Regulation and integration of plant jasmonate signaling: a comparative view of monocot and dicot

The phytohormone jasmonate plays a pivotal role in various aspects of plant life, including developmental programs and defense against pests and pathogens. A large body of knowledge on jasmonate biosynthesis, signal transduction as well as its functions in diverse plant processes has been gained in the past two decades. In addition, there exists extensive crosstalk between jasmonate pathway and other phytohormone pathways, such as salicylic acid(SA) and gibberellin(GA), in co-regulation of plant...     

IL‐23 plays a significant role in the augmentation of particulate matter‐mediated allergic airway inflammation

It has been recently that particulate matter (PM) exposure increases the risk and exacerbation of allergic asthma. However, the underlying mechanisms and factors associated with increased allergic responses remain elusive. We evaluated IL‐23 and IL‐23R (receptor) expression, as well as changes in the asthmatic phenotype in mice administered PM and a low dose of house dust mite (HDM). Next, changes in the phenotype and immune responses were evaluated after intranasal administration of anti‐IL‐23 antibody during co‐exposure to PM and low‐dose HDM. We also performed in vitro experiments to investigate the effect of IL‐23. IL‐23 expression was significantly increased in Epcam+CD45− and CD11c+ cells, while that of IL‐23R was increased in Epcam+CD45− cells only in mice administered PM and low‐dose HDM. Administration of anti‐IL‐23 antibody led to decreased airway hyperresponsiveness, eosinophils, and activation of dendritic cells, reduced populations of Th2 Th17, ILC2, the level of IL‐33 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Inhibition of IL‐23 in PM and low‐dose HDM stimulated airway epithelial cell line resulted in decreased IL‐33, GM‐CSF and affected ILC2 and the activation of BMDCs. PM augmented the phenotypes and immunologic responses of asthma even at low doses of HDM. Interestingly, IL‐23 affected immunological changes in airway epithelial cells.     

The danger of applying the breeder's equation in observational studies of natural populations

The breeder's equation, which predicts evolutionary change when a phenotypic covariance exists between a heritable trait and fitness, has provided a key conceptual framework for studies of adaptive microevolution in nature. However, its application requires strong assumptions to be made about the causation of fitness variation. In its univariate form, the breeder's equation assumes that the trait of interest is not correlated with other traits having causal effects on fitness. In its multivariate form, the validity of predicted change rests on the assumption that all such correlated traits have been measured and incorporated into the analysis. Here, we (i) highlight why these assumptions are likely to be seriously violated in studies of natural, rather than artificial, selection and (ii) advocate wider use of the Robertson–Price identity as a more robust, and less assumption‐laden, alternative to the breeder's equation for applications in evolutionary ecology.     

Circulating soluble CD4 directly prevents host resistance and delayed-type hypersensitivity response to Cryptococcus neoformans in mice

In the present study, we examined the effect of soluble CD4 (sCD4) on host resistance and delayed-type hypersensitivity (DTH) response to Cryptococcus neoformans using a novel mutant mouse that exhibits a defect in the expression of membrane-bound CD4 but secretes high levels of sCD4 in the serum. In these mice, host resistance to this pathogen was impaired as indicated by an increased number of live pathogens in the lung. To elucidate the mechanism of immunodeficiency, three different sets of experiments were conducted. First, administration of anti-CD4 mAb restored the attenuated host defense. Second, in CD4 gene-disrupted (CD4KO) mice, host resistance was not attenuated compared to control mice. Third, implantation of sCD4 gene-transfected myeloma cells rendered the CD4KO mice susceptible to this infection, while similar treatment with mock-transfected cells did not show such an effect. These results indicated that immunodeficiency in the mutant mice was attributed to the circulating sCD4 rather than to the lack of CD4+ T cells. In addition, DTH response to C. neoformans evaluated by footpad swelling was reduced in the mutant mice compared to that in the control, and the reduced response was restored by the administration of anti-CD4 mAb. Finally, serum levels of IFN-gamma, IL-12 and IL-18 in the mutant mice were significantly reduced, while there was no difference in Th2 cytokines, such as IL-4 and IL-10. Considered collectively, our results demonstrated that sCD4 could directly prevent host resistance and DTH response to C. neoformans through interference with the production of Th1-type cytokines.     

Extension of the CS past the US can facilitate conditioning of the rabbit's nictitating membrane response

Five experiments were conducted in which the onset of a tone conditioned stimulus (CS) preceded the unconditioned stimulus (US) by 500 ms. Across experiments, the offset of the CS was extended past the offset of the US by values ranging from 0 ms to 40000 ms. Extensions of the CS of 2000 ms or greater produced acquisition of a conditioned response (CR) that was as fast or faster than in the no-extension condition (0 ms). While extension of a forward tone CS after the US enhanced excitatory conditioning, insertion of another CS (light) in a purely backward relationship with the US passed only a retardation test, indicative of latent inhibition, and not a summation test needed for conditioned inhibition. The results add to the evidence that excitatory and inhibitory processes are both engaged following US offset. Alternative theories of CS processing are discussed.     

基于炎症免疫调节探讨艾拉莫德联合硫酸羟氯喹治疗类风湿关节炎的疗效及作用机制

摘要 目的：基于炎症免疫调节探讨艾拉莫德联合硫酸羟氯喹治疗类风湿关节炎（RA）的疗效及作用机制。方法：选择2021年4月~2023年3月期间武汉科技大学附属天佑医院和武汉市第四医院收治的120例RA患者。根据随机数字表法将患者分为对照组和研究组,每组各为60例。对照组接受硫酸羟氯喹治疗,研究组接受艾拉莫德联合硫酸羟氯喹治疗。对比两组疗效、临床症状缓解时间、炎症因子[肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）、干扰素α（IFN-α）、干扰素-γ（IFN-γ）]、视觉疼痛模拟评分（VAS）和简易健康生活质量评分（SF-36）、免疫因子[T淋巴细胞亚群（CD4⁺、CD8⁺、CD4⁺/CD8⁺）、免疫球蛋白（Ig）G、IgM、IgA]。同时观察两组用药安全性。结果：与对照组相比,研究组的临床总有效率更高（P<0.05）。研究组的关节疼痛、关节肿胀、关节晨僵缓解时间均短于对照组（P<0.05）。治疗6个月后,两组TNF-α、IL-6、IFN-γ、IFN-α下降,且研究组低于对照组（P<0.05）。治疗6个月后,两组CD8⁺升高,且研究组高于对照组;CD4⁺、CD4⁺/CD8⁺降低,且研究组低于对照组（P<0.05）。治疗6个月后,两组IgG、IgM、IgA下降,且研究组低于对照组（P<0.05）。治疗6个月后,两组VAS评分下降,且研究组低于对照组;SF-36评分升高,且研究组高于对照组（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。结论：艾拉莫德联合硫酸羟氯喹治疗RA,疗效确切,能缩短临床症状缓解时间,缓解关节疼痛和提高患者生活质量,且用药安全、副作用少,其作用机制可能与调节炎症反应、免疫反应有关。     

右美托咪定联合帕瑞昔布钠对老年腹腔镜胃癌手术患者应激反应、细胞免疫功能和认知功能的影响

摘要 目的：探讨帕瑞昔布钠和右美托咪定联合麻醉对老年腹腔镜胃癌手术患者细胞免疫功能、应激反应和认知功能的影响。方法：纳入2019年8月~2022年7月期间西安交通大学第二附属医院收治的150例老年腹腔镜胃癌手术患者。按照随机数字表法将患者分为帕瑞昔布钠组（n=50,帕瑞昔布钠）、右美托咪定组（n=50,右美托咪定）和联合组（n=50,右美托咪定联合帕瑞昔布钠）。对比三组临床指标、视觉模拟评分法（VAS）、简易精神状态检查表（MMSE）评分、术后认知功能障碍（POCD）发生率、应激反应指标[皮质醇（Cor）、肾上腺素（E）、促肾上腺皮质激素（ACTH）]、细胞免疫功能变化情况。结果：联合组的术后住院天数、肛门排气时间短于右美托咪定组、帕瑞昔布钠组（P<0.05）。联合组术后12 h、术后24 h、术后48 h VAS评分低于右美托咪定组、帕瑞昔布钠组（P<0.05）。联合组术后24 h、术后72 h MMSE评分高于右美托咪定组、帕瑞昔布钠组（P<0.05）。联合组的POCD发生率低于右美托咪定组、帕瑞昔布钠组（P<0.05）。三组术后1 d Cor、E、ACTH升高,但联合组低于帕瑞昔布钠组、右美托咪定组同期（P<0.05）。三组术后1 d CD8⁺升高,但联合组低于帕瑞昔布钠组、右美托咪定组同期;CD3⁺、CD4⁺、CD4⁺CD8⁺下降,但联合组高于帕瑞昔布钠组、右美托咪定组同期（P<0.05）。结论：右美托咪定联合帕瑞昔布钠应用于老年腹腔镜胃癌手术患者,镇痛效果显著,可减轻机体的应激反应、免疫抑制及对认知功能的损害。     

miR-455-5p靶向SOCS3抑制RSV感染致气道上皮炎症反应的机制研究

摘要 目的：揭示miR-455-5p对呼吸道合胞病毒（RSV）感染致气道上皮细胞炎症反应的作用机制。方法：qRT-PCR检测30例健康体检儿童（健康组）、RSV感染轻症组（n=41）和重症组（n=31）患儿血清miR-455-5p水平。将16HBE细胞分为Control组、NC-agomir组、miR-455-5p-agomir组、NC-antagomir组、miR-455-5p-antagomir组。使用Lipofectamine 3000转染16HBE细胞后培养48 h后,分为Blank组、NC组（转染了NC-agomir的细胞）、RSV+NC-agomir组、RSV+miR-455-5p-agomir组,用RSV病毒液感染RSV+NC-agomir组和RSV+miR-455-5p-agomir组16HBE细胞,Blank组和NC组16HBE细胞正常培养。用CCK-8法和EdU法检测细胞增殖、TUNEL法检测细胞凋亡、ELISA法检测上清液中TNF-α、IL-6、IL-8水平,qRT-PCR检测miR-455-5p和SOCS3的mRNA水平,Western blot检测SOCS3、IFN-α、STAT1、STAT2、p-STAT1和p-STAT2的蛋白水平。结果：与健康组相比,轻症组和重症组患儿的血清miR-455-5p水平降低（P<0.05）。与轻症组相比,重症组的血清miR-455-5p水平降低（P<0.05）。与Control组和NC-agomir组相比,miR-455-5p-agomir组16HBE细胞的miR-455-5p水平、相对细胞活力和EdU阳性率升高（P<0.05）,TUNEL阳性率降低（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平降低（P<0.05）,SOCS3 mRNA和蛋白水平降低（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平升高（P<0.05）。与Control组和NC-antagomir组相比,miR-455-5p-antagomir组16HBE细胞的miR-455-5p水平、相对细胞活力和EdU阳性率降低（P<0.05）,TUNEL阳性率升高（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平升高（P<0.05）,SOCS3 mRNA和蛋白水平升高（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平降低（P<0.05）。与Blank组和NC组相比,RSV+NC-agomir组16HBE细胞的miR-455-5p水平、相对细胞活力和EdU阳性率降低（P<0.05）,TUNEL阳性率升高（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平升高（P<0.05）,SOCS3 mRNA和蛋白水平升高（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平降低（P<0.05）。与RSV+NC-agomir组相比,RSV+miR-455-5p-agomir组的miR-455-5p水平、相对细胞活力和EdU阳性率升高（P<0.05）,TUNEL阳性率降低（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平降低（P<0.05）,SOCS3 mRNA和蛋白水平降低（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平升高（P<0.05）。结论：miR-455-5p在RSV感染患儿血清中下调,上调miR-455-5p通过抑制SOCS3的转录和表达从而激活RSV感染的16HBE细胞中IFN-α介导的抗病毒反应。