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关键词： 婴幼儿   呼吸道合胞病毒   特异性免疫   被动免疫   专家共识  

摘要： 呼吸道合胞病毒（RSV）是严重威胁婴幼儿健康最常见的病毒性病原体，引起的疾病负担重。为了更好地指导和规范我国婴幼儿RSV相关疾病的被动免疫预防工作，中华预防医学会联合多学科专家组成专门工作组，借鉴国外RSV被动免疫预防的实施经验，以问题为导向，整合了现有的证据和最新进展，形成了我国婴幼儿RSV被动免疫预防专家共识，旨在从技术上回答有关RSV感染及其免疫预防特别是被动免疫预防的一些专业问题，以期为各级医疗机构、疾病预防控制机构和基层医疗机构专业人员的免疫预防实践提供参考。

关键词： Black carp   HSC70   Innate immunity   RIG-I   Ubiquitination  

摘要： Heat shock cognate 70 (HSC70), a highly conserved molecular chaperone in the heat shock protein 70 (HSP70) family, plays an essential role in maintaining the homeostasis of the cellular environment. Furthermore, although previous studies have investigated potential function of HSC70 in innate antiviral immunity, further research is still required to fully elucidate its role. In this study, we cloned and characterized the HSC70 homolog gene from black carp (Mylopharyngodon piceus), which consists of 1950 nucleotides encoding 650 amino acids, migrates at approximately 71 kDa on SDS-PAGE, and is distributed in the cytoplasm. In response to different stimuli (SVCV, poly (I:C) and LPS), the transcription level of black carp HSC70 (bcHSC70) all increased to a certain extent. Luciferase reporter assay demonstrated that co-transfected bcHSC70 obviously reduced activity of interferon (IFN) promoters mediated by most factors in the RLRs pathway, and further qRT-PCR and plaque assay indicated that co-transfection of bcHSC70 with bcRIG-I decreased the bcRIG-I-mediated IFN transcription and antiviral ability resisting spring viremia of carp virus (SVCV), whereas knockdown of bcHSC70 improves the host cellular antiviral activity. Noteworthily, co-immunoprecipitation (co-IP) assay and immunofluorescence (IF) assay confirmed bcHSC70 interacts with bcRIG-I, and weaken K63-linked polyubiquitination of bcRIG-I. In summary, our study revealed that HSC70 negatively regulates IFN signaling pathway through impairing K63-linked ubiquitination of RIG-I in black carp, which provides an important basis for exploring innate immune regulatory mechanisms in teleost fish.

关键词： Autoimmune diseases   cytokine   IL-12   IL-23   IL-35  

摘要： In recent years, the discovery of IL-12 family cytokines, which includes IL-12, IL-23, IL-27, IL-35, and IL-39, whose biological functions directly or indirectly affect various autoimmune diseases. In autoimmune diseases, IL-12 family cytokines are aberrantly expressed to varying degrees. These cytokines utilize shared subunits to influence T-cell activation and differentiation, thereby regulating the balance of T-cell subsets, which profoundly impacts the onset and progression of autoimmune diseases. In such conditions, IL-12 family members are aberrantly expressed to varying degrees. By exploring their immunomodulatory functions, researchers have identified varying therapeutic potentials for each member. This review examines the physiological functions of the major IL-12 family members and their interactions, discusses their roles in several autoimmune diseases, and summarizes the progress of clinical studies involving monoclonal antibodies targeting IL-12 and IL-23 subunits currently available for treatment.

关键词： Zinc   BPA   Zinc transporter   Inflammation   Reproduction  

摘要： Bisphenol A (BPA) is an endocrine-disrupting chemical that is toxic to reproduction. Zinc (Zn) plays an important role in male reproductive health. Zn deficiency (ZD) can co-exist with BPA. In order to investigate the specific mechanism of reproductive damage caused by BPA exposure in ZD male mice, a mouse model of ZD, BPA exposure, and their combined exposure was established in this study. Forty 4-week-old SPF male ICR mice with an average body weight of 31.7 +/- 4.2 g were divided into four groups including normal Zn diet group 30 mg/(kg center dot d), BPA exposure group 150 mg/(kg center dot d), zinc deficiency diet group 7.5 mg/(kg center dot d), and BPA + ZD combined exposure group (BPA 150 mg/(kg center dot d) + ZD 7.5 mg/(kg center dot d)). The mice were kept for 8 weeks. The results showed that the testicular tissue structure was disturbed, and semen quality, serum Zn, testicular tissue Zn, and testicular tissue free Zn ions were decreased in the BPA-exposed and ZD groups. The expression of zinc transporters (ZIP7, ZIP8, ZIP13, and ZIP14) in testicular tissue was changed. The expressions of pro-inflammatory cytokines including TNF-alpha and IL-1 beta as well as inflammatory pathway-related proteins (IKB-alpha, p-IKB-alpha, NF-kappa B, p-NF-kappa B, Caspase8, and Caspase3) were increased, while the expressions of anti-inflammatory cytokines (TGF-beta and IL-10) were decreased. The changes in the above indexes in the BPA + ZD group were more obvious. Both BPA exposure and ZD can induce testicular tissue inflammation through the TNF-alpha/NF-kappa B/Caspase8 signaling pathway, and BPA further aggravates zinc deficiency-induced testicular tissue inflammation and apoptosis damage.

关键词： Cardiac hypertrophy   IL-37   Inflammation and oxidative stress   JAK2/STAT3   JAK2/STAT3  

摘要： Background: Inflammation and oxidative stress have drawn more and more interest in the realm of cardiovascular disease. In many different disorders, IL-37 acts as an anti-inflammatory and suppressor of inflammation. This study aimed to investigate whether IL-37 could alleviate cardiac hypertrophy by reducing inflammation and oxidative stress. Methods: In vivo, a cardiac hypertrophy model was induced by 14 d of daily isoproterenol (ISO, 30 mg/kg/d) injection, followed by weeks of treatment with recombinant human IL-37 (1000 ng/animal), administered three times weekly. Assessments concentrated on markers of inflammation and oxidative stress, apoptosis, myocardial disease, and cardiac shape and function. In vitro, neonatal rat cardiomyocytes (NRCMs) were subjected to ISO (10 mu M) to establish a cardiomyocytes hypertrophy model. Subsequent IL-37 treatment (100 ng/ml) was applied to determine its cardioprotective efficacy and to elucidate further the underlying mechanisms involved. Results: Significant cardioprotective benefits of IL-37 were seen (in vitro as well as in vivo), primarily through the reduction of oxidative stress, inflammation, apoptosis, and heart hypertrophy markers. Furthermore, IL-37 treatment was associated with a decrease in JAK2 and STAT3 phosphorylation. It is interesting to note that WP1066, a JAK2/STAT3 inhibitor, exhibited antioxidant and anti-inflammatory properties comparable to IL-37, as well as synergistic effects when mixed with the latter. Conclusion: ISO-induced cardiac hypertrophy is lessened by IL-37 through the reduction of oxidative stress and inflammation. Additionally, the effects of IL-37 are closely related to inactivation of the JAK2/STAT3 signaling pathway. It is anticipated that IL-37 will one day be used to treat cardiovascular illnesses such as heart hypertrophy.

关键词： 枣多糖   体外培养   巨噬细胞   免疫活性  

摘要： 试验旨在研究不同浓度乙醇提取的枣多糖（JP）对体外培养巨噬细胞免疫活性的影响。试验采用乙醇浓度分别为60%、70%、80%、90%提取4种枣多糖。采用4×4双因子试验设计，以小鼠巨噬细胞为研究对象，测定不同质量浓度（25、50、100、150 mg/L） 4种枣多糖（JP60、JP70、JP80、JP90）作用后巨噬细胞的吞噬活性、增殖率和细胞因子分泌水平，并以添加脂多糖（LPS）为阳性对照组，以添加蒸馏水为空白对照组。结果显示，与空白对照组相比，各试验浓度的JP60、JP70、JP80、JP90对巨噬细胞吞噬活性、增殖率和一氧化氮（NO）、肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)、白细胞介素-6 (IL-6)的分泌量均有促进作用。与LPS对照组相比，100、150 mg/L JP60组和100、150 mg/L JP90组的巨噬细胞增殖率和吞噬活性更好，100、150 mg/L JP60组和50 mg/L JP90组促进NO分泌的效果更好。研究表明，不同质量浓度JP能够增强巨噬细胞免疫活性，其中100 mg/L JP60的作用效果较好。

关键词： phrenic motor neuron death   breathing   respiration   plasticity   astrocyte   rat model  

摘要： Introduction: Intrapleural injections of cholera toxin B conjugated to saporin (CTB-SAP) result in selective respiratory (e.g., phrenic) motor neuron death and mimics aspects of motor neuron disease [(e.g., amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)], such as breathing deficits. This rodent model allows us to study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited. Microglial density in the phrenic motor nucleus as well as cervical gene expression of markers associated with inflammation (e.g., tumor necrosis factor alpha;TNF-alpha) are increased following CTB-SAP-induced phrenic motor neuron death, and ketoprofen (nonsteroidal anti-inflammatory drug) delivery attenuated phrenic long-term facilitation (pLTF) in 7 day (d) CTB-SAP rats but enhanced pLTF in 28d CTB-SAP rats. Methods: Here, we worked to determine the impact of TNF-alpha in the phrenic motor nucleus by: 1) quantifying TNFR1 (a high affinity transmembrane receptor for TNF-alpha) expression;2) investigating astrocytes (glial cells known to release TNF-alpha) by performing a morphological analysis in the phrenic motor nucleus;and 3) determining whether acute TNFR1 inhibition differentially affects phrenic plasticity over the course of CTB-SAP-induced motor neuron loss by delivering an inhibitor for TNF-alpha receptor 1 (sTNFR1i) in 7d and 28d male CTB-SAP and control rats. Results: Results revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats (p < 0.05), and that astrocytes were increased and exhibited reactive morphology (consistent with an activated phenotype;p < 0.05) in the phrenic motor nucleus of CTB-SAP rats. Additionally, we found that pLTF was attenuated in 7d CTB-SAP rats but enhanced in 28d CTB-SAP rats (p < 0.05) following intrathecal sTNFR1i delivery. Conclusion: This work suggests that we could harness TNFR1 as a potential therapeutic agent in

关键词： 射干麻黄汤   气道高反应   气道炎症   T淋巴细胞   细胞因子  

摘要： 观察射干麻黄汤对气道高反应（AHR）小鼠模型上、下气道T淋巴细胞亚群的影响，分析其“鼻肺同治”控制AHR的生物学基础。采用T细胞β受体基因敲除小鼠提纯γδT细胞；采用卵清蛋白气道致敏的AHR模型小鼠，平均随机分为正常对照组（Ctrl组）、气道高反应模型组（AHR组）、过继免疫γδT细胞组（AIT组）、射干麻黄汤干预组（SGMHT组）、射干麻黄汤+过继免疫组（SMA组），AIT组予以每日γδT细胞尾静脉注射，SGMHT组予以每日射干麻黄汤灌胃，SMA组予以每日γδT细胞尾静脉注射联合射干麻黄汤灌胃，干预7天。观察各组小鼠鼻黏膜和肺组织中T淋巴细胞亚群标记物干扰素-γ（IFN-γ）、白介素-4（IL-4）、视黄酸相关孤儿受体γt（RORγt）、叉头状转录因子P3（FoxP3）及γδT细胞受体（γδTCR）分布情况，外周血Th1、Th2、Th17、Treg、γδT细胞及其细胞因子的表达水平。结果显示，与Ctrl组相比，AHR组鼻黏膜和肺组织中IFN-γ、IL-4、FoxP3、RORγt、γδTCR表达较高，外周血Th2、Th17、γδT细胞比例较高，IFN-γ、IL-2、IL-4、IL-5及IL-17浓度均较高，IL-10、TGF-β则表达较低；与AHR组相比，AIT组、SGMHT组及SMA组鼻黏膜IFN-γ、IL-4、RORγt、γδTCR表达较低，肺组织IL-4、γδTCR较低，外周血Th1比例较高，Th17、γδT较低，SGMHT组和SMA组IFN-γ、IL-2、IL-4、IL-5及IL-17浓度较低，IL-10、TGF-β较高。实验明确了射干麻黄汤“鼻肺同治”改善AHR模型小鼠的作用，其机制与全面调控T淋巴细胞亚群有关。研究为揭示射干麻黄汤治疗AHR作用机制、促进临床应用奠定基础。

关键词： 甲型流感病毒   神经氨酸酶   抗原表位   抗体   抗体配位相似性  

摘要： 目的 基于甲型流感病毒神经氨酸酶（neuraminidase，NA）蛋白抗原抗体复合物结构数据，探究抗原蛋白表位与抗体的空间结构识别关系。方法 完整收集SAbDab数据库中NA蛋白抗原抗体复合物结构数据，对蛋白质结构进行处理分析，获取抗原表位和相应抗体配位氨基酸序列和空间分布信息，统计分析结合抗体序列、基因使用频率、氨基酸使用偏好性和CDR区氨基酸长度；分析抗体结合的热点区域，进一步对抗体配位空间结构相似性进行计算和层次聚类，深入探究抗原表位与抗体的空间识别关系，通过BLI实验验证靶向不同抗原表位的抗体的识别特异性。结果 SAbDab数据库中甲型流感病毒NA蛋白的抗原抗体复合物结构数据以H3N2、H7N9、H1N1亚型为主，抗原表位的热点位置主要集中在催化活性位点区域，抗体物种来源以人源和鼠源为主，鼠源抗体VJ基因组合使用频率最高的是IGHV1-12*01/IGHJ2*01，人源抗体VJ基因组合使用频率最高的是IGHV1-69*01/IGHJ6*01。结合在催化活性位点区域内与结合在催化活性位点区域以外其他区域的抗体，在重链CDR区氨基酸长度与氨基酸使用偏好性方面存在显著差异。抗原表位与抗体配位具有特定的识别关系，部分相似的抗体配位结构特异性地识别相同的表位，可在结构上观察到结合区域的重叠，BLI实验也验证了这类抗体对表位的竞争结合。结论 NA蛋白抗原表位位点分布以催化活性位点及周围环状区域为主，空间构象互补与静电相互作用在抗体与抗原的催化活性区域识别和结合过程中发挥重要作用。抗原与抗体存在不依赖于抗体惟一序列的空间识别关系，不同序列的抗体也可能形成识别同一抗原表位的局部空间结构。