Radiotherapy suppressed tumor-specific recruitment of regulator T cells via up-regulating microR-545 in Lewis lung carcinoma cells

Objective: Radiotherapy is an important treatment for cancer. The main irradiated action is thought to be the irreversible damage to tumor cell DNA, but recent studies showed that high dose radiotherapy related to the tumor immune response. This study was designed to determine the relationship between Lewis lung tumor radiosensitivity and CD4+CD25+ regulatory T cells (Tregs) infiltration and elucidate the underlying mechanisms in vitro. Methods: With tumor transplantation method to establish mice Lewis lung tumor mice model, to observe the inhibition rate of radiotherapy to tumor growth. Proliferation profiles of CD4+CD25+ Tregs and CD4+ T cells were assessed by flow cytometry. MiR-545 and CCL-22 mRNA were determined by Quantitative Real-Time PCR. CCL-22 protein was determined by western blot assay. Results: Radiotherapy caused a time-dependent inhibition of tumor growth as well as a decrease in the percentage of tumor-infiltrating CD4+CD25+ Tregs of CD4+ T cells compared with no treatment group. And the miR-545 was significantly upregulated and CCL-22 was significantly down-regulated in irradiated tumor and Lewis lung cancer cells. In Lewis lung cancer cell transfection experiments, mimic or inhibitor for miR-545 negatively regulated CCL-22 expression when cells treated or treated without irradiation. Silenced miR-545 promotes CD4+CD25+ Treg proliferation. Additionally, silenced miR-545 reversed radiosensitivity of Lewis lung cancer. Conclusion: Radiotherapy suppressed specific recruitment of regulator CD4+CD25+ Treg cells in Lewis lung carcinoma via up-regulating microR-545.     

Exenatide对多囊卵巢综合征大鼠胰腺组织SIRT1表达的影响

[目的]观察Exenatide对多囊卵巢综合征(PCOS)大鼠胰腺沉默信息调节因子1(SIRT1)表达的影响,探讨其对PCOS大鼠的干预治疗效果及可能机制.[方法]采用脱氢表雄酮(DHEA)诱导建立(n=50)PCOS雌性大鼠模型,随机分成Exenatide组(EX组,10只),给予EX颈部皮下注射;二甲双胍组(MF组,10只),给予MF无菌蒸馏水溶解灌胃;PCOS组(9只)及正常对照组(NC组,10只).连续给药4周后检测各组大鼠血清空腹胰岛素(FINS)、并进行糖耐量试验(OGTT),计算HOMA-IR指数.采用免疫组化及Real-time PCR法测定各组大鼠胰腺SIRT1的表达情况.[结果]①免疫组化和Q-PCR在蛋白水平和mRNA水平表明SIRT1表达于正常的胰腺内分泌组织中.PCOS组与NC组相比SIRT1表达明显降低(P＜0.05),经过药物干预后的EX和MF组与PCOS组相比表达均有不同程度升高(P＜0.05),而EX和MF之间相比没有统计学差异.②SIRT1表达与血清FPG、FINS、HOMA-IR呈明显负相关.[结论]Exenatide的干预改善了大鼠的血糖水平和胰岛素抵抗状态.SIRT1的表达下降可能在PCOS的发生发展中具有重要作用,Exenatide可能会通过上调SITR1的表达具有治疗PCOS的潜在作用.     

SIRT1、PGC-1α在原发性开角型青光眼患者小梁网组织中的表达及意义

目的　检测原发性开角型青光眼（primary open-angle glaucoma，POAG）患者小梁网组织中沉默信息调节因子2相关酶1（silent information regulator factor 2 related enzyme 1，SIRT1）和过氧化物酶体增殖物激活受体γ辅激活因子1α（peroxisome proliferator-activated receptor γ coactivator-1α，PGC-1α）表达水平，探讨其与POAG小梁网组织功能损伤的关系。方法　收集2017年1月至2018年4月在海南医学院第一附属医院手术切除确诊为POAG 40例（40眼）患者的小梁网组织为POAG组样本，另取30例眼球供体的小梁网组织为对照组样本，采用RT-PCR法检测2组小梁网组织中SIRT1、PGC-1α mRNA表达，免疫组织化学染色法检测SIRT1、PGC-1α蛋白表达，同时检测过氧化物酶（peroxidase dismutase，POD）和超氧化物歧化酶（superoxide dismutase，SOD）水平。结果　POAG组小梁网组织中SIRT1、PGC-1α mRNA表达水平（0.11±0.03、0.32±0.10）均低于对照组（0.24±0.07、0.67±0.21）（均为P＜0.05）；POAG组小梁组织中SIRT1表达与PGC-1α表达呈正相关关系（r=0.759，P＜0.05）；POAG组小梁网组织中POD水平［（102.59±22.37）×10³ U·L^-1］高于对照组［（73.46±15.81）×10³U·L^-1］（P＜0.05），SOD水平［（347.62±50.73）U·L^-1］低于对照组［（412.57±61.25）U·L^-1］（P＜0.05）；POAG组小梁网组织中SIRT1、PGC-1α表达与POD水平均呈负相关关系（r=-0.636、-0.737，均为P＜0.05），与SOD水平均呈正相关关系（r=0.662、0.614，均为P＜0.05）。结论　POAG患者小梁网组织中SIRT1和PGC-1α表达水平降低，可能在线粒体功能失调和氧化应激对小梁网的损伤中发挥重要调控作用。     

基于交直轴电流耦合的单电流调节器永磁同步电机弱磁控制

基于交直轴电流耦合的单电流调节器弱磁控制是一种新颖的永磁同步电机弱磁策略，能够解决双电流调节器在电机高速域相互冲突而易于饱和的问题。交轴电压指令如何确定是此方法的研究重点，直接影响电机的电压利用率、效率以及负载能力。该文基于电机电压方程对电流耦合调节弱磁控制基本原理进行描述，并提出改进的控制方法。利用id-iq坐标平面上的定子电流轨迹，对现有方法的缺点和所提出方法的预期控制效果进行了分析。在小信号范围内，对所提出方法的动态控制过程和可控性进行了阐述。所提出的电流耦合调节变交轴电压弱磁控制策略，交轴电压指令根据电机工况自行调节，无需查表，且不依赖电机参数，易于实现。仿真和实验结果验证了所提方法的可行性和性能优势。     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.