Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment

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IL‐35 recombinant protein reverses inflammatory bowel disease and psoriasis through regulation of inflammatory cytokines and immune cells

Interleukin‐35 (IL‐35), a member of the IL‐12 family, functions as a new anti‐inflammatory factor involved in arthritis, psoriasis, inflammatory bowel disease (IBD) and other immune diseases. Although IL‐35 can significantly prevent the development of inflammation in many diseases, there have been no early studies accounting for the role of IL‐35 recombinant protein in IBD and psoriasis. In this study, we assessed the therapeutic potential of IL‐35 recombinant protein in three well‐known mouse models: the dextransulfate sodium (DSS)‐induced colitis mouse model, the keratin14 (K14)‐vascular endothelial growth factor A (VEGF‐A)‐transgenic (Tg) psoriasis mouse model and the imiquimod (IMQ)‐induced psoriasis mouse model. Our results indicated that IL‐35 recombinant protein can slow down the pathologic process in DSS‐induced acute colitis mouse model by decreasing the infiltrations of macrophages, CD4⁺T and CD8⁺T cells and by promoting the infiltration of Treg cells. Further analysis demonstrated that IL‐35 recombinant protein may regulate inflammation through promoting the secretion of IL‐10 and inhibiting the expression of pro‐inflammatory cytokines such as IL‐6, TNF‐α and IL‐17 in acute colitis model. In addition, lower dose of IL‐35 recombinant protein could achieve long‐term treatment effects as TNF‐α monoclonal antibody did in the psoriasis mouse. In summary, the remarkable therapeutic effects of IL‐35 recombinant protein in acute colitis and psoriasis mouse models indicated that IL‐35 recombinant protein had a variety of anti‐inflammatory effects and was expected to become an effective candidate drug for the treatment of inflammatory diseases.     

Synthesis,Stability and Direct Antiproliferative Effect of New Cysteine Modified GnRH Analogs

International Journal of Peptide Research and Therapeutics - It is demonstrated that gonadotropin-releasing hormone (GnRH) analogs can directly inhibit the proliferation of reproductive tissue...     

2016年动物胃肠道微生物组研究十大亮点成果

动物胃肠道微生物对生产性能提高具有重要的作用,因此营养、微生物组与生产表型的互作研究已经成为国际研究热点。综述了2016年动物胃肠道微生物组学研究取得的十项重要成果,这些成果通过组学方法,研究了瘤胃纤维分解菌和尿素分解菌的功能基因多样性,揭示了微生物群落与日粮营养素、宿主基因型、环境的互作关系,阐明了反刍动物生产表型相关的瘤胃微生物种类和功能;首次构建猪肠道微生物组参考基因集,解析猪全肠道黏膜微生物组成,阐明了猪增重相关肠道微生物种类。这十大亮点成果将为国内动物营养学家开展动物胃肠道微生物组学研究提供参考。     

三种关于建立家兔人工气道方法的评价

目的比较关于家兔三种人工气道（artificial airway,AA）建立方法,为实验中快速建立家兔人工气道选择较好的方法提供参考。方法选用新西兰大耳白兔共30只,随机均分为3组。分别采用气管切开法、经口明视气管插管法、经口盲探气管插管法建立人工气道,比较各组建立人工气道的时间,首次成功率及并发症发生情况。结果经口盲探气管插管法建立人工气道的时间明显短于经口明视气管插管法和气管切开法,首次成功率由高到低依次是气管切开法、经口盲探气管插管法、经口明视气管插管法。经口盲探气管插管组并发症发生率最低,为（10±5）%,气管切开组和经口明视气管插管组并发症发生率分别为（20±10）%,（30±10）%。结论经口盲探气管插管是现阶段建立家兔人工气道时值得优先考虑的方法,简便易行、可操作性强,成功率高。     

IgE receptor type I-dependent regulation of a Rab3D-associated kinase: a possible link in the calcium-dependent assembly of SNARE complexes

Following activation through high affinity IgE receptors (FcepsilonRI), mast cells release, within a few minutes, their granule content of inflammatory and allergic mediators. FcepsilonRI-induced degranulation is a SNARE (soluble N-ethylmaleimide attachment protein receptors)-dependent fusion process. It is regulated by Rab3D, a subfamily member of Rab GTPases. Evidence exists showing that Rab3 action is calcium-regulated although the molecular mechanisms remain unclear. To obtain an understanding of Rab3D function we have searched for Rab3D-associated effectors that respond to allergic triggering through FcepsilonRI. Using the RBL-2H3 mast cell line we detected a Ser/Thr kinase activity, termed here Rak3D (from Rab3D-associated kinase), because it was specifically co-immunoprecipitated with anti-Rab3D antibody. Rak3D activity, as measured by its auto- or transphosphorylation, was maximal in resting cells and decreased upon stimulation. The down-regulation of the observed activity was blocked with EGTA, but not with other degranulation inhibitors, suggesting that its activity functions downstream of calcium influx. We found that Rak3D phosphorylates the NH(2)-terminal regulatory domain of the t-SNARE syntaxin 4, but not syntaxin 2 or 3. The phosphorylation of syntaxin 4 decreased its binding to its partner SNAP23. Thus, we propose a novel phosphorylation-dependent mechanism by which Rab3D controls SNARE assembly in a calcium-dependent manner.     

新生小鼠缺氧缺血性脑损伤模型的制作研究

目的：通过对动物模型的制作模拟新生儿围产期缺氧缺血性脑损伤,研究其脑组织病理变化,为新生儿缺氧缺血性脑损伤的病理生理的研究以及进一步有效的治疗提供实验基础。方法：将40只7d新生昆明小鼠分四组,分别为正常组（A组）、单侧颈总动脉结扎组（B组）、单侧颈总动脉结扎＋缺氧组（C组）和双侧颈总动脉结扎组（D组）。单侧颈总动脉结扎组（B组）行右侧颈总动脉结扎;单侧颈总动脉结扎＋缺氧组（C组）行右侧颈总动脉结扎后将其置于20℃的恒温50mL密闭容器中,分不同的时间将其取出;双侧颈总动脉结扎组（D组）行双侧颈总动脉结扎,各组术后均送回母鼠身边继续母乳喂养,三天后再作病理检测。结果：行单侧颈总动脉结扎加缺氧60min时,小鼠结扎侧皮质及海马区出现病理改变,随着缺氧时间延长（90rain、100min、120min）病变范围逐渐扩大,病理改变越明显。结论：本实验显示单侧颈总动脉结扎同时缺氧一定时间可以导致小鼠脑组织损伤,脑细胞发生病理改变,且皮层及海马区域的神经细胞对缺氧缺血最为敏感,从而为进一步研究新生儿缺氧缺血性脑损伤提供了较为可靠的模型。