从转化医学走向转化（中）兽医药

简述了转化医学产生的背景、概念及当前国内发展现状,分析了转化医学在中（兽）医药研发过程中应用的模式和难点,针对中（兽）医药转化研究的特点提出加强中（兽）医药转化研究的几点建议。盼望中国农业科学院兽医药物监督所率先创建中兽医药临床疗效评价中心。     

Descriptive analysis of haemangiosarcoma occurrence in dogs enrolled in the Golden Retriever lifetime study

Haemangiosarcoma is a relatively common malignant tumour in dogs, and one of the primary outcomes of interest for the Golden Retriever Lifetime Study. This study collects longitudinal data and samples from a cohort of golden retrievers, with the aim of identification of nutritional, genetic, environmental, lifestyle and reproductive risk factors for cancers and other important diseases in dogs. This analysis describes the accumulating data and samples, which are available for use by researchers to fulfil the study's objectives. As of September 2022, 233/3044 dogs enrolled in the study had been diagnosed with haemangiosarcoma (7.65%), with an incidence rate of 1.10 cases per 100 dog-years. Visceral haemangiosarcoma was the most common, affecting 211/3044 study dogs (6.9%). One hundred and twenty eight visceral haemangiosarcoma diagnoses specified the presence of splenic tumours (60.7%) and 119 specified the presence of cardiac tumours (56.4%). The probability of remaining without a haemangiosarcoma diagnosis declined from 100% from approximately 4 years of age, to a 12 year probability of 91.1% in intact females (95% CI 84.4%–98.3%), 60.7% in neutered females (95% CI 41.6%–88.6%), 72.9% in intact males (95% CI 62.9%–84.6%) and 70.0% in neutered males (95% CI 53.4%–92.0%). The 1 year survival probability for visceral haemangiosarcoma was 1.42% (95% CI 0.37%–5.47%); for cutaneous haemangiosarcoma, it was 84.6% (95% CI 67.1%–99.99%). The accumulated data and samples are a considerable resource for further investigation of canine haemangiosarcoma and have a potential role in translational medicine.     

Glyoxalase 1 expression is downregulated in preimplantation blastocysts of diabetic rabbits

In a diabetic pregnancy, an altered maternal metabolism led to increased formation of reactive α‐dicarbonyls such as glyoxal (GO) and methylglyoxal (MGO) in the reproductive organs and embryos. The enzyme glyoxalase (GLO) 1 detoxifies reactive α‐dicarbonyls thus protecting cells against malfunction or modifications of proteins by advanced glycated end products (AGEs). The aim of this study was to analyse the influence of a maternal insulin‐dependent diabetes mellitus (IDD) on GLO1 expression and activity in preimplantation embryos in vivo and human trophoblast cells (Ac‐1M88) in vitro. Maternal diabetes was induced in female rabbits by alloxan before conception and maintained during the preimplantation period. GLO1 expression and activity were investigated in 6‐day‐old blastocysts from healthy and diabetic rabbits. Furthermore, blastocysts and human trophoblast cells were exposed in vitro to hyperglycaemia, GO and MGO and analysed for GLO1 expression and activity. During gastrulation, GLO1 was expressed in all compartments of the rabbit blastocyst. Maternal diabetes decreased embryonic GLO1 protein amount by approx. 30 per cent whereas the enzymatic activity remained unchanged, indicating that the specific GLO1 activity increases along with metabolic changes. In in vitro cultured embryos, neither hyperglycaemia nor MGO and GO had an effect on GLO1 protein amount. In human trophoblast cells, a stimulating effect on the GLO1 expression was shown in the highest GO concentration, only. Our data show that maternal diabetes mellitus affects the specific activity of GLO1, indicating that GLO1 was post‐translationally modified due to changes in metabolic processes in the preimplantation embryos.     

影响伪狂犬病病毒同义密码子用法特点的因素分析

为了充分了解伪狂犬病病毒基因组结构和病毒进化机制,计算伪狂犬病病毒各基因(组)Nc值、RSCU值、GC3s含量和双核苷酸组成,分析伪狂犬痛病毒密码子用法特点.采用目前最普遍使用的多变量统计分析方法(对应分析)分析影响伪狂犬病病毒基因组同义密码子用法偏爱性的因素.结果表明:①在GC含量丰富的伪狂犬病病毒基因组中,所有基因都偏爱于以G或C结尾的密码子;②伪狂犬病病毒对CpG、CpC、GpC和GpG 4种双核苷酸具有显著偏爱性,而较少使用ApA、ApT、TpA和TpT 4种双核苷酸;③碱基组成限制、碱基突变压力、翻译选择和基因功能是形成伪狂犬病病毒密码子用法特点的4种因素.伪狂犬病病毒所有基因Nc-GC3s分布图显示有些基因如LLT ORF1、LLT ORF2等的偏向性完全是由于碱基的组成限制.GC3s-GC12s散点图则显示碱基突变和自然选择都是PRV密码子偏向性的形成因素.根据RSCU值进行的对应分析表明伪狂犬病病毒大多数基因密码子用法受基因表达水平和基因功能影响.综上所述,伪狂犬病病毒偏爱于G或C结尾的密码子,且碱基组成限制、碱基突变、翻译选择和基因功能是影响伪狂犬病病毒同义密码子用法特点的主要因素.