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Corrigendum to: ‘A scientific review of the reported effects of vegan nutrition on the occurrence and prevalence of cancer and cardiovascular disease’ “关于纯素营养对癌症和心血管疾病发生和流行的影响的科学综述”的勘误表
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT008
Brighid O'Neill
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引用次数: 0
Effect of woodstack structure on invertebrate abundance and diversity 木桩结构对无脊椎动物丰度和多样性的影响
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT004
R. J. Sands
Reduced quantities of dead wood in managed forests have resulted in a reduction in the abundance and diversity of saproxylic invertebrates to the extent that many are now considered red list species. To mitigate against this loss, one conservation measure is the provision of dead wood, in the form of piles of chopped logs, i.e. ‘woodstacks’. The heterogeneity and volume of dead wood habitat is considered to be an important component of habitat suitability. However, the value of different wood stack types to invertebrate conservation has rarely been quantified and there is little consensus on how to best to survey the invertebrate fauna of woodstacks. This study used both sticky traps and pitfall traps to sample the invertebrate fauna of three types of sycamore woodstack. Woodstacks were made from 10 logs, 20 logs and 10 scorched logs plus a control woodstack made of unplasticised polyvinyl chloride (uPVC) plastic piping and observed over a 4-week period. A total of 1446 invertebrates from 16 orders, including 127 Coleoptera, were caught during the sampling period. A generalized linear model was used to analyse invertebrate abundance between woodstack and between trap types, and diversity was determined using Shannon diversity indices and analysed using a two-way Analysis of Variance (ANOVA). The woodstack type had no effect on the abundance of invertebrates. However, Shannon diversity was highest on the scorched woodstacks, with little difference between the 10 and 20 log stacks and the control uPVC woodstacks. However, closer inspection of orders revealed the uPVC woodstacks to have the lowest abundance and diversity of Coleoptera. This study suggests that constructing woodstacks can provide suitable habitat for a variety of invertebrates. However, these invertebrates may have simply used the structures for shelter and the true value with saproxylic invertebrates could not be measured in this 4-week study. To fully appreciate the conservation value of woodstacks will require longer term studies that examine how and when saproxylic invertebrates use dead and decaying wood.
管理森林中枯木数量的减少导致腐木无脊椎动物的丰度和多样性减少,许多物种现在被认为是红色名录物种。为了减轻这种损失,一项保护措施是提供枯木,即成堆的砍断原木,即“柴堆”。枯木生境的异质性和体积被认为是生境适宜性的重要组成部分。然而,不同类型的木桩对无脊椎动物保护的价值很少被量化,如何最好地调查木桩的无脊椎动物区系也没有达成共识。本研究采用粘捕法和陷阱法对三种悬铃木柴堆的无脊椎动物区系进行了取样。柴堆由10根原木、20根原木和10根烧焦的原木制成,再加上一个由未塑化聚氯乙烯(uPVC)塑料管道制成的对照柴堆,观察时间为4周。共捕获16目无脊椎动物1446只,其中鞘翅目127只。采用广义线性模型分析不同类型木桩和捕集器之间的无脊椎动物丰度,采用Shannon多样性指数确定多样性,并采用双向方差分析(ANOVA)对多样性进行分析。柴堆类型对无脊椎动物的丰度没有影响。然而,香农多样性在焦柴堆上最高,10和20个柴堆与对照uPVC柴堆差异不大。然而,更近距离的观察表明,uPVC木垛的鞘翅目丰度和多样性最低。该研究表明,构筑林垛可以为多种无脊椎动物提供适宜的栖息地。然而,这些无脊椎动物可能只是将这些结构用作庇护所,并且在为期4周的研究中无法测量出腐殖酸无脊椎动物的真实价值。要充分认识到木桩的保护价值,需要进行更长期的研究,研究腐木无脊椎动物如何以及何时使用死亡和腐烂的木材。
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引用次数: 5
The role of hydrogen sulphide in lung diseases 硫化氢在肺部疾病中的作用
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT009
C. H. K. Wu
Hydrogen sulphide (H2S) is a recently discovered gasotransmitter. It is endogenously synthesized by cystathionine β synthetase, cystathionine γ lyase, cysteine aminotransferase, 3-mercaptopyruvate sulphurtransferase and cysteine lyase. Its metabolism leads to the production of sulphate (SO4 2− ), methanthiol, dimethylsulphide and thiocynate. The gas interacts with ion channels, protein kinases and transcription factors. It is also involved in post-translational modification of proteins via S-sulphhydration. Although debate continues as to whether H2S is pro- or anti-inflammatory, its anti-inflammatory properties seem to have beneficial effects in various lung diseases. Serum levels of H 2S differ between asthma, chronic obstructive pul monary disease and pulmonary fibrosis, which makes it difficult for the gas to be used as a biomarker for lung diseases. Apart from exogenous sources of H2S, targets to enhance or inhibit the gas can be found in its synthesis and metabolism pathway. H2S-releasing non-steroidal anti-inflammatory drugs are currently being developed. Further research will aid to determine the precise role of H2S in respiratory diseases.
硫化氢(H2S)是最近发现的一种气体变送器。它由半胱甘氨酸β合成酶、半胱甘氨酸γ裂解酶、半胱氨酸转氨酶、3-巯基丙酮酸硫转移酶和半胱氨酸裂解酶内源性合成。它的代谢导致硫酸盐(SO4 2−)、甲硫醇、二甲基硫化物和硫辛酸盐的产生。这种气体与离子通道、蛋白激酶和转录因子相互作用。它还通过s -硫酸作用参与蛋白质的翻译后修饰。尽管关于H2S是促炎还是抗炎的争论仍在继续,但它的抗炎特性似乎对各种肺部疾病有有益作用。哮喘、慢性阻塞性肺疾病和肺纤维化患者的血清h2s水平不同,这使得这种气体难以作为肺部疾病的生物标志物。除了H2S的外源来源外,还可以在其合成和代谢途径中找到增强或抑制H2S的目标。目前正在开发释放h2s的非甾体抗炎药。进一步的研究将有助于确定H2S在呼吸道疾病中的确切作用。
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引用次数: 4
mGlu5 as a potential therapeutic target for the treatment of fragile X syndrome mGlu5作为治疗脆性X综合征的潜在治疗靶点
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT001
L. Robertson
Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most common known cause of autism. It is caused by the expansion of a CGG trinucleotide repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene, which encodes the fragile X mental retardation protein (FMRP). FMRP negatively regulates group 1 (Grp 1) metabotropic glutamate receptor (mGlu a.k.a. mGluR) activity, and many FXS phenotypes are thought to be due to the over activity of the Grp 1 mGlu, mGlu5. This review evaluates the evidence for mGlu5 as a potential therapeutic target in the treatment of FXS. A 50% reduction in mGlu5 expression in Fmr1 knockout (KO) mice has been shown to reverse many FXS-relevant phenotypes including alterations in synaptic plasticity, increased dendritic spine density, increased basal hippocampal protein synthesis, inhibitory avoidance extinction and susceptibility to audiogenic seizures. A negative modulator of mGlu5 may, therefore, be expected to have the same effect. In Fmr1 KO mice, Grp 1 mGlu antagonists, such as 2-methyl6-(phenylethynyl)pyridine (MPEP), fenobam and AFQ056, have been shown to reduce audiogenic seizures, reverse altered dendritic spine morphology, reduce excessive protein synthesis and improve behavioural abnormalities. MPEP, however, has failed to reverse altered long-term potentiation in the sensory neocortex or reduce machroorchidism. Clinical trials of mGlu5negative modulators have had some positive outcomes but have had too few participants and were not performed over a long enough period to detect significant effects. Nevertheless, the prospects for development of mGlu5-negative modulators as FXS therapeutics are good and most research supports mGlu5 as a potential therapeutic target.
脆性X染色体综合征(FXS)是遗传性智力低下的最常见形式,也是自闭症最常见的已知原因。它是由脆性X智力发育迟缓1 (FMR1)基因5 '非翻译区CGG三核苷酸重复扩增引起的,该基因编码脆性X智力发育迟缓蛋白(FMRP)。FMRP负性调节组1 (Grp 1)代谢性谷氨酸受体(mGlu,又称mGluR)活性,许多FXS表型被认为是由于Grp 1 mGlu, mGlu5的过度活性。本综述评估了mGlu5作为FXS治疗潜在靶点的证据。在Fmr1基因敲除(KO)小鼠中,mGlu5表达减少50%已被证明可以逆转许多fxs相关表型,包括突触可塑性改变、树突棘密度增加、基底海马蛋白合成增加、抑制性回避消失和对听源性癫痫的易感性。因此,mGlu5的负调制器可能具有相同的效果。在Fmr1 KO小鼠中,grp1mglu拮抗剂,如2-甲基6-(苯乙基)吡啶(MPEP),非诺巴姆和AFQ056,已被证明可以减少听源性癫痫发作,逆转改变的树突脊柱形态,减少过度的蛋白质合成并改善行为异常。然而,MPEP并不能逆转感觉新皮层长期增强的改变或减少雄激素分泌。mglu5阴性调节剂的临床试验已经取得了一些积极的结果,但参与者太少,而且进行的时间不够长,无法检测到显著的效果。然而,mGlu5阴性调节剂作为FXS治疗药物的发展前景良好,大多数研究支持mGlu5作为潜在的治疗靶点。
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引用次数: 2
Stem cell therapy for Alzheimer's disease: hype or hope? 干细胞治疗阿尔茨海默病:炒作还是希望?
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT011
A. K. Liu
Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting millions of people in the world. Cognitive impairments such as progressive memory loss are devastating manifestations from this disease. Current pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. As a result, cell-replacement therapy using stem cells is an emerging potential treatment to AD. In the last decade, there have been animal trials using stem cells to treat and modulate cognitive impairment in AD models via three different mechanisms—replacing the damaged or dead cholinergic neurons; protecting neurons by reducing toxic amyloid protein aggregates or insoluble tau neurofibrillary tangles and promoting neurogenesis in hippocampus by neurotrophic secretions from stem cells. All of the trials showed promising results and improved our understandings about the mechanism of dementia in AD. With the continued improvement in safety profile of stem cell therapy and the creation of a better animal AD model in which to test them, it is feasible that stem cells could be trialled in humans for AD treatment in the next 5–10 years.
阿尔茨海默病(AD)是世界上影响数百万人的最常见的神经退行性疾病。认知障碍,如进行性记忆丧失是这种疾病的破坏性表现。目前的药物治疗效果有限,只能缓解症状,不能长期治愈。因此,使用干细胞的细胞替代疗法是一种新兴的潜在治疗阿尔茨海默病的方法。在过去的十年中,已经有动物试验使用干细胞通过三种不同的机制来治疗和调节阿尔茨海默病模型中的认知障碍:替代受损或死亡的胆碱能神经元;通过减少有毒淀粉样蛋白聚集体或不溶性tau神经原纤维缠结,并通过干细胞的神经营养分泌物促进海马神经发生来保护神经元。所有的试验都显示出令人鼓舞的结果,并提高了我们对阿尔茨海默病痴呆机制的理解。随着干细胞治疗安全性的不断提高,以及更好的动物AD模型的建立,在未来5-10年内,干细胞治疗AD的人类试验是可行的。
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引用次数: 15
Evaluation of Cepheid SmartCycler and EuroClone Duplicareal time Dual Easy CT assay for confirmation of Chlamydia trachomatis 造父变星SmartCycler和EuroClone double - time Dual Easy CT检测对沙眼衣原体诊断的评价
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT005
Tolulope Oyebanji
assay for the confirmation of Roche COBAS TaqMan positive tests by comparing results obtained by each method. Consecutive clinical C. trachomatis positive (n = 67) and random negative (n = 17) urogenital samples received at a general district hospital in the North East of England over a 6-month period were examined. Of the total 67 TaqMan-positive samples, 62 (92.5%) of them were also positive by the SmartCycler/EuroClone. There were 5 discrepancies in total (7.5%) and 17 samples were negative on both Roche TaqMan and SmartCycler/EuroClone. The sensitivity and specificity of the method were 92.5 and 100%, respectively. To further assess its specificity, the SmartCycler/EuroClone method was challenged with additional organisms and proved to possess the ability of avoiding false-positive results by correctly identifying these as C. trachomatis DNA negative. Finally, it was found that confirmation of positive C. trachomatis by the SmartCycler/EuroClone method increases the turn around time of chlamydia investigation by 2-folds. In conclusion, the SmartCycler/EuroClone method gave good concordance with the established Roche TaqMan method and proved to be highly suitable for confirmation testing of C. trachomatis positive samples. The remarkable specificity and acceptable sensitivity also confirms its suitability and reliability for this purpose.
通过比较每种方法获得的结果,确定罗氏COBAS TaqMan阳性试验。在英格兰东北部的一家综合性地区医院接受了连续临床沙眼原体阳性(n = 67)和随机阴性(n = 17)的泌尿生殖器样本,为期6个月。在67份taqman阳性样本中,62份(92.5%)的SmartCycler/EuroClone也呈阳性。总共有5个差异(7.5%),17个样本在罗氏TaqMan和SmartCycler/EuroClone上均为阴性。方法的灵敏度为92.5%,特异度为100%。为了进一步评估其特异性,用其他生物体挑战了SmartCycler/EuroClone方法,并证明了通过正确识别这些沙眼衣原体DNA阴性来避免假阳性结果的能力。最后发现,使用SmartCycler/EuroClone方法确认沙眼衣原体阳性,使衣原体调查的周转时间增加了2倍。综上所述,SmartCycler/EuroClone方法与已建立的Roche TaqMan方法具有较好的一致性,适用于沙眼衣原体阳性样品的确认检测。其显著的特异性和可接受的灵敏度也证实了其适用性和可靠性。
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引用次数: 1
The potential effect of vanadium compounds on glucose-6-phosphatase 钒化合物对葡萄糖-6-磷酸酶的潜在影响
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT002
Saima Shehzad
glucose-6-phosphatase from bovine liver microsomes using differential centrifugation, and then the enzyme was assayed in the presence and absence of vanadium compounds. The study found that vanadyl compounds inhibit glucose-6-phosphatase, as mean specific enzyme activity was calculated which showed that VOSO 4 at a concentration of 48 µM inhibited glucose6-phosphatase activity by 36.9% (P < 0.0003) and Vace at a concentration of 200 µM inhibited glucosse-6-phosphatase activity by 50% (P < 0.0001) similar to findings in the previous research. However, this study also found using Lineweaver–Burk plot analysis that VOSO4 is a competitive inhibitor of glucose-6-phophatase and Vace is a mixed: non-competitive and uncompetitive inhibitors of glucose-6-phosphatase. The mechanism of inhibitory action of these vanadyl compounds had not been reported previously. The difference in the concentration of inhibitor required may be due to the type of inhibition. This supports the hypothesis to some extent as the results were found to be statistically significant; however, further data will be required to clarify these findings.
用差速离心法分离牛肝微粒体中的葡萄糖-6-磷酸酶,并在钒化合物存在和不存在的情况下测定酶活性。研究发现,钒基化合物对葡萄糖-6-磷酸酶有抑制作用,计算平均比酶活性,结果表明,48µM浓度的voso4对葡萄糖-6-磷酸酶活性的抑制作用为36.9% (P < 0.0003), 200µM浓度的Vace对葡萄糖-6-磷酸酶活性的抑制作用为50% (P < 0.0001),与前期研究结果相似。然而,本研究还通过Lineweaver-Burk图分析发现,VOSO4是葡萄糖-6-磷酸酶的竞争性抑制剂,而Vace是葡萄糖-6-磷酸酶的非竞争性和非竞争性抑制剂。这些钒基化合物的抑制作用机制尚未见报道。所需抑制剂浓度的差异可能是由于抑制类型的不同。这在一定程度上支持了假设,因为结果被发现具有统计显著性;然而,需要进一步的数据来澄清这些发现。
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引用次数: 14
Phenotypic analyses support investigations of phylogeny in the Skyrian pony and other breeds 表型分析支持斯基良小马和其他品种的系统发育研究
Q2 Agricultural and Biological Sciences Pub Date : 2013-01-01 DOI: 10.1093/BIOHORIZONS/HZT010
S. Brown, M. Moore-Colyer, D. Hannant
Although genetic analyses suggest that the Skyrian pony is unrelated to other breeds, it shares some physical features with Exmoor ponies, thought to originate in the primitive pony referred to as Pony Type 1, and the Caspian horse, thought to be descended from Horse Type 4. To test the hypothesis that the Skyrian shares the Exmoor’s origin in Pony Type 1, comparisons were made of defined physical characters and morphometric measurements amongst Skyrian ponies, Exmoor ponies and Caspian horses. The average mean character differences were 0.56 ± 0.12 between the Skyrians and Exmoors, 0.43 ± 0.15 between the Skyrians and Caspians and 0.83 ± 0.06 between the Caspians and Exmoors. This approximates to reports comparing other horse breeds and breeds in other species, confirming that the Skyrian is a distinct breed. Using two-way analysis of variance (ANOVA), Friedman’s ANOVA and post hoc tests, no significant differences were found between Skyrians and Caspians in the eye, neck, body and limb shape (P = 1.000) nor shoulder angle (P = 0.222) nor in the ratios of body length:elbow height, neck length:neck circumference and heart girth: height to withers. However, there were significant differences ( P < 0.001) between Skyrians and Exmoors for these physical characters and ratios. While significant differences existed between Skyrians and Caspians in cephalic profile, parietal crest and tail placement (P < 0.001) and there were similarities between Skyrians and Exmoors in these physical characters (P = 1.000 or 0.098), overall the Skyrians appeared phenotypically closer to the Caspian, but unrelated to either breed. This investigation enabled the evaluation of a methodology comprising systematic, comprehensive investigations of phenotype, with data reduced and analysed by appropriate statistical methods, to clarify equine breed ancestry and phylogeny. The studies confirmed that the analysis of phenotype has utility and potential for investigations of phylogeny in species where there may be a paucity of information from the genetic base. Moreover, this approach has been shown to support and augment knowledge derived from studies based on genetic testing and provide a cost-effective and easily performed method of determining relatedness amongst equine breeds.
尽管基因分析表明斯基里安小马与其他品种无关,但它与埃克斯穆尔小马有一些共同的身体特征,埃克斯穆尔小马被认为起源于被称为小马1型的原始小马,而里海马被认为是马4型的后裔。为了验证斯基良马与埃克斯穆尔马在Pony Type 1中的起源相同这一假设,研究人员对斯基良马、埃克斯穆尔马和里海马的定义物理特征和形态测量进行了比较。Skyrians与Exmoors的平均性格差异为0.56±0.12,Skyrians与caspian的平均性格差异为0.43±0.15,caspian与Exmoors的平均性格差异为0.83±0.06。这近似于比较其他马品种和其他马品种的报告,证实了斯基莱恩是一个独特的品种。采用双向方差分析(ANOVA)、弗里德曼方差分析(Friedman’s ANOVA)和事后检验,skyrian和caspian在眼睛、颈部、身体和肢体形状(P = 1.000)、肩角(P = 0.222)、体长:肘部高度、颈长:颈围和心围:高度与肩胛骨的比值均未发现显著差异。然而,Skyrians和Exmoors在这些身体特征和比例上存在显著差异(P < 0.001)。尽管斯基里安人和里海人在头侧轮廓、顶冠和尾巴位置上存在显著差异(P < 0.001),而斯基里安人和埃克斯摩尔人在这些物理特征上存在相似性(P = 1.000或0.098),但总的来说,斯基里安人在表型上更接近里海人,但与这两个品种无关。这项调查能够评估一种方法,包括系统的、全面的表型调查,通过适当的统计方法减少和分析数据,以澄清马的品种血统和系统发育。这些研究证实了表型分析在物种系统发育研究中具有实用性和潜力,这些物种可能缺乏遗传基础的信息。此外,这种方法已被证明支持和增强了基于基因检测的研究所得的知识,并提供了一种成本效益高且易于执行的确定马品种之间亲缘关系的方法。
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引用次数: 1
Optogenetics: shining a light on the brain 光遗传学:用光照射大脑
Q2 Agricultural and Biological Sciences Pub Date : 2012-01-01 DOI: 10.1093/BIOHORIZONS/HZR020
J. Butler
© The Author 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 1 Optogenetics: shining a light on the brain
©作者2012。牛津大学出版社出版。这是一篇在知识共享署名非商业许可(http://creativecommons.org/licenses/by-nc/2.5)条款下发布的开放获取文章,该许可允许在任何媒介上不受限制的非商业使用、分发和复制,前提是正确引用原始作品。光遗传学:用光照射大脑
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引用次数: 10
Novel histone deacetylase (HDAC) inhibitors with improved selectivity for HDAC2 and 3 protect against neural cell death 新型组蛋白去乙酰化酶(HDAC)抑制剂具有提高HDAC2和3选择性的保护神经细胞死亡
Q2 Agricultural and Biological Sciences Pub Date : 2012-01-01 DOI: 10.1093/BIOHORIZONS/HZS003
B. Durham
Neurodegenerative disorders, such as motor neurone disease, Alzheimer’s disease and responses to brain traumas such as stroke, involve the unwanted death of neural cells. Although the exact underlying mechanisms leading to neural cell death are not well defined, one contributory event in many situations is the over-excitation of cells caused by too much of the neurotransmitter glutamate. Drugs that inhibit enzymes called histone deacetylases (HDACs) can protect neural cells from glutamate excitotoxicity. However, current inhibitors lack specificity and although they function in vitro, they have a substantial potential for adverse side effects in vivo. HDAC2 and 3 have been implicated in neurotoxicity and here we investigated the neuroprotective potential of three novel HDAC inhibitors that show selectivity for these. The ability of these HDAC inhibitors to protect against glutamate excitotoxicity was tested using cultured organotypic cerebral slices from 7-day-old (P7) Wistar rats. Glutamate excitotoxicity was induced by 200 µM of the glutamate transporter blocker, DL-threo-β-benzyloxyaspartate (DL-TBOA). This was applied alone and alongside 1 µM of the novel HDAC2 and 3 selective inhibitors AH51, AH61 and AH62. Neural cell viability in slices was quantified from assays using the fluorescent stains, 4′,6-diamidino-2-phenylindole and ethidium homodimer-1. The induction of glutamate excitotoxicity by DL-TBOA resulted in 41.3 ± 6.1% (n = 7, P < 0.01) loss in cell viability as judged by ethidium homodimer-1 staining. All three novel HDAC inhibitors significantly prevented neural cell death in response to DL-TBOA (P < 0.01), with cell viabilities of 107.5 ± 6.01% (n = 4), 97.1 ± 16.5% (n = 3) and 106.7 ± 6.45% (n = 4) for AH51, AH61 and AH62, respectively. This study has shown that inhibitors selective for HDAC2 and 3 can protect neural cells from death and thus have potential as therapeutic agents against neurotoxicity.
神经退行性疾病,如运动神经元疾病、阿尔茨海默病和对脑创伤的反应,如中风,都涉及到神经细胞的不必要死亡。虽然导致神经细胞死亡的确切潜在机制尚不清楚,但在许多情况下,一个促成事件是由过多的神经递质谷氨酸引起的细胞过度兴奋。抑制组蛋白去乙酰化酶(HDACs)的药物可以保护神经细胞免受谷氨酸兴奋毒性的影响。然而,目前的抑制剂缺乏特异性,尽管它们在体外起作用,但它们在体内有很大的潜在不良副作用。HDAC2和3与神经毒性有关,在这里,我们研究了三种新型HDAC抑制剂的神经保护潜力,这些抑制剂对这些具有选择性。这些HDAC抑制剂对谷氨酸兴奋毒性的保护能力通过7日龄Wistar大鼠培养的器官型脑切片进行了测试。用200µM谷氨酸转运蛋白阻断剂dl - 3 -β-苄氧天冬氨酸(DL-TBOA)诱导谷氨酸兴奋毒性。这是单独应用,并与1µM的新型HDAC2和3选择性抑制剂AH51, AH61和AH62。采用荧光染色、4′,6-二氨基-2-苯基吲哚和乙锭同二聚体-1测定切片神经细胞活力。乙锭二聚体-1染色结果显示,DL-TBOA诱导谷氨酸兴奋毒性导致细胞活力下降41.3±6.1% (n = 7, P < 0.01)。三种新型HDAC抑制剂均能显著预防DL-TBOA引起的神经细胞死亡(P < 0.01), AH51、AH61和AH62的细胞存活率分别为107.5±6.01% (n = 4)、97.1±16.5% (n = 3)和106.7±6.45% (n = 4)。本研究表明,选择性HDAC2和3抑制剂可以保护神经细胞免于死亡,因此有潜力作为治疗神经毒性的药物。
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引用次数: 17
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Bioscience Horizons
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