transcriptomic

转录组
  • 文章类型: Journal Article
    在海上风电场的运营阶段,低频水下噪声的产生因其对鱼类健康的潜在不利影响而受到广泛关注。本研究对山东省海上风电场的水下噪声进行了实地调查,中国。随后,进行了一项小规模实验,以研究对黑石鱼(Sebastesschlegelii)的胁迫。鱼暴露于主频为80Hz的噪声中,125Hz和250Hz。这些频率与实际现场的风力噪声(wpn)的频率相同。经过40天的实验,转录组测序是在大脑上进行的,肝脏,和黑石鱼的肾脏组织,以阐明对来自海上风电场的噪声应力的响应所涉及的潜在分子机制。结果表明,125Hz组表现出最高数量的差异表达基因(DEG)之间的噪声暴露和对照组(CK组),大脑中总共有797个,1076在肝脏中,和2468在肾脏。基因本体论(GO)分析表明,DEGs在与细胞过程相关的条目中显著富集,膜组件,绑定,和新陈代谢。京都基因和基因组百科全书(KEGG)分析显示,DEGs主要富集在代谢,豁免权,凋亡,信号转导,和疾病。研究结果表明,长时间暴露于海上风电场的水下噪声可能会导致代谢失衡,免疫功能障碍,黑石鱼的心肌疾病风险增加。
    During the operational phase of offshore wind farms, the generation of low-frequency underwater noise has received widespread attention due to its potential adverse impact on fish health. This study conducted a field survey of underwater noise at offshore wind farms located in Shandong province, China. Subsequently, a small-scale experiment was conducted to study the stress on black rockfish (Sebastes schlegelii). The fish were exposed to noise with dominant frequency of 80 Hz, 125 Hz and 250 Hz. These frequencies are same with the frequencies from wind power noise (wpn) at the actual site. After a 40-day experimental period, transcriptome sequencing was conducted on brain, liver, and kidney tissues of black rockfish to elucidate the underlying molecular mechanisms involved in the response to noise stress originating from offshore wind farms. The results revealed that the 125 Hz group exhibited the highest number of differentially expressed genes (DEGs) between the noise-exposed and control check group (CK group), with a total of 797 in the brain, 1076 in the liver, and 2468 in the kidney. Gene Ontology (GO) analysis showed that DEGs were significantly enriched in entries related to cellular processes, membrane components, binding, and metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were enriched mainly in metabolism, immunity, apoptosis, signal transduction, and diseases. The findings indicate that prolonged exposure to underwater noise from offshore wind farms may induce metabolic imbalance, immune dysfunction, and an increased risk of myocardial diseases in black rockfish.
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  • 文章类型: Journal Article
    目的:探讨异鼠李素治疗DMED的疗效及作用机制。
    方法:利用高糖环境诱导海绵体内皮细胞损伤,并结合铁凋亡抑制剂等干预剂观察细胞损伤和修复的过程,通过CCK-8和DAPI评估细胞状态;建立STZ诱导的糖尿病大鼠模型,检测勃起功能和组织变化;对异鼠李素处理的大鼠模型和样品进行转录组测序,分析差异表达基因及其GO功能;结合铁凋亡数据库确定关键通路;流式细胞仪检测ROS和线粒体膜电位,RT-PCR用于验证基因表达,海马检测线粒体耗氧率,揭示异鼠李素的作用机制。
    结果:铁凋亡抑制剂和异鼠李素可有效逆转高糖和铁凋亡激动剂诱导的海绵体内皮细胞损伤。异鼠李素具有恢复糖尿病大鼠勃起功能的能力,同时增强内皮细胞的数量和改善胶原纤维的形态。免疫组织化学显示糖尿病大鼠阴茎组织中存在铁凋亡。转录组学分析显示,异鼠李素通过调节基因如GFER,IGHM,GPX4和HMOX1,涉及多种途径和生物过程。流式细胞术和RT-PCR证实异鼠李素能降低活性氧水平,恢复必需的基因表达,提高线粒体膜电位,减轻氧化应激和铁中毒。海马检测发现异鼠李素可恢复线粒体耗氧率。结论:异鼠李素通过抑制铁凋亡和氧化应激,减轻高糖对海绵状内皮细胞的损伤。恢复勃起功能,改善糖尿病大鼠的组织形态,及其多途径、多靶点的调控机制提示其有望成为治疗DMED的有效药物。
    OBJECTIVE: Exploring the therapeutic effect and mechanism of isorhamnetin in the treatment of DMED.
    METHODS: Using a high glucose environment to induce endothelial cells damage in the corpus cavernosum, and combining with intervention agents such as ferroptosis inhibitors to observe the process of cell damage and repair, evaluating cell status through CCK-8 and DAPI; To establish the STZ-induced diabetes rat model and detect the erectile function and tissue changes; Perform transcriptomic sequencing on rat models and samples treated with isorhamnetin to analyze differentially expressed genes and their GO functions; Identify critical pathways by combining with the ferroptosis database; Flow cytometry was used to detect ROS and mitochondrial membrane potential, and RT-PCR was used to verify gene expression, Seahorse detects mitochondrial oxygen consumption rate, revealing the mechanism of action of isorhamnetin.
    RESULTS: Ferroptosis inhibitors and isorhamnetin can effectively reverse the damage of corpus cavernosum endothelial cells induced by high glucose and ferroptosis agonists. Isorhamnetin has the ability to reinstate the erectile function of diabetic rats, while enhancing the quantity of endothelial cells and refining the morphology of collagen fibers. Immunohistochemistry revealed that ferroptosis existed in the penis tissue of diabetes rats. Transcriptomic analysis showed that isorhamnetin improves gene expression in DM rats by regulating genes such as GFER, IGHM, GPX4 and HMOX1, involving multiple pathways and biological processes. Flow cytometry and RT-PCR confirmed that isorhamnetin can reduce reactive oxygen species levels, restore essential gene expression, improve mitochondrial membrane potential, and alleviate oxidative stress and ferroptosis. Seahorse detection found that isorhamnetin can restore mitochondrial oxygen consumption rate.
    CONCLUSIONS: Isorhamnetin attenuates high glucose damage to cavernous endothelial cells by inhibiting ferroptosis and oxidative stress, restores erectile function and improves tissue morphology in diabetic rats, and its multi-pathway and multi-targeting regulatory mechanism suggests that it is promising to be an effective drug for the treatment of DMED.
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  • 文章类型: Journal Article
    乳腺炎是奶牛养殖中最常见的疾病之一,而病原菌生物膜的形成可能是传统抗生素治疗不能解决某些乳品乳腺炎的重要原因。我们从中国重庆奶牛场的奶牛乳房炎样品中分离并鉴定了3株具有强生物膜形成能力的A.lwoffii。为了研究新型抗生物膜肽CRAMP-34对A.lwoffii生物膜的影响,抗生物膜作用通过结晶紫染色,生物膜活菌计数和共聚焦激光扫描显微镜(CLSM)。此外,转录组测序分析,通过qRT-PCR和表型验证来探讨其作用机制。结果表明,CRAMP-34对A.lwoffii生物膜具有剂量依赖性的根除作用。转录组测序分析表明,在亚抑制浓度的CRAMP-34干预后,检测到36个差异表达基因(11个上调,25个下调)。这些差异表达的基因可能与酶合成有关,菌毛,铁吸收系统,荚膜多糖等毒力因子通过差异基因的功能分析。随后的细菌运动性和粘附性试验结果表明,经CRAMP-34干预后,A.lwoffii的运动性增强,但粘附性无明显变化。推测CRAMP-34可能通过增强生物膜菌的运动性促进生物膜菌的分散,从而达到根除生物膜的效果。因此,这些结果,以及我们之前的其他发现,建议CRAMP-34有望作为一种新的生物膜根除剂,值得进一步研究和开发。
    Dairy mastitis is one of the most common diseases in dairy farming, and the formation of pathogenic bacteria biofilms may be an important reason why traditional antibiotic therapy fails to resolve some cases of dairy mastitis. We isolated and identified three strains of A. lwoffii were with strong biofilm forming ability from dairy cow mastitis samples from Chongqing dairy farms in China. In order to investigate the effect of novel anti-biofilm peptide CRAMP-34 on A.lwoffii biofilms, the anti-biofilm effect was evaluated by crystal violet staining, biofilms viable bacteria counting and confocal laser scanning microscopy (CLSM). In addition, transcriptome sequencing analysis, qRT-PCR and phenotypic verification were used to explore the mechanism of its action. The results showed that CRAMP-34 had a dose-dependent eradicating effect on A. lwoffii biofilms. Transcriptome sequencing analysis showed that 36 differentially expressed genes (11 up-regulated and 25 down-regulated) were detected after the intervention with the sub-inhibitory concentration of CRAMP-34. These differentially expressed genes may be related to enzyme synthesis, fimbriae, iron uptake system, capsular polysaccharide and other virulence factors through the functional analysis of differential genes. The results of subsequent bacterial motility and adhesion tests showed that the motility of A.lwoffii were enhanced after the intervention of CRAMP-34, but there was no significant change in adhesion. It was speculated that CRAMP-34 may promote the dispersion of biofilm bacteria by enhancing the motility of biofilm bacteria, thereby achieving the effect of eradicating biofilms. Therefore, these results, along with our other previous findings, suggest that CRAMP-34 holds promise as a new biofilm eradicator and deserves further research and development.
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  • 文章类型: Journal Article
    转化代表了抗生素抗性基因(ARGs)水平转移的最重要途径之一,这使得有能力的细菌能够从周围环境中获得细胞外ARGs。重金属和辐照都已被证明会影响细菌转化过程。然而,普遍存在的放射性重金属对ARGs转化的影响在很大程度上仍然未知。这里,我们展示了一个有代表性的放射性核素,铀(U),在环境浓度(0.005-5毫克/升),以浓度依赖性方式将抗性质粒pUC19向大肠杆菌的转化频率提高了0.10-0.85倍。在U胁迫下增强的ARGs转化能力被证明与活性氧(ROS)过量生产有关,膜损伤,以及与DNA摄取和重组相关的基因的上调。膜通透性和ROS产生是影响转化能力的主要直接和间接因素,分别。我们的发现为U对ARGs转化过程的影响的潜在机制提供了宝贵的见解,并强调了对放射性重金属污染的生态系统中ARGs扩散加剧的担忧。特别是在有核活动或事故的地区。
    Transformation represents one of the most important pathways for the horizontal transfer of antibiotic resistance genes (ARGs), which enables competent bacteria to acquire extracellular ARGs from the surrounding environment. Both heavy metals and irradiation have been demonstrated to influence the bacterial transformation process. However, the impact of ubiquitously occurring radioactive heavy metals on the transformation of ARGs remains largely unknown. Here, we showed that a representative radioactive nuclide, uranium (U), at environmental concentrations (0.005-5 mg/L), improved the transformation frequency of resistant plasmid pUC19 into Escherichia coli by 0.10-0.85-fold in a concentration-dependent manner. The enhanced ARGs transformation ability under U stress was demonstrated to be associated with reactive oxygen species (ROS) overproduction, membrane damage, and up-regulation of genes related to DNA uptake and recombination. Membrane permeability and ROS production were the predominant direct and indirect factors affecting transformation ability, respectively. Our findings provide valuable insight into the underlying mechanisms of the impacts of U on the ARGs transformation process and highlight concerns about the exacerbated spread of ARGs in radioactive heavy metal-contaminated ecosystems, especially in areas with nuclear activity or accidents.
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  • 文章类型: Journal Article
    百合browniivar。viridulum,被称为LongyaLily,是我国著名的药食植物。鳞茎腐病是龙眼百合栽培的常见病,严重影响百合的产量和品质。根据实地调查,我们发现同一田地中不同的龙牙百合植物对根腐病的抗性程度不同。找出导致差异的原因,我们对不同程度的龙舌兰进行了代谢组学和转录组学分析。转录组学分析显示,早期和中期感染(LYBH2和LYBH3)中差异表达基因的数量增加,而在晚期感染(LYBH4)中下降。与健康灯泡(LYBH1)相比,总共2309个DEGs在患病灯泡中显示出相同的表达趋势。DEGs的转录因子(TFs)分析表明,几种常见的TFs,像WRKY一样,bHLH,AP2/ERF-ERF和MYB,在衰减后的灯泡中被显著激活。代谢组学分析表明,有794种差异积累的代谢物,相对含量显著变化的代谢物主要是酚酸,其次是类黄酮和氨基酸及衍生物。转录组和代谢组的联合分析表明,苯丙素生物合成途径在龙舌兰抗鳞茎腐病中至关重要。因此,我们推测龙舌兰对鳞茎腐烂的不同抗性程度可能与苯丙素生物合成途径中基因转录水平和代谢物含量有关。总的来说,这些结果阐明了龙眼百合对鳞茎腐烂的分子反应,为选育抗病品种奠定了理论基础。
    Lilium brownii var. viridulum, known as Longya lily, is a well-known medicinal and edible plant in China. Bulb rot is a common disease in Longya lily cultivation that severely affects the yield and quality of lilies. According field investigations, we found that different Longya lily plants in the same field had different degrees of resistance to root rot. To find the reasons leading to the difference, we performed metabolomic and transcriptomic analyses of Longya lily with different degrees of disease. The transcriptomic analyses showed that the number of differentially expressed genes increased in early and mid-stage infections (LYBH2 and LYBH3), while decreased in late-stage infection (LYBH4). A total of 2309 DEGs showed the same expression trend in diseased bulb compared healthy bulb (LYBH1). The transcription factors (TFs) analysis of DEGs showed that several common TFs, like WRKY, bHLH, AP2/ERF-ERF and MYB, were significantly activated in bulbs after decay. The metabolomic analyses showed that there were 794 differentially accumulated metabolites, and metabolites with significant changes in relative content largely were phenolic acids, followed by flavonoids and amino acids and derivatives. The combined analysis of transcriptome and metabolome indicated that phenylpropanoid biosynthesis pathway was crucial in Longya lily resistance to bulb rot. Therefore, we speculated that the different degree of resistance to bulb rot in Longya lily may be related to the transcript levels of gene and contents of metabolites in the phenylpropanoid biosynthesis pathway. Overall, these results elucidate the molecular responses of Longya lily to bulb rot and lay a theoretical foundation for breeding resistant varieties.
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  • 文章类型: Journal Article
    缺氧是水生生态系统中常见的环境胁迫源,在培养过程中,巨齿斑病容易死亡,因为它不耐受缺氧,给农民带来巨大的经济损失。脑垂体是鱼类的重要内分泌腺,它主要参与分泌,storage,和激素的调节。在本研究中,我们比较了缺氧敏感(HS)和缺氧耐受(HT)的脑垂体对严重缺氧的转录反应。根据缺氧处理期间失去平衡所需的时间对鱼进行分类。总共获得129,251,170个原始读数。原始序列过滤后,HS获得了43,461,745、42,609,567和42,730,282个干净的读数,HT,和C0组,分别。转录组比较揭示了在C0与C0中差异表达的1234个基因。HS,虽然获得了C0与C0的1646个差异表达基因HT。此外,HS与HS的结果HT显示,对于总共408个差异表达基因,获得了367个上调和41个下调的差异表达基因。C0与C0的KEGG分析HS,C0vs.HT,和HSvs.HT确定了315、322和219个富集的途径,分别。类似的缺氧诱导的转录模式表明,下调的DEGs和富集的通路与多种疾病的神经变性通路有关。癌症的通路,产热,microRNAs在癌症中,糖尿病性心肌病,和肾素分泌。然而,在上调的DEG中,PI3K-Akt信号通路(C0vs.HS),癌症中的microRNAs(C0vs.HT),和HIF-1信号通路(HSvs.HT)显著富集。关于垂体在低氧应激中的作用尚不清楚。这些结果不仅为脑垂体组织应对缺氧应激的机制提供了新的见解,而且为培育具有耐缺氧性状的小脑提供了基础。
    Hypoxia is a common environmental stressor in aquatic ecosystems, and during the cultivation process, Megalobrama amblycephala is prone to death because it is hypoxia-intolerant, which brings huge economic losses to farmers. The pituitary gland is a crucial endocrine gland in fish, and it is mainly involved in the secretion, storage, and regulation of hormones. In the present study, we compared the transcriptional responses to serious hypoxia in the pituitary gland among hypoxia-sensitive (HS) and hypoxia-tolerant (HT) M. amblycephala and a control group that received a normal oxygen supply (C0). The fish were categorized according to the time required to lose balance during a hypoxia treatment. A total of 129,251,170 raw reads were obtained. After raw sequence filtering, 43,461,745, 42,609,567, and 42,730,282 clean reads were obtained for the HS, HT, and C0 groups, respectively. A transcriptomic comparison revealed 1234 genes that were differentially expressed in C0 vs. HS, while 1646 differentially expressed genes were obtained for C0 vs. HT. In addition, the results for HS vs. HT showed that 367 upregulated and 41 downregulated differentially expressed genes were obtained for a total of 408 differentially expressed genes. A KEGG analysis of C0 vs. HS, C0 vs. HT, and HS vs. HT identified 315, 322, and 219 enriched pathways, respectively. Similar hypoxia-induced transcription patterns suggested that the downregulated DEGs and enriched pathways were related to pathways of neurodegeneration in multiple diseases, pathways in cancer, thermogenesis, microRNAs in cancer, diabetic cardiomyopathy, and renin secretion. However, in the upregulated DEGs, the PI3K-Akt signaling pathway (C0 vs. HS), microRNAs in cancer (C0 vs. HT), and HIF-1 signaling pathway (HS vs. HT) were significantly enriched. There is a lack of clarity regarding the role of the pituitary gland in hypoxic stress. These results not only provide new insights into the mechanism by which pituitary tissue copes with hypoxia stress in M. amblycephala but also offer a basis for breeding M. amblycephala with hypoxia-resistant traits.
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  • 文章类型: Journal Article
    油棕是具有多种应用的多功能油料作物。近年来,组织学技术在油棕研究中的应用取得了重大进展。对油棕进行了全基因组测序,以解释有序基因组的功能和结构,促进分子标记的开发和遗传图谱的构建,这对于研究油棕的重要性状和遗传资源至关重要。转录组学为研究植物生物学的各个方面提供了强大的工具,包括非生物和生物胁迫,脂肪酸组成和积累,和有性生殖,虽然蛋白质组学和代谢组学提供了研究脂质合成和应激反应的机会,根据不同的基因和代谢物水平调节脂肪酸组成,阐明对非生物胁迫的生理机制,并解释油棕中有趣的生物过程。本文从多组学角度对油棕研究现状进行了综述,希望为油棕的进一步深入研究提供参考。
    Oil palm is a versatile oil crop with numerous applications. Significant progress has been made in applying histological techniques in oil palm research in recent years. Whole genome sequencing of oil palm has been carried out to explain the function and structure of the order genome, facilitating the development of molecular markers and the construction of genetic maps, which are crucial for studying important traits and genetic resources in oil palm. Transcriptomics provides a powerful tool for studying various aspects of plant biology, including abiotic and biotic stresses, fatty acid composition and accumulation, and sexual reproduction, while proteomics and metabolomics provide opportunities to study lipid synthesis and stress responses, regulate fatty acid composition based on different gene and metabolite levels, elucidate the physiological mechanisms in response to abiotic stresses, and explain intriguing biological processes in oil palm. This paper summarizes the current status of oil palm research from a multi-omics perspective and hopes to provide a reference for further in-depth research on oil palm.
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  • 文章类型: Journal Article
    海洋软体动物,包括牡蛎,对高水平的镉(Cd)有很高的耐受性,但是他们对急性Cd暴露的分子反应的分子机制尚不清楚。在这项研究中,太平洋牡蛎Crassostreagigas被用作生物模型,暴露于急性Cd胁迫96小时。对其g进行转录组学分析,和代谢组学分析进一步验证了这些结果。在我们的研究中,在急性Cd暴露下,总共鉴定出111个差异表达的代谢物(DEM)和2108个差异表达的基因(DEG)。进一步的分析揭示了与重金属应激反应相关的关键基因和代谢途径的改变。Cd暴露引发牡蛎的生理和代谢反应,包括增强的氧化应激和能量代谢紊乱,这些变化揭示了牡蛎对急性Cd胁迫的生物学反应。此外,牡蛎通过激活ABC转运体能有效增强对急性镉暴露的耐受性和解毒能力,增强g细胞中谷胱甘肽代谢和硫中继系统,调节能量代谢。本研究通过结合代谢组学和转录组分析,揭示了牡蛎急性Cd胁迫的分子机制,探索了牡蛎对Cd高耐受性的分子机制。
    Marine mollusks, including oysters, are highly tolerant to high levels of cadmium (Cd), but the molecular mechanisms underlying their molecular response to acute Cd exposure remain unclear. In this study, the Pacific oyster Crassostrea gigas was used as a biological model, exposed to acute Cd stress for 96 h. Transcriptomic analyses of their gills were performed, and metabolomic analyses further validated these results. In our study, a total of 111 differentially expressed metabolites (DEMs) and 2108 differentially expressed genes (DEGs) were identified under acute Cd exposure. Further analyses revealed alterations in key genes and metabolic pathways associated with heavy metal stress response. Cd exposure triggered physiological and metabolic responses in oysters, including enhanced oxidative stress and disturbances in energy metabolism, and these changes revealed the biological response of oysters to acute Cd stress. Moreover, oysters could effectively enhance the tolerance and detoxification ability to acute Cd exposure through activating ABC transporters, enhancing glutathione metabolism and sulfur relay system in gill cells, and regulating energy metabolism. This study reveals the molecular mechanism of acute Cd stress in oysters and explores the molecular mechanism of high tolerance to Cd in oysters by using combined metabolomics and transcriptome analysis.
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  • 文章类型: Journal Article
    背景:PogostemonisHerba长期以来一直用于中医治疗炎症性疾病。广藿香精油(PEO)是PogostemonisHerba的主要成分,并且已建议在用于治疗溃疡性结肠炎(UC)时提供治愈潜力。然而,PEO治疗UC的药理机制尚待阐明.
    目的:阐明PEO治疗UC的药理机制。
    结果:在本研究中,结合转录组和网络药理学方法来阐明PEO治疗UC的机制。我们的结果表明,在UC模型小鼠中直肠PEO给药可显着缓解UC的症状。此外,PEO有效抑制结肠炎症和氧化应激。机械上,PEO可以通过调节肠道菌群来改善UC小鼠,抑制炎症靶点(OPTC,PTN,IFIT3,EGFR,和TLR4),并抑制PI3K-AKT途径。接下来,确定了在PEO的抗UC机制中起作用的11种潜在的生物活性成分,并部分验证了pogestone(一种生物活性成分)在UC小鼠中的治疗效果。
    结论:本研究强调了PEO治疗UC的机制,为未来开发和应用PEO治疗UC提供了严格的科学基础。
    BACKGROUND: Pogostemonis Herba has long been used in traditional Chinese medicine to treat inflammatory disorders. Patchouli essential oil (PEO) is the primary component of Pogostemonis Herba, and it has been suggested to offer curative potential when applied to treat ulcerative colitis (UC). However, the pharmacological mechanisms of PEO for treating UC remain to be clarified.
    OBJECTIVE: To elucidate the pharmacological mechanisms of PEO for treating UC.
    RESULTS: In the present study, transcriptomic and network pharmacology approaches were combined to clarify the mechanisms of PEO for treating UC. Our results reveal that rectal PEO administration in UC model mice significantly alleviated symptoms of UC. In addition, PEO effectively suppressed colonic inflammation and oxidative stress. Mechanistically, PEO can ameliorate UC mice by modulating gut microbiota, inhibiting inflammatory targets (OPTC, PTN, IFIT3, EGFR, and TLR4), and inhibiting the PI3K-AKT pathway. Next, the 11 potential bioactive components that play a role in PEO\'s anti-UC mechanism were identified, and the therapeutic efficacy of the pogostone (a bioactive component) in UC mice was partially validated.
    CONCLUSIONS: This study highlights the mechanisms through which PEO can treat UC, providing a rigorous scientific foundation for future efforts to develop and apply PEO for treating UC.
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  • 文章类型: Journal Article
    背景:顺磁性铁,反磁性淀粉样β(Aβ)斑块及其相互作用在阿尔茨海默病(AD)的发病机制中至关重要,复杂的非侵入性磁共振成像前驱AD检测。
    方法:我们使用最先进的亚体素定量磁化率图方法同时测量死后人脑中的Aβ和铁水平,通过组织学验证。使用Allen人脑图谱的进一步转录组学分析阐明了潜在的生物过程。
    结果:在内侧前额叶观察到局部增加的顺磁性和反磁性磁化率,顶骨内侧,和海马旁皮质与AD大脑中铁沉积(R=0.836,p=0.003)和Aβ积累(R=0.853,p=0.002)相关。与细胞周期相关的基因表达水平较高,翻译后蛋白质修饰,并观察到细胞对应激的反应。
    结论:这些发现提供了对皮质区域对较高水平Aβ聚集的可变脆弱性的定量见解,铁过载,以及随后的神经变性,表明临床症状之前的变化。
    结论:不同脑区对β淀粉样蛋白(Aβ)和铁积累的脆弱性各不相同。对离体人脑的染色切片进行组织学验证。易感性的区域变化与基因表达谱有关。同时定量离体脑中的铁和Aβ水平。
    BACKGROUND: The paramagnetic iron, diamagnetic amyloid beta (Aβ) plaques and their interaction are crucial in Alzheimer\'s disease (AD) pathogenesis, complicating non-invasive magnetic resonance imaging for prodromal AD detection.
    METHODS: We used a state-of-the-art sub-voxel quantitative susceptibility mapping method to simultaneously measure Aβ and iron levels in post mortem human brains, validated by histology. Further transcriptomic analysis using Allen Human Brain Atlas elucidated the underlying biological processes.
    RESULTS: Regional increased paramagnetic and diamagnetic susceptibility were observed in medial prefrontal, medial parietal, and para-hippocampal cortices associated with iron deposition (R = 0.836, p = 0.003) and Aβ accumulation (R = 0.853, p = 0.002) in AD brains. Higher levels of gene expression relating to cell cycle, post-translational protein modifications, and cellular response to stress were observed.
    CONCLUSIONS: These findings provide quantitative insights into the variable vulnerability of cortical regions to higher levels of Aβ aggregation, iron overload, and subsequent neurodegeneration, indicating changes preceding clinical symptoms.
    CONCLUSIONS: The vulnerability of distinct brain regions to amyloid beta (Aβ) and iron accumulation varies. Histological validation was performed on stained sections of ex-vivo human brains. Regional variations in susceptibility were linked to gene expression profiles. Iron and Aβ levels in ex-vivo brains were simultaneously quantified.
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