Therapeutic antibodies: their mechanisms of action and the pathological findings they induce in toxicity studies

Antibodies can swiftly provide therapeutics to target disease-related molecules discovered in genomic research. Antibody engineering techniques have been actively developed and these technological innovations have intensified the development of therapeutic antibodies. From the mid-1990’s, a series of therapeutic antibodies were launched that are now being used in clinic. The disease areas that therapeutic antibodies can target have subsequently expanded, and antibodies are currently utilized as pharmaceuticals for cancer, inflammatory disease, organ transplantation, cardiovascular disease, infection, respiratory disease, ophthalmologic disease, and so on. This paper briefly describes the modes of action of therapeutic antibodies. Several non-clinical study results of the pathological changes induced by therapeutic antibodies are also presented to aid the future assessment of the toxic potential of an antibody developed as a therapeutic.     

靶向甲型流感病毒血凝素的人源单克隆抗体研究进展

甲型流感病毒感染性强,宿主广泛,主要感染禽类,其次为哺乳动物。当跨物种传染事件发生时,有可能造成流感大流行,因此,对病毒实施及时有效的监控,以及研发抗流感病毒药物刻不容缓。流感病毒表面的糖蛋白血凝素在病毒入侵宿主细胞的过程中发挥了关键的作用,可作为单克隆抗体药物的主要靶点。针对血凝素的单克隆抗体能够有效抑制病毒传播,保护宿主。因此,本文综述了目前报道的针对甲型流感病毒血凝素糖蛋白的人单克隆抗体,为后续抗流感药物的研发提供新的思路和展望。     

Stimulation of acetylcholinesterase activity by triiodothyronine in the brain of Singi fish,Heteropneustes fossilis (Bloch)

Three consecutive days of injections of triiodothyronine (T₃)(0.038, 0.075, 0.15 and 1.54 nmoles/g) significantly elevated the acetylcholinesterase (AchE) activity in the brain of Singi fish, Heteropneustes fossilis (Bloch). The higher doses of 0.075, 0.15 and 1.54 nmoles of T₃/g induced a greater increase in enzyme activity than 0.038 nmoles/g. A T₃ dose of 0.019 nmoles/g was found to be ineffective. The T₃ action on AchE activity was blocked by cycloheximide. Thiourea treatment for 30 days decreased the AchE activity below the control level. This reduced level of the enzyme activity was brought back even above the control level by T₃ injections. It is, therefore, suggested that thyroid hormone is involved in the sustenance of AchE activity in fish brain.     

三种中药提取物体外抗猪繁殖与呼吸综合征病毒的作用

在前期筛选具有抗猪繁殖与呼吸综合征病毒(PRRSV)作用的中药研究基础上,选取药效较好的三种中药：穿心莲、芦根和夏枯草。为进一步研究其有效抗病毒成分,采用MTT 法观察了穿心莲内酯盐、芦根多糖和夏枯草多糖成分对猴肾上皮细胞系(Marc-145) 生长的影响,分别采用阻断、抑制、直接杀灭3种作用方式观察了各成分抗RPPSV感染作用。结果显示：穿心莲内酯盐对细胞最大安全浓度为0.16 mg/mL,芦根多糖为0.575 mg/mL,夏枯草多糖为1.125 mg/mL;芦根多糖在三种方式上均有不同程度的抗PRRSV作用,而穿心莲内酯盐和夏枯草多糖阻断PRRSV作用不明显,抑制和杀灭PRRSV作用明显。结果表明穿心莲内酯盐、芦根多糖和夏枯草多糖均有抗病毒作用,为抗病毒中药的主要药效成分。     

A型口蹄疫病毒VP1蛋白间接ELISA检测方法的建立

以原核表达经纯化复性制备的A型口蹄疫病毒(FMDV)VP1蛋白代替传统病毒抗原包被,建立快速、安全、有效的A型FMDV抗体ELISA检测方法。对前期制备的A型VP1蛋白进行Western-Blot检测,结果表明,VP1蛋白能够特异性识别A型FMDV阳性牛血清,可作为检测抗原建立检测A型FMDV抗体的方法。以最佳质量浓度1mg/L VP1蛋白为检测抗原,方阵滴定法确定最佳检测血清稀释度为1∶50[V(血清)∶V(封闭液)],最佳的酶标二抗稀释度为1∶2 000[V(酶标二抗)∶V(封闭液)],建立A型FMDV抗体ELISA检测方法。该方法的敏感性为94.32%,特异性为99.09%,批内与批间重复试验变异系数均小于8%。采用该方法检测201份临床血清,与液相阻断ELISA试剂盒的符合率达92.54%。研制的VP1-ELISA试剂盒特异、敏感、稳定、操作简便,可用来监控A型口蹄疫抗体水平。     

Electromechanical effects of acetylcholine on the atrial tissues of the cultured tilapia (Oreochromis nilotica × O. aureus)

The effects of acetylcholine (ACh) on the action potential and twitch force of atrial tissues isolated from 15 tilapia (Oreochromis nilotica × O. aureus) were studied by means of conventional microelectrode techniques. In isolated whole atrium or sinoatrial tissue, scattered pacemaker-like cells with spontaneous diastolic depolarization were found mainly near the sinoatrial junction but also occasionally throughout the atrial wall. However, most of the atrial cells recorded were myocardial fibers as judged by a stable diastolic potential and a markedly reduced action potential duration (APD) in response to low concentrations of ACh (0.1–1 M). The shortening in APD in atrial myocardial fibers was correlated with a significant fall in twitch force in the atrial preparations. ACh at high concentrations (10–300 M) decreased moderately the APD and the slope of diastolic depolarization of the pacemakers and prolonged the spontaneous cycle length but did not induce hyperpolarization. The negative chronotropic action of ACh was competitively inhibited by atropine, a muscarinic antagonist. The means (± SEM) negative logarithm of the dissociation constant (pK_b or pA₂ value) for atropine against the ACh action on muscarinic receptors were 9.10 (± 0.13) (n = 6), similar to those values obtained in mammalian atria. The present findings indicate that while the negative inotropic effects of ACh in tilapia atria are comparable to those observed in mammalian hearts, unique electrophysiological responses to ACh exist in different types of tilapia atrial cells.     

玉米赤霉烯酮的生殖毒性研究进展

玉米赤霉烯酮是一种特殊毒性的生物毒素,它的强雌激素样作用对动物机体的伤害很大,不仅引起动物流产、死胎、低产仔率等生殖机能异常,还可以导致繁殖功能下降、不育、畸形等.已有研究表明,ZEA对肝脏、肾脏、生殖系统和免疫系统产生明显的损伤,对细胞和遗传性也有毒性作用.目前,虽然国内外学者做了大量的研究,来揭示玉米赤霉烯酮损害机体生殖功能的机制,但关于它影响机体的生殖性能更详尽的机制还亟待进一步的研究.文章主要针对玉米赤霉烯酮的生殖毒性进行了综述,总结出ZEA对生殖系统的毒性机制,从而为临床预防及治疗繁殖疾病提供理论依据.     

Marine Low Molecular Weight Natural Products as Potential Cancer Preventive Compounds

Due to taxonomic positions and special living environments, marine organisms produce secondary metabolites that possess unique structures and biological activities. This review is devoted to recently isolated and/or earlier described marine compounds with potential or established cancer preventive activities, their biological sources, molecular mechanisms of their action, and their associations with human health and nutrition. The review covers literature published in 2003–2013 years and focuses on findings of the last 2 years.     

神农香菊化学成分及药理作用研究进展

介绍了神农香菊主要化学成分的研究成果,比较了花、茎、全草和叶等不同组织中主要活性成分的异同,并综述了其抑菌能力、抗氧化能力以及药用价值的最新研究进展。     

植物病原效应蛋白功能研究方法

植株病原会分泌一些与植物相互作用的效应蛋白,这些蛋白在病原菌与寄主植物互作过程中起着重要作用。结合几种细菌、真菌分泌的效应蛋白研究进展,介绍了用于病原菌效应蛋白研究的试验方法及其独特之处,包括图位克隆、异源表达分析等,提出研究一个单一效应蛋白需要多种分析方法。