Perspectives on developing small molecule inhibitors targeting HIV-1 integrase

HIV-1 integrase (IN) is a crucial enzyme in the life cycle of HIV-1 and also a validated target for developing anti-HIV inhibitors. Recent progress in drug design has significantly accelerated the development of anti-AIDS IN inhibitors. A large amount of novel inhibitors that interact specifically with IN were developed along with the expanding and application of methods to drug design. This article reviewed the anti-HIV IN inhibitors discovered by the rational drug design approaches in the recent 5-year.     

Decoupling location specificity from perceptual learning of orientation discrimination

Perceptual learning of orientation discrimination is reported to be precisely specific to the trained retinal location. This specificity is often taken as evidence for localizing the site of orientation learning to retinotopic cortical areas V1/V2. However, the extant physiological evidence for training improved orientation turning in V1/V2 neurons is controversial and weak. Here we demonstrate substantial transfer of orientation learning across retinal locations, either from the fovea to the periphery or amongst peripheral locations. Most importantly, we found that a brief pretest at a peripheral location before foveal training enabled complete transfer of learning, so that additional practice at that peripheral location resulted in no further improvement. These results indicate that location specificity in orientation learning depends on the particular training procedures, and is not necessarily a genuine property of orientation learning. We suggest that non-retinotopic high brain areas may be responsible for orientation learning, consistent with the extant neurophysiological data.     

氢氧化铁蔗糖复合物配合促红细胞生成素治疗慢性肾功能不全贫血疗效探讨

目的:探讨氢氧化铁蔗糖复合物(维乐福,venofer)配合促红细胞生成素(Epo)治疗慢性肾功能不全(CRF)患者贫血的疗效。方法:选择CRF行血液透析(HD)并用Epo治疗贫血患者50例,其中25例选用静脉注射氢氧化铁蔗糖复合物治疗,25例选用口服多糖铁复合物(力蜚能,Niferex)治疗,观察3个月。结果:用Epo后,2组患者贫血均改善,多糖铁复合物组Hb每月上升14.8 g/L,Epo用量比蔗糖铁组多19.5%;而蔗糖铁组可迅速改善CRF透析患者贫血,Hb每月上升19.2 g/L,Epo用量较小,与多糖铁复合物组比较差异有显著性(P<0.01)。结论:静脉注射氢氧化铁蔗糖复合物可作为HD患者长期补铁方式,配合Epo治疗,疗效确切。     

96例妊娠期缺铁性贫血的预防和治疗分析

目的:观察红源达在预防治疗妊娠期缺铁性贫血的临床疗效及应用价值.方法:选择在我院确诊的铁储备不足的孕妇96例按孕妇意愿分为治疗组和对照组,均定期检查血常规及铁缺乏指标,治疗期间每4周访视一次直至分娩.结果:治疗组孕妇与新生儿体内铁储存状态在妊娠早、中、晚期体内均有相关性;对照组仅在妊娠中、晚期有相关性.结论:红源达多糖铁复合物胶囊在临床预防和治疗妊娠期缺铁性贫血具有应用价值,值得临床推广.     

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??OBJECTIVE To study preliminarily the cadmium absorption and accumulation in Ligusticum Wallichii to provide a scientific basis for solving the problem of cadmium excess. METHODS The aboveground and underground parts of Ligusticum Wallichii in different growth periods and the rhizosphere soil were collected from Aoping Town, Pengzhou City and Yongshou Town, Meishan City. The cadmium content was determined, and the enrichment coefficient and transfer coefficient were calculated. RESULTS The average cadmium content in the underground part was 77.21% higher than that in the aboveground part. The cadmium enrichment coefficients and cadmium transfer coefficients of different parts were both greater than 0.5, and the enrichment coefficient of the underground part was 64.75% higher than the aboveground part. CONCLUSION Ligusticum Wallichii has a certain capacity to absorb and transfer cadmium, and most cadmium is enriched in the medicinal roots.     

基于网络药理学探究血尿胶囊治疗急性肾盂肾炎的作用机制

目的:采用网络药理学和实验验证的方法探究血尿胶囊治疗急性肾盂肾炎(APN)的作用机制.方法:通过APN大鼠模型研究血尿胶囊对APN的作用效果.使用中药系统药理学数据库与分析平台(TCMSP),化学专业数据库,中医证候关联(SymMap)数据库检索菝葜、薏苡仁、棕榈子的化学成分,PharmMapper与SwissTarg...     

三烯霉素J——来自深海细菌Ochrobactrum sp.的新安莎霉素

目的探究深海来源细菌Ochrobactrum sp. OUCMDZ-2164中的细胞毒活性代谢产物。方法利用硅胶柱色谱、凝胶柱色谱和高效液相色谱等手段对发酵产物进行分离纯化,运用紫外、红外、质谱、核磁共振及圆二色谱等方法鉴定化合物的结构,采用MTT和细胞计数试剂盒-8(CCK-8)法分别评价化合物对乳腺癌MCF-7细胞和肺癌A549细胞及慢性髓性白血病K562细胞的增殖抑制活性。结果从细菌Ochrobactrum sp. OUCMDZ-2164的发酵产物中分离获得了4个化合物,分别鉴定为3-O-去甲基三烯霉醇(1)、flazin(2)、flazin-3-carboxylicacid(3)和胸腺嘧啶(4)。化合物1在10μmol/L浓度下对MCF-7细胞的增殖抑制率为61.5%。结论化合物1为新的安沙霉素类化合物,命名为三烯霉素J,其具有一定的乳腺癌细胞毒活性。     

慢性粒细胞白血病端粒酶的相关研究

目的：对慢性粒细胞白血病端粒酶进行研究,采用 PCR －ELISA 半定量法测定端粒酶活性,同时观察端粒酶活性变化的相关性。方法：选取15例慢性粒细胞白血病患者骨髓标本和15例正常骨髓（取自非肿瘤病人需行骨髓检查者）样本分为慢性粒细胞白血病组（CML 组）和正常对照组,采用 PCR －ELISA 法来测定CML 组和正常对照组的端粒酶活性。结果：正常对照组端粒酶具有微弱的活性,而 CML 组则具有较强的活性,且端粒酶活性 CML 组高于正常对照组,两者差异性非常显著。其中,CML 组男性与女性组间端粒酶活性差异无统计学意义。结论：正常组端粒酶具有微弱的活性,而 CML 组则具有较强的活性。端粒酶活性可能反映了一个高度增生的状态,是一种新的肿瘤标记物,与肿瘤发生密切相关。     

缺氧条件下缺氧诱导因子-1α抑制剂YC-1对人卵巢癌Skov3干细胞耐药的逆转作用

目的:探讨缺氧诱导因子-1α抑制剂YC-1在缺氧条件下逆转人卵巢癌干细胞Skov3耐药的机制。方法:选用人卵巢癌Skov3细胞通过无血清悬浮培养法富集肿瘤干细胞。分别于常氧及缺氧条件下检测不同浓度顺铂干预Skov3贴壁细胞及干细胞后测定顺铂对于两种细胞的抑制作用,及缺氧后干性指标、耐药指标ABCG2及HIF-1α的表达。当给予HIF-1α抑制剂YC-1后,测定顺铂对Skov3干细胞的抑制作用。并且检测干细胞干性指标、ABCG2及HIF-1α的mRNA表达。结果:悬浮培养的Skov3干细胞的干性指标CD44、NANOG、OCT-4及耐药指标ABCG2较贴壁细胞升高,且缺氧培养后,随着HIF-1α表达的升高,CD44、NANOG、OCT-4及ABCG2的表达也明显升高,P<0.05。干细胞的耐药性高于贴壁细胞,且缺氧培养耐药性增加。当给予YC-1后,干细胞耐药性下调,HIF-1α出现抑制,同时其干性指标CD44、NANOG、OCT-4、耐药ABCG2明显下调,P<0.05。结论:YC-1在缺氧条件下通过抑制HIF-1α下调ABCG2的表达逆转Skov3干细胞耐药。     

细胞-纳米药物载体递送系统在肿瘤诊疗中的应用

目前,针对肿瘤治疗药物在体内应用中的局限性,出现了许多高效的药物递送系统的研究,其中纳米药物载体技术和细胞药物载体技术较为热门,并取得了许多成果。纳米药物载体具有的优点,如防止药物发生降解及灭活,增加药物的靶向性,降低药物的毒副作用,可量产等。细胞载体更是利用细胞本身固有的特性,具有主动靶向肿瘤部位、低免疫原性和穿过体内生理屏障等优点,在药物递送研究中有广阔的应用前景,但是仍然存在很多问题及不足。研究人员创造性地将两者结合,使他们的优势互补,极大地强化了递送药的效率,增加了体内靶向性,降低了周围组织的细胞毒性等。本文从近几年来细胞-纳米药物载体系统研究的文献中,总结了红细胞、干细胞、单核/巨噬细胞、T细胞、树突状细胞（dendritic cell,DC）等作为纳米药物细胞载体的优缺点及目前的应用现状。