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关键词： allergic contact dermatitis   atopic dermatitis   cytokine signatures   irritant contact dermatitis   translational study  

摘要： In this work, we show that the combination of radiation therapy (RT) and an IL15/IL15Rα fusion complex (denoted IL15c) fails to confer anti-tumor efficacy; however, a CD8-driven anti-tumor immune response can be elicited with the concurrent administration of an aCD25 Treg-depleting antibody. Using IL15-/- and Rag1-/- knockout mouse models, we show that the response to RT + IL15c + aCD25 is dependent on both IL15 and CTLs. Furthermore, despite an equivalent survival benefit following treatment with RT + IL15c + aCD25 and combination RT and PD1-IL2v, a novel immunocytokine with PD-1 and IL2Rbg binding domains, CTL immunophenotyping and phospho-proteomic analysis of intracellular metabolites showed a significant upregulation of activation and functionality in CD8 T cells in the RT + PD1-IL2v regimen. Finally, we show that in the absence of functional IL15 signaling, the immunostimulatory response to RT + PD1-IL2v is significantly diminished with a concurrent lack of TCF+ CD8 T cell generation, suggesting a necessity of IL15 for CD8 stem cells in mediating a durable response to treatment. Together, our results are illustrative of a mechanism wherein unimpeded effector T cell activation through IL2Rb signaling and Treg inhibition are necessary in mediating an anti-tumor immune response.

关键词： 葛根素   类风湿关节炎   疗效   AKT   FOXO1  

摘要： 目的 基于蛋白激酶B(AKT)/磷酸化叉头框蛋白O1(FOXO1)-白介素（IL）-9（AKT-FOXO1-IL-9）信号通路，探究葛根素治疗类风湿关节炎（RA）大鼠的疗效机制。方法 将36只大鼠随机分为空白组，模型组，阳性对照组，葛根素低、中、高剂量组，除空白组外，其余组采用Ⅱ型胶原诱导建立RA大鼠模型。造模成功后，给予不同剂量葛根素和甲氨蝶呤治疗，检测大鼠体质量和足趾厚度，采用生化方法检测大鼠血液流变学指标，采用X光观察大鼠关节形态变化，采用番红固绿染色和阿利新蓝染色观察大鼠关节组织的病理学，ELISA法检测大鼠血清中IL-9及类风湿因子水平及Western blot检测蛋白AKT、FOXO1的变化。结果 与空白组相比，模型组大鼠足趾厚度最厚，X线光片显示关节狭窄比较明显，边缘性骨侵袭较重；番红固绿染色显示关节边缘出现毛刺样改变，伴有炎症细胞的渗出，软骨细胞增殖分泌加剧；炎症因子IL-9及类风湿因子水平表达最高，AKT、FOXO1蛋白表达量最高（P＜0.05）。与模型组相比，不同剂量葛根素治疗组大鼠足趾厚度降低；X光片显示，葛根素治疗组大鼠脚掌关节狭窄及边缘性骨侵袭有改善；番红固绿染色结果显示，不同剂量的葛根素治疗后，炎症细胞渗出减少，炎症因子IL-9及类风湿因子、AKT、FOXO1蛋白表达水平降低且差异均有统计学意义(P＜0.05)，其中高剂量葛根素组最明显。与高剂量的葛根素组相比，阳性对照组以上结果均降低且差异均有统计学意义(P＜0.05)。结论 葛根素通过抑制AKT-FOXO1-IL-9通路对RA大鼠具有良好的疗效，其中葛根素高剂量组（60 mg/kg）的疗效最好且存在剂量反应关系。

关键词： 慢性荨麻疹   苦参素   免疫球蛋白E   白细胞介素-4   Janus激酶1   信号转导和转录激活因子6  

摘要： 目的 探究IL-4/JAK1/STAT6通路下苦参素对慢性荨麻疹大鼠的保护作用。方法 将72只雄性SD大鼠分为对照组、模型组、西药组及低、中、高剂量苦参素（oxymatrine，OM）组。西药组给予氯雷他定1 mg/(kg·d)灌胃，各剂量OM组分别给予0.2、0.4、0.6 g/(kg·d)苦参素灌胃，连续7 d。ELISA法检测血清免疫球蛋白E（IgE）、组胺、白三烯水平，中性红染色检测肥大细胞脱颗粒百分率，HE染色观察皮肤组织形态学改变，采用酶标仪检测耳部皮肤血管通透性，Western blot检测皮肤组织中IL-4、磷酸化（p）-JAK1、p-JAK2、p-STAT3、p-STAT6的表达水平。结果 模型组的搔抓耳部次数、血清IgE、组胺、白三烯水平、肥大细胞脱颗粒百分率、耳部皮肤血管通透性、皮肤组织中IL-4、p-JAK1、p-JAK2、p-STAT3、p-STAT6表达水平均高于对照组（P<0.05）；西药组及各剂量OM组的搔抓耳部次数、血清IgE、组胺、白三烯水平、肥大细胞脱颗粒百分率、耳部皮肤血管通透性、皮肤组织中IL-4、p-JAK1、p-STAT6表达水平均低于模型组（P<0.05），西药组皮肤组织中p-JAK2、p-STAT3的表达水平低于模型组（P<0.05），各剂量OM组皮肤组织中p-JAK2、p-STAT3的表达水平与模型组比较差异无统计学意义（P>0.05）；西药组与高剂量OM组各项指标的比较差异无统计学意义（P>0.05）。结论 OM对慢性荨麻疹大鼠具有保护作用且高剂量OM的保护作用与氯雷他定相当；OM的上述作用与抑制IL-4/JAK1/STAT6通路相关，而与JAK2/STAT3通路不相关。

关键词： IL-17 signaling pathway   OPC   Oral commensal bacteria   Safety evaluation   β-Defensin  

摘要： Oropharyngeal candidiasis (OPC) commonly occurs in immunocompromised individuals, and enhancing endogenous antimicrobial defenses with probiotics has emerged as an effective prevention strategy. Given the critical role of human β-defensin-2 (HBD-2) in combating Candida albicans infection in the oral cavity, this study aimed to identify oral commensal bacteria promoting HBD-2 production in the host. Thirty-five Streptococcus salivarius strains were screened using the HOK-16B cell line, and two were identified as significantly promoting HBD-2 secretion. These strains were further validated in a murine OPC model. The results indicated that oral intervention with S. salivarius CCFM1416 activated the IL-17/IKBζ signaling pathway in the host (IKBζ from 67.73 to 122.27 pg/mg), upregulating the expression of β-defensin (from 13.64 to 25.21 pg/mg). Consequently, C. albicans colonization and adhesion in the oral cavity were markedly reduced. Finally, a 14-day oral toxicity study demonstrated that oral administration of S. salivarius CCFM1416 is safe in vivo. In summary, the research results indicated that S. salivarius CCFM1416 can effectively prevent the occurrence of OPC and is an excellent probiotic candidate for the prevention of oral mucosal infections.

关键词： 慢性心力衰竭   可溶性人基质裂解素2   血管紧张素   白细胞介素-6  

摘要： 目的:分析慢性心力衰竭(CHF)患者血清可溶性人基质裂解素2(sST2)、血管紧张素Ⅱ(AngⅡ)、白细胞介素-6(IL-6)水平与心功能的相关性及其预后预测价值。方法:选取2021年1月～2023年6月收治的205例CHF患者为观察组,根据NYHA心功能分级分为Ⅱ级组、Ⅲ级组、Ⅳ级组各55、80、70例,另选取同期心律失常非CHF患者100例为对照组。根据6个月内是否发生主要不良心血管事件(MACE)将观察组分为预后不良组(n=45)和预后良好组(n=160),比较各组血清sST2、AngⅡ、IL-6水平,Spearman相关分析其与NYHA心功能分级的相关性,绘制ROC曲线评估sST2、AngⅡ、IL-6水平对CHF预后的预测价值。结果:观察组血清sST2、AngⅡ、IL-6水平均高于对照组(P<0.05)。随着NYHA分级增加,sST2、AngⅡ、IL-6水平均逐渐升高(P<0.05);Spearman相关分析显示,sST2、AngⅡ、IL-6水平与NYHA心功能分级呈正相关(P<0.05)。预后不良组sST2、AngⅡ、IL-6水平均高于预后良好组(P<0.05)。ROC曲线分析显示,sST2、AngⅡ、IL-6水平联合预测CHF预后不良的灵敏度为91.12%,AUC为0.920,均高于单独指标预测(P<0.05)。结论:CHF患者血清sST2、AngⅡ、IL-6水平与心功能密切相关,且联合检测对CHF预后预测价值较高。

关键词： Granulopoiesis   IL-6   Neutrophil   Psoriasis   Spleen  

摘要： BACKGROUND:Psoriasis is an immune-mediated chronic inflammatory condition characterized by significant neutrophil infiltration in the skin. Given that the spleen is the largest peripheral immune organ in the body, it is important to investigate whether it has any impact on skin inflammation in psoriasis. METHODS:To investigate this mechanism, a psoriatic mouse model was established by IMQ application. Flow cytometry and immunohistochemistry analyses were performed to determine the percentage of various immune cells in the spleen. The role of neutrophils was specifically assessed using the anti-Gr-1 antibody. Splenic granulopoiesis was evaluated using EdU labeling. To understand the spleen's role in skin inflammation, splenectomy was performed on the experimental mice. IL-6 levels were measured by ELISA, and P-STAT3 in neutrophils was detected via immunofluorescence. Further examination of IL-6's effects on neutrophil formation involved treating mice with IL-6 antibody. The severity of psoriasis was evaluated through histological staining and PASI scoring. RESULTS:Our study revealed that the spleens of psoriatic mice were enlarged compared to those of vehicle mice. Among immune cell populations, neutrophils showed the most significant changes, with marked increases in both spleen and skin of psoriatic mice and patients, contributing to disease progression. Post-splenectomy, neutrophil infiltration in the skin was reduced by approximately 60% in psoriatic mice. This indicates that the neutrophils in the skin were primarily derived from the spleen. Additionally, the spleen showed a notable capacity for granulopoiesis with elevated neutrophils. Moreover, we found elevated IL-6 levels in the skin, blood, and spleen in the model, which was decreased after splenectomy. Treatment with an IL-6 antibody reduced neutrophil formation in both the spleen and skin, which alleviated skin inflammation in psoriatic mice. Additionally, P-STAT3 signaling was decreased following IL-6 an

关键词： Akt/ERK   Epilepsy   Ferroptosis   IL-1   Saikosaponin a  

摘要： Saikosaponin A (SSa), a triterpenoid saponin isolated from Astragalus membranaceus, possesses multiple pharmacological properties, including anticonvulsant, antiepileptic, and anti-inflammatory activities. This study aimed to elucidate the molecular mechanisms by which SSa exerts therapeutic effects in temporal lobe epilepsy (TLE), with a particular focus on the involvement of ferroptosis pathways. In a kainic acid-induced TLE mouse model, electroencephalography (EEG) was used to monitor seizure frequency. Behavioral tests were employed to evaluate cognitive, learning, and memory functions. Additionally, molecular biology techniques were used to investigate the neuroprotective mechanisms of SSa. EEG recordings showed that SSa treatment significantly reduced seizure frequency and severity. Behavioral assessments indicated improvements in cognition, learning, and memory. Histological analysis revealed decreased neuronal death in the hippocampus. Transmission electron microscopy and Golgi-Cox staining demonstrated a marked increase in hippocampal neuron density following SSa treatment. At the cellular level, SSa significantly downregulated the expression of IL-17, phosphorylated Akt (p-Akt), and phosphorylated ERK (p-ERK) in Erastin-induced ferroptotic hippocampal neurons. Notably, the inhibitory effect of SSa on ferroptosis was reversed by IL-17 agonist treatment, suggesting that IL-17 plays a pivotal role in this pathway. In conclusion, SSa alleviates seizures and improves cognitive function in TLE by inhibiting IL-17/Akt/ERK-mediated ferroptosis in hippocampal neurons.

关键词： Biomarker   Diagnostic accuracy   IL-6   Interleukin-6   Late-onset neonatal sepsis  

摘要： Late-onset neonatal sepsis (LONS) remains a leading cause of morbidity and mortality in neonates, particularly among preterm and low birth weight infants. Interleukin-6 (IL-6) has emerged as a promising biomarker for early detection of LONS, yet the diagnostic performance of IL-6 remains inconsistent across studies. This meta-analysis aimed to evaluate the overall diagnostic accuracy of IL-6 in detecting LONS and to assess the certainty of evidence using the GRADE approach. A comprehensive search of five databases was conducted up to July 15, 2025. Twenty-two studies were eligible for inclusion, of which 20 (n = 3527 neonates) were included in the meta-analysis. A bivariate random-effects model was used to estimate pooled sensitivity and specificity, and the area under the SROC curve was used to assess overall diagnostic accuracy. Pooled sensitivity and specificity were 85.2% (95% CI: 80.0–89.3%) and 84.1% (95% CI: 77.5–89.0%), respectively. The positive and negative likelihood ratios were 5.43 and 0.18, with a diagnostic odds ratio of 31.4. The AUC was 0.91, indicating excellent diagnostic accuracy. Subgroup and sensitivity analyses confirmed the robustness of the findings, and no significant threshold effect was detected. However, suspected publication bias was noted. The GRADE assessment rated the certainty of evidence as moderate. Conclusion: IL-6 demonstrates high diagnostic accuracy for LONS and may serve as a valuable tool for early identification, though standardization of cutoff thresholds and further validation studies are warranted.