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关键词： ASFV A151R   cGAS-STING pathway   Lipid peroxidation   Ferroptosis   Innate immunity  

摘要： The African swine fever virus (ASFV) has been reported to cause oxidative damage and inhibit IFN-beta production. However, the precise mechanisms through which ASFV-induced lipid peroxidation modulates the innate immune response remain to be elucidated. Here, we investigated the regulatory mechanism underlying ASFV A151R-induced lipid peroxidation and ferroptosis in restricting IFN-beta production The results demonstrated that A151R negatively inhibited IFN-beta production via the cGAS-STING pathway by facilitating ROS accumulation, lipid peroxidation, and the carbonylative modification of STING. Concurrently, the translocation of STING from the ER to the Golgi, the generation of GSH, and the system xc(-)/GSH/GPX4 axis were impaired. However, GPX4 activation ameliorated lipid peroxidation mediated by A151R. Importantly, A151R facilitated NCOA4 mediated ferritinophagy. The downregulation of NCOA4 suppressed ferroptosis and lipid peroxidation, upregulated GPX4 expression, and attenuated ferroptosis. GPX4 activation abolished A151R-induced protein carbonylation, subsequently activating the TBK1-IRF3 pathway and enhancing the transcription of IFN-beta and ISGs. Consistent with the in vitro findings, ASFV infection significantly reduced GPX4 and FTH levels in porcine lungs and spleens. Pharmacological inhibition of ferroptosis and knockdown of A151R in ASFV enhanced the transcription of INF-beta and ISGs, reduced lipid peroxidation, and restored the expression of GPX4. Overall, our study reveals a novel mechanism whereby ASFV A151R induces STING carbonylation and triggers ferritinophagy-induced ferroptosis, thereby impairing cGAS-STING-mediated antiviral immunity. This work establishes a new paradigm for understanding ferritinophagy-driven ferroptosis and provides mechanistic insights into ASFV immune evasion strategies.

关键词： Allogreffe de cellules souches hématopoïétiques   HLA immunisation   HLA immunization   Hematopoietic stem cell transplantation   Platelet refractoriness   Transfusion   État réfractaire  

摘要： L’augmentation des allogreffes non HLA identiques, due à l’emploi de la prophylaxie avec cyclophosphamide post-greffe, a mis en évidence l’impact de la présence d’anticorps anti-HLA chez le receveur, en particulier ceux dirigés contre les antigènes du donneur ( donor specific antibodies [DSA]) en tant que facteur de risque supplémentaire pour la réussite de la greffe. La transfusion de produits sanguins labiles, en particulier de concentrés plaquettaires, est une source d’immunisation anti-HLA et les patients en attente d’allogreffe sont exposés à un risque accru d’immunisation dû à leurs besoins transfusionnels importants. Cet atelier rassemble des experts en immunogénétique et en médecine transfusionnelle afin d’aborder la question de la prévention de l’immunisation anti-HLA chez les patients en attente d’allogreffe de cellules souches hématopoïétiques non HLA identique, à travers la sélection des concentrés plaquettaires adaptés et donc de préserver le donneur sélectionné et d’optimiser les chances de prise de greffe. The increase of HLA-mismatched allogeneic stem cell transplantation, due to the use of post-transplant high-dose cyclophosphamide, has highlighted the detrimental impact of anti-HLA antibodies in the recipient, especially those directed against the donor (donor specific antibodies [DSA]), on transplant success. Blood products transfusions, in particular platelets, are a source of immunisation against donor HLA antigens and patients candidates to HLA-mismatched transplantation are at risk of developing DSA because of the elevated transfusion need. This Atelier gathers Immunogenetics and Transfusion Medicine experts to deal with the prevention of anti-HLA immunisation of patients waiting to HLA-mismatched transplantation, through the appropriate selection of blood products thus avoiding the appearance of DSA and optimising the engraftment rate.

关键词： IL-1β   NETs   AIM2   Trauma-induced heterotopic ossification   Lysine   Chirality  

摘要： Introduction The limitations of clinical treatment for trauma-induced heterotopic ossification (tHO) make it of great significance to fully study its pathogenesis for the treatment of this disease. The infiltration of inflammatory cells, as an important indicator of disease progression, should be further studied. Objectives In our study, we found that in the early stages of acute tendon injury, increased IL-1β can induce NETosis in neutrophils. Neutrophils and macrophages are early infiltrating cells in acute tendon injury, and their relationship has aroused our curiosity. Methods In our study, we used techniques such as high-throughput sequencing, tissue transmission electron microscopy, cell scanning electron microscopy, and multi-label immunofluorescence staining co-localization. Results We found that as inflammation progresses, NETs secreted by neutrophils can induce macrophage pyroptosis by promoting the activation of AIM2. The pyroptosis macrophages can promote abnormal differentiation of tendon stem cells, thereby promoting the formation of tHO. To find an effective solution, we creatively combined different chiral lysines with bacterial cellulose and successfully prevented the formation of tHO. Conclusion Our research not only reveals from a new perspective that the IL-1β-NETs-AIM2 axis participates in the formation of tHO by orchestrating crosstalk between neutrophils and macrophages, but also provides a novel approach for the future clinical treatment of tHO.

关键词： interleukin-6   periodontitis   COVID-19   saliva   inflammation  

摘要： Background: Research suggests that periodontal disease may exacerbate symptoms of coronavirus disease (COVID-19). The etiology of this condition has been associated with cytokines such as IL-6. The inflammatory response in COVID-19 can be partially attributed to periodontopathic bacteria and their metabolites. Furthermore, the aspiration of periodontal pathogens and the stimulation of ACE2 expression may lead to an increased production of inflammatory cytokines, potentially worsening COVID-19 symptoms in patients with periodontitis. Materials and Methods: A cross-sectional study was conducted involving patients with both periodontal disease and COVID-19, patients with either condition alone, and healthy subjects. All participants underwent RT-PCR testing for SARS-CoV-2, and a self-reported periodontal disease (Self-RPD) questionnaire was administered. Saliva samples were collected to assess IL-6 levels using the ELISA technique. Results: A total of 28 patients were classified as COVID-19/Self-RPD+, 32 patients had only COVID-19, 25 were Self-RPD+ only, and 17 were healthy controls. The COVID-19/Self-RPD+ group frequently exhibited symptoms such as fever, body aches, nasal congestion, and olfactory disturbances and showed significantly higher IL-6 levels compared to the other groups. Cough with phlegm was significantly more frequent in the COVID-19-only group. Additionally, IL-6 levels in saliva were elevated in patients with nasal congestion and in those with 11 or more symptoms in the Self-RPD+ group.

关键词： 多糖   溃疡性结肠炎   细胞因子   氧化应激   免疫组化  

摘要： 目的：探究羊肚菌柄粗多糖对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎的缓解效果。方法：对羊肚菌柄粗多糖的单糖组成和分子量进行测定，将小鼠分为正常组、模型组、多糖低剂量组、中剂量组和高剂量组，开始3周的多糖提前摄入；建立溃疡性结肠炎（UC）模型，通过测定小鼠体重、疾病活动指数及结肠形态考察羊肚菌柄粗多糖对溃疡性结肠炎小鼠的缓解效果。进一步分析小鼠血清中炎症因子含量、结肠组织中氧化应激状态、抗氧化酶体系的变化和结肠蛋白免疫组化结果，探讨其机制。结果：经过羊肚菌柄粗多糖干预，小鼠体重下降情况得到缓解，疾病活动指数降低，结肠形态明显改善（P＜0.05）。与Model组相比，多糖组小鼠血清中的TNF-α和IL-6水平显著降低（P＜0.05），IL-10水平显著升高（P＜0.05），结肠组织中MDA含量和MPO酶活力显著降低（P＜0.05），GSH-Px和CAT的酶活力显著升高（P＜0.05），结肠紧密连接蛋白Claudin-1、ZO-1和结肠黏液蛋白MUC-2的表达增加。结论：羊肚菌柄粗多糖可以在一定程度上缓解炎症反应，保护结肠上皮细胞间的连接，恢复肠道的机械屏障，从而缓解小鼠的结肠炎症状。

关键词： 肺癌   慢性阻塞性肺疾病   下呼吸道感染   病原菌分布   病情严重程度  

摘要： 目的：探讨肺癌合并慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）患者化疗后下呼吸道感染病原菌分布及血清降钙素原（procalcitonin,PCT）、白介素（interleukin,IL）-6、C反应蛋白（C-reactive protein,CRP）水平与病情严重程度和预后的关系。方法：选取2022年9月—2024年3月就诊的116例肺癌合并COPD患者化疗后下呼吸道感染者的临床资料进行研究，另选同期50例肺癌合并COPD患者化疗后下呼吸道未感染者作为非感染组，根据急性生理与慢性健康（acute physiology and chronic health evaluation II,APACHEⅡ）评分将感染患者分为轻中度组和重度组。观察各组患者的PCT、IL-6、CRP水平变化。对感染组进行了3个月的随访，根据预后情况分为死亡组和存活组。采用ROC分析方法，评估血清PCT、IL-6、CRP对肺癌合并COPD患者化疗后下呼吸道感染预后的预测效能。结果：肺癌合并COPD患者化疗后下呼吸道感染的病原菌以革兰阴性菌为主（55.86%），其次为革兰阳性菌（38.62%）和真菌（5.52%）。感染组PCT、IL-6、CRP水平高于非感染组（P<0.05）；重度感染组患者PCT、IL-6、CRP水平均高于轻中度感染组（P<0.05）；感染组患者中，死亡组患者的血清PCT、IL-6、CRP水平均高于存活组（P<0.05）。Logistic回归分析显示，PCT>5.133 ng/mL、IL-6>52.630 pg/mL、CRP>87.949mg/L是患者预后不良的危险因素（P<0.05）。ROC曲线分析显示，血清PCT、IL-6、CRP水平联合用于评估肺癌合并COPD患者化疗后下呼吸道感染者预后敏感度和特异度均较高（80.00%、83.33%）。结论：肺癌合并COPD患者化疗后下呼吸道感染的病原菌分布复杂多样，革兰阴性菌是主要致病菌。血清PCT、IL-6、CRP水平可作为评估病情严重程度和预后的重要指标。

关键词： 滴滴涕   单克隆抗体   多巴胺包金纳米材料   荧光量子点   可视化-反向荧光增强双信号免疫层析试纸条  

摘要： 设计并合成了滴滴涕（DDT）半抗原，制备获得了鼠源单克隆抗体，利用合成的多巴胺包金纳米材料与荧光量子点标记技术，建立了一种可视化-反向荧光增强双信号免疫层析技术，并应用于鸡肉样品中DDT的残留检测。结果表明，该试纸条在多巴胺包金裸眼检测模式下的检测限为2 μg/mL，荧光点亮模式下的检测限为0.25 μg/mL，灵敏度提升了约10倍，15 min内可完成检测，与其他DDT结构类似物未有交叉识别作用。以鸡肉作为添加样本进行方法验证，本方法的检测结果与气相层析-质谱法（GC-MS/MS）结果一致。

关键词： dermatomyositis   polymyositis   idiopathic inflammatory myopathies   polymorphism  

摘要： Aim of the study: Idiopathic inflammatory myopathies (IIM) are autoimmune diseases with a low prevalence and incidence worldwide. The levels of IFN-gamma production by T-lymphocytes are related to disease activity. IFN-gamma +874 T/A (rs2430561) has been shown to alter the serum levels of IFN-gamma in different pathologies. The aim of this work is to explore the role of IFN-gamma +874 T/A polymorphism in IIM. Methods: Using a specific sequence primer-polymerase chain reaction (SSP-PCR), the genotype was defined for normal healthy controls (HC) and patients with IIM. Markers of muscle damage, clinical features and treatment were collected from chart at the time of diagnosis and at recruitment point. All the data were analyzed by demographic characteristics, genotype, type of IIM, treatment, clinical features, and enzymatic levels. Results: No association was found comparing the genotypes or alleles of the IIM patients vs. HC. On the other hand, the TT genotype, previously described as a high producer of INF gamma, showed higher levels of CPK at diagnosis in IIM patients, whereas females at diagnosis and males in remission presented higher levels. Conclusions: Even with a limited number of patients due to the rarity of this disease, no association was found between the disease development. Further, the TT genotype promoted muscle damage due to CPK elevation in the sera compared to the TA/AA genotype in patients with IIM. This could be genetic evidence of the impact of IFN-gamma in the disease activity of IIM patients. A larger cohort is needed to confirm these results.

关键词： colorectal cancer cell lines   interleukin   CXCL8   betulin   derivatives   mRNA   protein   molecular docking  

摘要： Colorectal cancer (CRC) remains one of the most prevalent malignancies of the gastrointestinal tract worldwide, with chronic inflammation recognized as a key factor in its progression. Among pro-inflammatory cytokines, interleukin 8 (IL-8) plays a pivotal role in promoting angiogenesis, tumor cell migration, and metastasis. Elevated IL-8 expression is frequently associated with advanced CRC stages. This study investigated the effects of betulin and its semi-synthetic derivatives, EB5 and ECH147, on IL-8 expression in CRC cell lines characterized by differing malignancy grades. IL-8 transcript and protein levels were quantified using real-time RT-qPCR and a proximity ligation assay, respectively, following compound exposure at 2, 8, and 24 h. Basal IL-8 levels were significantly higher in low-grade CRC cell lines. Among the compounds tested, ECH147 exerted the most pronounced, time-dependent inhibitory effect on CXCL8 expression. Furthermore, molecular docking analyses revealed that ECH147 exhibits stronger binding affinity toward the IL-8 protein compared to conventional chemotherapeutics. These findings suggest that the modification of the betulin structure via the incorporation of a propynoyl moiety enhances both its molecular interaction with CXCL8 and its anti-inflammatory potential. ECH147 and EB5 thus emerge as promising candidates for further development as immunomodulatory agents targeting the IL-8-associated pathway in CRC.