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关键词： 真菌毒素   免疫毒性   树突状细胞   抗原提呈细胞  

摘要： 真菌毒素是病原真菌产生的次级代谢产物，常污染多种农作物，通过食物链对人畜健康造成严重危害。真菌毒素具有多种毒性作用，包括神经毒性、肝毒性、免疫毒性、致畸性和致癌性等，但其免疫毒性机制尚不完全清楚。树突状细胞（DCs）作为功能最强大的抗原提呈细胞，在启动先天免疫和获得性免疫应答中发挥重要作用。现有研究发现真菌毒素能够影响DCs的内吞作用、刺激T细胞活化的能力以及细胞因子和趋化因子的分泌，本文旨在综述真菌毒素对DCs免疫应答的影响，为后续研究阐明真菌毒素的免疫毒性机制提供参考。

关键词： alleles   chronic pruritus   human leukocyte antigens  

关键词： endometriosis   GSDME   IL-16   infertility   inflammation   interleukin-16   iron overload   ovarian endometriosis   pyroptosis  

摘要： Endometriosis, affecting 6%–10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an in vitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions. © 2024 The Author(s)

关键词： 类鼻疽   肺部感染   感染性心内膜炎   急性淋巴细胞白血病  

摘要： 患者，男，30岁，因“反复发热1月余”于2020年11月14日收入我院。患者1月余前无明显诱因出现发热，最高体温为39.0 ℃,伴乏力、头晕、头痛，无咳嗽、咳痰等不适，于外院就诊，查血常规未见WBC计数降低，血培养示假鼻疽伯克霍尔德菌(BP),考虑败血症，予哌拉西林钠他唑巴坦、左氧氟沙星及复方新诺明治疗后，体温降至正常再无发热，头晕、头痛症状好转后出院，院外规律口服复方磺胺甲噁唑片治疗10天后自行停药。14天前患者再次出现发热，

关键词： Cannabidiol   Macrophage polarization   Innate immunity   TNF-alpha   TUMOR-NECROSIS-FACTOR   EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS   NF-KAPPA-B   MULTIPLE-SCLEROSIS   INFLAMMATION   ACTIVATION   RECEPTOR   INHIBITION   EXPRESSION   PROTECTION  

摘要： Cannabidiol (CBD) is a phytocannabinoid derived from Cannabis sativa that exerts anti-inflammatory mechanisms. CBD is being examined for its putative effects on the neuroinflammatory disease, multiple sclerosis (MS). One of the major immune mediators that propagates MS and its mouse model experimental autoimmune encephalomyelitis (EAE) are macrophages. Macrophages can polarize into an inflammatory phenotype (M1) or an anti-inflammatory phenotype (M2a). Therefore, elucidating the impact on macrophage polarization with CBD pre-treatment is necessary to understand its anti-inflammatory mechanisms. To study this effect, murine macrophages (RAW 264.7) were pre-treated with CBD (10 mu M) or vehicle (ethanol 0.1 %) and were either left untreated (naive; cell media only), or stimulated under M1 (IFN-gamma + lipopolysaccharide, LPS) or M2a (IL-4) conditions for 24 hr. Cells were analyzed for macrophage polarization markers, and supernatants were analyzed for cytokines and chemokines. Immunofluorescence staining was performed on M1-polarized cells for the metalloprotease, tumor necrosis factor-alpha-converting enzyme (TACE), as this enzyme is responsible for the secretion of TNF-alpha. Overall results showed that CBD decreased several markers associated with the M1 phenotype while exhibiting less effects on the M2a phenotype. Significantly, under M1 conditions, CBD increased the percentage of intracellular and surface TNF-alpha but decreased secreted TNF-alpha. This phenomenon might be mediated by TACE as staining showed that CBD sequestered TACE intracellularly. CBD also prevented RelA nuclear translocation. These results suggest that CBD may exert its anti-inflammatory effects by reducing M1 polarization and decreasing TNF-alpha secretion via inappropriate localization of TACE and RelA.

关键词： 高胆红素血症   强光疗   新生儿   细胞免疫   不良反应  

摘要： 目的 探讨强光疗对高胆红素血症患儿细胞免疫功能及近期免疫不良反应的影响。方法 对180例高胆红素血症患儿给予不同光照强度治疗，对其疗效、细胞免疫功能、出院6个月内的免疫不良反应进行比较。结果 光疗后，两组患儿血清白细胞介素(IL-6)均较光疗前降低，CD4+(%)、CD4+/CD8+较光疗前升高。强光组总胆红素下降速度明显快于传统光组，总光疗时间、住院时间均短于传统光组(P<0.05)。住院期间两组患儿腹泻、皮疹、发热、低钙血症发生率及出院后6个月内免疫相关不良反应的发生率差异均无统计学意义。结论 对比传统光疗，强光疗可以更快的降低血清胆红素水平、缩短光疗及住院时间，未增加患儿住院期间常见不良反应及出院后6个月内免疫相关不良反应的发生率。

关键词： 鲍曼不动杆菌   生物膜相关蛋白   单克隆抗体   酶联免疫吸附试验  

摘要： 目的 制备鲍曼不动杆菌生物膜相关蛋白(biofilm-associated protein,Bap)单克隆抗体，并初步建立鲍曼不动杆菌的免疫学检测技术。方法 化学合成Bap基因序列，经原核系统表达及亲和层析技术纯化目的蛋白后，获得重组蛋白Bap-His。将重组蛋白Bap-His免疫2只雌性BLAB/c小鼠的脾部细胞与SP2/0骨髓瘤细胞融合，间接ELISA法筛选获得阳性杂交瘤细胞株，用其制备单克隆抗体，进行SDS-PAGE分析及Western blot鉴定。基于间接ELISA法，采用获得的单克隆抗体建立鲍曼不动杆菌的免疫学检测技术，并验证其特异性及最低检出限。结果 共筛选出2株杂交瘤细胞，制备获得mAb-2F和mAb-7E 2株单克隆抗体，纯度均达90%以上，均可与鲍曼不动杆菌天然蛋白发生特异性结合。采用2株单克隆抗体建立的免疫学检测技术仅可用于检测鲍曼不动杆菌，无法检测其他呼吸道病原体，最低检出限分别达1.6×105和8.0×104cfu/mL。结论 制备的Bap单克隆抗体具有较高纯度，可为Bap相关功能研究提供生物材料；建立的鲍曼不动杆菌免疫学检测技术具有良好的特异性及敏感性，为鲍曼不动杆菌的检测提供了技术支持。

关键词： Atopic dermatitis   IL-26   MC903 model   S aureus   Type 2 skin inflammation  

摘要： Atopic dermatitis (AD) is a debilitating inflammatory skin disorder. Biologics targeting the IL-4/IL-13 axis are effective in AD, but there is still a large proportion of patients who do not respond to IL-4R blockade. Further exploration of potentially pathogenic T-cell–derived cytokines in AD may lead to new effective treatments. This study aimed to investigate the downstream effects of IL-26 on skin in the context of type 2 skin inflammation. We found that IL-26 alone exhibited limited inflammatory activity in the skin. However, in the presence of IL-1β, IL-26 potentiated the secretion of TSLP, CXCL1, and CCL20 from human epidermis through Jak/signal transducer and activator of transcription signaling. Moreover, in an in vivo AD-like skin inflammation model, IL-26 exacerbated skin pathology and locally increased type 2 cytokines, most notably of IL13 in skin T helper cells. Neutralization of IL-1β abrogated IL-26–mediated effects, indicating that the presence of IL-1β is required for full IL-26 downstream action in vivo. These findings suggest that the presence of IL-1β enables IL-26 to be a key amplifier of inflammation in the skin. As such, IL-26 may contribute to the development and pathogenesis of inflammatory skin disorders such as AD. © 2024 The Authors

关键词： Ischemic stroke   Pericytes   PI3Kδ   Reperfusion   TNF-α   TRPV2  

摘要： The pericytes (PCs) surrounding capillaries are vital regulators of capillary constriction. Persistent PC contraction results in the increased capillary constriction, therefore leading to the impaired cerebral blood flow (CBF) recovery after reperfusion and worsening the clinical outcomes in stroke patients. However, the potential determinants of PC functions during ischemia/reperfusion are poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit Delta (PIK3CD/PI3Kδ) is a crucial factor involved with neuronflammation during ischemic stroke. PI3Kδ has shown the expression in PCs, while its effect on PC functions has not been explored yet. In this study, a rodent ischemia/reperfusion model was established in C57BL/6 mice via transient middle cerebral artery occlusion and reperfusion (MCAO/R). The PI3Kδ expression in ischemic penumbra was remarkably upregulated following MCAO/R induction. PI3Kδ inhibitor CAL-101 improved the CBF recovery, ischemic brain injury, and suppressed capillary constriction in MCAO/R mice. Besides, the production of tumor necrosis factor alpha (TNF-α), an inducer for tissue injury, and the expression of transient receptor potential vanilloid type 2 (TRPV2), a channel protein permitting calcium (Ca2+) uptake, were significantly reduced in ischemic penumbra after CAL-101 treatment. In vitro, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of PI3Kδ and TRPV2 in primary mouse PCs. CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke. © 2024 Elsevier Inc.

关键词： 人参皂苷   辛酸酯衍生物   肝癌   免疫原性细胞死亡   内质网应激  

摘要： 目的：探讨人参皂苷辛酸酯（Rh2-O）能否诱导Huh-7肝癌细胞免疫原性细胞死亡及可能机制。方法：体外培养Huh-7细胞，设置空白对照组、Rh2-O药物组及阳性对照组（米托蒽醌处理），CCK-8、流式细胞术分别检测细胞活力和凋亡，ELISA及化学发光法分别检测细胞上清高迁移率族蛋白1(HMGB1)和三磷酸腺苷（ATP）含量，免疫荧光法检测细胞钙网蛋白（CRT）的膜外翻，荧光探针DCFH-DA检测细胞内ROS水平，Western blot检测细胞内质网应激信号通路相关蛋白表达。结果：Rh2-O可显著降低细胞活力，促进细胞凋亡，诱导细胞HMGB1分泌、ATP释放及CRT膜外翻，使细胞内蓄积大量ROS，提高内质网应激信号通路相关蛋白PERK、eIF2α、p-eIF2α表达（均P<0.05）。内质网应激抑制剂4-苯基丁酸（4-PBA）预处理可显著减弱Rh2-O诱导的CRT膜外翻（P<0.05）。结论：Rh2-O可诱导肝癌细胞发生免疫原性细胞死亡，其机制可能与Rh2-O激活内质网应激促进细胞CRT膜外翻有关。