摘要：Originally identified as allelochemicals involved in plant-parasite interactions, more recently, Strigolactones （SLs） have been shown to play multiple key roles in the rhizosphere communication between plants and mycorrhizal fungi. Even more recent is the hormonal role ascribed to SLs which broadens the biological impact of these relatively simple molecules. In spite of the crucial and multifaceted biological role of SLs, there are no data on the receptor（s） which bind（s） such active molecules, neither in the producing plants nor in parasitic weeds or AM fungi. Information about the putative receptor of SLs can be gathered by means of structural, molecular, and genetic approaches. Our contribution on this topic is the design and synthesis of fluorescent labeled SL analogs to be used as probes for the detection in vivo of the receptor（s）. Knowledge of the putative receptor structure will boost the research on analogs of the natural substrates as required for agricultural applications.

摘要：Introducing chimeric antigen receptor into immune cells against malignancies has contributed to a revolutionary innovation in cancer immunotherapy. As an important type of adaptive immune cells, T cells first caught researchers' attention and became great success in chimeric antigen receptor-based immunotherapy. However, engineered T cells seem to hit their bottleneck when resistance of cancerous cells, less encouraging responses in solid tumors and unwanted toxicities to the host remain to be ***, innate immune cells get to join the race. Representatives such as natural killer cells, natural killer T cells, γδT cells and macrophages also prove to be well redirected with chimeric antigen receptors. Compared to chimeric antigen receptor engineered T cells, these engineered innate immune cells may possess multiple targeting and killing mechanisms, have the potential to crack the barrier of solid tumors and have less side effects in the host. Besides, possible universal access to cell resources and improvements in expansion and transduction techniques make these cells promising candidates with huge potential in translational medicine. Therefore, innate immune cells claim a brand-new dimension and are likely to supplement T cells greatly in the field of chimeric antigen receptor-based immunotherapy.

摘要：T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.

摘要：Proprotein convertase subtilisin/kexin type 9(PCSK9)modulators may attenuate PCSK9-induced low-density lipoprotein receptor(LDLR)degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol(LDL-C).A novel series of tetrahydroprotoberberine derivatives(THPBs)were designed,synthesized,and evaluated as PCSK9 modulators for the treatment of *** them,eight compounds exhibited excellent activities in downregulatinghepatic PCSK9 expression better than berberine in HepG2 *** addition,five compounds 15,18,22,(R)-22,and(S)-22 showed better performance in the low-density lipoprotein,labeled with 1,1’-dioctadecyl-3,3,3’,3’-tetramethyl-indocarbocyanine perchlorate(Dil-LDL)uptake assay,compared with berberine at the same *** 22,selected for in vivo evaluation,demonstrated significant reductions of total cholesterol(TC)and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic *** exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 *** results of human ether-ago-go related gene(hERG)inhibition assay indicated the potential druggability for compound 22,which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.

摘要：吉非替尼（gefitinib）是针对肺癌表皮生长因子受体（epidermal growth factor receptor，EGFR）设计的肿瘤靶向药物，已使众多的非小细胞肺癌（NSCLC）患者获益，但其疗效与EGFR基因突变相关。通过EGFR基因第19外显子可筛选gefitinib药物的最适合患者进行个体化治疗，提高疗效，减少盲目用药。我们检测了62例NSCLC患者的EGFR基因第19外显子突变，并分析突变DNA特征及氨基酸变化规律。

摘要：目的:初步建立子宫内膜癌雌激素受体亚型α(estrogenreceptorα, ERα)弱表达细胞模型,探讨ERα在子宫内膜癌发病机制中的作用,研究 17β 雌二醇(17β estradiol, E2 )及三苯氧胺(tamoxifen, TAM)在子宫内膜癌发病过程中与ERα的关系。方法:设计针对ERα的反义寡核苷酸 (antisenseoligodexyribonucleotides, AS ODN),转染入子宫内膜癌HEC 1B细胞,Westernblot测定转染后细胞ERα的表达;检测转染反义寡核苷酸后E2 和TAM对子宫内膜癌细胞生长影响的变化。结果: (1)针对ERα翻译启动区设计的反义寡核苷酸可以选择性下调ERα的表达。(2)E2 和TAM可以促进子宫内膜癌细胞系HEC 1B的生长。转染ERα AS ODN后可抑制E2 对子宫内膜癌细胞HEC 1B的促生长作用,这种抑制作用以转染后的 24, 48及 72h尤为明显。转染ERα AS ODN可抑制TAM对子宫内膜癌细胞HEC 1B的促生长作用,这种抑制作用在转染后的 48h最为明显。结论: 初步建立了ERα弱表达的子宫内膜癌细胞模型。反义核酸技术可以作为一种有效的特异性下调子宫内膜癌细胞中ERα的实验手段。在HEC 1B细胞中,ERα抑制E2 和TAM的促进子宫内膜癌细胞生长的作用。

摘要：目的筛选有效抑制小胶质细胞上TLR4(Toll-like receptor 4)表达的小干扰RNA(simall interference RNA,siR-NA)序列,并检测转染复合物的细胞毒性。方法设计并合成针对TLR4的siRNA4条(siRNA312,siRNA439,siRNA1495,siRNA2062)及1条与TLR4基因无同源性的带绿色荧光标记的阴性对照siRNA:在LipofectamineTM 2000介导下转染小胶质细胞。用RT-PCR方法测定干扰后小胶质细胞上TLR4mRNA表达,Western blot方法测定干扰后TLR4蛋白表达,比较其抑制率,筛选出有效抑制靶基因表达的siRNA。采用MTT法检测转染复合物的细胞毒性。结果①siRNA(40nmol·L-1)和LipofectamineTM 2000(1μl)有较高的转染效率;②与阴性对照组相比,TLR4 siRNA(40nmol·L-1)干扰小胶质细胞24h后TLR4 mRNA的相对表达量降低,分别为:85%(siRNA439)、73%(siRNA312)、67%(siRNA1495)和33%(siRNA2062)。③siRNA439干扰小胶质细胞48h后TLR4蛋白表达最低(P<0.01)。④LipofectamineTM 20001μl复合低于40nmol·L-1的siRNA的各组细胞存活率均在85%以上。结论①siRNA439对小胶质细胞上TLR4表达的抑制效果最大。②siRNA浓度40nmol·L-1,LipofectamineTM 2000浓度1μl,细胞毒性很低,适合转染。

摘要：记得1999年第一次去美国亚特兰大参加美国临床肿瘤学会（American Society of Clinical Oncology, ASCO）年会，当时将“分子靶向治疗”这个还觉陌生的名词仅仅与细胞和动物联系在了一起，感觉“服一片药代替化疗能够治疗肿瘤”就像“天方夜谭”或“美丽的童话”般遥远。而现实是时隔三年的2002年，第一个肺癌分子靶向治疗药物吉非替尼进入临床实践，此后更多分子靶向药物如雨后春笋般涌现。而其中表皮生长因子受体（epidermal growth factor receptor, EGFR）突变与EGFR酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）疗效关系的精彩故事真正掀开了个体化分子靶向治疗的序幕。基于新的理念、新的思维设计的药物及全新的临床试验思路，从2007年肺癌患者A L K靶点发现至2011年针对间变性淋巴瘤激酶融合基因（anaplastic lymphoma kinase, ALK）的抑制剂克唑替尼获得美国食品药品监督管理局（Food and Drug Administration, FDA）许可上市，仅仅用4年的时间，便走完了EGF→EGFR→EGFR-TKI近乎40年的历程，转化性研究速度之快令人惊讶。

摘要：General anesthetics constitute some of the most important and widely-used therapeutic drugs in the pharmacotherapeutic armamentarium. They are routinely used effectively and with adequate precaution-safety throughout the world for a multitude of clinical applications, predominantly as adjunctive agents for surgical procedures. Nevertheless, they have potential adverse effects (such as a drop in blood pressure and the inhibition of steroid production), particularly in vulnerable populations such as the very young and the frail elderly. It would be desirable therefore to have alternative agents that are just as efficacious, but have a better safety profile in a broader spectrum of patients. Toward this end, an anesthetic based on a unique chemical core (viz., an N-arylpyrrole derivative) has been reported in preclinical models to produce anesthetic effects without hemodynamic suppression. This lead could pave the way for new general anesthetics that are safer and easier to use.

摘要：目的:观察温肾方治疗乙肝肝硬化合并肝性脑病肾阳虚证患者的临床疗效及其对高迁移率族蛋白B1(high mobility group protein B1,HMGB1),Toll样受体4(Toll-like receptor 4,TLR4)含量的影响。方法:纳入成都中医药大学附属医院2013年8月至2015年1月收治的66例乙肝肝硬化合并肝性脑病患者。采用前瞻性、平行对照方法设计,将纳入的66例患者按1∶1分为治疗组和对照组,每组各33例。对照组给予常规内科综合治疗、结肠透析和安慰剂灌肠。治疗组给予常规内科综合治疗、结肠透析和温肾方灌肠。疗程均为10日。治疗前后分别检测患者肝功能水平、数字连接试验(number connect test,NCT)时间、数字符号试验(digit-symbol test,DST)评分及血氨水平,外周血HMGB1,TLR4含量。治疗结束后,分别计算两组患者清醒时间及总有效率。结果:两组患者基线具有可比性。治疗结束后,治疗组总有效率优于对照组(P <0. 05)。治疗组在血氨下降幅度,肝功能恢复程度,NCT时间下降幅度,SDT评分增加程度以及患者清醒时间缩短幅度等方面均优于对照组(P <0. 05)。治疗结束后,治疗组外周血HMGB1,TLR4含量低于对照组(P <0. 05)。结论:温肾方可显著提高乙肝肝硬化合并肝性脑病肾阳虚证患者的临床疗效,其作用机制可能与抑制HMGB1,TLR4含量,进而抑制炎症因子释放,降低血氨水平有关。