噻唑烷二酮和芳酮酸类PPARγ激动剂三维定量构效关系研究

目的建立PPARγ激动剂-噻唑烷二酮和芳酮酸类化合物的三维定量构效关系,为设计高活性PPARγ激动剂提供结构信息。方法与结果用比较分子力场分析方法得到噻唑烷二酮和芳酮酸类化合物CoMFA模型,其交叉验证相关系数R²=0.656,非交叉验证相关系数R²=0.982,F_10,37=201.1,绝对误差SE=0.115。结论从CoMFA系数等势图中揭示芳酮酸类化合物较噻唑烷二酮类化合物活性更高的原因,提示芳酮酸类化合物与PPARγ结合时形成了不同于BRL-PPARγ复合物晶体的结合腔。     

别孕烯醇酮对6-羟基多巴胺损伤的细胞系SH-SY5Y的保护作用

目的 明确别孕烯醇酮(APα)对6-羟多巴胺(6-OHDA)损伤的SH-SY5Y细胞系的保护作用,并阐明可能的分子机制.方法 向体外培养的SH-SY5Y细胞系中分别加入6-OHDA、APα、γ-氨基丁酸A受体(GABAAR)拮抗剂荷包牡丹碱(Bic)和电压门控L型Ca2+通道拮抗剂硝苯地平(nifedipine),采用...     

甲基化酶抑制剂对变应性鼻炎大鼠Th1/Th2细胞及相关因子的影响

目的:探讨甲基化酶抑制剂5-杂氮-2-脱氧胞苷(5-aza-2-deoxycytidine,5-aza)对变异性鼻炎大鼠辅助性T细胞(helper T cell,Th)亚群Th1和Th2细胞的分化及白细胞介素(interleukin,IL)-4、干扰素(interferon,IFN)-γ水平表达的影响。方法:将30只S...     

Pharmacological approaches to mitigate neuroinflammation in Alzheimer’s disease

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases characterized by the formation of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Growing evidence suggested that there is an association between neuronal dysfunction and neuroinflammation (NI) in AD, coordinated by the chronic activation of astrocytes and microglial cells along with the subsequent excessive generation of the proinflammatory molecule. Therefore, a better understanding of the relationship between the nervous and immune systems is important in order to delay or avert the neurodegenerative events of AD. The inflammatory/immune pathways and the mechanisms to control these pathways may provide a novel arena to develop new drugs in order to target NI in AD. In this review, we represent the influence of cellular mediators which are involved in the NI process, with regards to the progression of AD. We also discuss the processes and the current status of multiple anti-inflammatory agents which are used in AD and have gone through or going through clinical trials. Moreover, new prospects for targeting NI in the development of AD drugs have also been highlighted.     

A novel likely pathogenic PLCG2 variant in a patient with a recurrent skin blistering disease and B-cell lymphopenia

Pathogenic variants of PLCG2 encoding phospholipase C gamma 2 (PLCγ2) were first reported in 2012 and their clinical manifestations vary widely. PLCG2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation (APLAID) are representative examples of PLCG2 pathogenic variants. In this report, we describe a 17-year-old male with recurrent blistering skin lesions, B-cell lymphopenia, and asthma. Distinct from the patients in previous reports, this patient had the heterozygous de novo c.2119T > C missense variant (NM_002661.4) resulting in a serine to proline amino acid substitution (p.Ser707Pro). The variant located to the PLCγ2 C-terminal Src homology 2 (cSH2) domain, which is a critical site for the restriction of intrinsic enzyme activity. This variant could be classified as “likely pathogenic” according to American College of Medical Genetics and Genomics guidelines. Laboratory results showed a reduction in circulating B cells without a decrease of serum IgG and IgA. Our findings expand the variety of clinical phenotypes for PLCG2 missense variants.     

炎症相关细胞因子在弥漫大B细胞淋巴瘤中作用的研究进展

IL-6由肿瘤细胞自分泌，与肿瘤侵袭性密切相关；TNF-α在机体肿瘤免疫应答中起到了重要作用，可引起肿瘤细胞坏死，且可诱导IL-6的表达；IFN-γ具有抗病毒，抗肿瘤和免疫调控的作用；IL-10 具有双向免疫调节作用，在肿瘤环境中对免疫应答具有负向调节作用，同时也能发挥刺激作用。上述细胞因子在弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）的发生发展中或起到协同作用，并可能作为DLBCL诊断及预后的指标。     

针刺"治风六穴"治疗慢性荨麻疹疗效观察

目的观察针刺“治风六穴”治疗慢性荨麻疹的临床疗效。方法将106例慢性荨麻疹患者随机分为观察组和对照组,每组53例。观察组予“治风六穴”针刺治疗;对照组给予氯雷他定口服。观察两组治疗前后症状总积分,血清白细胞介素4(IL-4)、免疫球蛋白E(IgE)、γ-干扰素(IFNγ-)水平变化,并比较两组临床疗效。结果观察组总有效率为92.5%,明显高于对照组的75.5%(P<0.05)。观察组治疗后临床症状各项评分、皮肤病生活质量指数(DLQI)评分明显低于对照组(P<0.05);观察组血清IL-4和IgE水平明显低于对照组,IFNγ-水平明显高于对照组,差异有统计学意义(P<0.05)。结论针刺“治风六穴”能明显改善慢性荨麻疹患者瘙痒、风团症状及生活质量,对血清IL-4、IgE和IFNγ-水平有明显的调节作用。