical, genetic, and histological assessments. APAP induced profound hepatic damage that was evident through all biochemical, histological, and molecular assessments. NEF pretreatment opposed the elevation of liver injury biomarkers and attenuated hepatic histological disruption. At the molecular level, NEF increased the hepatic level and protein expression of SIRT-1. NEF increased the hepatic mRNA and protein expression of Nrf2 and HO-1. NEF also decreased hepatic level of oxidative stress biomarker, MDA and increased the hepatic levels of antioxidants: GSH, GR, GST, TAC, and SOD, NEF also counteracted the activation of NF-κB and inhibited the upregulation of different inflammatory cytokines as TNF-α and interleukins- (IL-1β and IL-6). Furthermore, NEF pretreatment decreased the hepatic level and mRNA expression of COX-II and iNOS. NEF ameliorated APAP-induced liver injury in mice where the higher dose of NEF (20 mg/kg) was more effective than the lower (10 mg/kg) compared to NAC. This effect is association with upregulation of SIRT-1/Nrf2/HO-1 and interruption of NF-κB/cytokines/iNOS/COX-II signaling cascades.

关键词： GVHD prophylaxis   allo‐HSCT   dosing regimens   graft‐versus‐host disease   methotrexate  

摘要： Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m on day 1, 7 mg/m on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m on day 1, 10 mg/m on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II-IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III-IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice.