表观遗传学与肿瘤

表观遗传学是指研究基因表达或蛋白表达的改变不涉及DNA序列变化,但又可以通过细胞分裂和增殖而稳定遗传现象的遗传学分支领域。其研究对象是表观遗传修饰,目前认识到的表观遗传修饰主要包括DNA甲基化、组蛋白修饰和染色质重塑等。近年来,随着人们对表观遗传学认识的深入,尤其是DNA甲基转移酶抑制物、组蛋白乙酰化抑制剂等在治疗肿瘤患者的成功临床应用,表观遗传学逐渐成为肿瘤研究的热点。主要对DNA甲基化和组蛋白修饰两种表观遗传修饰的分子调控机制、与肿瘤发生的关系及其在肿瘤的表观遗传治疗中的研究进展作一综述。     

表观遗传学与肿瘤

表观遗传学是指研究基因表达或蛋白表达的改变不涉及DNA序列变化,但又可以通过细胞分裂和增殖而稳定遗传现象的遗传学分支领域。其研究对象是表观遗传修饰,目前认识到的表观遗传修饰主要包括DNA甲基化、组蛋白修饰和染色质重塑等。近年来,随着人们对表观遗传学认识的深入,尤其是DNA甲基转移酶抑制物、组蛋白乙酰化抑制剂等在治疗肿瘤患者的成功临床应用,表观遗传学逐渐成为肿瘤研究的热点。主要对DNA甲基化和组蛋白修饰两种表观遗传修饰的分子调控机制、与肿瘤发生的关系及其在肿瘤的表观遗传治疗中的研究进展作一综述。     

表观遗传学:家畜遗传育种的新挑战

表观遗传变异是在DNA序列并没有发生改变的情况下,基因表达调控发生了可遗传性的变化,并最终导致了基因功能甚至个体表型的变化。表观遗传修饰主要包括DNA甲基化修饰、组蛋白修饰和非编码RNA调控等。目前,表观遗传学正渗透到家畜遗传育种领域,论文着重探讨了表观遗传学在家畜遗传育种中的研究进展及其所面临的新挑战。     

表观遗传调控机制在犬肿瘤中的研究进展

犬肿瘤性疾病是兽医临床上常发的一种疾病，其发病率较高，是造成世界范围内犬死亡的重要原因之一，由于其病理学分类、自发性、基因和信号通路等方面与人类肿瘤有相似之处，可作为人类肿瘤的研究模型。表观遗传是基于DNA序列没有发生改变的情况下所致基因功能和表达水平发生了可遗传的变化，主要通过基因转录或翻译过程的调控，影响其功能和特性。表观遗传改变主要包括DNA甲基化水平改变、组蛋白修饰、染色质重塑和非编码RNA调控等。DNA异常甲基化在犬的多种肿瘤中均有研究，包括犬白血病、淋巴瘤及黑色素瘤等，且犬与人类肿瘤的DNA异常甲基化模式相似。在肿瘤中组蛋白各种修饰酶表达失调，是抗肿瘤药物开发分子靶点研究的主要焦点，但目前在犬肿瘤中的研究较少。非编码RNA中microRNA与lncRNA是目前的研究热点，已有较多研究致力于开发针对非编码RNA的靶向研究药物，但目前在兽医领域应用较少。作者主要综述了犬肿瘤疾病的流行病学、DNA甲基化、组蛋白修饰、非编码RNA等表观遗传学变化在犬肿瘤中的研究进展，揭示表观遗传异常与犬肿瘤发生发展的关系，以期为开发犬肿瘤性疾病诊断、靶向治疗及预后的特异性标志物提供参考依据。     

表观遗传学在雌性蜜蜂级型分化研究中的应用

表观遗传学是研究细胞核DNA序列没有改变的情况下,基因功能的可逆的、可遗传的改变,并最终导致了表型变化的一门遗传学分支学科;其研究内容主要包括DNA甲基化、组蛋白修饰、染色质重塑、非编码RNA调控等。表观遗传学在雌性蜜蜂级型分化研究中的应用主要体现在DNA甲基化、非编码RNA调控等方面。本文对其作了综述,并讨论了表观遗传学在蜜蜂科学研究中的应用前景及它们之间的相互促进作用。     

营养素对动物表观遗传的影响及其机制

表观遗传是环境因素和细胞内的遗传物质相互作用的结果.表观遗传学是在DNA碱基序列不变的前提下引起的基因表达或细胞表观型变化的一种遗传现象,具体表现在以下3个既相互独立又相互作用的方面:DNA甲基化、组蛋白修饰和microRNA (miRNA)调控.本文就表观遗传的研究进展及营养素对动物表观遗传的影响及其机制进行综述.     

睾酮合成的表观遗传调控机制研究进展

睾酮是一种主要由睾丸间质细胞合成分泌的类固醇激素，参与调节生殖和其他生理活动，对精子发生及维持雄性生殖健康具有重要作用。睾酮合成是一个非常复杂的过程，受到激素、转录因子及信号转导等调控。表观遗传是在基因序列不变的基础上基因表达发生的可遗传变化，其主要类型包括DNA甲基化、组蛋白甲基化、组蛋白乙酰化、组蛋白泛素化、非编码RNA和RNA甲基化调控等。表观遗传作为睾酮合成的重要调节途径，近年来越来越受关注。本文简要介绍了表观遗传对睾酮合成的调控，总结了DNA甲基化、组蛋白甲基化、组蛋白乙酰化、组蛋白泛素化、非编码RNA和RNA甲基化调控睾酮合成的相关研究进展，以期为进一步研究睾酮合成机制提供参考。     

lncRNAs调控表观遗传的研究进展

表观遗传学(epigenetic)是不改变DNA序列而使基因的表达发生可遗传的变化,包括DNA甲基化、组蛋白修饰、基因组印迹、随机染色体失活及长链非编码RNA(lncRNAs)的调节作用等。lncRNAs是一类转录本长度超过200nt的RNA分子,它们并不编码蛋白,而是以RNA的形式在多种层面上调控基因的表达水平。lncRNAs的功能往往受到表观遗传作用的影响,同时lncRNAs通过染色质修饰、基因组印迹、剂量补偿效应等过程,在基因表达中发挥表观遗传学作用。论文对lncRNAs表观遗传调控的研究进展情况进行了综述,以期为深入研究lncRNAs调控性状的机理提供思路。     

营养与表观遗传修饰关系的研究进展

表观遗传学是在DNA碱基序列不变的前提下引起的基因表达或细胞表观型变化的一种遗传现象。经典遗传学理论认为DNA序列的遗传能够主导亲代基因传递给后代,但越来越多的证据表明营养等环境因素对基因表达具有重要的修饰作用,如营养因素可通过DNA甲基化、组蛋白修饰和microRNA(miRNA)调控等作用来影响表观遗传,且营养素对机体健康的保持有着非常重要的作用(尤其是生命早期的营养)。作者就动物或人长期暴露在蛋白质缺乏、能量不足、高脂和采食过度等营养不平衡日粮条件下,以及一些特殊的营养素作用条件下,其表观遗传修饰的变化及作用机制方面的最新研究进展进行综述,旨在为后续的深入研究提供参考。     

牧草表观遗传学研究进展

表观遗传是指在DNA序列不变的情况下基因表达发生变化的现象。表观遗传现象与外界环境条件的变化紧密相关,它参与植物的生长发育、胁迫响应、衰老死亡等重要生命过程并在其中起到了关键作用。表观遗传学作为一门新兴学科在近20年间得到了快速发展,成为当前动植物和医学领域的研究热点。目前植物表观遗传学的相关研究主要集中在DNA甲基化、组蛋白修饰、RNA甲基化、染色质重塑和非编码RNA修饰等方面,并取得了许多重要成果。然而,相对于模式植物拟南芥和其他主要作物而言,牧草的表观遗传学研究仍处于起步阶段。因此,开展牧草表观遗传学研究对我国草牧业的可持续发展具有重要意义。本研究对表观遗传学的概念、研究方法、研究内容(包括DNA甲基化、组蛋白修饰、RNA甲基化、染色质重塑和非编码RNA修饰等)及牧草表观遗传学相关研究进行了全面总结和综述,并对表观遗传在草牧业中的发展前景进行了展望。     

Phase I evaluation of CCNU (lomustine) in tumor-bearing cats

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.     

Furosemide continuous rate infusion in the horse: evaluation of enhanced efficacy and reduced side effects

Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses.     

Prevalence of gastric lesions in racing Alaskan sled dogs

Human and equine athletes are reported to have a high prevalence of gastric disease, and anecdotal evidence suggests a similar phenomenon applies to racing sled dogs. To investigate the prevalence of gastric disease in racing sled dogs, we conducted 2 gastroscopy studies on dogs competing in the annual Iditarod Sled Dog Race. A pilot study of dogs that were either dropped from the 2000 Iditarod Sled Dog Race because of illness or that finished the race indicated that, approximately 5 days after competing, 10 of 28 dogs (35%) had endoscopic evidence of gastric ulceration, erosion, or hemorrhage. The next year, an endoscopic study of 73 dogs participating in the 2001 Iditarod race was performed in order to evaluate a larger population of dogs. Data from 70 of these dogs could be used; 34 (48.5%) had ulceration, erosion, gastric hemorrhage, or some combination of these findings. When this group of 70 dogs was compared retrospectively to a control group of 87 dogs presented to the Texas A&M University (TAMU) Veterinary Medical Teaching Hospital, the Iditarod sled dogs had a significantly higher prevalence (P = .049) of gastric lesions. These findings suggest that, similar to athletes of other species, elite canine athletes have an increased prevalence of gastric disease compared to the canine population at large.     

Internal Parasites and Haematological Values in Cattle Slaughtered in Buea Subdivision of Cameroon

Tropical Animal Health and Production -     

The Epidemiology of Gastrointestinal Nematodes of Dairy Cattle in Central Kenya

The epidemiology of H. placei and of other gastrointestinal nematodes in yearling dairy cattle was examined on two farms in Kiambu District, central Kenya during each of 13 one-month periods from April 1993 to April 1994. On each farm, 32 newly weaned dairy calves were given a single dose of albendazole and then placed on experimental pastures. Twelve of the animals were designated for bi-monthly slaughter (n = 2) and analysis of worm population characteristics and 20 were designated for blood and faecal collection and for weighing. Two parasite-free tracer calves were grazed alongside the weaner calves each month throughout the study period and were also slaughtered for analysis of worm populations. Faecal egg counts, haematological and serum pepsinogen determinations, herbage larval counts, and animal live weight changes were recorded monthly. The study revealed that Haemonchus placei, Trichostrongylus axei, Cooperia spp. and Oesophagostomum radiatum were responsible for parasitic gastroenteritis and that H. placei was the predominant nematode present in the young cattle on both farms. Faecal egg counts from resident cattle and necropsy worm counts revealed that pasture larval levels were directly related to the amount of rainfall. The total worm burdens in the animals were highest during the rainy season (March–June and October–December) and lowest during the dry seasons (July–September and January–February). The very low recovery of immature larvae of H. placei from the tracer calves indicated that arrested development is not a feature of the life cycle of this parasite in central Kenya. The maintenance of the parasite population depended on continuous cycling of infection between the host and the pasture. The agroclimatic conditions of the study area were such that, in general, favourable weather conditions for the development and survival of the free-living stages of gastrointestinal nematodes existed all year round.     

Diversity of Ectoparasites in Sheep Flocks in Sa~o Paulo,Brazil

The occurrence of ectoparasites in sheep flocks is frequently reported but seldom quantified. Sheep production used to be a predominantly family activity in the state of Sa~o Paulo (Brazil), but it began to become a commercial activity in the past decade. Thus, information about the ectoparasites existing in sheep flocks has become necessary. The present data were obtained by means of questionnaires sent to all sheep breeders belonging to the `Associaça~o Paulista de Criadores de Ovinos' (ASPACO; Sa~o Paulo State Association of Sheep Breeders). Response reliability was tested by means of random visits paid to 10.6% of the respondents. Most of the properties (89.5%) reported the presence of one or more ectoparasites. Screw-worm (Cochliomyia hominivorax) was the most frequent ectoparasite (72.5%), followed by bot fly larvae (Dermatobia hominis, 45.0%), ticks (Amblyomma cajennense) and Boophilus microplus, 31.3%) and finally lice (Damalinia ovis, 13.8%). Combined infestations also occurred, the most common one being screw-worm with bot fly larvae (36.0%) followed by bot fly larvae with ticks (13.9%), screw-worm with ticks (9.3%), bot fly larvae with lice (6.9%), and ticks with lice (5.0%). The most common triple combination was screw-worm, bot fly larvae and ticks (12.8%). Breeds raised for meat or wool were attacked by bot fly larvae and ticks more often than other breeds. Lice were only absent from animals of indigenous breeds. The relationships among these ectoparasites are discussed in terms of sheep breeds, flock size, seasonality and the ectoparasitic combinations on the host.     

Chemotaxis of macrophage in inflammation

Our particular attention in this article was given to natural mediators for macrophages isolated from the sites of tissue injury. A number of chemotactic factors, which may satisfy many criteria making them acceptable as inflammatory leucocyte chemotactic factors, has been separated. Among them, our laboratory has isolated three macrophage (monocyte) chemotactic factors (MCF-a, -b and -c). Their purification, characterization and functional specificity are discussed.     

Evaluation of biohydrogenation rate of canola vs. soya bean seeds as unsaturated fatty acids sources for ruminants in situ

An experiment was conducted to study disappearance of C14 to C18 fatty acids, lag times and biohydrogenation (BH) rates of C18 fatty acids of ground soya bean and canola seeds in situ. Three ruminally fistulated Dallagh sheep were used to determine ruminal BH of unsaturated fatty acids (UFAs). Differences in the disappearance of fatty acids through the bags and lag times were observed between the oilseeds. We saw that the longer the incubation time of the oilseeds in the rumen, the lower the content of C18:2 and C18:3. Significantly higher lag times for both C18:2 and C18:3 were observed in ground canola compared to ground soya bean. BH rates of C18:2 and C18:3 fatty acids in soya bean were three times higher than those of canola. These results suggest that the fatty acid profile of fat source can affect the BH of UFAs by rumen micro‐organisms. So that UFAs of canola had higher ability to escape from ruminal BH. It seems that fatty acid profile of ruminant products is more affected by canola seed compared to soya bean seed.     

Serum biochemical values and mineral element contents of tissues in yaks

Serum biochemical values and the wet weight to dry weight ratios of tissues were determined in yaks in Shandan county of Gansu province. The liver, kidney, heart and muscle contents of seven elements in yaks were also analysed. Most serum biochemical values were similar to those of cattle, camels and sheep, but the calcium concentration was considerably above the normal range for other ruminants. The liver contained the highest concentrations of copper, manganese and cobalt and the kidney of selenium, iron and calcium.Abbreviations Alb albumin - ALT alanine aminotransferase - AST aspartate aminotransferase - BUN blood urea nitrogen - Chol cholesterol - Glob globulin - -GT -glutamyl transpeptidase - IP inorganic phosphorus - TP total protein